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Conserved domains on  [gi|767974747|ref|XP_011536834|]
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DCC-interacting protein 13-beta isoform X3 [Homo sapiens]

Protein Classification

DCC-interacting protein 13-alpha/beta( domain architecture ID 10312068)

DCC-interacting protein 13-alpha/beta (DIP13A/B) is a multifunctional adapter protein that binds to various membrane receptors, nuclear factors and signaling proteins to regulate many processes, such as cell proliferation, immune response, endosomal trafficking and cell metabolism

Gene Ontology:  GO:0005515|GO:0140090|GO:0044877|GO:0007165
PubMed:  10610414|8987385|15567406|14993925|15016378

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
BAR super family cl12013
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
 1-197 1.99e-135

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


The actual alignment was detected with superfamily member cd07632:

Pssm-ID: 472257  Cd Length: 215  Bit Score: 394.39  E-value: 1.99e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  81 TEVSTLKDLFGLASNdvclflEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:cd07632  105 TEVSTLKDLFGIASN------EHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAML 178

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767974747 161 EPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 197
Cdd:cd07632  179 EPMLGYTHGQINFFKKGAELFSKKLDSFLSSVSDMNQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 445-578 9.38e-83

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain; APPL interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


:

Pssm-ID: 269980  Cd Length: 135  Bit Score: 256.12  E-value: 9.38e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 445 FPEAEDSLLQQMFIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 524
Cdd:cd13158    1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767974747 525 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 578
Cdd:cd13158   81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 215-339 1.61e-73

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain; APPL (also called DCC-interacting protein (DIP)-13alpha) interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 270067  Cd Length: 125  Bit Score: 231.49  E-value: 1.61e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 215 QELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 294
Cdd:cd13247    1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 767974747 295 AVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQ 339
Cdd:cd13247   81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125
 
Name Accession Description Interval E-value
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 1-197 1.99e-135

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 394.39  E-value: 1.99e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  81 TEVSTLKDLFGLASNdvclflEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:cd07632  105 TEVSTLKDLFGIASN------EHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAML 178

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767974747 161 EPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 197
Cdd:cd07632  179 EPMLGYTHGQINFFKKGAELFSKKLDSFLSSVSDMNQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 445-578 9.38e-83

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain; APPL interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269980  Cd Length: 135  Bit Score: 256.12  E-value: 9.38e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 445 FPEAEDSLLQQMFIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 524
Cdd:cd13158    1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767974747 525 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 578
Cdd:cd13158   81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 215-339 1.61e-73

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain; APPL (also called DCC-interacting protein (DIP)-13alpha) interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270067  Cd Length: 125  Bit Score: 231.49  E-value: 1.61e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 215 QELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 294
Cdd:cd13247    1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 767974747 295 AVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQ 339
Cdd:cd13247   81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
 1-210 2.48e-67

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 219.36  E-value: 2.48e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747    1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNfalgKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:pfam16746  38 CKRMIEAGKEYSAAQRLFANSLLDFKFEF----IGDEETDESLKKFSQLLQEMENFHTILLDQAQRTIIKPLENFRKEDL 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   81 TEVSTLKDLFGLASNDvclfleHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:pfam16746 114 KEVKELKKKFDKASEK------LDAALEKNAQLSKKKKPSELE-EADNELAATRKCFHHASLDYVLQINELQERKKFEIL 186

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 767974747  161 EPMIGFAHGQINFFKKGAEMFsKRMDSFLSSVADMVQSIQVELEAEAEKM 210
Cdd:pfam16746 187 EPLLSFMHAQFTFFHQGYELF-KDLEPFMKDLQAQLQQTREDTREEKEEL 235
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 457-572 4.47e-11

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 60.79  E-value: 4.47e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   457 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENK 536
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 767974747   537 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 572
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 241-338 9.98e-11

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 58.71  E-value: 9.98e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   241 IQKAGYLNLRNKTGLvtTTWERLYFFTQGGNLMC-----QPRGAVAGGLIqDLDNCSVMAVDCED---RRYCFQITTPNG 312
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYykskkDKKSYKPKGSI-DLSGCTVREAPDPDsskKPHCFEIKTSDR 77

                           90       100
                   ....*....|....*....|....*.
gi 767974747   313 KSgIILQAESRKENEEWICAINNISR 338
Cdd:smart00233  78 KT-LLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 241-338 7.17e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 50.64  E-value: 7.17e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  241 IQKAGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQITTP--N 311
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100
                  ....*....|....*....|....*..
gi 767974747  312 GKSGIILQAESRKENEEWICAINNISR 338
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWIKAIQSAIR 105
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
457-572 1.61e-04

