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Conserved domains on  [gi|767973290|ref|XP_011536253|]
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copine-8 isoform X3 [Homo sapiens]

Protein Classification

copine family protein( domain architecture ID 10134311)

copine family protein is involved in membrane trafficking, protein-protein interactions, and perhaps cell division and growth

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 24-145 4.84e-66

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 205.88  E-value: 4.84e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  24 TRVEVSVSCRNLLDRDTFSKSDPICVLYVQGVGNKEWREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSK 103
Cdd:cd04048    1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767973290 104 SPNLSKHDFLGQVFCTLGEIVGSQGSRLEKPIvgIPGKKCGT 145
Cdd:cd04048   81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 158-269 2.56e-60

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.56e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 158 DAVLMQFCANKLDKKDFFGKSDPFLVFYRSNEDGSFTICHKTEVVKNTLNPVWQAFKISVRALCNGDYDRTIKVEVYDWD 237
Cdd:cd04047    1 DVVELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYD 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767973290 238 RDGSHDFIGEFTTSYRELSrgQSQFNVYEVVN 269
Cdd:cd04047   81 SSGKHDLIGEFETTLDELL--KSSPLEFELIN 110
vWFA super family cl00057
Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation ...
 279-379 4.34e-43

Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of fold. The vWA domain, since its discovery, has drawn great interest because of its widespread occurrence and its involvement in a wide variety of important cellular functions. These include basal membrane formation, cell migration, cell differentiation, adhesion, haemostasis, signaling, chromosomal stability, malignant transformation and in immune defenses In integrins these domains form heterodimers while in vWF it forms multimers. There are different interaction surfaces of this domain as seen by the various molecules it complexes with. Ligand binding in most cases is mediated by the presence of a metal ion dependent adhesion site termed as the MIDAS motif that is a characteristic feature of most, if not all A domains.


The actual alignment was detected with superfamily member cd01459:

Pssm-ID: 469594  Cd Length: 254  Bit Score: 150.98  E-value: 4.34e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 279 YTNSGTVTLLSFLVETevSFLDYIKGGTQINFTVAIDFTASNGNPAQPTSLHYMNPYQLNAYGMALKAVGEIVQDYDSDK 358
Cdd:cd01459    5 YKSSGEVTLTDCRVQP--TFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82

                         90       100
                 ....*....|....*....|.
gi 767973290 359 MFPALGFGAKLPPDGRISHEF 379
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFF 103
 
Name Accession Description Interval E-value
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 24-145 4.84e-66

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 205.88  E-value: 4.84e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  24 TRVEVSVSCRNLLDRDTFSKSDPICVLYVQGVGNKEWREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSK 103
Cdd:cd04048    1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767973290 104 SPNLSKHDFLGQVFCTLGEIVGSQGSRLEKPIvgIPGKKCGT 145
Cdd:cd04048   81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 158-269 2.56e-60

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.56e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 158 DAVLMQFCANKLDKKDFFGKSDPFLVFYRSNEDGSFTICHKTEVVKNTLNPVWQAFKISVRALCNGDYDRTIKVEVYDWD 237
Cdd:cd04047    1 DVVELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYD 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767973290 238 RDGSHDFIGEFTTSYRELSrgQSQFNVYEVVN 269
Cdd:cd04047   81 SSGKHDLIGEFETTLDELL--KSSPLEFELIN 110
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
 279-379 4.34e-43

VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding.


Pssm-ID: 238736  Cd Length: 254  Bit Score: 150.98  E-value: 4.34e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 279 YTNSGTVTLLSFLVETevSFLDYIKGGTQINFTVAIDFTASNGNPAQPTSLHYMNPYQLNAYGMALKAVGEIVQDYDSDK 358
Cdd:cd01459    5 YKSSGEVTLTDCRVQP--TFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82

                         90       100
                 ....*....|....*....|.
gi 767973290 359 MFPALGFGAKLPPDGRISHEF 379
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFF 103
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
 328-381 1.18e-23

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.


Pssm-ID: 462064  Cd Length: 214  Bit Score: 97.79  E-value: 1.18e-23
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767973290  328 SLHYMNPYQLNAYGMALKAVGEIVQDYDSDKMFPALGFGAKLPPDGRISHEFAL 381
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVL 54
C2 pfam00168
C2 domain;
166-259 3.58e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 81.98  E-value: 3.58e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  166 ANKLDKKDFFGKSDPFLVFYRSNEdgsfTICHKTEVVKNTLNPVW-QAFKISVRAlcngDYDRTIKVEVYDWDRDGSHDF 244
Cdd:pfam00168  10 AKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRDDF 81

                          90
                  ....*....|....*
gi 767973290  245 IGEFTTSYRELSRGQ 259
Cdd:pfam00168  82 IGEVRIPLSELDSGE 96
C2 pfam00168
C2 domain;
25-128 8.07e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 78.13  E-value: 8.07e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290   25 RVEVSV-SCRNLLDRDTFSKSDPICVLYVQGvgnkeWREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSk 103
Cdd:pfam00168   2 RLTVTViEAKNLPPKDGNGTSDPYVKVYLLD-----GKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDR- 75

                          90       100
                  ....*....|....*....|....*
gi 767973290  104 spnLSKHDFLGQVFCTLGEIVGSQG 128
Cdd:pfam00168  76 ---FGRDDFIGEVRIPLSELDSGEG 97
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 164-261 5.96e-17

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: 75.60  E-value: 5.96e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290   164 FCANKLDKKDFFGKSDPFLVFYRsneDGSFTICHKTEVVKNTLNPVW-QAFKISVRALCngdyDRTIKVEVYDWDRDGSH 242
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79

                           90
                   ....*....|....*....
gi 767973290   243 DFIGEFTTSYRELSRGQSQ 261
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRH 98
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 30-129 1.24e-14

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: 69.44  E-value: 1.24e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290    30 VSCRNLLDRDTFSKSDPICVLYVQGVGNKEwrefGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDskspNLSK 109
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD----RFGR 78

