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Conserved domains on  [gi|1790094194|ref|NP_001364264|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta isoform 2 [Homo sapiens]

Protein Classification

phosphatidylinositol 3-kinase( domain architecture ID 10466624)

phosphatidylinositol 3-kinase catalyzes the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 959-1312 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 743.36  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd00895      1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd00895     81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd00895    161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1278
Cdd:cd00895    241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd00895    321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 622-794 9.77e-77

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


:

Pssm-ID: 175979  Cd Length: 171  Bit Score: 251.51  E-value: 9.77e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  622 QEACHFARSLAFTVYATHRIPIIWATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIVWDQQICFPVQVNRLPR 701
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  702 ETLLCATLYALPIPPPGSSseaNKQRRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENPSARWSAPNFHQPDSVIL 781
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                          170
                   ....*....|...
gi 1790094194  782 QIDFPTSAFDIKF 794
Cdd:cd04012    158 QIDFPSSAFDVIF 170
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1341-1449 1.80e-76

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


:

Pssm-ID: 132823  Cd Length: 109  Bit Score: 248.30  E-value: 1.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRRE 1420
Cdd:cd07290      1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd07290     81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1477-1599 1.14e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


:

Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.88  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1477 GGEVKLSISYKNNKLFIMVMHIRGLQLLQdGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1556
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1790094194 1557 QRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALG 1599
Cdd:cd08381     80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Ka super family cl00271
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 813-953 3.09e-71

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


The actual alignment was detected with superfamily member cd00869:

Pssm-ID: 412275  Cd Length: 169  Bit Score: 235.81  E-value: 3.09e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  813 EEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHSE----------------------------WTHMNHQDALGLLHA 864
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEpnalplvlasapswdwanlmdvyqllhqWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  865 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRYQ 944
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 1790094194  945 YLLAALLCC 953
Cdd:cd00869    161 DLGAALRCQ 169
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 364-466 2.16e-35

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


:

Pssm-ID: 395642  Cd Length: 106  Bit Score: 130.49  E-value: 2.16e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  364 AVTPSPEHL--GDEVNLKVTVLCDRLQEALTFTCNCSSTVDLLIYQTLCYTHDDLRNVDVG-DFVLKPCGLEEFLQNKHA 440
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 1790094194  441 LGSHEYIQYCRKFDIDIRLQLMEQKV 466
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 959-1312 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 743.36  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd00895      1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd00895     81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd00895    161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1278
Cdd:cd00895    241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd00895    321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 622-794 9.77e-77

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 251.51  E-value: 9.77e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  622 QEACHFARSLAFTVYATHRIPIIWATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIVWDQQICFPVQVNRLPR 701
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  702 ETLLCATLYALPIPPPGSSseaNKQRRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENPSARWSAPNFHQPDSVIL 781
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                          170
                   ....*....|...
gi 1790094194  782 QIDFPTSAFDIKF 794
Cdd:cd04012    158 QIDFPSSAFDVIF 170
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1341-1449 1.80e-76

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 248.30  E-value: 1.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRRE 1420
Cdd:cd07290      1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd07290     81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1052-1263 2.14e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 244.90  E-value: 2.14e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1052 VIFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEH---------- 1117
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1118 ---------------GVTGSFKDRPLADWLQKHNPGEDE-YEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHM 1181
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1182 FHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPE 1261
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ..
gi 1790094194  1262 LS 1263
Cdd:smart00146  236 WR 237
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1477-1599 1.14e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.88  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1477 GGEVKLSISYKNNKLFIMVMHIRGLQLLQdGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1556
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1790094194 1557 QRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALG 1599
Cdd:cd08381     80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 813-953 3.09e-71

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 235.81  E-value: 3.09e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  813 EEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHSE----------------------------WTHMNHQDALGLLHA 864
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEpnalplvlasapswdwanlmdvyqllhqWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  865 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRYQ 944
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 1790094194  945 YLLAALLCC 953
Cdd:cd00869    161 DLGAALRCQ 169
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1050-1245 6.78e-66

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 223.36  E-value: 6.78e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1050 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDM-RMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG-----VTGSF 1123
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1124 KD-----------------------RPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIML-KTTG 1179
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1790094194 1180 HMFHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTH 1245
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLN 222
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 810-963 1.37e-61

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 208.65  E-value: 1.37e-61
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   810 SLREEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHS-----------------------------EWTHMNHQDALG 860
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnnpkalpkfllsvkwsdadevaqalslllSWAPLDPEDALE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   861 LLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFS 940
Cdd:smart00145   82 LLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVS 161

                           170       180
                    ....*....|....*....|...
gi 1790094194   941 IRYQYLLAALLCCCGKGLREEFN 963
Cdd:smart00145  162 IRFGLLLEAYLRGCGTHLKELLK 184
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 364-466 2.16e-35

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 130.49  E-value: 2.16e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  364 AVTPSPEHL--GDEVNLKVTVLCDRLQEALTFTCNCSSTVDLLIYQTLCYTHDDLRNVDVG-DFVLKPCGLEEFLQNKHA 440
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 1790094194  441 LGSHEYIQYCRKFDIDIRLQLMEQKV 466
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 648-788 7.26e-35

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 130.18  E-value: 7.26e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  648 SYEDFYLSCSLSHGGKELCSPLQTRRAHFSKylfHLIVWDQQICFPVQVNRLPRETLLCATLYALPIPppgssseanKQR 727
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSN---SSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------EKS 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1790094194  728 RVPeaLGWVTTPLFNFRQVLTCGRKLLGLWPATQ-ENPSARW---------SAPNFHQPDSViLQIDFPTS 788
Cdd:pfam00792   69 FVP--IGWVNTSLFDKKGILRQGKQKLRLWPSKStPGRSNVDemnrlekllKKYERGQVSSV-DWLDFLTF 136
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 812-962 3.37e-34

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 130.14  E-value: 3.37e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  812 REEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHS------------EWTHMNHQ----------------DALGLLH 863
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLvpkaltklllsvKWSDLSEVaealslllkwapidpvDALELLD 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  864 ATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRY 943
Cdd:pfam00613   86 PKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRF 165

                          170
                   ....*....|....*....
gi 1790094194  944 QYLLAALLCCCGKGLREEF 962
Cdd:pfam00613  166 GSLLELYLRSCGTSLLGLN 184
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1034-1313 4.45e-30

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 130.67  E-value: 4.45e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1034 VPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMR----MVIFRCFSTGRGRGMVEMIPNAET 1109
Cdd:COG5032   1783 RPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRrdlwIRPYKVIPLSPGSGIIEWVPNSDT 1860

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1110 LRKI--------------------QVEHGVTG---------SFKDRP-LADWLQKHNPGEDEYEKAVENFIYSCAGCCVA 1159
Cdd:COG5032   1861 LHSIlreyhkrknisidqekklaaRLDNLKLLlkdefftkaTLKSPPvLYDWFSESFPNPEDWLTARTNFARSLAVYSVI 1940

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1160 TYVLGICDRHNDNIML-KTTGHMFHIDFGRFLGhAQMFGNIKRDRAPFVFTSDMAYVING-GDKPSsrfhdFVDLCCQAY 1237
Cdd:COG5032   1941 GYILGLGDRHPGNILIdRSSGHVIHIDFGFILF-NAPGRFPFPEKVPFRLTRNIVEAMGVsGVEGS-----FRELCETAF 2014

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1238 NLIRKHTHL------FLNLLGLMLSCGIPELSD--LEDLKYVYDALRPQDTEANATTYFTRLIESSLGSVATKL-NFFih 1308
Cdd:COG5032   2015 RALRKNADSlmnvleLFVRDPLIEWRRLPCFREiqNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQAtDPF-- 2092


                   ....*
gi 1790094194 1309 NLAQM 1313
Cdd:COG5032   2093 QLATM 2097
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 621-722 5.83e-29

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 112.05  E-value: 5.83e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   621 VQEACHFARSLAFTVYATHRIPIIWATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYlfhlIVWDQQICFPVQVNRLP 700
Cdd:smart00142    3 IESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPS----VKWNEWLTFPIQISDLP 78

                            90       100
                    ....*....|....*....|..
gi 1790094194   701 RETLLCATLYALPIPPPGSSSE 722
Cdd:smart00142   79 REARLCITIYAVKNPSKGSEFG 100
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1351-1447 8.56e-25

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 100.11  E-value: 8.56e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1351 FHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSR--GEAVAERRREELNGYIWH 1428
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNnfSEEFIEKRRRGLEKYLQS 86

                            90
                    ....*....|....*....
gi 1790094194  1429 LIHAPPEVAECDLVYTFFH 1447
Cdd:smart00312   87 LLNHPELINHSEVVLEFLE 105
C2 pfam00168
C2 domain;
1489-1598 4.00e-23

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 95.46  E-value: 4.00e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1489 NKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLpdpQKTTKRKTKVARKTCNPTYNEMLVYDgIPkgDLQQRELQLSVLSEQ 1568
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS-VP--DPENAVLEIEVYDYD 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 1790094194 1569 GFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1490-1595 1.57e-21

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 1.57e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1490 KLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKttKRKTKVARKTCNPTYNEMLVYDGIPkgdLQQRELQLSVLSEQG 1569
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 1790094194  1570 FWENVLLGEVNIRLRELDLAQEKTGW 1595
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 364-464 9.68e-17

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 77.37  E-value: 9.68e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   364 AVTPSPEHLGDEV---NLKVTVLCDRLQEALTFTCNCSSTVDLLIYQTLCYTHDDLRNVDVG--DFVLKPCGLEEFLQNK 438
Cdd:smart00144    1 TSPSVPEPLPLKTianKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTseDYILKVCGRDEYLLGD 80

