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Conserved domains on  [gi|1907074597|ref|XP_036011638|]
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DCC-interacting protein 13-beta isoform X1 [Mus musculus]

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 ...
 27-209 1.25e-126

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: 372.44  E-value: 1.25e-126
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07632    33 NEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKD 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:cd07632   113 LFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFF 192

                         170       180
                  ....*....|....*....|...
gi 1907074597 187 KRGAEMFSKSMDGFLSSVKDMVQ 209
Cdd:cd07632   193 KKGAELFSKKLDSFLSSVSDMNQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 455-588 7.18e-82

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: 253.81  E-value: 7.18e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 455 FPEAEDSLLQQMFIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 534
Cdd:cd13158     1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907074597 535 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 588
Cdd:cd13158    81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 227-351 4.69e-72

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: 228.02  E-value: 4.69e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 227 QELLSVSESVYTPDIDVATAQINRNLIQKTGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 306
Cdd:cd13247     1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907074597 307 AVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWICAVNNISRQ 351
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 ...
 27-209 1.25e-126

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: 372.44  E-value: 1.25e-126
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07632    33 NEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKD 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:cd07632   113 LFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFF 192

                         170       180
                  ....*....|....*....|...
gi 1907074597 187 KRGAEMFSKSMDGFLSSVKDMVQ 209
Cdd:cd07632   193 KKGAELFSKKLDSFLSSVSDMNQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 455-588 7.18e-82

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: 253.81  E-value: 7.18e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 455 FPEAEDSLLQQMFIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 534
Cdd:cd13158     1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907074597 535 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 588
Cdd:cd13158    81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 227-351 4.69e-72

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: 228.02  E-value: 4.69e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 227 QELLSVSESVYTPDIDVATAQINRNLIQKTGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 306
Cdd:cd13247     1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907074597 307 AVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWICAVNNISRQ 351
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 ...
 27-222 1.99e-66

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: 217.43  E-value: 1.99e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNfalgKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:pfam16746  46 KEYSAAQRLFANSLLDFKFEF----IGDEETDESLKKFSQLLQEMENFHTILLDQAQRTIIKPLENFRKEDLKEVKELKK 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:pfam16746 122 KFDKASEKLDAALEKNAQLSKKKKPSELE-EADNELAATRKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFF 200

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1907074597 187 KRGAEMFsKSMDGFLSSVKDMVQSIQVELEAEADKM 222
Cdd:pfam16746 201 HQGYELF-KDLEPFMKDLQAQLQQTREDTREEKEEL 235
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 467-582 2.14e-10

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: 58.86  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  467 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQTLRLIDPQTQVSRACFELTSVTQFAAHQENK 546
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907074597  547 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 582
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 253-350 1.11e-09

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: 56.02  E-value: 1.11e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  253 IQKTGYLNLRNKTGLvtTTWERLYFFTQGGNLMC-----QPRGAVAGGLIqDLDNCSVMAVDCED---RRYCFQISTPSG 324
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYykskkDKKSYKPKGSI-DLSGCTVREAPDPDsskKPHCFEIKTSDR 77

                           90       100
                   ....*....|....*....|....*.
gi 1907074597  325 KPgIILQAESRKEYEEWICAVNNISR 350
Cdd:smart00233  78 KT-LLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 253-353 2.06e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 49.48  E-value: 2.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 253 IQKTGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQISTP--S 323
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907074597 324 GKPGIILQAESRKEYEEWIcavNNISRQIY 353
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWI---KAIQSAIR 105
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
467-582 1.08e-03

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 39.65  E-value: 1.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 467 FIVRFLGSMAVKTDSTA------EVIYEAMRQVLAA------RAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 534
Cdd:pfam00640   1 FAVRYLGSVEVPEERAPdkntrmQQAREAIRRVKAAkinkirGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907074597 535 SVTqFAAHQE--NKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 582
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 ...
 27-209 1.25e-126

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: 372.44  E-value: 1.25e-126
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07632    33 NEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKD 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:cd07632   113 LFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFF 192

                         170       180
                  ....*....|....*....|...
gi 1907074597 187 KRGAEMFSKSMDGFLSSVKDMVQ 209
Cdd:cd07632   193 KKGAELFSKKLDSFLSSVSDMNQ 215
BAR_APPL cd07601
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 27-209 6.86e-98