                           90       100
                   ....*....|....*....|
gi 767973290   110 HDFLGQVFCTLGEIVGSQGS 129
Cdd:smart00239  79 DDFIGQVTIPLSDLLLGGRH 98
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
176-264 4.16e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 52.07  E-value: 4.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  176 GKSDPFLVFYRSNEDgsftiCHKTEVVKNTLNPVW-QAFKISV--RALCNgdydrtIKVEVYDWDRDGSHDFIGeftTSY 252
Cdd:COG5038  1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLG---TAE 1124

                          90
                  ....*....|....*.
gi 767973290  253 RELS----RGQSQFNV 264
Cdd:COG5038  1125 IDLSklepGGTTNSNI 1140
 
Name Accession Description Interval E-value
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 24-145 4.84e-66

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 205.88  E-value: 4.84e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  24 TRVEVSVSCRNLLDRDTFSKSDPICVLYVQGVGNKEWREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSK 103
Cdd:cd04048    1 PKVELSISCRNLLDKDVLSKSDPFVVVYVKTGGSGQWVEIGRTEVIKNNLNPDFVTTFTVDYYFEEVQKLRFEVYDVDSK 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767973290 104 SPNLSKHDFLGQVFCTLGEIVGSQGSRLEKPIvgIPGKKCGT 145
Cdd:cd04048   81 SKDLSDHDFLGEAECTLGEIVSSPGQKLTLPL--KGGKGKGT 120
C2B_Copine cd04047
C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 158-269 2.56e-60

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176012 [Multi-domain]  Cd Length: 110  Bit Score: 190.47  E-value: 2.56e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 158 DAVLMQFCANKLDKKDFFGKSDPFLVFYRSNEDGSFTICHKTEVVKNTLNPVWQAFKISVRALCNGDYDRTIKVEVYDWD 237
Cdd:cd04047    1 DVVELQFSGKKLDKKDFFGKSDPFLEISRQSEDGTWVLVYRTEVIKNTLNPVWKPFTIPLQKLCNGDYDRPIKIEVYDYD 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767973290 238 RDGSHDFIGEFTTSYRELSrgQSQFNVYEVVN 269
Cdd:cd04047   81 SSGKHDLIGEFETTLDELL--KSSPLEFELIN 110
vWA_copine_like cd01459
VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. ...
 279-379 4.34e-43

VWA Copine: Copines are phospholipid-binding proteins originally identified in paramecium. They are found in human and orthologues have been found in C. elegans and Arabidopsis Thaliana. None have been found in D. Melanogaster or S. Cereviciae. Phylogenetic distribution suggests that copines have been lost in some eukaryotes. No functional properties have been assigned to the VWA domains present in copines. The members of this subgroup contain a functional MIDAS motif based on their preferential binding to magnesium and manganese. However, the MIDAS motif is not totally conserved, in most cases the MIDAS consists of the sequence DxTxS instead of the motif DxSxS that is found in most cases. The C2 domains present in copines mediate phospholipid binding.


Pssm-ID: 238736  Cd Length: 254  Bit Score: 150.98  E-value: 4.34e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 279 YTNSGTVTLLSFLVETevSFLDYIKGGTQINFTVAIDFTASNGNPAQPTSLHYMNPYQLNAYGMALKAVGEIVQDYDSDK 358
Cdd:cd01459    5 YKSSGEVTLTDCRVQP--TFLDYRSAGLESNLIVAIDFTKSNGWPGEKRSLHYISPGRLNPYQKAIRIVGEVLQPYDSDK 82

                         90       100
                 ....*....|....*....|.
gi 767973290 359 MFPALGFGAKLPPDGRISHEF 379
Cdd:cd01459   83 LIPAFGFGAIVTKDQSVFSFF 103
Copine pfam07002
Copine; This family represents a conserved region approximately 220 residues long within ...
 328-381 1.18e-23

Copine; This family represents a conserved region approximately 220 residues long within eukaryotic copines. Copines are Ca(2+)-dependent phospholipid-binding proteins that are thought to be involved in membrane-trafficking, and may also be involved in cell division and growth.


Pssm-ID: 462064  Cd Length: 214  Bit Score: 97.79  E-value: 1.18e-23
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 767973290  328 SLHYMNPYQLNAYGMALKAVGEIVQDYDSDKMFPALGFGAKLPPDGRISHEFAL 381
Cdd:pfam07002   1 SLHYISPSQPNPYEQALRIVGEILQDYDSDKLFPAFGFGARIPPDATVSHCFVL 54
C2 pfam00168
C2 domain;
166-259 3.58e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 81.98  E-value: 3.58e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  166 ANKLDKKDFFGKSDPFLVFYRSNEdgsfTICHKTEVVKNTLNPVW-QAFKISVRAlcngDYDRTIKVEVYDWDRDGSHDF 244
Cdd:pfam00168  10 AKNLPPKDGNGTSDPYVKVYLLDG----KQKKKTKVVKNTLNPVWnETFTFSVPD----PENAVLEIEVYDYDRFGRDDF 81

                          90
                  ....*....|....*
gi 767973290  245 IGEFTTSYRELSRGQ 259
Cdd:pfam00168  82 IGEVRIPLSELDSGE 96
C2 pfam00168
C2 domain;
25-128 8.07e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 78.13  E-value: 8.07e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290   25 RVEVSV-SCRNLLDRDTFSKSDPICVLYVQGvgnkeWREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSk 103
Cdd:pfam00168   2 RLTVTViEAKNLPPKDGNGTSDPYVKVYLLD-----GKQKKKTKVVKNTLNPVWNETFTFSVPDPENAVLEIEVYDYDR- 75

                          90       100
                  ....*....|....*....|....*
gi 767973290  104 spnLSKHDFLGQVFCTLGEIVGSQG 128
Cdd:pfam00168  76 ---FGRDDFIGEVRIPLSELDSGEG 97
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 164-261 5.96e-17

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: 75.60  E-value: 5.96e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290   164 FCANKLDKKDFFGKSDPFLVFYRsneDGSFTICHKTEVVKNTLNPVW-QAFKISVRALCngdyDRTIKVEVYDWDRDGSH 242
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSL---DGDPKEKKKTKVVKNTLNPVWnETFEFEVPPPE----LAELEIEVYDKDRFGRD 79