                            90       100
                    ....*....|....*....|....*.
gi 1790094194   439 HALGSHEYIQYCRKFDIDIRLQLMEQ 464
Cdd:smart00144   81 HPLGSFEYIRNCLKNGTEPHLVLMTL 106
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1364-1448 2.02e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 75.74  E-value: 2.02e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1364 MRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRgEAVAERRREELNGYIWHLIHApPEVAECDLVY 1443
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQH-PELRNSEVLL 78


                   ....*
gi 1790094194 1444 TFFHP 1448
Cdd:pfam00787   79 EFLES 83
 
Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 959-1312 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 743.36  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd00895      1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd00895     81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd00895    161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1278
Cdd:cd00895    241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd00895    321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 959-1312 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 682.86  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNgSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd05166      1 REEFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLEN-SFRLPLDPALEVTGVDVRSCSYFNSNALPLKL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd05166     80 VFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd05166    160 LTGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGN 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSdLEDLKYVYDALRPQ 1278
Cdd:cd05166    240 FKRDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT-QDDLRYVQDALLPE 318

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd05166    319 LTDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 959-1312 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 592.72  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNgSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd05176      1 REELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKN-KCRLPLSPSLVAKELNIKACSFFSSNAVPLKV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd05176     80 ALVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd05176    160 VTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGS 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1278
Cdd:cd05176    240 FKRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQ 319

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd05176    320 TTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 959-1297 5.25e-159

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 485.54  E-value: 5.25e-159
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFalngSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELPK----KFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVE-H 1117
Cdd:cd00891     77 VFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKyG 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1118 GVTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFG 1197
Cdd:cd00891    157 GFGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKF 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1198 NIKRDRAPFVFTSDMAYVINGGDkpSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRP 1277
Cdd:cd00891    237 GIKRERAPFVFTPEMAYVMGGED--SENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQL 314

                          330       340
                   ....*....|....*....|
gi 1790094194 1278 QDTEANATTYFTRLIESSLG 1297
Cdd:cd00891    315 DLSDEEAAEHFRKLIHESLN 334
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 959-1312 1.40e-156

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 480.16  E-value: 1.40e-156
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1038
Cdd:cd05177      1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1039 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 1118
Cdd:cd05177     81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1119 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1198
Cdd:cd05177    161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1199 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1278
Cdd:cd05177    241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1790094194 1279 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd05177    321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 962-1312 1.29e-121

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 385.83  E-value: 1.29e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  962 FNRQCWLVNALAKLAQQVREAAPS-ARQGILRTGLEEVKQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKLSF 1040
Cdd:cd05165      4 LSRQVEALNKLKKLSDILKEKKKSkEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRPLWLVF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1041 QNVDPL---GENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEH 1117
Cdd:cd05165     84 ENADPLalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIANIQKKK 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1118 G--VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQM 1195
Cdd:cd05165    164 GkvATLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFLGNFKK 243

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1196 FGNIKRDRAPFVFTSDMAYVI-NGGDKPSS-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYD 1273
Cdd:cd05165    244 KFGIKRERVPFVLTHDFVYVIaRGQDNTKSeEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDIEYLRK 323

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1790094194 1274 ALRPQDTEANATTYFTRLIESSL-GSVATKLNFFIHNLAQ 1312
Cdd:cd05165    324 TLALDKTEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 960-1314 7.86e-87

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 288.30  E-value: 7.86e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  960 EEFNRQCWLVNALAKLAQQVR----EAAPSARQGI--LRTGLEEVkQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNA 1033
Cdd:cd00894      2 HDFTQQVQVIEMLQKVTLDIKslsaEKYDVSSQVIsqLKQKLENL-QNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1034 VPLKLSFQNVDPLG---ENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETL 1110
Cdd:cd00894     81 KPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1111 RKIQVEH-GVTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRF 1189
Cdd:cd00894    161 AKIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1190 LGHAQMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDL 1268
Cdd:cd00894    241 LGNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1790094194 1269 KYVYDALRPQDTEANATTYFTRLIESSLGSVAT-KLNFFIHNLAQMK 1314
Cdd:cd00894    321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTvQFNWFLHLVLGIK 367
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 1011-1312 6.48e-81

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 271.54  E-value: 6.48e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1011 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFR 1090
Cdd:cd05174     59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYG 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1091 CFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPGeDEYEKAVENFIYSCAGCCVATYVLGICD 1167
Cdd:cd05174    139 CLSTGDKTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPG-DALDQAIEEFTLSCAGYCVATYVLGIGD 217

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1168 RHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHTHL 1246
Cdd:cd05174    218 RHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHGLL 297

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1790094194 1247 FLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYF-TRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd05174    298 FLHLFALMKAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 364
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 959-1312 1.90e-79

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 266.32  E-value: 1.90e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  959 REEFNRQCWLVNALAKLAQQVREAAPSARQGI--LRTGLEEVKQF-FALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVP 1035
Cdd:cd00896      1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIerLRELLSDSELGlLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1036 LKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQV 1115
Cdd:cd00896     81 LKLTFKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADILK 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1116 EHGvtgsfkdrPLADWLQKHNPGED----EYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLG 1191
Cdd:cd00896    159 KYG--------SILNFLRKHNPDESgpygIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1192 haqmfgnikRDRAPFV----FTSDMayvING-GDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLE 1266
Cdd:cd00896    231 ---------RDPKPFPppmkLCKEM---VEAmGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEP 298

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1790094194 1267 D--LKYVYDALRPQDTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd00896    299 DkaVLKVQEKFRLDLSDEEAEQYFQNLIDESVNALFPAVVETIHKIAQ 346
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 622-794 9.77e-77

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 251.51  E-value: 9.77e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  622 QEACHFARSLAFTVYATHRIPIIWATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIVWDQQICFPVQVNRLPR 701
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  702 ETLLCATLYALPIPPPGSSseaNKQRRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENPSARWSAPNFHQPDSVIL 781
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                          170
                   ....*....|...
gi 1790094194  782 QIDFPTSAFDIKF 794
Cdd:cd04012    158 QIDFPSSAFDVIF 170
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 1011-1312 1.70e-76

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 258.74  E-value: 1.70e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1011 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFR 1090
Cdd:cd05173     56 PLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYG 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1091 CFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPGeDEYEKAVENFIYSCAGCCVATYVLGICD 1167
Cdd:cd05173    136 CLATGDRSGLIEVVSSAETIADIQLNSsnvAAAAAFNKDALLNWLKEYNSG-DDLERAIEEFTLSCAGYCVATYVLGIGD 214

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1168 RHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGdKP--SSRFHDFVDLCCQAYNLIRKHTH 1245
Cdd:cd05173    215 RHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQG-KTgnTEKFGRFRQYCEDAYLILRKNGN 293

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1790094194 1246 LFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYFTRLIESSLG-SVATKLNFFIHNLAQ 1312
Cdd:cd05173    294 LFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALReSWTTKVNWMAHTVRK 361
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1341-1449 1.80e-76

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 248.30  E-value: 1.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRRE 1420
Cdd:cd07290      1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd07290     81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1052-1263 2.14e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 244.90  E-value: 2.14e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1052 VIFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEH---------- 1117
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1118 ---------------GVTGSFKDRPLADWLQKHNPGEDE-YEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHM 1181
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1182 FHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPE 1261
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ..
gi 1790094194  1262 LS 1263
Cdd:smart00146  236 WR 237
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1477-1599 1.14e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.88  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1477 GGEVKLSISYKNNKLFIMVMHIRGLQLLQdGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1556
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLD-GSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1790094194 1557 QRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALG 1599
Cdd:cd08381     80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 813-953 3.09e-71

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 235.81  E-value: 3.09e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  813 EEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHSE----------------------------WTHMNHQDALGLLHA 864
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEpnalplvlasapswdwanlmdvyqllhqWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  865 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRYQ 944
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 1790094194  945 YLLAALLCC 953
Cdd:cd00869    161 DLGAALRCQ 169
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 954-1312 1.45e-67

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 233.03  E-value: 1.45e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  954 CGKGLREeFNRQCW----LVNALAKLAQQVREAAPSARQGILRTGLEEVKQFFALNGSCRlPLSPSLLVKGIVPRDCSYF 1029
Cdd:cd05175      1 CGMYLKH-LSRQVEamekLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLS-PLNPAHQLGNLRLEECRIM 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1030 NSNAVPLKLSFQNVDPLGE----NIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIP 1105
Cdd:cd05175     79 SSAKRPLWLNWENPDIMSEllfqNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVR 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1106 NAETLRKIQVEHGVTGS--FKDRPLADWLQKHNPGEDeYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFH 1183
Cdd:cd05175    159 NSHTIMQIQCKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFH 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1184 IDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSSR---FHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIP 1260
Cdd:cd05175    238 IDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKtreFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMP 317

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1790094194 1261 ELSDLEDLKYVYDALRPQDTEANATTYFTRLI-ESSLGSVATKLNFFIHNLAQ 1312
Cdd:cd05175    318 ELQSFDDIAYIRKTLALDKTEQEALEYFMKQMnDAHHGGWTTKMDWIFHTIKQ 370
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1050-1245 6.78e-66

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 223.36  E-value: 6.78e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1050 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDM-RMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG-----VTGSF 1123
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1124 KD-----------------------RPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIML-KTTG 1179
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1790094194 1180 HMFHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTH 1245
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLN 222
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 810-963 1.37e-61