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: 298.75  E-value: 6.86e-98
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07601    33 NELKSATQALSKKLGEYEKQKFELGRDDEILVSTLKQFSKVVDELSTMHSTLSSQLADTVLHPISQFMESDLAEIMTLKE 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:cd07601   113 LFKAASNDHDGVLSKYSRLSKKRENTKVKIEVNDEVYACRKKQHQTAMNYYCALNLLQYKKTTALLEPMIGYLQAQIAFF 192

                         170       180
                  ....*....|....*....|...
gi 1907074597 187 KRGAEMFSKSMDGFLSSVKDMVQ 209
Cdd:cd07601   193 KMGPEMFTRQTEEFLSDINTSVQ 215
PTB_APPL cd13158
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif (APPL; also called ...
 455-588 7.18e-82

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: 253.81  E-value: 7.18e-82
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 455 FPEAEDSLLQQMFIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 534
Cdd:cd13158     1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907074597 535 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 588
Cdd:cd13158    81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135
BAR-PH_APPL cd13247
Adaptor protein containing PH domain, PTB domain, and Leucine zipper motif Bin1/amphiphysin ...
 227-351 4.69e-72

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: 228.02  E-value: 4.69e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 227 QELLSVSESVYTPDIDVATAQINRNLIQKTGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 306
Cdd:cd13247     1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1907074597 307 AVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWICAVNNISRQ 351
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 ...
 27-222 1.99e-66

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: 217.43  E-value: 1.99e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNfalgKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:pfam16746  46 KEYSAAQRLFANSLLDFKFEF----IGDEETDESLKKFSQLLQEMENFHTILLDQAQRTIIKPLENFRKEDLKEVKELKK 121

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:pfam16746 122 KFDKASEKLDAALEKNAQLSKKKKPSELE-EADNELAATRKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFF 200

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1907074597 187 KRGAEMFsKSMDGFLSSVKDMVQSIQVELEAEADKM 222
Cdd:pfam16746 201 HQGYELF-KDLEPFMKDLQAQLQQTREDTREEKEEL 235
BAR_APPL1 cd07631
The Bin/Amphiphysin/Rvs (BAR) domain of Adaptor protein, Phosphotyrosine interaction, PH ...
 27-209 3.63e-65

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: 213.41  E-value: 3.63e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  27 NEMCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07631    33 NELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKE 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFF 186
Cdd:cd07631   113 VFQIASNDHDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFF 192

                         170       180
                  ....*....|....*....|...
gi 1907074597 187 KRGAEMFSKSMDGFLSSVKDMVQ 209
Cdd:cd07631   193 KMGSENLNEQLEEFLTNIGTSVQ 215
BAR cd07307
The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects ...
 26-195 3.55e-17

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: 80.18  E-value: 3.55e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  26 MNEMCLATQQLSRQLLAYEKQnfALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLK 105
Cdd:cd07307    23 LKELPAAAEKLSEALQELGKE--LPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRR 100

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 106 DLFGLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINF 185
Cdd:cd07307   101 KKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLEEKRKELFLSLLLSFIEAQSEF 180

                         170
                  ....*....|
gi 1907074597 186 FKRGAEMFSK 195
Cdd:cd07307   181 FKEVLKILEQ 190
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 255-351 1.98e-12

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: 63.39  E-value: 1.98e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNLRNKTGLvtTTWERLYFFTQGGNLMCQPRG-----AVaggLIQDLDNCSVMAVDCEDRRYCFQISTPSGKpgII 329
Cdd:cd13250     1 KEGYLFKRSSNAF--KTWKRRWFSLQNGQLYYQKRDkkdepTV---MVEDLRLCTVKPTEDSDRRFCFEVISPTKS--YM 73

                          90       100
                  ....*....|....*....|...
gi 1907074597 330 LQAESRKEYEEWICAVNN-ISRQ 351
Cdd:cd13250    74 LQAESEEDRQAWIQAIQSaIASA 96
PTB cd00934
Phosphotyrosine-binding (PTB) PH-like fold; PTB domains have a common PH-like fold and are ...
 467-582 2.45e-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: 61.37  E-value: 2.45e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 467 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAiHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELTSVTQFAAHQENK 546
Cdd:cd00934     3 FQVKYLGSVEVGSSRGVDVVEEALKALAAALK-SSKRKPGPVLLEVSSKGVKLLDLDTKELLLRHPLHRISYCGRDPDNP 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907074597 547 RLVGFVIRVPESTGEESlstYIFESNS--EGEKICYAI 582
Cdd:cd00934    82 NVFAFIAGEEGGSGFRC---HVFQCEDeeEAEEILQAI 116
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 255-345 3.30e-11