                           90
                   ....*....|....*....
gi 767973290   243 DFIGEFTTSYRELSRGQSQ 261
Cdd:smart00239  80 DFIGQVTIPLSDLLLGGRH 98
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 176-247 5.30e-16

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: 73.37  E-value: 5.30e-16
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767973290 176 GKSDPFLVFYRSNEDgsftiCHKTEVVKNTLNPVW-QAFKISVralcNGDYDRTIKVEVYDWDRDGSHDFIGE 247
Cdd:cd04040   18 GKSDPFVKFYLNGEK-----VFKTKTIKKTLNPVWnESFEVPV----PSRVRAVLKVEVYDWDRGGKDDLLGS 81
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 25-130 9.64e-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: 72.48  E-value: 9.64e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNLLDRDTFSKSDPICVLYVQGvgnkewREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSks 104
Cdd:cd00030    2 RVTV-IEARNLPAKDLNGKSDPYVKVSLGG------KQKFKTKVVKNTLNPVWNETFEFPVLDPESDTLTVEVWDKDR-- 72

                         90       100
                 ....*....|....*....|....*.
gi 767973290 105 pnLSKHDFLGQVFCTLGEIVGSQGSR 130
Cdd:cd00030   73 --FSKDDFLGEVEIPLSELLDSGKEG 96
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 165-249 1.26e-15

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: 72.10  E-value: 1.26e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 165 CANKLDKKDFFGKSDPFLVFYRSNEdgsftICHKTEVVKNTLNPVW-QAFKISVralcNGDYDRTIKVEVYDWDRDGSHD 243
Cdd:cd00030    7 EARNLPAKDLNGKSDPYVKVSLGGK-----QKFKTKVVKNTLNPVWnETFEFPV----LDPESDTLTVEVWDKDRFSKDD 77


                 ....*.
gi 767973290 244 FIGEFT 249
Cdd:cd00030   78 FLGEVE 83
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 160-260 2.59e-15

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 71.83  E-value: 2.59e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 160 VLMQFCANKLDKKDFFGKSDPFLVFY-RSNEDGSFTICHKTEVVKNTLNPVWQAfKISVralcngDY----DRTIKVEVY 234
Cdd:cd04048    3 VELSISCRNLLDKDVLSKSDPFVVVYvKTGGSGQWVEIGRTEVIKNNLNPDFVT-TFTV------DYyfeeVQKLRFEVY 75

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767973290 235 DWD----RDGSHDFIGEFTTSYREL--SRGQS 260
Cdd:cd04048   76 DVDskskDLSDHDFLGEAECTLGEIvsSPGQK 107
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 30-129 1.24e-14

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: 69.44  E-value: 1.24e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290    30 VSCRNLLDRDTFSKSDPICVLYVQGVGNKEwrefGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDskspNLSK 109
Cdd:smart00239   7 ISARNLPPKDKGGKSDPYVKVSLDGDPKEK----KKTKVVKNTLNPVWNETFEFEVPPPELAELEIEVYDKD----RFGR 78

                           90       100
                   ....*....|....*....|
gi 767973290   110 HDFLGQVFCTLGEIVGSQGS 129
Cdd:smart00239  79 DDFIGQVTIPLSDLLLGGRH 98
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 176-255 7.43e-11

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: 59.58  E-value: 7.43e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 176 GKSDPFlVFYRSNEDGSFTICHKTEVVKNTLNPVWQ---AFKISvralcNGDYDRTIKVEVYDWDRDGSHDFIGEFTTSY 252
Cdd:cd04026   32 GLSDPY-VKLKLIPDPKNETKQKTKTIKKTLNPVWNetfTFDLK-----PADKDRRLSIEVWDWDRTTRNDFMGSLSFGV 105


                 ...
gi 767973290 253 REL 255
Cdd:cd04026  106 SEL 108
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 168-247 4.59e-08

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: 51.58  E-value: 4.59e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 168 KLDKKDFFGKSDPF--LVFYRSNEDGSFTICHkTEVVKNTLNPVW-QAFKISVRALCNgdydrTIKVEVYDWDRDGSHDF 244
Cdd:cd04033   11 DLAKKDIFGASDPYvkISLYDPDGNGEIDSVQ-TKTIKKTLNPKWnEEFFFRVNPREH-----RLLFEVFDENRLTRDDF 84


                 ...
gi 767973290 245 IGE 247
Cdd:cd04033   85 LGQ 87
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 166-249 5.89e-08

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: 51.11  E-value: 5.89e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEdgsfticHK----TEVVKNTLNPVWQ---AFKISVRALCNgdydRTIKVEVYDWDR 238
Cdd:cd08385   25 AADLPAMDMGGTSDPYVKVYLLPD-------KKkkfeTKVHRKTLNPVFNetfTFKVPYSELGN----KTLVFSVYDFDR 93

                         90
                 ....*....|.
gi 767973290 239 DGSHDFIGEFT 249
Cdd:cd08385   94 FSKHDLIGEVR 104
C2_ArfGAP cd04038
C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...
 172-247 8.23e-08

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (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: 176003 [Multi-domain]  Cd Length: 145  Bit Score: 51.17  E-value: 8.23e-08
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767973290 172 KDFFGkSDPFLVFYRSNEDGsftichKTEVVKNTLNPVW-QAFKISVRalcngDYDRTIKVEVYDWDRDGSHDFIGE 247
Cdd:cd04038   17 RDFTS-SDPYVVLTLGNQKV------KTRVIKKNLNPVWnEELTLSVP-----NPMAPLKLEVFDKDTFSKDDSMGE 81
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 147-249 8.97e-08

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: 50.32  E-value: 8.97e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 147 ILTAEELNCCRDAVLmqfcankldkkdffgkSDPFLVFY----RSNEdgsfticHK--TEVVKNTLNPVWQA----FKIS 216
Cdd:cd04031   22 VLQARDLPPRDDGSL----------------RNPYVKVYllpdRSEK-------SKrrTKTVKKTLNPEWNQtfeySNVR 78