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 208.65  E-value: 1.37e-61
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   810 SLREEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHS-----------------------------EWTHMNHQDALG 860
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnnpkalpkfllsvkwsdadevaqalslllSWAPLDPEDALE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   861 LLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFS 940
Cdd:smart00145   82 LLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVS 161

                           170       180
                    ....*....|....*....|...
gi 1790094194   941 IRYQYLLAALLCCCGKGLREEFN 963
Cdd:smart00145  162 IRFGLLLEAYLRGCGTHLKELLK 184
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
 1341-1449 2.37e-58

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 196.42  E-value: 2.37e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRRE 1420
Cdd:cd06883      1 EVSVFGFQKRYSPEKYYIYVVKVTRENQTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRSHIKQVAERRKI 80

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd06883     81 ELNSYLKSLFNASPEVAESDLVYTFFHPL 109
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 1052-1303 6.12e-53

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 188.57  E-value: 6.12e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1052 VIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIqvehgvtGSFKDRPLADW 1131
Cdd:cd05167     52 AIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQI-------GRETDNGLYEY 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1132 LQKH--NPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGrFlghaqMF-----GNIKRDRA 1204
Cdd:cd05167    125 FLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-F-----IFeispgGNLGFESA 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1205 PFVFTSDMAYVInGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSD--LEDLKyvyDALRPQDTEA 1282
Cdd:cd05167    199 PFKLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRGqtIKNLR---ERFALEMSER 274

                          250       260
                   ....*....|....*....|.
gi 1790094194 1283 NATTYFTRLIESSLGSVATKL 1303
Cdd:cd05167    275 EAANFMIKLIADSYLKIRTKG 295
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 1052-1303 1.16e-51

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 184.00  E-value: 1.16e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1052 VIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGVTGSFKDrpLADW 1131
Cdd:cd00893     30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFNKFVS--LSDF 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1132 LqKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQmfGNIKRDRAPFVFTSD 1211
Cdd:cd00893    108 F-DDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP--GFYGFEGAPFKLSSE 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1212 MAYVIngGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYFTRL 1291
Cdd:cd00893    185 YIEVL--GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVLSL 262

                          250
                   ....*....|..
gi 1790094194 1292 IESSLGSVATKL 1303
Cdd:cd00893    263 INKSLDNWRTRW 274
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 1050-1303 1.05e-47

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 173.05  E-value: 1.05e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1050 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGVTGSFKDRpla 1129
Cdd:cd05168     31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDY--- 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1130 dWLQKH-NPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQmfGNIKRDRAPFVF 1208
Cdd:cd05168    108 -FERTFgDPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKL 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1209 TSDMAYVINGGDkpSSRFHDFVDLCCQAYNLIRKHTHL------FLNLLGLMLSCGIPELSDLEDLKyvyDALRPQDTEA 1282
Cdd:cd05168    185 TQEYVEVMGGLE--SDMFRYFKTLMIQGFLALRKHADRivllveIMQQGSKLPCFFGGGEFTIEQLR---ERFKLNLTEE 259

                          250       260
                   ....*....|....*....|.
gi 1790094194 1283 NATTYFTRLIESSLGSVATKL 1303
Cdd:cd05168    260 ECAQFVDSLIDKSLNNWRTRQ 280
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 814-936 6.17e-46

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


Pssm-ID: 238440  Cd Length: 152  Bit Score: 162.38  E-value: 6.17e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  814 EDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHSE----------------------------WTHMNHQDALGLLHAT 865
Cdd:cd00864      2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVpkalpkllksvnwnddeevselyqllkwWAPLSPEDALELLSPK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1790094194  866 FPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKD 936
Cdd:cd00864     82 YPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1341-1449 7.51e-40

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 143.53  E-value: 7.51e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRRE 1420
Cdd:cd07289      1 EVSVFTYHKRYNPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd07289     81 ELNSYIQSLMNSSTEVAECDLVYTFFHPL 109
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 1021-1244 1.94e-38

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 143.63  E-value: 1.94e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1021 IVPRDCSYFNSNAVPLKLSFqnVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGRGM 1100
Cdd:cd00142      3 LDVGILKVIHSKQRPKKITL--IGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1101 VEMIPNAETLrkiqveHGvtgsfkdrpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGH 1180
Cdd:cd00142     81 IEIVKDAQTI------ED---------LLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGN 145

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1790094194 1181 MFHIDFGRFLGHAQMFgnIKRDRAPFVFTSDMAYVINGGDKpssrFHDFVDLCCQAYNLIRKHT 1244
Cdd:cd00142    146 IFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAMGTAGV----NGPFQISMVKIMEILREHA 203
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 813-955 3.22e-38

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 141.30  E-value: 3.22e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  813 EEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHS----------------------------EWTHMNHQDALGLLHA 864
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKkpqalpklllsvkwnkrddvaqmyqllkRWPKLKPEQALELLDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  865 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRYQ 944
Cdd:cd00872     81 NFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRFG 160

                          170
                   ....*....|.
gi 1790094194  945 YLLAALLCCCG 955
Cdd:cd00872    161 LLLEAYLRGCG 171
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 364-466 2.16e-35

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 130.49  E-value: 2.16e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  364 AVTPSPEHL--GDEVNLKVTVLCDRLQEALTFTCNCSSTVDLLIYQTLCYTHDDLRNVDVG-DFVLKPCGLEEFLQNKHA 440
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 1790094194  441 LGSHEYIQYCRKFDIDIRLQLMEQKV 466
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 648-788 7.26e-35

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 130.18  E-value: 7.26e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  648 SYEDFYLSCSLSHGGKELCSPLQTRRAHFSKylfHLIVWDQQICFPVQVNRLPRETLLCATLYALPIPppgssseanKQR 727
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSN---SSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------EKS 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1790094194  728 RVPeaLGWVTTPLFNFRQVLTCGRKLLGLWPATQ-ENPSARW---------SAPNFHQPDSViLQIDFPTS 788
Cdd:pfam00792   69 FVP--IGWVNTSLFDKKGILRQGKQKLRLWPSKStPGRSNVDemnrlekllKKYERGQVSSV-DWLDFLTF 136
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 1478-1598 2.32e-34

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 128.54  E-value: 2.32e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd04030      3 GRIQLTIRYssQRQKLIVTVHKCRNLPPCDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEEL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1556 QQRELQLSVLSEQGF--WENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd04030     82 KRRTLDVAVKNSKSFlsREKKLLGQVLIDLSDLDLSKGFTQWYDL 126
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 812-962 3.37e-34

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 130.14  E-value: 3.37e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  812 REEDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHS------------EWTHMNHQ----------------DALGLLH 863
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLvpkaltklllsvKWSDLSEVaealslllkwapidpvDALELLD 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  864 ATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAVSDLRVTHYFFWLLKDGLKDSQFSIRY 943
Cdd:pfam00613   86 PKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRF 165

                          170
                   ....*....|....*....
gi 1790094194  944 QYLLAALLCCCGKGLREEF 962
Cdd:pfam00613  166 GSLLELYLRSCGTSLLGLN 184
PX_PI3K_C2_68D cd06884
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases ...
 1348-1449 4.79e-31

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.


Pssm-ID: 132794  Cd Length: 111  Bit Score: 118.29  E-value: 4.79e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1348 EKIFHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRREELNGYIW 1427
Cdd:cd06884     10 QKRYDPEKYYVYVVEVTRENQASPQHVFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQDIQQFLN 89

                           90       100
                   ....*....|....*....|..
gi 1790094194 1428 HLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd06884     90 SLFKMAEEVSHSDLVYTFFHPL 111
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 1478-1598 3.88e-30

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 116.20  E-value: 3.88e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYkNNKLFIMVMHIRGLQLLQDGND----PDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKG 1553
Cdd:cd08521      1 GEIEFSLSY-NYKTGSLEVHIKECRNLAYADEkkkrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKS 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1554 DLQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08521     79 QLETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1034-1313 4.45e-30

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 130.67  E-value: 4.45e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1034 VPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMR----MVIFRCFSTGRGRGMVEMIPNAET 1109
Cdd:COG5032   1783 RPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRrdlwIRPYKVIPLSPGSGIIEWVPNSDT 1860

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1110 LRKI--------------------QVEHGVTG---------SFKDRP-LADWLQKHNPGEDEYEKAVENFIYSCAGCCVA 1159
Cdd:COG5032   1861 LHSIlreyhkrknisidqekklaaRLDNLKLLlkdefftkaTLKSPPvLYDWFSESFPNPEDWLTARTNFARSLAVYSVI 1940

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1160 TYVLGICDRHNDNIML-KTTGHMFHIDFGRFLGhAQMFGNIKRDRAPFVFTSDMAYVING-GDKPSsrfhdFVDLCCQAY 1237
Cdd:COG5032   1941 GYILGLGDRHPGNILIdRSSGHVIHIDFGFILF-NAPGRFPFPEKVPFRLTRNIVEAMGVsGVEGS-----FRELCETAF 2014

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1238 NLIRKHTHL------FLNLLGLMLSCGIPELSD--LEDLKYVYDALRPQDTEANATTYFTRLIESSLGSVATKL-NFFih 1308
Cdd:COG5032   2015 RALRKNADSlmnvleLFVRDPLIEWRRLPCFREiqNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQAtDPF-- 2092


                   ....*
gi 1790094194 1309 NLAQM 1313
Cdd:COG5032   2093 QLATM 2097
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 621-722 5.83e-29

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 112.05  E-value: 5.83e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   621 VQEACHFARSLAFTVYATHRIPIIWATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYlfhlIVWDQQICFPVQVNRLP 700
Cdd:smart00142    3 IESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPS----VKWNEWLTFPIQISDLP 78