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: 59.86  E-value: 3.30e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNLRnkTGLVTTTWERLYFFTQGGNLMC----QPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQISTPSGKPgIIL 330
Cdd:cd00821     1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYykskKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRT-YYL 77

                          90
                  ....*....|....*
gi 1907074597 331 QAESRKEYEEWICAV 345
Cdd:cd00821    78 QADSEEERQEWLKAL 92
BAR_GRAF2 cd07635
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion 2; BAR ...
 54-192 3.37e-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: 63.09  E-value: 3.37e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  54 DEEVI-STLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLP-KKKEN 131
Cdd:cd07635    61 DERCIdASLQEFSNFLKNLEEQREIMALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSaKKKEP 140

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907074597 132 EKAKTEIvkEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEM 192
Cdd:cd07635   141 QLQEADV--QVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYEL 199
PTB smart00462
Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain; PTB/PI domain ...
 467-582 2.14e-10

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: 58.86  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  467 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQTLRLIDPQTQVSRACFELTSVTQFAAHQENK 546
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1907074597  547 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 582
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117
PH_SIP3 cd13280
Snf1p-interacting protein 3 Pleckstrin homology (PH) domain; SIP3 interacts with SNF1 protein ...
 254-354 3.65e-10

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: 57.27  E-value: 3.65e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 254 QKTGYLNLRNKTGLVT-TTWERLYFFTQG---GNLMCQPrgavAGGLIQDLD-----NCSVMAVDCEDRRYCFQISTpSG 324
Cdd:cd13280     1 EKSGWLYMKTSVGKPNrTIWVRRWCFVKNgvfGMLSLSP----SKTYVEETDkfgvlLCSVRYAPEEDRRFCFEVKI-FK 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907074597 325 KPGIILQAESRKEYEEWICAVNNiSRQIYL 354
Cdd:cd13280    76 DISIILQAETLKELKSWLTVFEN-AKRYAL 104
BAR_ACAP2 cd07638
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 30-195 4.82e-10

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: 59.63  E-value: 4.82e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  30 CLATQQLS---RQLLAYEKQnfalgkgDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 106
Cdd:cd07638    36 CQANKQFMngiRDLAQYSSK-------DAVIETSLTKFSDTLQEMINYHTILFDQAQRSIKAQLQTFVKEDLRKFKDAKK 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 107 LFGLASSEHDLSMAKYSRLPKKKENEkakTEIVKEVAAARRK--QHLsSLQYYCALNALQYRKRAAMMEPLIGFAHGQIN 184
Cdd:cd07638   109 QFDKVSEEKENALVKNAQVQRNKQHE---VEEATNILTATRKcfRHI-ALDYVLQINVLQSKRRSEILKSMLSFMYAHLT 184

                         170
                  ....*....|.
gi 1907074597 185 FFKRGAEMFSK 195
Cdd:cd07638   185 FFHQGYDLFSE 195
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 253-350 1.11e-09

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: 56.02  E-value: 1.11e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  253 IQKTGYLNLRNKTGLvtTTWERLYFFTQGGNLMC-----QPRGAVAGGLIqDLDNCSVMAVDCED---RRYCFQISTPSG 324
Cdd:smart00233   1 VIKEGWLYKKSGGGK--KSWKKRYFVLFNSTLLYykskkDKKSYKPKGSI-DLSGCTVREAPDPDsskKPHCFEIKTSDR 77

                           90       100
                   ....*....|....*....|....*.
gi 1907074597  325 KPgIILQAESRKEYEEWICAVNNISR 350
Cdd:smart00233  78 KT-LLLQAESEEEREKWVEALRKAIA 102
BAR_GAP10-like cd07634
The Bin/Amphiphysin/Rvs (BAR) domain of Rho GTPase activating protein 10-like; BAR domains are ...
 26-192 1.47e-09