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 41.97  E-value: 1.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  457 FIVRFLGSMAVKTDST------TEVIYEAMRQVLAA------RAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 524
Cdd:pfam00640   1 FAVRYLGSVEVPEERApdkntrMQQAREAIRRVKAAkinkirGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 767974747  525 SVTqFAAHQE--NKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 572
Cdd:pfam00640  81 SIS-FCADGDpdLMRYFAYIARDKAT---NKFACHVFESEDGAQDIAQSI 126
 
Name Accession Description Interval E-value
BAR_APPL2 cd07632
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 1-197 1.99e-135

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. Both APPL proteins interact with the transcriptional repressor Reptin, acting as activators of beta-catenin/TCF-mediated trancription. APPL2 is essential for cell proliferation. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153316  Cd Length: 215  Bit Score: 394.39  E-value: 1.99e-135
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  81 TEVSTLKDLFGLASNdvclflEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:cd07632  105 TEVSTLKDLFGIASN------EHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAML 178

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767974747 161 EPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 197
Cdd:cd07632  179 EPMLGYTHGQINFFKKGAELFSKKLDSFLSSVSDMNQ 215
BAR_APPL cd07601
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 1-197 7.36e-108

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains, and are localized to cytoplasmic membranes. Vertebrates contain two APPL proteins, APPL1 and APPL2. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153285  Cd Length: 215  Bit Score: 323.78  E-value: 7.36e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07601   25 CKRVYDAQNELKSATQALSKKLGEYEKQKFELGRDDEILVSTLKQFSKVVDELSTMHSTLSSQLADTVLHPISQFMESDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  81 TEVSTLKDLFGLASNDvclfleHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:cd07601  105 AEIMTLKELFKAASND------HDGVLSKYSRLSKKRENTKVKIEVNDEVYACRKKQHQTAMNYYCALNLLQYKKTTALL 178

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767974747 161 EPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 197
Cdd:cd07601  179 EPMIGYLQAQIAFFKMGPEMFTRQTEEFLSDINTSVQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 445-578 9.38e-83

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called DCC-interacting protein (DIP)-13alpha) Phosphotyrosine-binding (PTB) domain; APPL interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269980  Cd Length: 135  Bit Score: 256.12  E-value: 9.38e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 445 FPEAEDSLLQQMFIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 524
Cdd:cd13158    1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 767974747 525 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 578
Cdd:cd13158   81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 215-339 1.61e-73

Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin/Rvs167 (BAR)-Pleckstrin homology (PH) domain; APPL (also called DCC-interacting protein (DIP)-13alpha) interacts with oncoprotein serine/threonine kinase AKT2, tumor suppressor protein DCC (deleted in colorectal cancer), Rab5, GIPC (GAIP-interacting protein, C terminus), human follicle-stimulating hormone receptor (FSHR), and the adiponectin receptors AdipoR1 and AdipoR2. There are two isoforms of human APPL: APPL1 and APPL2, which share about 50% sequence identity. APPL has a BAR and a PH domain near its N terminus, and the two domains are thought to function as a unit (BAR-PH domain). C-terminal to this is a PTB domain. Lipid binding assays show that the BAR, PH, and PTB domains can bind phospholipids. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270067  Cd Length: 125  Bit Score: 231.49  E-value: 1.61e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 215 QELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 294
Cdd:cd13247    1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 767974747 295 AVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQ 339
Cdd:cd13247   81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 1-197 4.79e-70

The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Adaptor protein, Phosphotyrosine interaction, PH domain and Leucine zipper containing (APPL) proteins are effectors of the small GTPase Rab5 that function in endosome-mediated signaling. They contain BAR, pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. They form homo- and hetero-oligomers that are mediated by their BAR domains. Vertebrates contain two APPL proteins, APPL1 and APPL2. APPL1 interacts with diverse receptors (e.g. NGF receptor TrkA, FSHR, adiponectin receptors) and signaling proteins (e.g. Akt, PI3K), and may function as an adaptor linked to many distinct signaling pathways. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153315  Cd Length: 215  Bit Score: 226.12  E-value: 4.79e-70
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07631   25 MHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  81 TEVSTLKDLFGLASNDvclfleHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:cd07631  105 KEILTLKEVFQIASND------HDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALL 178

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767974747 161 EPMIGFAHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 197
Cdd:cd07631  179 EPLLGYMQAQISFFKMGSENLNEQLEEFLTNIGTSVQ 215
BAR_3 pfam16746
BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or ...
 1-210 2.48e-67

BAR domain of APPL family; BAR_12 is the BAR coiled-coil domain at the N-terminus of APPL or adaptor protein containing PH domain, PTB domain, and leucine zipper motif proteins in higher eukaryotes. This BAR domain contains four helices whereas the other classical BAR domains contain only three helices. The first three helices form an antiparallel coiled-coil, while the fourth helix, is unique to APPL1. BAR domains take part in many varied biological processes such as fission of synaptic vesicles, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, apoptosis, secretory vesicle fusion, and tissue differentiation.


