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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   1 MCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLF 80
Cdd:cd07632    35 MCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKDLF 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  81 GLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKR 160
Cdd:cd07632   115 GIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKK 194

                         170       180
                  ....*....|....*....|.
gi 1039732723 161 GAEMFSKSMDGFLSSVKDMVQ 181
Cdd:cd07632   195 GAELFSKKLDSFLSSVSDMNQ 215

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 199 QELLSVSESVYTPDIDVATAQINRNLIQKTGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 278
Cdd:cd13247     1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1039732723 279 AVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWICAVNNISRQ 323
Cdd:cd13247    81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   1 MCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLF 80
Cdd:cd07632    35 MCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKDLF 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  81 GLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKR 160
Cdd:cd07632   115 GIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKK 194

                         170       180
                  ....*....|....*....|.
gi 1039732723 161 GAEMFSKSMDGFLSSVKDMVQ 181
Cdd:cd07632   195 GAELFSKKLDSFLSSVSDMNQ 215

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 199 QELLSVSESVYTPDIDVATAQINRNLIQKTGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 278
Cdd:cd13247     1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1039732723 279 AVDCEDRRYCFQISTPSGKPGIILQAESRKEYEEWICAVNNISRQ 323
Cdd:cd13247    81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  439 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQTLRLIDPQTQVSRACFELTSVTQFAAHQENK 518
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1039732723  519 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 554
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 225 IQKTGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQISTP--S 295
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039732723 296 GKPGIILQAESRKEYEEWIcavNNISRQIY 325
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWI---KAIQSAIR 105

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   1 MCLATQQLSRQLLAYEKQNFALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLF 80
Cdd:cd07632    35 MCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDLTEVSTLKDLF 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  81 GLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKR 160
Cdd:cd07632   115 GIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGYTHGQINFFKK 194

                         170       180
                  ....*....|....*....|.
gi 1039732723 161 GAEMFSKSMDGFLSSVKDMVQ 181
Cdd:cd07632   195 GAELFSKKLDSFLSSVSDMNQ 215

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 427 FPEAEDSLLQQMFIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 506
Cdd:cd13158     1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1039732723 507 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 560
Cdd:cd13158    81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   1 MCLATQQLSRQLLAYEKQNfalgKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLF 80
Cdd:pfam16746  48 YSAAQRLFANSLLDFKFEF----IGDEETDESLKKFSQLLQEMENFHTILLDQAQRTIIKPLENFRKEDLKEVKELKKKF 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  81 GLASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKR 160
Cdd:pfam16746 124 DKASEKLDAALEKNAQLSKKKKPSELE-EADNELAATRKCFHHASLDYVLQINELQERKKFEILEPLLSFMHAQFTFFHQ 202

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1039732723 161 GAEMFsKSMDGFLSSVKDMVQSIQVELEAEADKM 194
Cdd:pfam16746 203 GYELF-KDLEPFMKDLQAQLQQTREDTREEKEEL 235

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   1 MCLATQQLSRQLLAYEKQnfALGKGDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLF 80
Cdd:cd07307    26 LPAAAEKLSEALQELGKE--LPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKEYLKKDLKEIKKRRKKL 103

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  81 GLASSEHDLSMAKYSRLPKKKENEKAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKR 160
Cdd:cd07307   104 DKARLDYDAAREKLKKLRKKKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLEEKRKELFLSLLLSFIEAQSEFFKE 183

                  ....*..
gi 1039732723 161 GAEMFSK 167
Cdd:cd07307   184 VLKILEQ 190

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 227 KTGYLNLRnkTGLVTTTWERLYFFTQGGNLMC----QPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQISTPSGKPgIIL 302
Cdd:cd00821     1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYykskKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRT-YYL 77

                          90
                  ....*....|....*
gi 1039732723 303 QAESRKEYEEWICAV 317
Cdd:cd00821    78 QADSEEERQEWLKAL 92

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  26 DEEVI-STLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLP-KKKEN 103
Cdd:cd07635    61 DERCIdASLQEFSNFLKNLEEQREIMALNVTETLIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSaKKKEP 140

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1039732723 104 EKAKTEIvkEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEM 164
Cdd:cd07635   141 QLQEADV--QVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYEL 199

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 226 QKTGYLNLRNKTGLVT-TTWERLYFFTQG---GNLMCQPrgavAGGLIQDLD-----NCSVMAVDCEDRRYCFQISTpSG 296
Cdd:cd13280     1 EKSGWLYMKTSVGKPNrTIWVRRWCFVKNgvfGMLSLSP----SKTYVEETDkfgvlLCSVRYAPEEDRRFCFEVKI-FK 75

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039732723 297 KPGIILQAESRKEYEEWICAVNNiSRQIYL 326
Cdd:cd13280    76 DISIILQAETLKELKSWLTVFEN-AKRYAL 104

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   2 CLATQQLS---RQLLAYEKQnfalgkgDEEVISTLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKD 78
Cdd:cd07638    36 CQANKQFMngiRDLAQYSSK-------DAVIETSLTKFSDTLQEMINYHTILFDQAQRSIKAQLQTFVKEDLRKFKDAKK 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  79 LFGLASSEHDLSMAKYSRLPKKKENEkakTEIVKEVAAARRK--QHLsSLQYYCALNALQYRKRAAMMEPLIGFAHGQIN 156
Cdd:cd07638   109 QFDKVSEEKENALVKNAQVQRNKQHE---VEEATNILTATRKcfRHI-ALDYVLQINVLQSKRRSEILKSMLSFMYAHLT 184