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: 58.12  E-value: 1.47e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  26 MNEMCLATQQLSRQLLAYEKQNFALGKGDEEV--ISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVST 103
Cdd:cd07634    32 LRNLSMAVQKFSQSLQDFQFECIGDAETDDEIsiAQSLKEFARLLIAVEEERRRLIQNANDVLIAPLEKFRKEQIGAAKD 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 104 LKDLFGLASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQI 183
Cdd:cd07634   112 GKKKFDKESEKYYSILEKHLNLSAKKKESHLQ-RADTQIDREHQNFYEASLEYVFKIQEVQEKKKFEFVEPLLAFLQGLF 190


                  ....*....
gi 1907074597 184 NFFKRGAEM 192
Cdd:cd07634   191 TFYHEGYEL 199
BAR_RhoGAP_OPHN1-like cd07602
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin1-like Rho GTPase Activating Proteins; BAR ...
 25-193 7.94e-08

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: 53.09  E-value: 7.94e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  25 EMNEMCLATQQLSRQLLAYEK--QNFAL---GKG---DEEVIS-TLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFRE 95
Cdd:cd07602    24 ECKNLISATKNLSKAQRSFAQtlQNFKFeciGETqtdDEIEIAeSLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRK 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  96 KDLTEVSTLKDLFGLASSEHDLSMAKYSRL-PKKKEN--EKAKTEIVKEvaaaRRKQHLSSLQYYCALNALQYRKRAAMM 172
Cdd:cd07602   104 EQIGGAKEEKKKFDKETEKFCSSLEKHLNLsTKKKENqlQEADAQLDME----RRNFHQASLEYVFKLQEVQERKKFEFV 179

                         170       180
                  ....*....|....*....|.
gi 1907074597 173 EPLIGFAHGQINFFKRGAEMF 193
Cdd:cd07602   180 ETLLSFMYGWLTFYHQGHEVA 200
BAR_ACAPs cd07603
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 49-195 1.18e-07

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: 52.30  E-value: 1.18e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  49 ALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLPKK 128
Cdd:cd07603    51 DYFRDDSLVQNCLNKFIQALQEMNNFHTILLDQAQRTVSTQLQNFVKEDIKKVKESKKHFEKISDDLDNALVKNAQAPRS 130

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907074597 129 KENEKAKTEivkEVAAARRK--QHLSsLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEMFSK 195
Cdd:cd07603   131 KPQEAEEAT---NILTATRScfRHTA-LDYVLQINVLQAKKRHEILSTLLSYMHAQFTFFHQGYDLLED 195
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 253-353 2.06e-07

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 49.48  E-value: 2.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 253 IQKTGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQISTP--S 323
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907074597 324 GKPGIILQAESRKEYEEWIcavNNISRQIY 353
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWI---KAIQSAIR 105
BAR_ACAP3 cd07637
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, ANK repeat and PH domain ...
 52-189 5.72e-07

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: 50.38  E-value: 5.72e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  52 KGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLPKKKEN 131
Cdd:cd07637    54 KKDEMISECLDKFGDSLQEMVNYHMILFDQAQRSVRQQLHSFVKEDVRKFKETKKQFDKVREDLEIALVKNAQAPRHKPH 133

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907074597 132 EkakteiVKEVAAA---RRK--QHLSsLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRG 189
Cdd:cd07637   134 E------VEEATSTltiTRKcfRHLA-LDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQG 189
BAR_GRAF cd07636
The Bin/Amphiphysin/Rvs (BAR) domain of GTPase Regulator Associated with Focal adhesion kinase; ...
 54-192 1.19e-06

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: 49.67  E-value: 1.19e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  54 DEEVIS-TLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLPKKKEnE 132
Cdd:cd07636    61 DEICIArSLQEFAAVLRNLEDERTRMIENASEVLITPLEKFRKEQIGAAKEAKKKYDKETEKYCAVLEKHLNLSSKKK-E 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 133 KAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEM 192
Cdd:cd07636   140 SQLHEADSQVDLVRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYEL 199
BAR_ASAP2 cd07642
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 52-189 2.12e-06

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: 48.88  E-value: 2.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  52 KGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVS-TLKDLFGLASSEHDLSMAKYSRlpKKKE 130
Cdd:cd07642    56 RDDPDLGSAFLKFSVFTKELTALFKNLVQNMNNIITFPLDSLLKGDLKGVKgDLKKPFDKAWKDYETKVTKIEK--EKKE 133