Pssm-ID: 465256  Cd Length: 235  Bit Score: 219.36  E-value: 2.48e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747    1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNfalgKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:pfam16746  38 CKRMIEAGKEYSAAQRLFANSLLDFKFEF----IGDEETDESLKKFSQLLQEMENFHTILLDQAQRTIIKPLENFRKEDL 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   81 TEVSTLKDLFGLASNDvclfleHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMM 160
Cdd:pfam16746 114 KEVKELKKKFDKASEK------LDAALEKNAQLSKKKKPSELE-EADNELAATRKCFHHASLDYVLQINELQERKKFEIL 186

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 767974747  161 EPMIGFAHGQINFFKKGAEMFsKRMDSFLSSVADMVQSIQVELEAEAEKM 210
Cdd:pfam16746 187 EPLLSFMHAQFTFFHQGYELF-KDLEPFMKDLQAQLQQTREDTREEKEEL 235
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
 2-183 4.04e-16

The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions including organelle biogenesis, membrane trafficking or remodeling, and cell division and migration. Mutations in BAR containing proteins have been linked to diseases and their inactivation in cells leads to altered membrane dynamics. A BAR domain with an additional N-terminal amphipathic helix (an N-BAR) can drive membrane curvature. These N-BAR domains are found in amphiphysins and endophilins, among others. BAR domains are also frequently found alongside domains that determine lipid specificity, such as the Pleckstrin Homology (PH) and Phox Homology (PX) domains which are present in beta centaurins (ACAPs and ASAPs) and sorting nexins, respectively. A FES-CIP4 Homology (FCH) domain together with a coiled coil region is called the F-BAR domain and is present in Pombe/Cdc15 homology (PCH) family proteins, which include Fes/Fes tyrosine kinases, PACSIN or syndapin, CIP4-like proteins, and srGAPs, among others. The Inverse (I)-BAR or IRSp53/MIM homology Domain (IMD) is found in multi-domain proteins, such as IRSp53 and MIM, that act as scaffolding proteins and transducers of a variety of signaling pathways that link membrane dynamics and the underlying actin cytoskeleton. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The I-BAR domain induces membrane protrusions in the opposite direction compared to classical BAR and F-BAR domains, which produce membrane invaginations. BAR domains that also serve as protein interaction domains include those of arfaptin and OPHN1-like proteins, among others, which bind to Rac and Rho GAP domains, respectively.


Pssm-ID: 153271 [Multi-domain]  Cd Length: 194  Bit Score: 77.10  E-value: 4.04e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   2 QRVYGAQNEMCLATQQLSKQLLAYEKQnfALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLT 81
Cdd:cd07307   17 KKLLDSLKELPAAAEKLSEALQELGKE--LPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKEYLKKDLK 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  82 EVSTLKDLFGLASNDVclflehDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMME 161
Cdd:cd07307   95 EIKKRRKKLDKARLDY------DAAREKLKKLRKKKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLEEKRKELFLS 168

                        170       180
                 ....*....|....*....|..
gi 767974747 162 PMIGFAHGQINFFKKGAEMFSK 183
Cdd:cd07307  169 LLLSFIEAQSEFFKEVLKILEQ 190
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 243-339 1.81e-13

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270070  Cd Length: 98  Bit Score: 66.47  E-value: 1.81e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNLRNKTGLvtTTWERLYFFTQGGNLMCQPRG-----AVaggLIQDLDNCSVMAVDCEDRRYCFQITTPNgKSgII 317
Cdd:cd13250    1 KEGYLFKRSSNAF--KTWKRRWFSLQNGQLYYQKRDkkdepTV---MVEDLRLCTVKPTEDSDRRFCFEVISPT-KS-YM 73

                         90       100
                 ....*....|....*....|...
gi 767974747 318 LQAESRKENEEWICAINN-ISRQ 339
Cdd:cd13250   74 LQAESEEDRQAWIQAIQSaIASA 96
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
 242-342 6.52e-12

Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein kinase and activates transcription when anchored to DNA. It may function in the SNF1 pathway. SIP3 contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain followed by a PH domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270098  Cd Length: 105  Bit Score: 62.28  E-value: 6.52e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 242 QKAGYLNLRNKTGLVT-TTWERLYFFTQG---GNLMCQPrgavAGGLIQDLD-----NCSVMAVDCEDRRYCFQITTPNG 312
Cdd:cd13280    1 EKSGWLYMKTSVGKPNrTIWVRRWCFVKNgvfGMLSLSP----SKTYVEETDkfgvlLCSVRYAPEEDRRFCFEVKIFKD 76