                            90       100
                    ....*....|....*....|..
gi 1790094194   701 RETLLCATLYALPIPPPGSSSE 722
Cdd:smart00142   79 REARLCITIYAVKNPSKGSEFG 100
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 1478-1598 1.29e-25

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 103.28  E-value: 1.29e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGND-PDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGD 1554
Cdd:cd08393      2 GSVQFALDYdpKLRELHVHVIQCQDLAAADPKKQrSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VEREE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1790094194 1555 LQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08393     81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1351-1447 8.56e-25

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 100.11  E-value: 8.56e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1351 FHPNKGYIYVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSR--GEAVAERRREELNGYIWH 1428
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNnfSEEFIEKRRRGLEKYLQS 86

                            90
                    ....*....|....*....
gi 1790094194  1429 LIHAPPEVAECDLVYTFFH 1447
Cdd:smart00312   87 LLNHPELINHSEVVLEFLE 105
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1476-1583 1.23e-24

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 100.40  E-value: 1.23e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1476 VGGEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKG 1553
Cdd:cd04031      1 ITGRIQIQLWYdkVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1790094194 1554 DLQQRELQLSVLSEQGFWENVLLGEVNIRL 1583
Cdd:cd04031     81 TLKERTLEVTVWDYDRDGENDFLGEVVIDL 110
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 1478-1598 1.49e-24

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 100.21  E-value: 1.49e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDG-NDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGD 1554
Cdd:cd04029      2 GEILFSLSYdyKTQSLNVHVKECRNLAYGDEAkKRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS-ISHSQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1790094194 1555 LQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd04029     81 LETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPL 124
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 1478-1595 2.98e-23

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 97.78  E-value: 2.98e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--------------KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNE 1543
Cdd:cd04020      2 GELKVALKYvppesegalkskkpSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1790094194 1544 MLVYDGIPKGDLQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGW 1595
Cdd:cd04020     82 TFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDW 133
C2 pfam00168
C2 domain;
1489-1598 4.00e-23

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 95.46  E-value: 4.00e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1489 NKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLpdpQKTTKRKTKVARKTCNPTYNEMLVYDgIPkgDLQQRELQLSVLSEQ 1568
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS-VP--DPENAVLEIEVYDYD 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 1790094194 1569 GFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 814-931 4.69e-23

Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III phosphorylate phosphoinositol (PtdIns) only. The prototypical PI3K class III, yeast Vps34, is involved in trafficking proteins from Golgi to the vacuole.


Pssm-ID: 238442  Cd Length: 166  Bit Score: 97.40  E-value: 4.69e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  814 EDQRKLKDIMQKESLYWLTDADKKRLWEKRYYCHSE----------------------------WTHMNHQDALGLLHAT 865
Cdd:cd00870      9 KERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNkkaltkflksvnwsdeqevkqalelmpkWAKIDIEDALELLSPY 88

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1790094194  866 FPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECY-------LDSPLVRFLLKRAVSDLRVTHYFFWLLK 931
Cdd:cd00870     89 FTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLK 161
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1478-1598 2.11e-22

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 94.32  E-value: 2.11e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHIRGLQLL-QD-GNDPDPYVKIYLLPDPQKttKRKTKVARKTCNPTYNEMLVYDGIPKGDL 1555
Cdd:cd08386      3 GRIQFSVSYDFQESTLTLKILKAVELPaKDfSGTSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08386     81 QQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTFWKDL 123
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1490-1595 1.57e-21

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 91.01  E-value: 1.57e-21
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  1490 KLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKttKRKTKVARKTCNPTYNEMLVYDGIPkgdLQQRELQLSVLSEQG 1569
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 1790094194  1570 FWENVLLGEVNIRLRELDLAQEKTGW 1595
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1478-1593 1.68e-20

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 88.49  E-value: 1.68e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKGDL 1555
Cdd:cd04035      2 GTLEFTLLYdpANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEEDI 81

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1790094194 1556 QQRELQLSVLSEQGFwENVLLGEVNIRLRELDLAQEKT 1593
Cdd:cd04035     82 QRKTLRLLVLDEDRF-GNDFLGETRIPLKKLKPNQTKQ 118
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1478-1581 3.97e-20

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 88.02  E-value: 3.97e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd00276      1 GELLLSLSYlpTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFD-VPAEQL 79

                           90       100
                   ....*....|....*....|....*.
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEVNI 1581
Cdd:cd00276     80 EEVSLVITVVDKDSVGRNEVIGQVVL 105
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 630-791 1.04e-19

C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes of PI3Ks. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains members with the first C2 repeat, C2A, and a type-I topology, as well as some with a single C2 repeat.


Pssm-ID: 176026  Cd Length: 156  Bit Score: 87.42  E-value: 1.04e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  630 SLAFTVYATHRIPIIW------ATSYEDFYLSCSLSHGGKELCSPLQTRRAHFSKYlfhlIVWDQQICFPVQVNRLPRET 703
Cdd:cd08380      2 SLWDINFNLRIKIHGItninllDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTS----VTWNEWLTFDILISDLPREA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  704 LLCATLYAlpipppgSSSEANKQrrvPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENPSARWSAPNfhQPDSVILQI 783
Cdd:cd08380     78 RLCLSIYA-------VSEPGSKK---EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIACTPCN--NSNENSTRL 145


                   ....*...
gi 1790094194  784 DFPTSAFD 791
Cdd:cd08380    146 LIELPEFS 153
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1478-1600 2.21e-19

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 85.39  E-value: 2.21e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKttKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08385      3 GKLQFSLDYdfQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFK-VPYSEL 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALGS 1600
Cdd:cd08385     80 GNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEEWRDLES 124
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1478-1604 3.39e-18

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 82.31  E-value: 3.39e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHIRGLQLLqdgnDP----DPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKG 1553
Cdd:cd04026      2 GRIYLKISVKDNKLTVEVREAKNLIPM----DPnglsDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPA 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1790094194 1554 DLQQReLQLSVLSEQGFWENVLLGEVNIRLRELdLAQEKTGWFALGSRSHG 1604
Cdd:cd04026     77 DKDRR-LSIEVWDWDRTTRNDFMGSLSFGVSEL-IKMPVDGWYKLLNQEEG 125
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1483-1598 3.49e-18

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 81.92  E-value: 3.49e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1483 SISYKN--NKLFIMVMHIRGLQLL-QDGNDPDPYVKIYLLPDPQKTtkRKTKVARKTCNPTYNEMLVYDgIPKGDLQQRE 1559
Cdd:cd08390      6 SVQYDLeeEQLTVSLIKARNLPPRtKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQ-VSFKELQRRT 82

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1790094194 1560 LQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08390     83 LRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVVWRDL 121
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1478-1598 1.66e-17

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 80.89  E-value: 1.66e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHIRGLQLLQDGND-PDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDGIPKGdlq 1556
Cdd:cd04028     18 GDIQLGLYDKKGQLEVEVIRARGLVQKPGSKVlPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSPTG--- 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1790094194 1557 qRELQLSVLSEQGFWEN-VLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd04028     95 -KTLQVIVWGDYGRMDKkVFMGVAQILLDDLDLSNLVIGWYKL 136
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 364-464 9.68e-17

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 77.37  E-value: 9.68e-17
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194   364 AVTPSPEHLGDEV---NLKVTVLCDRLQEALTFTCNCSSTVDLLIYQTLCYTHDDLRNVDVG--DFVLKPCGLEEFLQNK 438
Cdd:smart00144    1 TSPSVPEPLPLKTianKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTseDYILKVCGRDEYLLGD 80

                            90       100
                    ....*....|....*....|....*.
gi 1790094194   439 HALGSHEYIQYCRKFDIDIRLQLMEQ 464
Cdd:smart00144   81 HPLGSFEYIRNCLKNGTEPHLVLMTL 106
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1364-1448 2.02e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 75.74  E-value: 2.02e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1364 MRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRgEAVAERRREELNGYIWHLIHApPEVAECDLVY 1443
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQH-PELRNSEVLL 78


                   ....*
gi 1790094194 1444 TFFHP 1448
Cdd:pfam00787   79 EFLES 83
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1491-1598 4.99e-16

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 75.18  E-value: 4.99e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1491 LFIMVMHIRGLQLLQDGNDPDPYVKIYLLPdpqkTTKRKTKVARKTCNPTYNEMLVydgIPKGDLQQRELQLSVLSEQGF 1570
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGG----KQKFKTKVVKNTLNPVWNETFE---FPVLDPESDTLTVEVWDKDRF 73

                           90       100
                   ....*....|....*....|....*....
gi 1790094194 1571 WENVLLGEVNIRLREL-DLAQEKTGWFAL 1598
Cdd:cd00030     74 SKDDFLGEVEIPLSELlDSGKEGELWLPL 102
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 1478-1588 6.14e-15

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 72.94  E-value: 6.14e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYkNNKLFIMVMHIRGLQLLQDGNDP----DPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKG 1553
Cdd:cd08392      2 GEIEFALHY-NFRTSCLEITIKACRNLAYGDEKkkkcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEAD 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1790094194 1554 DLQQRELQLSVLSEQGFWENVLLGEVNIRLRELDL 1588
Cdd:cd08392     80 LLSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDF 114
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 1053-1196 9.65e-15

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 75.30  E-value: 9.65e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1053 IFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIqvehgvtgsFKDRPL 1128
Cdd:cd05172     33 LVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI---------LENDLL 103