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907074597 131 NEK---------AKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRG 189
Cdd:cd07642   134 HAKmhgmirteiSGAEIAEEMEKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDG 201
BAR-PH_GRAF_family cd01249
GTPase Regulator Associated with Focal adhesion and related proteins Pleckstrin homology (PH) ...
 255-344 4.49e-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: 45.79  E-value: 4.49e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNLRNKTGLvTTTWERLY-FFTQGGNLM------CQPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQIsTPSGKPG 327
Cdd:cd01249     2 KEGYLYLQEKKPL-GSTWTKHYcTYRKESKMFtmipynQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDI-EVVDRPT 79

                          90
                  ....*....|....*...
gi 1907074597 328 II-LQAESRKEYEEWICA 344
Cdd:cd01249    80 VLtLQALSEEDRKLWLEA 97
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 255-345 5.00e-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: 46.08  E-value: 5.00e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNlrnKTGLVTTTWERLYFFTQGgNLMC--------QPRGAVAggliqdLDNCSVMAVDCEDRrYCFQISTPSGKP 326
Cdd:cd13288    10 KEGYLW---KKGERNTSYQKRWFVLKG-NLLFyfekkgdrEPLGVIV------LEGCTVELAEDAEP-YAFAIRFDGPGA 78

                          90       100
                  ....*....|....*....|
gi 1907074597 327 GI-ILQAESRKEYEEWICAV 345
Cdd:cd13288    79 RSyVLAAENQEDMESWMKAL 98
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 255-352 1.01e-05

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: 44.62  E-value: 1.01e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNlrnKTGLVTTTWERLYFFTQGGNLM----------CQPRGAVaggliqDLDNCSVM--AVDCEDRRYCFQISTP 322
Cdd:cd13276     1 KAGWLE---KQGEFIKTWRRRWFVLKQGKLFwfkepdvtpySKPRGVI------DLSKCLTVksAEDATNKENAFELSTP 71

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907074597 323 SGKpgIILQAESRKEYEEWIcavNNISRQI 352
Cdd:cd13276    72 EET--FYFIADNEKEKEEWI---GAIGRAI 96
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 299-353 1.44e-04

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: 41.23  E-value: 1.44e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1907074597 299 DLDNCSVMAVDCEDRRYCFQISTPSGKpgIILQAESRKEYEEWICAVNNIS-RQIY 353
Cdd:cd13274    43 DLSDASVAECSTKNVNNSFTVITPFRK--LILCAESRKEMEEWISALKTVQqREFY 96
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 253-347 1.57e-04

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: 41.04  E-value: 1.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 253 IQKTGYLNLRNKTglvTTTWERLYFftqggnLMCQP--------RGAVAGGLIqDLDNCSV-----MAvDCEDRRYCFQI 319
Cdd:cd01233     6 VSKRGYLLFLEDA---TDGWVRRWV------VLRRPylhiysseKDGDERGVI-NLSTARVeyspdQE-ALLGRPNVFAV 74

                          90       100
                  ....*....|....*....|....*...
gi 1907074597 320 STPSGkpGIILQAESRKEYEEWICAVNN 347
Cdd:cd01233    75 YTPTN--SYLLQARSEKEMQDWLYAIDP 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 255-350 2.88e-04

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: 40.36  E-value: 2.88e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 255 KTGYLNlrnKTGLVTTTWERLYFFTQGGNLMC---------QPRGAVAggliqdLDN-CSVMavdCEDRRYCFQISTPsg 324
Cdd:cd13282     1 KAGYLT---KLGGKVKTWKRRWFVLKNGELFYykspndvirKPQGQIA------LDGsCEIA---RAEGAQTFEIVTE-- 66

                          90       100
                  ....*....|....*....|....*.
gi 1907074597 325 KPGIILQAESRKEYEEWICAVNNISR 350
Cdd:cd13282    67 KRTYYLTADSENDLDEWIRVIQNVLR 92
BAR_ASAPs cd07604
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 49-192 4.19e-04