                         90       100       110
                 ....*....|....*....|....*....|
gi 767974747 313 KSgIILQAESRKENEEWICAINNiSRQIYL 342
Cdd:cd13280   77 IS-IILQAETLKELKSWLTVFEN-AKRYAL 104
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 243-333 6.56e-12

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 61.79  E-value: 6.56e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNLRnkTGLVTTTWERLYFFTQGGNLMC----QPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQITTPNGKSgIIL 318
Cdd:cd00821    1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYykskKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRT-YYL 77

                         90
                 ....*....|....*
gi 767974747 319 QAESRKENEEWICAI 333
Cdd:cd00821   78 QADSEEERQEWLKAL 92
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 457-572 1.53e-11

Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to bind peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains.


Pssm-ID: 269911  Cd Length: 120  Bit Score: 61.76  E-value: 1.53e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 457 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAiHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENK 536
Cdd:cd00934    3 FQVKYLGSVEVGSSRGVDVVEEALKALAAALK-SSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDNP 81

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767974747 537 RLVGFVIRVPESTGEESlstYIFESNS--EGEKICYAI 572
Cdd:cd00934   82 NVFAFIAGEEGGSGFRC---HVFQCEDeeEAEEILQAI 116
BAR_GRAF2 cd07635
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR ...
 7-180 2.12e-11

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase 2 (GRAF2), also called Rho GTPase activating protein 10 (ARHGAP10) or PS-GAP, is a GAP with activity towards Cdc42 and RhoA which regulates caspase-activated p21-activated protein kinase-2 (PAK-2p34). GRAF2 interacts with PAK-2p34, leading to its stabilization and decrease of cell death. It is highly expressed in skeletal muscle and also interacts with PKNbeta, which is a target of Rho. GRAF2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153319  Cd Length: 207  Bit Score: 63.48  E-value: 2.12e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   7 AQNEMCLATQQLSKQLLAYEKQNFALGKGDEE--VISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVS 84
Cdd:cd07635   31 ATKSLSAAQRKFAHSLRDFKFEFIGDAETDDErcIDASLQEFSNFLKNLEEQREIMALNVTETLIKPLERFRKEQLGAVK 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  85 TLKDLFGLASNDVCLFLEHDLSMAKysrlpKKKENEKVKTEVgkEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMI 164
Cdd:cd07635  111 EEKKKFDKETEKNYSLLEKHLNLSA-----KKKEPQLQEADV--QVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPML 183

                        170
                 ....*....|....*.
gi 767974747 165 GFAHGQINFFKKGAEM 180
Cdd:cd07635  184 SFFQGVFTFYHQGYEL 199
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 457-572 4.47e-11

Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain structure similar to those of pleckstrin homology (PH) and IRS-1-like PTB domains.


Pssm-ID: 214675  Cd Length: 134  Bit Score: 60.79  E-value: 4.47e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   457 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENK 536
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 767974747   537 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 572
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 241-338 9.98e-11

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 58.71  E-value: 9.98e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   241 IQKAGYLNLRNKTGLvtTTWERLYFFTQGGNLMC-----QPRGAVAGGLIqDLDNCSVMAVDCED---RRYCFQITTPNG 312
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYykskkDKKSYKPKGSI-DLSGCTVREAPDPDsskKPHCFEIKTSDR 77

                           90       100
                   ....*....|....*....|....*.
gi 767974747   313 KSgIILQAESRKENEEWICAINNISR 338
Cdd:smart00233  78 KT-LLLQAESEEEREKWVEALRKAIA 102
BAR_RhoGAP_OPHN1-like cd07602
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR ...
 9-181 4.12e-09

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of Rho and Rac GTPase activating proteins (GAPs) with similarity to oligophrenin1 (OPHN1). Members contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. Some members contain a C-terminal SH3 domain. Vertebrates harbor at least three Rho GAPs in this subfamily including OPHN1, GTPase Regulator Associated with Focal adhesion kinase (GRAF), GRAF2, and an uncharacterized protein called GAP10-like. OPHN1, GRAF and GRAF2 show GAP activity towards RhoA and Cdc42. In addition, OPHN1 is active towards Rac. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of OPHN1 and GRAF directly interact with their Rho GAP domains and inhibit their activity. The autoinhibited proteins are able to bind membranes and tubulate liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domains can occur simultaneously.