                         90       100       110
                 ....*....|....*....|....*....|...
gi 767973290 217 VRALcngdYDRTIKVEVYDWDRDGSHDFIGEFT 249
Cdd:cd04031   79 RETL----KERTLEVTVWDYDRDGENDFLGEVV 107
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 176-260 1.01e-07

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: 50.37  E-value: 1.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 176 GKSDPFLVFyrsnEDGSFTIchKTEVVKNTLNPVW-QAFKisvrALCNGDYDRTIKVEVYDWDRDgSHDFIGEFTTSYRE 254
Cdd:cd08391   26 GKSDPYVIV----RVGAQTF--KSKVIKENLNPKWnEVYE----AVVDEVPGQELEIELFDEDPD-KDDFLGRLSIDLGS 94


                 ....*.
gi 767973290 255 LSRGQS 260
Cdd:cd08391   95 VEKKGF 100
C2_Smurf-like cd08382
C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 ...
 164-218 1.45e-07

C2 domain present in Smad ubiquitination-related factor (Smurf)-like proteins; A single C2 domain is found in Smurf proteins, C2-WW-HECT-domain E3s, which play an important role in the downregulation of the TGF-beta signaling pathway. Smurf proteins also regulate cell shape, motility, and polarity by degrading small guanosine triphosphatases (GTPases). 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 type-II topology.


Pssm-ID: 176028 [Multi-domain]  Cd Length: 123  Bit Score: 49.61  E-value: 1.45e-07
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767973290 164 FCANKLDKKDFFGKSDPFLVFyrSNEDGSftiCHKTEVVKNTLNPVW-QAFKISVR 218
Cdd:cd08382    7 LCADGLAKRDLFRLPDPFAVI--TVDGGQ---THSTDVAKKTLDPKWnEHFDLTVG 57
C2A_Ferlin cd08373
C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 174-263 1.60e-07

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 176019 [Multi-domain]  Cd Length: 127  Bit Score: 49.94  E-value: 1.60e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 174 FFGKSDPFL-VFYRSnedgsftICHKTEVVKNTLNPVW-QAFKISVRAlcNGDYDRTIKVEVYDWDRDGSHDFIGEFTTS 251
Cdd:cd08373   11 LKGKGDRIAkVTFRG-------VKKKTRVLENELNPVWnETFEWPLAG--SPDPDESLEIVVKDYEKVGRNRLIGSATVS 81

                         90
                 ....*....|...
gi 767973290 252 YREL-SRGQSQFN 263
Cdd:cd08373   82 LQDLvSEGLLEVT 94
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 166-261 2.01e-07

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: 49.41  E-value: 2.01e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFL-VFYRSNEdgsfticHKTEVVKNTLNPVW-QAFKISVRalcnGDYDRTIKVEVYDWDRDGSHD 243
Cdd:cd04025    9 ARDLAPKDRNGTSDPFVrVFYNGQT-------LETSVVKKSCYPRWnEVFEFELM----EGADSPLSVEVWDWDLVSKND 77

                         90
                 ....*....|....*...
gi 767973290 244 FIGEFTTSYRELSRGQSQ 261
Cdd:cd04025   78 FLGKVVFSIQTLQQAKQE 95
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 25-127 2.73e-07

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: 48.83  E-value: 2.73e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNLLDRDTF------SKSDPICVLYVqgvGNKEWRefgrTEVIDNTLNPDF--VRKFILDYffEERENLRFD 96
Cdd:cd08391    4 RIHV-IEAQDLVAKDKFvgglvkGKSDPYVIVRV---GAQTFK----SKVIKENLNPKWneVYEAVVDE--VPGQELEIE 73

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767973290  97 LYDVDskspnLSKHDFLGQVFCTLGEIVGSQ 127
Cdd:cd08391   74 LFDED-----PDKDDFLGRLSIDLGSVEKKG 99
C2C_MCTP_PRT cd08377
C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 164-246 3.66e-07

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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: 176023 [Multi-domain]  Cd Length: 119  Bit Score: 48.45  E-value: 3.66e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 164 FCANKLDKKDFFGKSDPFLVFYRSNEDgsfticHKTEVVKNTLNPVW-QAFKISVRalcngDYDRTIKVEVYDWDRDGSH 242
Cdd:cd08377    8 IRASGLAAADIGGKSDPFCVLELVNAR------LQTHTIYKTLNPEWnKIFTFPIK-----DIHDVLEVTVYDEDKDKKP 76


                 ....
gi 767973290 243 DFIG 246
Cdd:cd08377   77 EFLG 80
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 166-254 3.71e-07

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: 48.95  E-value: 3.71e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEDGSFTIcHKTEVVKNTLNPVWQ---AFKISVRALcngdYDRTIKVEVYDWDRDGSH 242
Cdd:cd08405   24 ARNLKAMDINGTSDPYVKVWLMYKDKRVEK-KKTVIKKRTLNPVFNesfIFNIPLERL----RETTLIITVMDKDRLSRN 98

                         90
                 ....*....|..
gi 767973290 243 DFIGEFTTSYRE 254
Cdd:cd08405   99 DLIGKIYLGWKS 110
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
176-264 4.16e-07

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 52.07  E-value: 4.16e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  176 GKSDPFLVFYRSNEDgsftiCHKTEVVKNTLNPVW-QAFKISV--RALCNgdydrtIKVEVYDWDRDGSHDFIGeftTSY 252
Cdd:COG5038  1059 GYSDPFVKLFLNEKS-----VYKTKVVKKTLNPVWnEEFTIEVlnRVKDV------LTINVNDWDSGEKNDLLG---TAE 1124

                          90
                  ....*....|....*.
gi 767973290  253 RELS----RGQSQFNV 264
Cdd:COG5038  1125 IDLSklepGGTTNSNI 1140
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 25-128 6.74e-07

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: 48.04  E-value: 6.74e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVSV-SCRNLLDRDTFSKSDPICVLYVqgVGNKEWREFGRTEVIDNTLNPDFVRKFilDYFFEERE-NLRFDLYDVDS 102
Cdd:cd04030   17 KLIVTVhKCRNLPPCDSSDIPDPYVRLYL--LPDKSKSTRRKTSVKKDNLNPVFDETF--EFPVSLEElKRRTLDVAVKN 92