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, 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 ASAPs (ArfGAP with SH3 domain, ANK repeat and PH domain containing proteins), which are Arf GTPase activating proteins (GAPs) with similarity to ACAPs (ArfGAP with Coiled-coil, ANK repeat and PH domain containing proteins) in that they contain an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain, and ankyrin (ANK) repeats. However, ASAPs contain an additional C-terminal SH3 domain. ASAPs function in regulating cell growth, migration, and invasion. Vertebrates contain at least three members, ASAP1, ASAP2, and ASAP3. ASAP1 and ASAP2 shows GTPase activating protein (GAP) activity towards Arf1 and Arf5. They do not show GAP activity towards Arf6, but is able to mediate Arf6 signaling by binding stably to GTP-Arf6. ASAP3 is an Arf6-specific GAP. 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: 153288  Cd Length: 215  Bit Score: 42.01  E-value: 4.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  49 ALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVS-TLKDLFGLASSEHDlsmAKYSRLPK 127
Cdd:cd07604    53 ALSREEEDLGAAFLKFSVFTKELAALFKNLMQNLNNIIMFPLDSLLKGDLKGSKgDLKKPFDKAWKDYE---TKASKIEK 129

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907074597 128 KK----------ENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEM 192
Cdd:cd07604   130 EKkqlakeagmiRTEITGAEIAEEMEKERRMFQLQMCEYLIKVNEIKTKKGVDLLQHLVEYYHAQNSYFQDGLKV 204
BAR_SFC_plant cd07606
The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); BAR domains are ...
 42-195 4.20e-04

The Bin/Amphiphysin/Rvs (BAR) domain of the plant protein SCARFACE (SFC); 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. The plant protein SCARFACE (SFC), also called VAscular Network 3 (VAN3), is a plant ACAP (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein), an Arf GTPase Activating Protein (GAP) that plays a role in the trafficking of auxin efflux regulators from the plasma membrane to the endosome. It is required for the normal vein patterning in leaves. SCF 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: 153290  Cd Length: 202  Bit Score: 42.09  E-value: 4.20e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  42 AYEKQ-NFA-----LGKGDEEVIST------LHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFG 109
Cdd:cd07606    34 AYDGDsAFAesleeFGGGHDDPISVavggpvMTKFTSALREIGSYKEVLRSQVEHMLNDRLAQFADTDLQEVKDARRRFD 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 110 LASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRG 189
Cdd:cd07606   114 KASLDYEQARSKFLSLTKDAKPEILA-AAEEDLGTTRSAFETARFDLMNRLHAADARKRVEFLERLSGSMDAHLAFFKSG 192


                  ....*.
gi 1907074597 190 AEMFSK 195
Cdd:cd07606   193 YELLRQ 198
BAR_ASAP1 cd07641
The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with SH3 domain, ANK repeat and PH domain ...
 64-195 4.83e-04

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: 41.97  E-value: 4.83e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  64 FSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVS-TLKDLFGLASSEHDlsmAKYSRLPKKKE----------NE 132
Cdd:cd07641    68 FSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYE---TKFTKIEKEKRehakqhgmirTE 144

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907074597 133 KAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEMFSK 195
Cdd:cd07641   145 ITGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADK 207
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 253-345 9.40e-04

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. 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: 270080  Cd Length: 103  Bit Score: 38.86  E-value: 9.40e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 253 IQKTGYLNlrnKTGLVTTTWERLYFFTQGGNLM---------CQPRGavagglIQDLDNCSVMAVDCE--DRRYCFQIST 321
Cdd:cd13260     3 IDKKGYLL---KKGGKNKKWKNLYFVLEGKEQHlyffdnekrTKPKG------LIDLSYCSLYPVHDSlfGRPNCFQIVV 73

                          90       100
                  ....*....|....*....|....*.
gi 1907074597 322 PSGKPGII--LQAESRKEYEEWICAV 345
Cdd:cd13260    74 RALNESTItyLCADTAELAQEWMRAL 99
PID pfam00640
Phosphotyrosine interaction domain (PTB/PID);
467-582 1.08e-03

Phosphotyrosine interaction domain (PTB/PID);


Pssm-ID: 395515  Cd Length: 133  Bit Score: 39.65  E-value: 1.08e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 467 FIVRFLGSMAVKTDSTA------EVIYEAMRQVLAA------RAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 534
Cdd:pfam00640   1 FAVRYLGSVEVPEERAPdkntrmQQAREAIRRVKAAkinkirGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907074597 535 SVTqFAAHQE--NKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 582
Cdd:pfam00640  81 SIS-FCADGDpdLMRYFAYIARDKAT---NKFACHVFESEDGAQDIAQSI 126
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 300-342 2.62e-03