Pssm-ID: 153286  Cd Length: 207  Bit Score: 56.94  E-value: 4.12e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   9 NEMCLATQQLSKQLLAYEK--QNFAL---GKG---DEEVIS-TLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKD 79
Cdd:cd07602   26 KNLISATKNLSKAQRSFAQtlQNFKFeciGETqtdDEIEIAeSLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRKEQ 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  80 LTEVSTLKDLFGLASNDVCLFLEHDLSMAkysrlPKKKENekVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAM 159
Cdd:cd07602  106 IGGAKEEKKKFDKETEKFCSSLEKHLNLS-----TKKKEN--QLQEADAQLDMERRNFHQASLEYVFKLQEVQERKKFEF 178

                        170       180
                 ....*....|....*....|..
gi 767974747 160 MEPMIGFAHGQINFFKKGAEMF 181
Cdd:cd07602  179 VETLLSFMYGWLTFYHQGHEVA 200
BAR_GAP10-like cd07634
The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are ...
 6-180 1.62e-08

The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This group is composed of uncharacterized proteins called Rho GTPase activating protein (GAP) 10-like. GAP10-like may be a GAP with activity towards RhoA and Cdc42. Similar to GRAF and GRAF2, it contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domains of the related proteins GRAF and OPHN1, directly interact with their Rho GAP domains and inhibit theiractivity. The autoinhibited proteins are capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153318 [Multi-domain]  Cd Length: 207  Bit Score: 55.04  E-value: 1.62e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747   6 GAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEV--ISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEV 83
Cdd:cd07634   30 GALRNLSMAVQKFSQSLQDFQFECIGDAETDDEIsiAQSLKEFARLLIAVEEERRRLIQNANDVLIAPLEKFRKEQIGAA 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  84 STLKDLFGLASNDVCLFLEHDLSMAKysrlpKKKENEKvkTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPM 163
Cdd:cd07634  110 KDGKKKFDKESEKYYSILEKHLNLSA-----KKKESHL--QRADTQIDREHQNFYEASLEYVFKIQEVQEKKKFEFVEPL 182

                        170
                 ....*....|....*..
gi 767974747 164 IGFAHGQINFFKKGAEM 180
Cdd:cd07634  183 LAFLQGLFTFYHEGYEL 199
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 241-338 7.17e-08

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 50.64  E-value: 7.17e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  241 IQKAGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQITTP--N 311
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100
                  ....*....|....*....|....*..
gi 767974747  312 GKSGIILQAESRKENEEWICAINNISR 338
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWIKAIQSAIR 105
BAR_GRAF cd07636
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; ...
 14-180 1.85e-07

The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. GTPase Regulator Associated with Focal adhesion kinase (GRAF), also called Rho GTPase activating protein 26 (ARHGAP26), is a GAP with activity towards RhoA and Cdc42 and is only weakly active towards Rac1. It influences Rho-mediated cytoskeletal rearrangements and binds focal adhesion kinase (FAK), which is a critical component of integrin signaling. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of GRAF directly interacts with its Rho GAP domain and inhibits its activity. Autoinhibited GRAF is capable of binding membranes and tubulating liposomes, showing that the membrane-tubulation and GAP-inhibitory functions of the BAR domain can occur simultaneously.


Pssm-ID: 153320 [Multi-domain]  Cd Length: 207  Bit Score: 51.98  E-value: 1.85e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  14 ATQQLSKQLLAYEKQNFALGKGDEE--VISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFG 91
Cdd:cd07636   38 AKRKFADSLNEFKFQCIGDAETDDEicIARSLQEFAAVLRNLEDERTRMIENASEVLITPLEKFRKEQIGAAKEAKKKYD 117

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  92 LASNDVCLFLEHDLSMAKysrlpKKKENEKvkTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQI 171
Cdd:cd07636  118 KETEKYCAVLEKHLNLSS-----KKKESQL--HEADSQVDLVRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLF 190


                 ....*....
gi 767974747 172 NFFKKGAEM 180
Cdd:cd07636  191 TFYHHGYEL 199
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 36-183 6.33e-07

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP2 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 2), also called centaurin beta-2, is an Arf6-specific GTPase activating protein (GAP) which mediates Arf6 signaling. Arf6 is involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration. ACAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153322  Cd Length: 200  Bit Score: 50.38  E-value: 6.33e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  36 DEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNdvclflEHDLSMAKYSRLPK 115
Cdd:cd07638   56 DAVIETSLTKFSDTLQEMINYHTILFDQAQRSIKAQLQTFVKEDLRKFKDAKKQFDKVSE------EKENALVKNAQVQR 129

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 116 KKENEkvkTEVGKEVAAARRK--QHLSsLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKGAEMFSK 183
Cdd:cd07638  130 NKQHE---VEEATNILTATRKcfRHIA-LDYVLQINVLQSKRRSEILKSMLSFMYAHLTFFHQGYDLFSE 195
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 243-340 1.41e-06