                         90       100
                 ....*....|....*....|....*..
gi 767973290 103 KSPNLSKH-DFLGQVFCTLGEIVGSQG 128
Cdd:cd04030   93 SKSFLSREkKLLGQVLIDLSDLDLSKG 119
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 25-148 7.60e-07

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: 47.56  E-value: 7.60e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNLLDRDTFSKSDPICVLYVQGvgnkewREFGRTEVIDNTLNPDFVRKFILDYFFEERENLRFDLYDVDSKS 104
Cdd:cd04040    2 TVDV-ISAENLPSADRNGKSDPFVKFYLNG------EKVFKTKTIKKTLNPVWNESFEVPVPSRVRAVLKVEVYDWDRGG 74

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 767973290 105 PNlskhDFLGQVFCTLGEIVGSQGSRLEKPIVGIPGKKCGTIIL 148
Cdd:cd04040   75 KD----DLLGSAYIDLSDLEPEETTELTLPLDGQGGGKLGAVFL 114
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 166-263 7.62e-07

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: 47.96  E-value: 7.62e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNeDGSFTICHKTEVVKNTLNPVWQ---AFKISVRALCNgdydRTIKVEVYDWDRDGSH 242
Cdd:cd00276   23 ARNLPPSDGKGLSDPYVKVSLLQ-GGKKLKKKKTSVKKGTLNPVFNeafSFDVPAEQLEE----VSLVITVVDKDSVGRN 97

                         90       100
                 ....*....|....*....|.
gi 767973290 243 DFIGEFTTSYRELSRGQSQFN 263
Cdd:cd00276   98 EVIGQVVLGPDSGGEELEHWN 118
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 165-246 2.34e-06

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: 46.57  E-value: 2.34e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 165 CANkLDKKDFFGKSDPFLVFYRSnEDGSFTICHKTEVVKNTLNPVWQ---AFKISVRALCNgdydRTIKVEVYDWDRDGS 241
Cdd:cd08384   22 CVN-LAAMDANGYSDPFVKLYLK-PDAGKKSKHKTQVKKKTLNPEFNeefFYDIKHSDLAK----KTLEITVWDKDIGKS 95


                 ....*
gi 767973290 242 HDFIG 246
Cdd:cd08384   96 NDYIG 100
C2A_Munc13-like cd08676
C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 16-128 3.35e-06

C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176058 [Multi-domain]  Cd Length: 153  Bit Score: 46.60  E-value: 3.35e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  16 QLSAAIPATRVEVsVSCRNLLDRDTFSKSDPICVLYVQ-----GVGNKEWREFG-----------------RTEVIDNTL 73
Cdd:cd08676   22 EAEPPIFVLKVTV-IEAKGLLAKDVNGFSDPYCMLGIVpasreRNSEKSKKRKShrkkavlkdtvpaksikVTEVKPQTL 100

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767973290  74 NPDFVRKFILDYFFEERENLRFDLYDVDSkspnlskhDFLGQVFCTLGEIVgSQG 128
Cdd:cd08676  101 NPVWNETFRFEVEDVSNDQLHLDIWDHDD--------DFLGCVNIPLKDLP-SCG 146
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 169-253 4.15e-06

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 46.00  E-value: 4.15e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 169 LDKKDFfgkSDPFL-VFYRSNedgsftiCHKTEVVKNTLNPVW-QAFKISVRALCNG--DYDR---TIKVEVYDWDRDGS 241
Cdd:cd04017   16 ADKSGL---SDPFArVSFLNQ-------SQETEVIKETLSPTWdQTLIFDEVELYGSpeEIAQnppLVVVELFDQDSVGK 85

                         90
                 ....*....|..
gi 767973290 242 HDFIGEFTTSYR 253
Cdd:cd04017   86 DEFLGRSVAKPL 97
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 33-135 6.43e-06

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: 45.09  E-value: 6.43e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  33 RNLLDRDTFSKSDPICVLYVQGVGNKEWRefgrTEVIDNTLNPDFVRKFIldyfFE------ERENLRFDLYDVDSkspn 106
Cdd:cd08387   26 RNLQPRDFSGTADPYCKVRLLPDRSNTKQ----SKIHKKTLNPEFDESFV----FEvppqelPKRTLEVLLYDFDQ---- 93

                         90       100
                 ....*....|....*....|....*....
gi 767973290 107 LSKHDFLGQVFCTLGEIVGSQGSRLEKPI 135
Cdd:cd08387   94 FSRDECIGVVELPLAEVDLSEKLDLWRKI 122
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 33-136 1.31e-05

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: 44.17  E-value: 1.31e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  33 RNLLDRD-TFSKSDP---ICVLYVQgvgnkewREFGRTEVIDNTLNPDFVRKFILDYFFEE--RENLRFDLYDVDSKSpn 106
Cdd:cd08390   24 RNLPPRTkDVAHCDPfvkVCLLPDE-------RRSLQSKVKRKTQNPNFDETFVFQVSFKElqRRTLRLSVYDVDRFS-- 94

                         90       100       110
                 ....*....|....*....|....*....|
gi 767973290 107 lsKHDFLGQVFCTLGEIVGSQGSRLEKPIV 136
Cdd:cd08390   95 --RHCIIGHVLFPLKDLDLVKGGVVWRDLE 122
C2A_MCTP_PRT cd04042
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 172-247 1.38e-05

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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: 176007 [Multi-domain]  Cd Length: 121  Bit Score: 44.19  E-value: 1.38e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767973290 172 KDFFGKSDPFLVFYRSNEdgsftICHKTEVVKNTLNPVW-QAFKISVRalcngDYDRTIKVEVYDWDRDGSHDFIGE 247
Cdd:cd04042   15 RDRGGTSDPYVKFKYGGK-----TVYKSKTIYKNLNPVWdEKFTLPIE-----DVTQPLYIKVFDYDRGLTDDFMGS 81
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 166-247 1.38e-05

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: 44.31  E-value: 1.38e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSnEDGSFTICHKTEVVKNTLNPVWQ---AFKISVRALcngdYDRTIKVEVYDWDRDGSH 242
Cdd:cd08402   24 AKNLKKMDVGGLSDPYVKIHLM-QNGKRLKKKKTTIKKRTLNPYYNesfSFEVPFEQI----QKVHLIVTVLDYDRIGKN 98