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1790094194 1129 ADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIML-KTTGHMFHIDFGRFLGHAQMF 1196
Cdd:cd05172    104 RRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQF 172
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1480-1564 1.97e-14

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 71.61  E-value: 1.97e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1480 VKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDLQQ 1557
Cdd:cd08384      2 ILVSLMYntQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLAK 80


                   ....*..
gi 1790094194 1558 RELQLSV 1564
Cdd:cd08384     81 KTLEITV 87
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 1029-1212 3.80e-14

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 73.46  E-value: 3.80e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1029 FNSNAVPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEG----LDMRMVIFRCFSTGRGRGMVEMI 1104
Cdd:cd05164     11 LASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWV 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1105 PNAETLRKIqvehgvtgsfkdrpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKT-TGHMFH 1183
Cdd:cd05164     89 DNTTTLKPV--------------LKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTkTGEVVH 154

                          170       180
                   ....*....|....*....|....*....
gi 1790094194 1184 IDFGRFLGHAQMFGniKRDRAPFVFTSDM 1212
Cdd:cd05164    155 IDFGMIFNKGKTLP--VPEIVPFRLTRNI 181
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 1478-1593 4.85e-14

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 70.46  E-value: 4.85e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHI--RGLQLLqDGND--PDPYVKIYLLPDpqKTTKRKTKVARKTCNPTYNEMLVYDGIPKG 1553
Cdd:cd08388      3 GTLFFSLRYNSEKKALLVNIIecRDLPAM-DEQSgtSDPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYN 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1790094194 1554 DLQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKT 1593
Cdd:cd08388     80 QLQDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEGE 119
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1478-1603 1.88e-13

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 68.99  E-value: 1.88e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYK--NNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08404      2 GELLLSLCYQptTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFD-IPSEEL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1790094194 1556 QQRELQLSVLSeqgfWENVLLGEVNIRLREldlaqektGWFALGSRSH 1603
Cdd:cd08404     81 EDISVEFLVLD----SDRVTKNEVIGRLVL--------GPKASGSGGH 116
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
 1341-1446 4.07e-13

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


Pssm-ID: 132768 [Multi-domain]  Cd Length: 106  Bit Score: 67.00  E-value: 4.07e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1341 DVFLCRHEKIFHPNKGYI-YVVKVMRENTHEATyIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEaVAERRR 1419
Cdd:cd06093      1 SVSIPDYEKVKDGGKKYVvYIIEVTTQGGEEWT-VYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPE-FIEERR 78

                           90       100
                   ....*....|....*....|....*..
gi 1790094194 1420 EELNGYIWHLIHApPEVAECDLVYTFF 1446
Cdd:cd06093     79 KQLEQYLQSLLNH-PELRNSEELKEFL 104
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1478-1600 1.88e-12

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 65.89  E-value: 1.88e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNK--LFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDpqKTTKRKTKVARKTCNPTYNEMLVYdGIPKGDL 1555
Cdd:cd08387      3 GELHFSLEYDKDMgiLNVKLIQARNLQPRDFSGTADPYCKVRLLPD--RSNTKQSKIHKKTLNPEFDESFVF-EVPPQEL 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALGS 1600
Cdd:cd08387     80 PKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLWRKIQS 124
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 1029-1186 7.35e-12

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 67.15  E-value: 7.35e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1029 FNSNAVPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQ--EGLDMRMVIfRCFST---GRGRGMVEM 1103
Cdd:cd00892     11 MPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpESRRRNLHI-RTYAViplNEECGIIEW 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1104 IPNAETLRKIqvehgVTGSFKDRpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIML-KTTGHMF 1182
Cdd:cd00892     88 VPNTVTLRSI-----LSTLYPPV-LHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILFdSTTGDVV 161


                   ....
gi 1790094194 1183 HIDF 1186
Cdd:cd00892    162 HVDF 165
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1478-1585 1.05e-11

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 63.98  E-value: 1.05e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYK--NNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08405      2 GELLLSLCYNptANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFN-IPLERL 80

                           90       100       110
                   ....*....|....*....|....*....|
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEVNIRLRE 1585
Cdd:cd08405     81 RETTLIITVMDKDRLSRNDLIGKIYLGWKS 110
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1491-1602 1.27e-11

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 63.93  E-value: 1.27e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1491 LFIMVMHIRGLQLLQDGNDpDPYVKIYLLpDPQKTTKRKTKVARKTCNPTYNEMLVYDGI------------PKGDLQQR 1558
Cdd:cd08675      1 LSVRVLECRDLALKSNGTC-DPFARVTLN-YSSKTDTKRTKVKKKTNNPRFDEAFYFELTigfsyekksfkvEEEDLEKS 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1790094194 1559 ELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFALGSRS 1602
Cdd:cd08675     79 ELRVELWHASMVSGDDFLGEVRIPLQGLQQAGSHQAWYFLQPRE 122
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 1478-1598 1.31e-11

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 63.24  E-value: 1.31e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHIRGLQLLQDGNDpDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDLQQ 1557
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTC-NSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD-VNERDYQK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1790094194 1558 RELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08685     79 RLLVTVWNKLSKSRDSGLLGCMSFGVKSIVNQKEISGWYYL 119
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 1478-1564 1.37e-11

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176051 [Multi-domain]  Cd Length: 136  Bit Score: 63.66  E-value: 1.37e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08406      2 GEILLSLSYlpTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFS-VPAIVL 80


                   ....*....
gi 1790094194 1556 QQRELQLSV 1564
Cdd:cd08406     81 QDLSLRVTV 89
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1478-1579 1.45e-11

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 63.57  E-value: 1.45e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08402      2 GDICFSLRYvpTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFE-VPFEQI 80

                           90       100
                   ....*....|....*....|....
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEV 1579
Cdd:cd08402     81 QKVHLIVTVLDYDRIGKNDPIGKV 104
PX_FISH cd06888
The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a ...
 1339-1448 1.82e-11

The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Five SH (FISH), also called Tks5, is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132798  Cd Length: 119  Bit Score: 62.83  E-value: 1.82e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1339 ISDVFLCRHEKIFHPNKGYIYVVKVMRENTHEATyIQRTFEEFQELHNKLRLLFP---------SSHLPSFPSRFVIGRS 1409
Cdd:cd06888      1 VKDVKVIDVEKRRAPSKHYVYIINVTWSDGSSNV-IYRRYSKFFDLQMQLLDKFPieggqkdpsQRIIPFLPGKILFRRS 79

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1790094194 1410 RGEAVAERRREELNGYIWHLIHAPPEVAECDLVYTFFHP 1448
Cdd:cd06888     80 HIRDVAVKRLKPIDEYCKALVRLPPHISQCDEVLRFFEA 118
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 1478-1577 2.02e-11

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 62.91  E-value: 2.02e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08403      1 GELMFSLCYlpTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFD-VPPENV 79

                           90       100
                   ....*....|....*....|..
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLG 1577
Cdd:cd08403     80 DNVSLIIAVVDYDRVGHNELIG 101
PX_p40phox cd06882
The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The ...
 1357-1452 1.05e-10

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.


Pssm-ID: 132792  Cd Length: 123  Bit Score: 60.53  E-value: 1.05e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1357 YIYVVKVmRENTHEATYIQRTFEEFQELHNKLRLLFPSSH--------LPSFPSRFVIGRSRgeAVAERRREELNGYIWH 1428
Cdd:cd06882     21 YVFVIEV-KTKGGSKYLIYRRYRQFFALQSKLEERFGPEAgssaydctLPTLPGKIYVGRKA--EIAERRIPLLNRYMKE 97

                           90       100
                   ....*....|....*....|....
gi 1790094194 1429 LIHAPPEVAECDLVYTFFHPLPRD 1452
Cdd:cd06882     98 LLSLPVWVLMDEDVRLFFYQTESD 121
PX_UP2_fungi cd06869
The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX ...
 1357-1447 1.59e-10

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132779  Cd Length: 119  Bit Score: 59.99  E-value: 1.59e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1357 YIYVVKVMRENTHEAT-YIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRsrgeavaERRREELNGYIwHLIHAPPE 1435
Cdd:cd06869     34 YEFIIRVRREGEEYRTiYVARRYSDFKKLHHDLKKEFPGKKLPKLPHKDKLPR-------EKLRLSLRQYL-RSLLKDPE 105

                           90
                   ....*....|..
gi 1790094194 1436 VAECDLVYTFFH 1447
Cdd:cd06869    106 VAHSSILQEFLT 117
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 1511-1602 1.96e-10

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 60.49  E-value: 1.96e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDG------------IPKGDLQQRELQLSVLSEQGFWENVLLGE 1578
Cdd:cd04010     20 DPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfeMPEEDAEKLELRVDLWHASMGGGDVFLGE 99

                           90       100
                   ....*....|....*....|....*
gi 1790094194 1579 VNIRLRELDLAQ-EKTGWFALGSRS 1602
Cdd:cd04010    100 VRIPLRGLDLQAgSHQAWYFLQPRE 124
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 1047-1187 2.96e-10

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 59.76  E-value: 2.96e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1047 GENIRVIFKCGDD--------LRQDMLTLQMIRIMSKIwvqegldmrmvIFRCFSTGRGRG----MVEMIPNAETLRKIQ 1114
Cdd:cd13968     16 CTTIGVAVKIGDDvnneegedLESEMDILRRLKGLELN-----------IPKVLVTEDVDGpnilLMELVKGGTLIAYTQ 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1790094194 1115 vehgvtgsfkdrpladwlqkhnpGEDEYEKAVENFIYSCAGCCVATYV--LGICDRHNDNIMLKTTGHMFHIDFG 1187
Cdd:cd13968     85 -----------------------EEELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
PX_p47phox cd06887
The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The ...
 1339-1450 3.68e-10

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.