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 47.31  E-value: 1.41e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNlrnKTGLVTTTWERLYFFTQGGNLM----------CQPRGAVaggliqDLDNCSVM--AVDCEDRRYCFQITTP 310
Cdd:cd13276    1 KAGWLE---KQGEFIKTWRRRWFVLKQGKLFwfkepdvtpySKPRGVI------DLSKCLTVksAEDATNKENAFELSTP 71

                         90       100       110
                 ....*....|....*....|....*....|
gi 767974747 311 NGKSGIIlqAESRKENEEWicaINNISRQI 340
Cdd:cd13276   72 EETFYFI--ADNEKEKEEW---IGAIGRAI 96
BAR-PH_GRAF_family cd01249
GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) ...
 243-333 2.69e-06

GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) domain; This hierarchy contains GRAF family members: OPHN1/oligophrenin1, GRAF1 (also called ARHGAP26/Rho GTPase activating protein 26), GRAF2 (also called ARHGAP10/ARHGAP42), AK057372, and LOC129897, all of which are members of the APPL family. OPHN1 is a RhoGAP involved in X-linked mental retardation, epilepsy, rostral ventricular enlargement, and cerebellar hypoplasia. Affected individuals have morphological abnormalities of their brain with enlargement of the cerebral ventricles and cerebellar hypoplasia. OPHN1 negatively regulates RhoA, Cdc42, and Rac1 in neuronal and non-neuronal cells. GRAF1 sculpts the endocytic membranes of the CLIC/GEEC (clathrin-independent carriers/GPI-enriched early endosomal compartments) endocytic pathway. It strongly interacts with dynamin and inhibition of dynamin abolishes CLIC/GEEC endocytosis. GRAF2, GRAF3 and oligophrenin are likely to play similar roles during clathrin-independent endocytic events. GRAF1 mutations are linked to leukaemia. All members are composed of a N-terminal BAR-PH domain, followed by a RhoGAP domain, a proline rich region, and a C-terminal SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269953  Cd Length: 105  Bit Score: 46.17  E-value: 2.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNLRNKTGLvTTTWERLY-FFTQGGNLM------CQPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQITTPNGKSG 315
Cdd:cd01249    2 KEGYLYLQEKKPL-GSTWTKHYcTYRKESKMFtmipynQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRPTV 80

                         90
                 ....*....|....*...
gi 767974747 316 IILQAESRKENEEWICAI 333
Cdd:cd01249   81 LTLQALSEEDRKLWLEAM 98
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 34-177 3.44e-06

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ACAP3 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 3), also called centaurin beta-5, is presumed to be an Arf GTPase activating protein (GAP) based on its similarity to the Arf6-specific GAPs ACAP1 and ACAP2. The specific function of ACAP3 is still unknown. ACAP3 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153321  Cd Length: 200  Bit Score: 48.07  E-value: 3.44e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  34 KGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNDVclflehDLSMAKYSRL 113
Cdd:cd07637   54 KKDEMISECLDKFGDSLQEMVNYHMILFDQAQRSVRQQLHSFVKEDVRKFKETKKQFDKVREDL------EIALVKNAQA 127

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767974747 114 PKKKENEkVKTEVGKEVAAARRKQHLSsLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKG 177
Cdd:cd07637  128 PRHKPHE-VEEATSTLTITRKCFRHLA-LDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQG 189
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 243-333 3.64e-06

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 46.46  E-value: 3.64e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNlrnKTGLVTTTWERLYFFTQGgNLMC--------QPRGAVAggliqdLDNCSVMAVDCEDRrYCFQITTPNGKS 314
Cdd:cd13288   10 KEGYLW---KKGERNTSYQKRWFVLKG-NLLFyfekkgdrEPLGVIV------LEGCTVELAEDAEP-YAFAIRFDGPGA 78

                         90       100
                 ....*....|....*....|
gi 767974747 315 GI-ILQAESRKENEEWICAI 333
Cdd:cd13288   79 RSyVLAAENQEDMESWMKAL 98
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 243-338 1.62e-05

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 43.83  E-value: 1.62e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 243 KAGYLNlrnKTGLVTTTWERLYFFTQGGNLMC---------QPRGAVAggliqdLDN-CSVMavdCEDRRYCFQITTPng 312
Cdd:cd13282    1 KAGYLT---KLGGKVKTWKRRWFVLKNGELFYykspndvirKPQGQIA------LDGsCEIA---RAEGAQTFEIVTE-- 66

                         90       100
                 ....*....|....*....|....*.
gi 767974747 313 KSGIILQAESRKENEEWICAINNISR 338
Cdd:cd13282   67 KRTYYLTADSENDLDEWIRVIQNVLR 92
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 241-335 1.83e-05