                 ....*
gi 767973290 243 DFIGE 247
Cdd:cd08402   99 DPIGK 103
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 25-124 1.83e-05

C2 domain first 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 43.95  E-value: 1.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNLL--DRDTFSKSDPICVLYVqgvGNKEWRefgrTEVIDNTLNPDFvrkfilDYFFE------ERENLRFD 96
Cdd:cd04024    4 RVHV-VEAKDLAakDRSGKGKSDPYAILSV---GAQRFK----TQTIPNTLNPKW------NYWCEfpifsaQNQLLKLI 69

                         90       100
                 ....*....|....*....|....*...
gi 767973290  97 LYDVDskspNLSKHDFLGQVFCTLGEIV 124
Cdd:cd04024   70 LWDKD----RFAGKDYLGEFDIALEEVF 93
C2A_Synaptotagmin-like cd04024
C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 166-248 2.67e-05

C2 domain first 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 first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175990 [Multi-domain]  Cd Length: 128  Bit Score: 43.57  E-value: 2.67e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFF--GKSDPFLVFYRsnedGSFTicHKTEVVKNTLNPVWQA-FKISVRALCNGdydrTIKVEVYDWDRDGSH 242
Cdd:cd04024   10 AKDLAAKDRSgkGKSDPYAILSV----GAQR--FKTQTIPNTLNPKWNYwCEFPIFSAQNQ----LLKLILWDKDRFAGK 79


                 ....*.
gi 767973290 243 DFIGEF 248
Cdd:cd04024   80 DYLGEF 85
C2E_Ferlin cd04037
C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 166-247 6.23e-05

C2 domain fifth 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176002 [Multi-domain]  Cd Length: 124  Bit Score: 42.15  E-value: 6.23e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFyrsnEDGSFTICHKTEVVKNTLNPVW-QAFKISvralCNGDYDRTIKVEVYDWDRDGSHDF 244
Cdd:cd04037    9 ARNLQPKDPNGKSDPYLKI----KLGKKKINDRDNYIPNTLNPVFgKMFELE----ATLPGNSILKISVMDYDLLGSDDL 80


                 ...
gi 767973290 245 IGE 247
Cdd:cd04037   81 IGE 83
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 166-247 6.58e-05

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: 42.22  E-value: 6.58e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEDgSFTICH--KTEVVKNTLNPVW-QAFKISVRALCNGDYDRTIKVEVYDWDRDGSH 242
Cdd:cd04009   25 ARNLLPLDSNGSSDPFVKVELLPRH-LFPDVPtpKTQVKKKTLFPLFdESFEFNVPPEQCSVEGALLLFTVKDYDLLGSN 103


                 ....*
gi 767973290 243 DFIGE 247
Cdd:cd04009  104 DFEGE 108
C2B_Munc13 cd04027
C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...
 165-256 6.77e-05

C2 domain second repeat in Munc13 (mammalian uncoordinated) 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175993 [Multi-domain]  Cd Length: 127  Bit Score: 42.17  E-value: 6.77e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 165 CANKLDKKDFFGKSDPFLVFYRSNEDgsfticHKTEVVKNTLNPVW-QAFKISvralCNGDYDRtIKVEVYDWDRD---- 239
Cdd:cd04027    9 CAQGLIAKDKTGTSDPYVTVQVGKTK------KRTKTIPQNLNPVWnEKFHFE----CHNSSDR-IKVRVWDEDDDiksr 77

                         90       100
                 ....*....|....*....|....
gi 767973290 240 -------GSHDFIGEFTTSYRELS 256
Cdd:cd04027   78 lkqkftrESDDFLGQTIIEVRTLS 101
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 175-246 6.78e-05

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 42.25  E-value: 6.78e-05
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767973290 175 FGKSDPFLVFyrSNEDGSFTIChKTEVVKNTLNPVW-QAFKISVRalcnGDYDRTIKVEVYDWDRDGSHDFIG 246
Cdd:cd04043   19 NGLSDPYVTL--VDTNGKRRIA-KTRTIYDTLNPRWdEEFELEVP----AGEPLWISATVWDRSFVGKHDLCG 84
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 166-246 1.58e-04

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: 41.23  E-value: 1.58e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPF----LVFYRSNEdgsfticHKTEVVKNTLNPVWQ-AFKISVRALCNGDydRTIKVEVYDWDRDG 240
Cdd:cd08387   25 ARNLQPRDFSGTADPYckvrLLPDRSNT-------KQSKIHKKTLNPEFDeSFVFEVPPQELPK--RTLEVLLYDFDQFS 95


                 ....*.
gi 767973290 241 SHDFIG 246
Cdd:cd08387   96 RDECIG 101
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 166-261 2.22e-04

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: 40.78  E-value: 2.22e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEDGsfticHK--TEVVKNTLNPVW------QAFKIsvralcNGDYDRTIKVEVYDWD 237
Cdd:cd08386   25 AVELPAKDFSGTSDPFVKIYLLPDKK-----HKleTKVKRKNLNPHWnetflfEGFPY------EKLQQRVLYLQVLDYD 93

                         90       100
                 ....*....|....*....|....
gi 767973290 238 RDGSHDFIGEFTTSYRELSRGQSQ 261
Cdd:cd08386   94 RFSRNDPIGEVSLPLNKVDLTEEQ 117
C2_NEDD4_NEDD4L cd04033
C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...
 25-134 2.29e-04

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: 40.80  E-value: 2.29e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNLLDRDTFSKSDPICVL-YVQGVGNKEWREFgRTEVIDNTLNPDFVRKFILDyfFEEREN-LRFDLYDVDs 102
Cdd:cd04033    3 RVKV-LAGIDLAKKDIFGASDPYVKIsLYDPDGNGEIDSV-QTKTIKKTLNPKWNEEFFFR--VNPREHrLLFEVFDEN- 77