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: 38.46  E-value: 2.62e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 1907074597 300 LDNCSVMAVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWI 342
Cdd:cd13281    69 LGGCSIEAVEDPGKPYAISISHSDFKGNIILAADSEFEQEKWL 111
PTB_TK_HMTK cd13161
Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK ...
 467-583 5.11e-03

Tyrosine-specific kinase/HM-motif TK (TM/HMTK) Phosphotyrosine-binding (PTB) PH-like fold; TK kinases catalyzes the transfer of the terminal phosphate of ATP to a specific tyrosine residue on its target protein. TK kinases play significant roles in development and cell division. Tyrosine-protein kinases can be divided into two subfamilies: receptor tyrosine kinases, which have an intracellular tyrosine kinase domain, a transmembrane domain and an extracellular ligand-binding domain; and non-receptor (cytoplasmic) tyrosine kinases, which are soluble, cytoplasmic kinases. In HMTK the conserved His-Arg-Asp sequence within the catalytic loop is replaced by a His-Met sequence. TM/HMTK have are 2-3 N-terminal PTB domains. PTB domains in TKs are thought to function analogously to the membrane targeting (PH, myristoylation) and pTyr binding (SH2) domains of Src subgroup kinases. 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: 269983  Cd Length: 120  Bit Score: 37.23  E-value: 5.11e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 467 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAihnifRMTESHLMVTSQTLRLIDPQTQ-VSRACF--ELTSVTQFAAhq 543
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLKL-----KPKPVVLVVSSEGIRVVERLTGeVLTNVPikDISFVTVDPK-- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907074597 544 eNKRLVGFVIRvpestgEESLST---YIFESNSEGEKICYAIN 583
Cdd:cd13161    77 -DKKLFAFISH------DPRLGRitcHVFRCKRGAQEICDTIA 112
BAR_OPHN1 cd07633
The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid ...
 26-180 6.73e-03

The Bin/Amphiphysin/Rvs (BAR) domain of Oligophrenin-1; BAR domains are dimerization, lipid binding and curvature sensing modules found in many different proteins with diverse functions. Oligophrenin-1 (OPHN1) is a GTPase activating protein (GAP) with activity towards RhoA, Rac, and Cdc42, that is expressed in developing spinal cord and in adult brain areas with high plasticity. It plays a role in regulating the actin cystoskeleton as well as morphology changes in axons and dendrites, and may also function in modulating neuronal connectivity. Mutations in the OPHN1 gene causes X-linked mental retardation associated with cerebellar hypoplasia, lateral ventricle enlargement and epilepsy. OPHN1 contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, and a Rho GAP domain. BAR domains form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions.


Pssm-ID: 153317 [Multi-domain]  Cd Length: 207  Bit Score: 38.45  E-value: 6.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597  26 MNEMCLATQQLSRQLLAYEKQNFALGKGDEE--VISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVST 103
Cdd:cd07633    32 IKEYSSAVQKFSQTLQSFQFDFIGDTLTDDEinIAESFKEFAELLQEVEEERMMMVQNASDLLIKPLENFRKEQIGFTKE 111

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907074597 104 LKDLFGLASSEHDLSMAKYSRLPKKKEnEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAH 180
Cdd:cd07633   112 RKKKFEKDSEKFYSLLDRHVNLSSKKK-ESQLQEADLQVDKERQNFYESSLEYVYQIQEVQESKKFDVVEPVLAFLH 187
PTB_CED-6 cd01273
Cell death protein 6 homolog (CED-6/GULP1) Phosphotyrosine-binding (PTB) domain; CED6 (also ...
 467-582 8.81e-03

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: 37.26  E-value: 8.81e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907074597 467 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHnifRMTESHLM-----VTSQTLRLIDPQTQVSRACFELTSVTQFAA 541
Cdd:cd01273    14 YLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLK---KSEGAKLPkvelqISIDGVKIQDPKTKVIMHQFPLHRISFCAD 90

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907074597 542 HQENKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 582
Cdd:cd01273    91 DKTDKRIFSFIAKDSES---EKHLCFVFDSEKLAEEITLTI 128
 
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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