Pssm-ID: 132797  Cd Length: 118  Bit Score: 59.08  E-value: 3.68e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1339 ISDVFLCRHEKIFHPNKGYIYVVKVMRENTHEATyIQRTFEEFQELHNKLRLLFPSS------------HLPSfPSRFvi 1406
Cdd:cd06887      1 IRHIALLGFEKRFVPSQHYVYMFLVKWQDLSEKL-VYRRFTEIYEFHKTLKEMFPIEagdinkenriipHLPA-PKWF-- 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1790094194 1407 grsRGEAVAERRREELNGYIWHLIHAPPEVAECDLVYTFFHPLP 1450
Cdd:cd06887     77 ---DGQRAAENRQGTLTEYCSTLLSLPPKISRCPHVLDFFKVRP 117
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1480-1543 4.89e-10

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 59.17  E-value: 4.89e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1790094194 1480 VKLSISYKNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPDPQ--KTTKRKTKVARKTCNPTYNE 1543
Cdd:cd04009      7 VKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLFPLFDE 72
C2B_Synaptotagmin-13 cd08407
C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking ...
 1478-1583 6.42e-10

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176052 [Multi-domain]  Cd Length: 138  Bit Score: 58.84  E-value: 6.42e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISY--KNNKLFIMVMHIRGLQ----LLQDGNDPDpyVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIP 1551
Cdd:cd08407      2 GEVLLSISYlpAANRLLVVVIKAKNLHsdqlKLLLGIDVS--VKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFE-LP 78

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1790094194 1552 KGDLQQRELQLSVLSEQGFWENVLLGEVNIRL 1583
Cdd:cd08407     79 SELLAASSVELEVLNQDSPGQSLPLGRCSLGL 110
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
 1351-1446 8.59e-10

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 57.23  E-value: 8.59e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1351 FHPNKGYIYVVKVMRENThEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEavaERRREELNGYIWHLI 1430
Cdd:cd06896      7 FSKKSSNLYLVQVTQSCN-LVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSD---HKRVRDLNHYLEQLL 82

                           90
                   ....*....|....*.
gi 1790094194 1431 HAPPEVAECDLVYTFF 1446
Cdd:cd06896     83 SGSREVANSDCVLSFF 98
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 651-772 2.30e-09

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176042  Cd Length: 159  Bit Score: 58.03  E-value: 2.30e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  651 DFYLSCSLSHGGKELCSPLQTRRAHFSKylfhLIVWDQQICFPVQVNRLPRETLLCATLYAlpIPPPGssseankqRRVP 730
Cdd:cd08397     31 DLFVTCQVFDDGKPLTLPVQTSYKPFKN----RRNWNEWLTLPIKYSDLPRNSQLAITIWD--VSGTG--------KAVP 96

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1790094194  731 eaLGWVTTPLFNFRQVLTCGRKLLGLWPATQENPSARWSAPN 772
Cdd:cd08397     97 --FGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPTSTGK 136
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 1100-1187 5.54e-09

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 59.03  E-value: 5.54e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1100 MVEMIPNAETLRKIQ-VE---HGVTGSfKDRPLAD--WLQKHNPgedeyEKAVE---NFIYSCAGCCVATYVLGICDRHN 1170
Cdd:cd05169    116 MLQMAPDYDNLTLIQkVEvfeYALENT-PGDDLRRvlWLKSPSS-----EAWLErrtNFTRSLAVMSMVGYILGLGDRHP 189

                           90
                   ....*....|....*...
gi 1790094194 1171 DNIML-KTTGHMFHIDFG 1187
Cdd:cd05169    190 SNIMLdRLTGKVIHIDFG 207
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 633-785 9.59e-09

C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, alpha isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176043  Cd Length: 158  Bit Score: 55.95  E-value: 9.59e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  633 FTVYATHRIPIIWAT--SYEDF---YLSCSLSHGGKELCSPLQTRRAHFSKYLfhlivWDQQICFPVQVNRLPRETLLCA 707
Cdd:cd08398      4 WKINSNLRIKILCATyvNVNDIdkiYVRTGIYHGGEPLCDNVNTQRVPCSNPR-----WNEWLDYDIYIPDLPRSARLCL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  708 TLYALpipppgssseaNKQRRVPE---ALGWVTTPLFNFRQVLTCGRKLLGLWPATQE-----NPSAR-WSAPNfhqPDS 778
Cdd:cd08398     79 SICSV-----------KGRKGAKEehcPLAWGNINLFDYTDTLVSGKMALNLWPVPHGledllNPIGVtGSNPN---KDT 144


                   ....*..
gi 1790094194  779 VILQIDF 785
Cdd:cd08398    145 PCLELEF 151
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 1478-1579 1.72e-08

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176054 [Multi-domain]  Cd Length: 137  Bit Score: 54.65  E-value: 1.72e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKN--NKLFIMVMHIRGLQLLqDGNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYdGIPKGDL 1555
Cdd:cd08409      2 GDIQISLTYNPtlNRLTVVVLRARGLRQL-DHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSF-KVTSRQL 79

                           90       100
                   ....*....|....*....|....
gi 1790094194 1556 QQRELQLSVLSEQGFWENVLLGEV 1579
Cdd:cd08409     80 DTASLSLSVMQSGGVRKSKLLGRV 103
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1479-1605 3.16e-08

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176053 [Multi-domain]  Cd Length: 138  Bit Score: 53.91  E-value: 3.16e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1479 EVKLSISYK--NNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLL-PDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08408      3 ELLLGLEYNalTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQ-VALFQL 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1556 QQRELQLSVLSEQGfwenvllgevniRLREldlaqEKTGWFALGSRSHGT 1605
Cdd:cd08408     82 SEVTLMFSVYNKRK------------MKRK-----EMIGWFSLGLNSSGE 114
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 658-759 4.45e-08

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 54.63  E-value: 4.45e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  658 LSHGGKELCSPLQTRRAhfSKYLFHliVWDQQICFPVQVNRLPRETLLCATLYALPIPPPG-SSSEANKQRRVPEA---L 733
Cdd:cd08693     35 LFHGGESLCKTVKTSEV--SGKNDP--VWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGkRSRKNQTKKKKKKDdnpI 110

                           90       100
                   ....*....|....*....|....*.
gi 1790094194  734 GWVTTPLFNFRQVLTCGRKLLGLWPA 759
Cdd:cd08693    111 AWVNTMVFDYKGQLKTGDHTLYMWTY 136
PX_SNX18 cd07286
The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a ...
 1368-1455 1.86e-06

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.


Pssm-ID: 132819  Cd Length: 127  Bit Score: 48.51  E-value: 1.86e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1368 THEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRReelnGYIWHLIH--APPEVAECDLVYTF 1445
Cdd:cd07286     28 SHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRK----GLIWWMDHmcSHPVLARCDAFQHF 103

                           90
                   ....*....|
gi 1790094194 1446 FHPLPRDEKA 1455
Cdd:cd07286    104 LTCPSTDEKA 113
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 1034-1187 3.04e-06

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 50.62  E-value: 3.04e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1034 VPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGL----DMRMVIFRCFSTGRGRGMVEMIPNAET 1109
Cdd:cd05171     16 LPKIITCIGSD--GKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIP 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1110 LRKIQV-EHGVTGS-FKDRPLaDWL----------QKHNPGEDEYEKAVE----------------------------NF 1149
Cdd:cd05171     94 LGEYLVgASSKSGAhARYRPK-DWTastcrkkmreKAKASAEERLKVFDEicknfkpvfrhfflekfpdpsdwferrlAY 172

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1790094194 1150 IYSCAGCCVATYVLGICDRHNDNIML-KTTGHMFHIDFG 1187
Cdd:cd05171    173 TRSVATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLG 211
PX_Bem1p cd06890
The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a ...
 1354-1449 5.37e-06

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).


Pssm-ID: 132800  Cd Length: 112  Bit Score: 46.90  E-value: 5.37e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1354 NKGYIYVVKVMRENtHEATYIQRTFEEFQELHNKLRLLFPSS--------HLPSFPSRfvIGRSRGEAVAERRREELNGY 1425
Cdd:cd06890     12 DNRYWYRVRATLSD-GKTRYLCRYYQDFYKLHIALLDLFPAEagrnsskrILPYLPGP--VTDVVNDSISLKRLNDLNEY 88

                           90       100
                   ....*....|....*....|....
gi 1790094194 1426 IWHLIHAPPEVAECDLVYTFFHPL 1449
Cdd:cd06890     89 LNELINLPAYIQTSEVVRDFFANR 112
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1491-1603 6.89e-06

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 46.40  E-value: 6.89e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1491 LFIMVMHIRGLQLLQDGNDPDPYVKIYLlpdpQKTTkRKTKVARKTCNPTYNE---MLVYDgiPKGDlqqrELQLSVLSE 1567
Cdd:cd04050      2 LFVYLDSAKNLPLAKSTKEPSPYVELTV----GKTT-QKSKVKERTNNPVWEEgftFLVRN--PENQ----ELEIEVKDD 70

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1790094194 1568 qgfWENVLLGEVNIRLRELDLAQEKT--GWFALGSRSH 1603
Cdd:cd04050     71 ---KTGKSLGSLTLPLSELLKEPDLTldQPFPLDNSGP 105
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 1510-1586 2.70e-05