                         90       100       110
                 ....*....|....*....|....*....|..
gi 767973290 103 kspNLSKHDFLGQVFCTLGEIVGSQGSRLEKP 134
Cdd:cd04033   78 ---RLTRDDFLGQVEVPLNNLPTETPGNERRY 106
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 176-255 2.35e-04

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: 40.82  E-value: 2.35e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 176 GKSDPF-LVFYRSnedGSFTICHKTEVVKNTLNPVW-QAFKISVRALCNGDYDRT-----------IKVEVYDWDRDGSH 242
Cdd:cd08675   17 GTCDPFaRVTLNY---SSKTDTKRTKVKKKTNNPRFdEAFYFELTIGFSYEKKSFkveeedlekseLRVELWHASMVSGD 93

                         90
                 ....*....|...
gi 767973290 243 DFIGEFTTSYREL 255
Cdd:cd08675   94 DFLGEVRIPLQGL 106
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 166-257 2.51e-04

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (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: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 40.32  E-value: 2.51e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDF-FGKSDPFLVFyrsnedgSFTICHK----TEVVKNTLNPVWQ--AFKISVRALCNGDYDrtIKVEVYDWDR 238
Cdd:cd04041   10 ATDLPKADFgTGSSDPYVTA-------SFAKFGKplysTRIIRKDLNPVWEetWFVLVTPDEVKAGER--LSCRLWDSDR 80

                         90
                 ....*....|....*....
gi 767973290 239 DGSHDFIGEFTTSYRELSR 257
Cdd:cd04041   81 FTADDRLGRVEIDLKELIE 99
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 5-116 2.84e-04

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: 40.48  E-value: 2.84e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290   5 YNSTAGIGDLNQLSaaipatrvevsvsCRNLLDRDTFSKSDPicvlYVqgvgnKEWREFG-------RTEVIDNTLNPDF 77
Cdd:cd08405   10 YNPTANRITVNIIK-------------ARNLKAMDINGTSDP----YV-----KVWLMYKdkrvekkKTVIKKRTLNPVF 67

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 767973290  78 VRKFILDYFFEE-RE-NLRFDLYDVDskspNLSKHDFLGQV 116
Cdd:cd08405   68 NESFIFNIPLERlREtTLIITVMDKD----RLSRNDLIGKI 104
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 170-257 3.50e-04

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 40.69  E-value: 3.50e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 170 DKKDFfgkSDPFLVFYRSNEDGsftichKTEVVKNTLNPVW-QAFKISVR--ALCngdydRTIKVEVYDWDRDGSHDFIG 246
Cdd:cd04018   30 EKKEL---VDPYVEVSFAGQKV------KTSVKKNSYNPEWnEQIVFPEMfpPLC-----ERIKIQIRDWDRVGNDDVIG 95

                         90
                 ....*....|.
gi 767973290 247 eftTSYRELSR 257
Cdd:cd04018   96 ---THFIDLSK 103
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 197-246 5.48e-04

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: 40.38  E-value: 5.48e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 767973290 197 HKTEVVKNTLNPVW-QAF---KISVRALcngdYDRTIKVEVYDWDRDGSHDFIG 246
Cdd:cd04020   66 QKTPVVKKSVNPVWnHTFvydGVSPEDL----SQACLELTVWDHDKLSSNDFLG 115
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 191-246 5.54e-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: 39.21  E-value: 5.54e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 191 GSFTicHKTEVVKNTLNPVW--QAFKISV--RALcngdYDRTIKVEVYDWDRDGSHDFIG 246
Cdd:cd08688   30 GSTT--YKTDVVKKSLNPVWnsEWFRFEVddEEL----QDEPLQIRVMDHDTYSANDAIG 83
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 32-132 5.77e-04

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: 39.64  E-value: 5.77e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  32 CRNLLDRDTFSKSDPICVLYVQGVGNKEWREfgRTEVIDNTLNPDFVRKFILDYFFEE--RENLRFDLYDVDskspnLSK 109
Cdd:cd08384   22 CVNLAAMDANGYSDPFVKLYLKPDAGKKSKH--KTQVKKKTLNPEFNEEFFYDIKHSDlaKKTLEITVWDKD-----IGK 94

                         90       100
                 ....*....|....*....|....
gi 767973290 110 H-DFLGQVfcTLGeiVGSQGSRLE 132
Cdd:cd08384   95 SnDYIGGL--QLG--INAKGERLR 114
C2_PSD cd04039
C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...
 179-261 6.71e-04

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain]  Cd Length: 108  Bit Score: 38.77  E-value: 6.71e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 179 DPFLV--FYRSnedgSFtichKTEVVKNTLNPVWQ---AFKisVRALcNGDYDrtIKVEVYDWDRDGSHDFIGEFTTSYR 253
Cdd:cd04039   27 DPFVIisFGRR----VF----RTSWRRHTLNPVFNerlAFE--VYPH-EKNFD--IQFKVLDKDKFSFNDYVATGSLSVQ 93


                 ....*...
gi 767973290 254 ELSRGQSQ 261
Cdd:cd04039   94 ELLNAAPQ 101
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 197-258 7.06e-04

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 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-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 39.45  E-value: 7.06e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767973290 197 HKTEVVK-NTLNPVW-QAFKISVR----ALcngdydrtIKVEVYDWDrDGSHDFIGEFTTSYRELSRG 258
Cdd:cd00275   44 FKTKVVKnNGFNPVWnETFEFDVTvpelAF--------LRFVVYDED-SGDDDFLGQACLPLDSLRQG 102
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 197-263 1.26e-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: 38.35  E-value: 1.26e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767973290 197 HKTEVVKNTLNPVWQAfkiSVRALCNgdyDRT---IKVEVYDwDRDGSHDFIGEFTTSYREL----SRGQSQFN 263
Cdd:cd04052   27 YTTRVKKKTNNPSWNA---STEFLVT---DRRksrVTVVVKD-DRDRHDPVLGSVSISLNDLidatSVGQQWFP 93
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 166-261 1.32e-03

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 38.39  E-value: 1.32e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEDgsfticHKTEVVKNTLNPVW-QAFKIsvrALCNgDYDRTIKVEVYDWDRDGSHDF 244
Cdd:cd08376    9 GKNLPPMDDNGLSDPYVKFRLGNEK------YKSKVCSKTLNPQWlEQFDL---HLFD-DQSQILEIEVWDKDTGKKDEF 78