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269939  Cd Length: 103  Bit Score: 43.74  E-value: 1.83e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 241 IQKAGYLNLRNKTglvTTTWERLYFftqggnLMCQP--------RGAVAGGLIqDLDNCSV-----MAvDCEDRRYCFQI 307
Cdd:cd01233    6 VSKRGYLLFLEDA---TDGWVRRWV------VLRRPylhiysseKDGDERGVI-NLSTARVeyspdQE-ALLGRPNVFAV 74

                         90       100
                 ....*....|....*....|....*...
gi 767974747 308 TTPNgkSGIILQAESRKENEEWICAINN 335
Cdd:cd01233   75 YTPT--NSYLLQARSEKEMQDWLYAIDP 100
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 287-341 4.12e-05

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270093  Cd Length: 97  Bit Score: 42.77  E-value: 4.12e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 767974747 287 DLDNCSVMAVDCEDRRYCFQITTPNGKsgIILQAESRKENEEWICAINNIS-RQIY 341
Cdd:cd13274   43 DLSDASVAECSTKNVNNSFTVITPFRK--LILCAESRKEMEEWISALKTVQqREFY 96
PTB_CED-6 cd01273
Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also ...
 457-572 8.12e-05

Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also known as GULP1: engulfment adaptor PTB domain containing 1) is an adaptor protein involved in the specific recognition and engulfment of apoptotic cells. CED6 has been shown to interact with the cytoplasmic tail of another protein involved in the engulfment of apoptotic cells, CED1. CED6 has a C-terminal PTB domain, which can bind to NPXY motifs. PTB domains have a common PH-like fold and are found in various eukaryotic signaling molecules. This domain was initially shown to binds peptides with a NPXY motif with differing requirements for phosphorylation of the tyrosine, although more recent studies have found that some types of PTB domains can bind to peptides lack tyrosine residues altogether. In contrast to SH2 domains, which recognize phosphotyrosine and adjacent carboxy-terminal residues, PTB-domain binding specificity is conferred by residues amino-terminal to the phosphotyrosine. PTB domains are classified into three groups: phosphotyrosine-dependent Shc-like, phosphotyrosine-dependent IRS-like, and phosphotyrosine-independent Dab-like PTB domains. This cd is part of the Dab-like subgroup.


Pssm-ID: 269971  Cd Length: 144  Bit Score: 43.04  E-value: 8.12e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 457 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHnifRMTESHLM-----VTSQSLRLIDPQTQVSRANFELTSVTQFAA 531
Cdd:cd01273   14 YLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLK---KSEGAKLPkvelqISIDGVKIQDPKTKVIMHQFPLHRISFCAD 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 767974747 532 HQENKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 572
Cdd:cd01273   91 DKTDKRIFSFIAKDSES---EKHLCFVFDSEKLAEEITLTI 128
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
457-572 1.61e-04

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 41.97  E-value: 1.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  457 FIVRFLGSMAVKTDST------TEVIYEAMRQVLAA------RAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 524
Cdd:pfam00640   1 FAVRYLGSVEVPEERApdkntrMQQAREAIRRVKAAkinkirGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 767974747  525 SVTqFAAHQE--NKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 572
Cdd:pfam00640  81 SIS-FCADGDpdLMRYFAYIARDKAT---NKFACHVFESEDGAQDIAQSI 126
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 34-177 3.02e-04

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP2 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 2) is also known as DDEF2 (Development and Differentiation Enhancing Factor 2), AMAP2, centaurin beta-3, or PAG3. ASAP2 mediates the functions of Arf GTPases vial dual mechanisms: it exhibits GTPase activating protein (GAP) activity towards class I (Arf1) and II (Arf5) Arfs; and binds class III Arfs (GTP-Arf6) stably without GAP activity. It binds paxillin and is implicated in Fcgamma receptor-mediated phagocytosis in macrophages and in cell migration. ASAP2 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153326  Cd Length: 215  Bit Score: 42.71  E-value: 3.02e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  34 KGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVS-TLKDLFGLASNDvclfleHDLSMAKYSR 112
Cdd:cd07642   56 RDDPDLGSAFLKFSVFTKELTALFKNLVQNMNNIITFPLDSLLKGDLKGVKgDLKKPFDKAWKD------YETKVTKIEK 129

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767974747 113 lpKKKENEK----VKTEV-GKEVA----AARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKG 177
Cdd:cd07642  130 --EKKEHAKmhgmIRTEIsGAEIAeemeKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDG 201
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 241-330 4.12e-04

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270099  Cd Length: 139  Bit Score: 40.77  E-value: 4.12e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 241 IQKAGYLNLRNKtGLVTTTWERLYF-----------------FTQGGNLMCQPRGavagglIQDLDNCSVMAVDCEDRRY 303
Cdd:cd13281   12 VQLHGILWKKPF-GHQSAKWSKRFFiikegfllyysesekkdFEKTRHFNIHPKG------VIPLGGCSIEAVEDPGKPY 84