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 45.35  E-value: 2.70e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1790094194 1510 PDPYVKIylLPDPQKTtkRKTKVARKTCNPTYNEMLVYDGIPkgdlqQRELQLSVLSEQGFWENVLLGEVNIRLREL 1586
Cdd:cd04021     22 PDPYVEV--TVDGQPP--KKTEVSKKTSNPKWNEHFTVLVTP-----QSTLEFKVWSHHTLKADVLLGEASLDLSDI 89
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 1124-1186 2.99e-05

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 48.02  E-value: 2.99e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1790094194 1124 KDRPlADWLQK----HNPGEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLK-TTGHMFHIDF 1186
Cdd:cd05170    166 AETP-RDLLARelwcSSPSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1476-1598 4.03e-05

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 44.54  E-value: 4.03e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1476 VGGEVKLSISYK--NNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLPdpQKTTKRKTKVaRKTCNPTYNEMLVYDGIPKG 1553
Cdd:cd08389      1 KCGDLDVAFEYDpsARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLP--SKKQRAKTKV-QRGPNPVFNETFTFSRVEPE 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1554 DLQQRELQLSVLSEQGFWENVLLGEVNIRLRELDLAQEKTGWFAL 1598
Cdd:cd08389     78 ELNNMALRFRLYGVERMRKERLIGEKVVPLSQLNLEGETTVWLTL 122
PX_HS1BP3 cd06868
The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a ...
 1349-1445 4.94e-05

The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132778  Cd Length: 120  Bit Score: 44.32  E-value: 4.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1349 KIFHPNkgyiYVVKVMrentheatyIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIgrsRGEAVAERRREELNGYIwH 1428
Cdd:cd06868     37 AKHKEE----DVVQFM---------VSKKYSEFEELYKKLSEKYPGTILPPLPRKALF---VSESDIRERRAAFNDFM-R 99

                           90
                   ....*....|....*..
gi 1790094194 1429 LIHAPPEVAECDLVYTF 1445
Cdd:cd06868    100 FISKDEKLANCPELLEF 116
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 1478-1564 6.91e-05

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176055 [Multi-domain]  Cd Length: 135  Bit Score: 44.50  E-value: 6.91e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1478 GEVKLSISYKNNKLFIMVMHIRGLQLLQD--GNDPDPYVKIYLLPDPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1555
Cdd:cd08410      1 GELLLSLNYLPSAGRLNVDIIRAKQLLQTdmSQGSDPFVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFK-VPQEEL 79


                   ....*....
gi 1790094194 1556 QQRELQLSV 1564
Cdd:cd08410     80 ENVSLVFTV 88
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1498-1578 1.24e-04

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 42.95  E-value: 1.24e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1498 IRGLQLLqdGNDPDPYVKIYLLPDpqkttKRKTKVARKTCNPTYNEMLVYD-GIPKGDLQQRELQLSVLSEQGFWENVLL 1576
Cdd:cd04011     11 IEARQLV--GGNIDPVVKVEVGGQ-----KKYTSVKKGTNCPFYNEYFFFNfHESPDELFDKIIKISVYDSRSLRSDTLI 83


                   ..
gi 1790094194 1577 GE 1578
Cdd:cd04011     84 GS 85
PX_NoxO1 cd06889
The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain ...
 1352-1448 1.34e-04

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.


Pssm-ID: 132799  Cd Length: 121  Bit Score: 43.15  E-value: 1.34e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1352 HPNKGYIYVVKVMRENtHEATYIQRTFEEFQELHNKLRLLFPSSH---------LPSFPSRFVIGRSRGEA--VAERRRe 1420
Cdd:cd06889     15 QKRRHKTYMFSVLWSD-GSELFVYRSLEEFRKLHKQLKEKFPVEAgllrssdrvLPKFKDAPSLGSLKGSTsrSLARLK- 92

                           90       100
                   ....*....|....*....|....*...
gi 1790094194 1421 ELNGYIWHLIHAPPEVAECDLVYTFFHP 1448
Cdd:cd06889     93 LLETYCQELLRLDEKVSRSPEVIQFFAP 120
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1507-1606 2.92e-04

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 42.16  E-value: 2.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1507 GNDPDPYVKIyllpdpqKTTKR----KTKVARKTCNPTYNE---MLVydgipkGDLQQReLQLSVLSEQGFWENVLLGEV 1579
Cdd:cd04044     21 GGTVDPYVTF-------SISNRrelaRTKVKKDTSNPVWNEtkyILV------NSLTEP-LNLTVYDFNDKRKDKLIGTA 86

                           90       100       110
                   ....*....|....*....|....*....|
gi 1790094194 1580 NIRLREL--DLAQE-KTGWFALGSRSHGTL 1606
Cdd:cd04044     87 EFDLSSLlqNPEQEnLTKNLLRNGKPVGEL 116
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 1480-1598 2.99e-04

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176062  Cd Length: 124  Bit Score: 42.22  E-value: 2.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1480 VKLSISY--KNNKLFIMVMHIRGLQLLQDGNDPDPYVKIYLLP-DPQKTTKRKTKVARKTCNPTYNEMLVYDgIPKGDLQ 1556
Cdd:cd08680      3 VQIGLRYdsGDSSLVISVEQLRNLSALSIPENSKVYVRVALLPcSSSTSCLFRTKALEDQDKPVFNEVFRVP-ISSTKLY 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1790094194 1557 QRELQLSV--LSEQGFWEnvLLGEVNIRLRELDLAQEK-TGWFAL 1598
Cdd:cd08680     82 QKTLQVDVcsVGPDQQEE--CLGGAQISLADFESSEEMsTKWYNL 124
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 641-758 3.03e-04

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 43.36  E-value: 3.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194  641 IPIIWATSYEDFYLSCSLSHGGKELCSplqtRRAHfSKYLFHLIVWDQQICFPVQVNRLPRETLLCATLYAlpIPPPGSS 720
Cdd:cd08399     21 IPVLPRNTDLTVFVEANIQHGQQVLCQ----RRTS-PKPFTEEVLWNTWLEFDIKIKDLPKGALLNLQIYC--GKAPALS 93

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1790094194  721 SEANKQRRVPEA------LGWVTTPLFNFRQVLTCGRKLLGLWP 758
Cdd:cd08399     94 SKKSAESPSSESkgkhqlLYYVNLLLIDHRFLLRTGEYVLHMWQ 137
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 1511-1596 6.42e-04

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 40.75  E-value: 6.42e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLLPDPQKTtkrktKVARKTCNPTYN-EMLVYDgIPKGDLQQRELQLSVLSEQGFWENVLLGEVNIRLREL--- 1586
Cdd:cd08688     22 DAFVEVKFGSTTYKT-----DVVKKSLNPVWNsEWFRFE-VDDEELQDEPLQIRVMDHDTYSANDAIGKVYIDLNPLllk 95

                           90
                   ....*....|
gi 1790094194 1587 DLAQEKTGWF 1596
Cdd:cd08688     96 DSVSQISGWF 105
PX_KIF16B_SNX23 cd06874
The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The ...
 1374-1441 6.95e-04

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132784  Cd Length: 127  Bit Score: 41.21  E-value: 6.95e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1790094194 1374 IQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGrSRGEAVAERRREELNGYIWHLIHAPPEVAECDL 1441
Cdd:cd06874     34 VFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFG-NKSERVAKERRRQLETYLRNFFSVCLKLPACPL 100
PX_RUN cd07277
The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX ...
 1357-1438 9.98e-04

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.


Pssm-ID: 132810  Cd Length: 118  Bit Score: 40.41  E-value: 9.98e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1357 YIYVVKVMRENTHEATYiqRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEAVAERRReELNGYIWHLI-HAPPE 1435
Cdd:cd07277     19 HVYQVYIRIRDDEWNVY--RRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRK-RLQVYLRRVVnTLIQT 95


                   ...
gi 1790094194 1436 VAE 1438
Cdd:cd07277     96 SPE 98
PX_SNX13 cd06873
The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a ...
 1333-1448 1.07e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.


Pssm-ID: 132783  Cd Length: 120  Bit Score: 40.33  E-value: 1.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1333 LKSSGRISDVFLCR-HEKIFHpnkgyIYVVKVMREN---THEATYIQRTFEEFQELHNKLRLLFPSSHLPSFPSR--Fvi 1406
Cdd:cd06873      3 FKLTAVIINTGIVKeHGKTYA-----VYAISVTRIYpngQEESWHVYRRYSDFHDLHMRLKEKFPNLSKLSFPGKktF-- 75

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1790094194 1407 gRSRGEAVAERRREELNGYIwHLIHAPPEVAECD----LVYTFFHP 1448
Cdd:cd06873     76 -NNLDRAFLEKRRKMLNQYL-QSLLNPEVLDANPglqeIVLDFLEP 119
PX_SNX19_like_plant cd06872
The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; ...
 1358-1445 1.11e-03

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132782  Cd Length: 107  Bit Score: 40.20  E-value: 1.11e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1358 IYVVKVmRENTHEATYIQRTFEEFQELHNKLRlLFPSSHLpSFPSRFVIGRSRGEAVAERRREELNGYIwHLIHAPPEVA 1437
Cdd:cd06872     20 VYSVAV-TDNENETWVVKRRFRNFETLHRRLK-EVPKYNL-ELPPKRFLSSSLDGAFIEERCKLLDKYL-KDLLVIEKVA 95


                   ....*...
gi 1790094194 1438 ECDLVYTF 1445
Cdd:cd06872     96 ESHEVWSF 103
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1511-1587 1.93e-03

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 39.47  E-value: 1.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLlpdpqkTTKR--KTKVARKTCNPTYNEMLVydgIPKGDLQQRELQLSVLSeqgfW----ENVLLGEVNIRLR 1584
Cdd:cd04040     21 DPFVKFYL------NGEKvfKTKTIKKTLNPVWNESFE---VPVPSRVRAVLKVEVYD----WdrggKDDLLGSAYIDLS 87


                   ...
gi 1790094194 1585 ELD 1587
Cdd:cd04040     88 DLE 90
PX_SNX22 cd06880
The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a ...
 1357-1431 2.06e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.