                         90
                 ....*....|....*..
gi 767973290 245 IGEFTTSYRELSRGQSQ 261
Cdd:cd08376   79 IGRCEIDLSALPREQTH 95
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 26-107 1.69e-03

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: 38.30  E-value: 1.69e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  26 VEVSV-SCRNLLDRDTFSKS-DPicvlYVQgVGNKEWREFGRTEVIDNTLNPDFVR-KFILDYFFEerENLRFDLYD-VD 101
Cdd:cd04044    4 LAVTIkSARGLKGSDIIGGTvDP----YVT-FSISNRRELARTKVKKDTSNPVWNEtKYILVNSLT--EPLNLTVYDfND 76


                 ....*.
gi 767973290 102 SKSPNL 107
Cdd:cd04044   77 KRKDKL 82
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 16-124 2.70e-03

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: 37.63  E-value: 2.70e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  16 QLSAAIPATRVEVSV-SCRNLLDRDTFSKSDPICVLYVQGVGNKEWREfgRTEVIDNTLNPDFVRKFILDYFFEEREN-L 93
Cdd:cd04026    5 YLKISVKDNKLTVEVrEAKNLIPMDPNGLSDPYVKLKLIPDPKNETKQ--KTKTIKKTLNPVWNETFTFDLKPADKDRrL 82

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767973290  94 RFDLYDVDSKSPNlskhDFLGQVFCTLGEIV 124
Cdd:cd04026   83 SIEVWDWDRTTRN----DFMGSLSFGVSELI 109
C2C_Tricalbin-like cd04045
C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 31-116 3.30e-03

C2 domain third 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 176010 [Multi-domain]  Cd Length: 120  Bit Score: 37.18  E-value: 3.30e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  31 SCRNLLDRDTFSKSDPICVLYVQGvgnkewREFGRTEVIDNTLNPDFvrKFILdYF--FEERENLRFDLYDVDskspNLS 108
Cdd:cd04045    9 KANDLKNLEGVGKIDPYVRVLVNG------IVKGRTVTISNTLNPVW--DEVL-YVpvTSPNQKITLEVMDYE----KVG 75


                 ....*...
gi 767973290 109 KHDFLGQV 116
Cdd:cd04045   76 KDRSLGSV 83
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 198-247 3.70e-03

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: 37.23  E-value: 3.70e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767973290 198 KTEVVKNTLNPVWQ---AFKISVRALCNgdydRTIKVEVYDWDRDGSHDFIGE 247
Cdd:cd08521   55 KTSVKKNTTNPVFNetlKYHISKSQLET----RTLQLSVWHHDRFGRNTFLGE 103
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 166-270 3.96e-03

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: 37.41  E-value: 3.96e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFL-VFYRSNEDgsfTICHK-TEVVKNTLNPVWQ---AFKISvralCNGDYDRTIKVEVYDWDRDG 240
Cdd:cd08404   24 ARHLPKMDVSGLADPYVkVNLYYGKK---RISKKkTHVKKCTLNPVFNesfVFDIP----SEELEDISVEFLVLDSDRVT 96

                         90       100       110
                 ....*....|....*....|....*....|
gi 767973290 241 SHDFIGEFTTSYRELSRGQSQFNvyEVVNP 270
Cdd:cd08404   97 KNEVIGRLVLGPKASGSGGHHWK--EVCNP 124
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 166-246 5.28e-03

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: 37.10  E-value: 5.28e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 166 ANKLDKKDFFGKSDPFLVFYRSNEdGSFTICHKTEVVKNTLNPVWQAFKISVRALCNGDyDRTIKVEVYDWDRDGSHDFI 245
Cdd:cd08403   23 ARNLKAMDITGFSDPYVKVSLMCE-GRRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD-NVSLIIAVVDYDRVGHNELI 100


                 .
gi 767973290 246 G 246
Cdd:cd08403  101 G 101
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 25-115 5.85e-03

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 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-II topology.


Pssm-ID: 175974 [Multi-domain]  Cd Length: 128  Bit Score: 36.75  E-value: 5.85e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  25 RVEVsVSCRNL--LDRDTFSKSDPICVLYVQGVGNKEWREFgRTEVI-DNTLNPDFVRKFILDYFFEERENLRFDLYDVD 101
Cdd:cd00275    5 TIKI-ISGQQLpkPKGDKGSIVDPYVEVEIHGLPADDSAKF-KTKVVkNNGFNPVWNETFEFDVTVPELAFLRFVVYDED 82

                         90
                 ....*....|....
gi 767973290 102 SkspnlSKHDFLGQ 115
Cdd:cd00275   83 S-----GDDDFLGQ 91
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 173-265 6.28e-03

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: 36.49  E-value: 6.28e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290 173 DFFGKSDPFLVFY-RSNEDGSFTICHKTevVKNTLNPVW----QAFKISVRALCNgdydRTIKVEVYDWDRDGsHDFIGE 247
Cdd:cd04035   31 DANGLSDPYVKLNlLPGASKATKLRTKT--VHKTRNPEFnetlTYYGITEEDIQR----KTLRLLVLDEDRFG-NDFLGE 103

                         90
                 ....*....|....*....
gi 767973290 248 FTTSYRELSRGQ-SQFNVY 265
Cdd:cd04035  104 TRIPLKKLKPNQtKQFNIC 122
COG5038 COG5038
Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];
166-246 8.21e-03

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];


Pssm-ID: 227371 [Multi-domain]  Cd Length: 1227  Bit Score: 38.59  E-value: 8.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767973290  166 ANKLDKKDFF--GKSDPFLVFYRSNEDGSftichKTEVVKNTLNPVW-QAFKISVRALcngdyDRTIKVEVYDWDRDGSH 242
Cdd:COG5038   445 AEGLKKSDSTinGTVDPYITVTFSDRVIG-----KTRVKKNTLNPVWnETFYILLNSF-----TDPLNLSLYDFNSFKSD 514


                  ....
gi 767973290  243 DFIG 246
Cdd:COG5038   515 KVVG 518
 
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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