                         90       100
                 ....*....|....*....|....*..
gi 767974747 304 CFQITTPNGKSGIILQAESRKENEEWI 330
Cdd:cd13281   85 AISISHSDFKGNIILAADSEFEQEKWL 111
BAR_ACAPs cd07603
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 31-183 5.48e-04

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. This subfamily is composed of ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) containing an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and C-terminal ankyrin (ANK) repeats. Vertebrates contain at least three members, ACAP1, ACAP2, and ACAP3. ACAP1 and ACAP2 are Arf6-specific GAPs, involved in the regulation of endocytosis, phagocytosis, cell adhesion and migration, by mediating Arf6 signaling. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153287  Cd Length: 200  Bit Score: 41.52  E-value: 5.48e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  31 ALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNDVclflehDLSMAKY 110
Cdd:cd07603   51 DYFRDDSLVQNCLNKFIQALQEMNNFHTILLDQAQRTVSTQLQNFVKEDIKKVKESKKHFEKISDDL------DNALVKN 124

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767974747 111 SRLPKKKENEkvkTEVGKEVAAARRK--QHLsSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKGAEMFSK 183
Cdd:cd07603  125 AQAPRSKPQE---AEEATNILTATRScfRHT-ALDYVLQINVLQAKKRHEILSTLLSYMHAQFTFFHQGYDLLED 195
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 236-346 9.35e-04

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 39.32  E-value: 9.35e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 236 INRNLIQKAGYLNlrnKTGLVTTTWERLYFFTQGGNLMCQpRGAVAGGLIQDLDNCSVMAV-DCEDRRY--CFQITTPNg 312
Cdd:cd13255    1 MISEAVLKAGYLE---KKGERRKTWKKRWFVLRPTKLAYY-KNDKEYRLLRLIDLTDIHTCtEVQLKKHdnTFGIVTPA- 75

                         90       100       110
                 ....*....|....*....|....*....|....
gi 767974747 313 kSGIILQAESRKENEEWICAINNIsRQIYLTDNP 346
Cdd:cd13255   76 -RTFYVQADSKAEMESWISAINLA-RQALRATIT 107
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
 242-335 9.46e-04

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270096  Cd Length: 111  Bit Score: 39.19  E-value: 9.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747 242 QKAGYLNLR-NKTGLVTTTWeRLYFFTQGGNLMC---QPRGAVAG---------GLIQDLDncsvmavdcEDR---RYCF 305
Cdd:cd13277    4 VKEGYLLKRrKKTLGSTGGW-KLRYGVLDGNILElyeSRGGQLLEsiklrnaqiERQPNLP---------DDKygtRHGF 73

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 767974747 306 QITTPNGKSGI-----ILQAESRKENEEWICAINN 335
Cdd:cd13277   74 LINEHKKSGLSsttkyYLCAETDKERDEWVSALSE 108
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 288-336 6.92e-03

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270087  Cd Length: 126  Bit Score: 36.92  E-value: 6.92e-03
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 767974747 288 LDNCSVMAVDCEDRRYCFQITTpNGKSGIILQAESRKENEEWICAINNI 336
Cdd:cd13267   65 LDSCTGVVQNSKRRKFCFELRM-QDKKSYVLAAESEAEMDEWISKLNKI 112
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 46-183 9.87e-03

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. ASAP1 (ArfGAP with SH3 domain, ANK repeat and PH domain containing protein 1) is also known as DDEF1 (Development and Differentiation Enhancing Factor 1), AMAP1, centaurin beta-4, or PAG2. ASAP1 is an Arf GTPase activating protein (GAP) with activity towards Arf1 and Arf5 but not Arf6 However, it has been shown to bind GTP-Arf6 stably without GAP activity. It has been implicated in cell growth, migration, and survival, as well as in tumor invasion and malignancy. It binds paxillin and cortactin, two components of invadopodia which are essential for tumor invasiveness. It also binds focal adhesion kinase (FAK) and the SH2/SH3 adaptor CrkL. ASAP1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, ankyrin (ANK) repeats, and a C-terminal SH3 domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions. The BAR domain of ASAP1 mediates membrane bending, is essential for function, and autoinhibits GAP activity by interacting with the PH and/or Arf GAP domains.


Pssm-ID: 153325  Cd Length: 215  Bit Score: 38.12  E-value: 9.87e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767974747  46 FSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVS-TLKDLFGLASNDvclfLEHDLSMAKYSRLPKKKENEKVKT 124
Cdd:cd07641   68 FSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKD----YETKFTKIEKEKREHAKQHGMIRT 143

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767974747 125 EV-----GKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKGAEMFSK 183
Cdd:cd07641  144 EItgaeiAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADK 207
 
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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