Pssm-ID: 132790  Cd Length: 110  Bit Score: 39.57  E-value: 2.06e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1790094194 1357 YIYVVKVMRENTHEatYIQRTFEEFQELHNKLRLLFpssHLPSFPSRFVigRSRGEAVAERRREELNGYIWHLIH 1431
Cdd:cd06880     20 TVFTIEVLVNGRRH--TVEKRYSEFHALHKKLKKSI---KTPDFPPKRV--RNWNPKVLEQRRQGLEAYLQGLLK 87
PX_CISK cd06870
The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The ...
 1340-1436 2.19e-03

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.


Pssm-ID: 132780  Cd Length: 109  Bit Score: 39.31  E-value: 2.19e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1340 SDVFLCRHEKIfHPNKGYIyVVKVMRENTHEATYIQRTFEEFQELHNKLRLLFPSSHLpSFPSRFVIGRSRGEAVAERRR 1419
Cdd:cd06870      4 SVSIPSSDEDR-EKKKRFT-VYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPASNL-KIPGKRLFGNNFDPDFIKQRR 80

                           90       100
                   ....*....|....*....|..
gi 1790094194 1420 EELNGYIWHLIHAP-----PEV 1436
Cdd:cd06870     81 AGLDEFIQRLVSDPkllnhPDV 102
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 1511-1603 2.76e-03

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175999 [Multi-domain]  Cd Length: 133  Bit Score: 39.64  E-value: 2.76e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLLpDPQKT---TKRKTKVARKTCNPTYNEMLVYDGIPkgdlQQRELQLSVLSEQGFWENVLLGEVNIRLRELD 1587
Cdd:cd04033     22 DPYVKISLY-DPDGNgeiDSVQTKTIKKTLNPKWNEEFFFRVNP----REHRLLFEVFDENRLTRDDFLGQVEVPLNNLP 96

                           90       100
                   ....*....|....*....|..
gi 1790094194 1588 LAQEKTGW------FALGSRSH 1603
Cdd:cd04033     97 TETPGNERrytfkdYLLRPRSS 118
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1509-1604 2.96e-03

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 39.12  E-value: 2.96e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1509 DPDPYVKIYLlpDPQKTtkRKTKVARKTCNPTYN---EMLVYDgipkgdlqQR--ELQLSVLSEQGFWENVlLGEVNIRL 1583
Cdd:cd04052     12 LLSPYAELYL--NGKLV--YTTRVKKKTNNPSWNastEFLVTD--------RRksRVTVVVKDDRDRHDPV-LGSVSISL 78

                           90       100
                   ....*....|....*....|..
gi 1790094194 1584 REL-DLAQEKTGWFALGSRSHG 1604
Cdd:cd04052     79 NDLiDATSVGQQWFPLSGNGQG 100
PX_PLD cd06895
The phosphoinositide binding Phox Homology domain of Phospholipase D; The PX domain is a ...
 1346-1438 3.03e-03

The phosphoinositide binding Phox Homology domain of Phospholipase D; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Phospholipase D (PLD) catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine to generate membrane-bound phosphatidic acid and choline. Members of this subfamily contain PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. PLD activity has been detected in viruses, bacteria, yeast, plants, and mammals, but the PX domain is not present in PLDs from viruses and bacteria. PLDs are implicated in many cellular functions like signaling, cytoskeletal reorganization, vesicular transport, stress responses, and the control of differentiation, proliferation, and survival. Vertebrates contain two PLD isozymes, PLD1 and PLD2. PLD1 is located mainly in intracellular membranes while PLD2 is associated with plasma membranes. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132805  Cd Length: 140  Bit Score: 39.67  E-value: 3.03e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1346 RHEKIFHPNKGYIYVVkvmrENTH-EATY-IQRTFEEFQELHNKL-------RLLFPS---------------------- 1394
Cdd:cd06895     13 RSGTTRHLLNPNLYTI----ELQHgQFTWtIKRRYKHFQELHQALklyrallRIPLPTrrhkeerlslkrsrkperekkn 88

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1790094194 1395 SHLPSFPSRFVIGRSrgEAVAERRREELNGYIWHLIHAP-----PEVAE 1438
Cdd:cd06895     89 RRLPSLPALPDILVS--EEQLDSRKKQLENYLQNLLKIPdyrnhPETLE 135
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 1511-1586 3.17e-03

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 39.14  E-value: 3.17e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1790094194 1511 DPYVKIYLLPDpqktTKRKTKVARKT-CNPTYNEMLVYDgIPKGDLQQRELQLSV--LSEQGFWENVLLGEVNIRLREL 1586
Cdd:cd04051     22 KVYAVVWIDPS----HKQSTPVDRDGgTNPTWNETLRFP-LDERLLQQGRLALTIevYCERPSLGDKLIGEVRVPLKDL 95
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1511-1606 3.22e-03

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.


Pssm-ID: 176037 [Multi-domain]  Cd Length: 121  Bit Score: 39.20  E-value: 3.22e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLlpdpqKTTKRKTKVARKTCNPTYNEmlVYDGIPKgDLQQRELQLSVLSEQG----FwenvlLGEVNIRLREL 1586
Cdd:cd08391     29 DPYVIVRV-----GAQTFKSKVIKENLNPKWNE--VYEAVVD-EVPGQELEIELFDEDPdkddF-----LGRLSIDLGSV 95

                           90       100
                   ....*....|....*....|
gi 1790094194 1587 DLAQEKTGWFALGSRSHGTL 1606
Cdd:cd08391     96 EKKGFIDEWLPLEDVKSGRL 115
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 1495-1601 4.52e-03

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 38.97  E-value: 4.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1495 VMHIRGLQLLQDGNDPDPYVKIYLLPDpqkttKRKTKVARKTCNPTYNEMLVYD--GIPKGDLQQRELQLSVLSEQGFWE 1572
Cdd:cd08682      5 VLQARGLLCKGKSGTNDAYVIIQLGKE-----KYSTSVKEKTTSPVWKEECSFElpGLLSGNGNRATLQLTVMHRNLLGL 79

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1790094194 1573 NVLLGEVNIRLRELDLAQ--EKTGWFALGSR 1601
Cdd:cd08682     80 DKFLGQVSIPLNDLDEDKgrRRTRWFKLESK 110
PX_MDM1p cd06876
The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a ...
 1359-1445 5.36e-03

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132786  Cd Length: 133  Bit Score: 38.83  E-value: 5.36e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1359 YVVKVMR-ENTHEAT--YIQRTFEEFQELHNKLRLLFPSSHLPSFPSRFVIGRSRGEA-VAERRREELNGYIWHLIhAPP 1434
Cdd:cd06876     41 YLIEVQRlNNDDQSSgwVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLKYSKTlLVEERRKALEKYLQELL-KIP 119

                           90
                   ....*....|.
gi 1790094194 1435 EVAECDLVYTF 1445
Cdd:cd06876    120 EVCEDEEFRKF 130
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1510-1605 5.51e-03

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 38.40  E-value: 5.51e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1510 PDPYVKIYLlpDPQKTTKRKTKVARktcNPTYNEMLVYDgIPKGDLQQRELQLSVLSEQGFweNVLLGEVNIRLRELDLA 1589
Cdd:cd08383     18 RDPYCTVSL--DQVEVARTKTVEKL---NPFWGEEFVFD-DPPPDVTFFTLSFYNKDKRSK--DRDIVIGKVALSKLDLG 89

                           90
                   ....*....|....*.
gi 1790094194 1590 QEKTGWFALGSRSHGT 1605
Cdd:cd08383     90 QGKDEWFPLTPVDPDS 105
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 1511-1606 5.58e-03

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 38.62  E-value: 5.58e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1511 DPYVKIYLlpdpqKTTKRKTKVARKTCNPTYNEMLvydgipkgDLQQRELQLSVLS-EQGFWE----NVLLGEVNIRLRE 1585
Cdd:cd04025     22 DPFVRVFY-----NGQTLETSVVKKSCYPRWNEVF--------EFELMEGADSPLSvEVWDWDlvskNDFLGKVVFSIQT 88

                           90       100
                   ....*....|....*....|....*..
gi 1790094194 1586 LDLAQEKTGWFALG------SRSHGTL 1606
Cdd:cd04025     89 LQQAKQEEGWFRLLpdpraeEESGGNL 115
PX_MONaKA cd06871
The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain ...
 1359-1448 9.12e-03

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132781  Cd Length: 120  Bit Score: 37.73  E-value: 9.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1790094194 1359 YVVKVMRENTHEATY-IQRTFEEFQELHNKLRLlfPSSHLPsFPSRFVIGRSRGEAVAERRReELNGYiWHLIHAPPEVA 1437
Cdd:cd06871     24 YIIRVQRGPSPENSWqVIRRYNDFDLLNASLQI--SGISLP-LPPKKLIGNMDREFIAERQQ-GLQNY-LNVILMNPILA 98

                           90
                   ....*....|.
gi 1790094194 1438 ECDLVYTFFHP 1448
Cdd:cd06871     99 SCLPVKKFLDP 109
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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