                         170
                  ....*....|.
gi 1039732723 157 FFKRGAEMFSK 167
Cdd:cd07638   185 FFHQGYDLFSE 195

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 225 IQKTGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQISTP--S 295
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039732723 296 GKPGIILQAESRKEYEEWIcavNNISRQIY 325
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWI---KAIQSAIR 105

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723   4 ATQQLSRQLLAYEK--QNFAL---GKG---DEEVIS-TLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVS 74
Cdd:cd07602    31 ATKNLSKAQRSFAQtlQNFKFeciGETqtdDEIEIAeSLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRKEQIGGAK 110

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  75 TLKDLFGLASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQ 154
Cdd:cd07602   111 EEKKKFDKETEKFCSSLEKHLNLSTKKKENQLQ-EADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFVETLLSFMYGW 189

                         170
                  ....*....|.
gi 1039732723 155 INFFKRGAEMF 165
Cdd:cd07602   190 LTFYHQGHEVA 200

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  26 DEEVIS-TLHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFGLASSEHDLSMAKYSRLPKKKEnE 104
Cdd:cd07636    61 DEICIArSLQEFAAVLRNLEDERTRMIENASEVLITPLEKFRKEQIGAAKEAKKKYDKETEKYCAVLEKHLNLSSKKK-E 139

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 105 KAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEM 164
Cdd:cd07636   140 SQLHEADSQVDLVRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYEL 199

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 227 KTGYLNlrnKTGLVTTTWERLYFFTQGgNLMC--------QPRGAVAggliqdLDNCSVMAVDCEDRrYCFQISTPSGKP 298
Cdd:cd13288    10 KEGYLW---KKGERNTSYQKRWFVLKG-NLLFyfekkgdrEPLGVIV------LEGCTVELAEDAEP-YAFAIRFDGPGA 78

                          90       100
                  ....*....|....*....|
gi 1039732723 299 GI-ILQAESRKEYEEWICAV 317
Cdd:cd13288    79 RSyVLAAENQEDMESWMKAL 98

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 227 KTGYLNlrnKTGLVTTTWERLYFFTQGGNLM----------CQPRGAVaggliqDLDNCSVM--AVDCEDRRYCFQISTP 294
Cdd:cd13276     1 KAGWLE---KQGEFIKTWRRRWFVLKQGKLFwfkepdvtpySKPRGVI------DLSKCLTVksAEDATNKENAFELSTP 71

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039732723 295 SGKpgIILQAESRKEYEEWIcavNNISRQI 324
Cdd:cd13276    72 EET--FYFIADNEKEKEEWI---GAIGRAI 96

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1039732723 271 DLDNCSVMAVDCEDRRYCFQISTPSGKpgIILQAESRKEYEEWICAVNNIS-RQIY 325
Cdd:cd13274    43 DLSDASVAECSTKNVNNSFTVITPFRK--LILCAESRKEMEEWISALKTVQqREFY 96

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  14 AYEKQ-NFA-----LGKGDEEVIST------LHYFSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVSTLKDLFG 81
Cdd:cd07606    34 AYDGDsAFAesleeFGGGHDDPISVavggpvMTKFTSALREIGSYKEVLRSQVEHMLNDRLAQFADTDLQEVKDARRRFD 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  82 LASSEHDLSMAKYSRLPKKKENEKAKtEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRG 161
Cdd:cd07606   114 KASLDYEQARSKFLSLTKDAKPEILA-AAEEDLGTTRSAFETARFDLMNRLHAADARKRVEFLERLSGSMDAHLAFFKSG 192

                  ....*.
gi 1039732723 162 AEMFSK 167
Cdd:cd07606   193 YELLRQ 198

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723  36 FSKVMDELNGLHTELAKQLADTMVLPVIQFREKDLTEVS-TLKDLFGLASSEHDlsmAKYSRLPKKKE----------NE 104
Cdd:cd07641    68 FSTLTKELSTLLKNLLQGLSHNVIFTLDSLLKGDLKGVKgDLKKPFDKAWKDYE---TKFTKIEKEKRehakqhgmirTE 144

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039732723 105 KAKTEIVKEVAAARRKQHLSSLQYYCALNALQYRKRAAMMEPLIGFAHGQINFFKRGAEMFSK 167
Cdd:cd07641   145 ITGAEIAEEMEKERRLFQLQMCEYLIKVNEIKTKKGVDLLQNLIKYYHAQCNFFQDGLKTADK 207

Phosphotyrosine interaction domain (PTB/PID);

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 439 FIVRFLGSMAVKTDSTA------EVIYEAMRQVLAA------RAIHNIFRMTESHLMVTSQTLRLIDPQTQVSRACFELT 506
Cdd:pfam00640   1 FAVRYLGSVEVPEERAPdkntrmQQAREAIRRVKAAkinkirGLSGETGPGTKVDLFISTDGLKLLNPDTQELIHDHPLV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1039732723 507 SVTqFAAHQE--NKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 554
Cdd:pfam00640  81 SIS-FCADGDpdLMRYFAYIARDKAT---NKFACHVFESEDGAQDIAQSI 126

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039732723 439 FIVRFLGSMAVKTDSTAEVIYEAMRQVLAARAihnifRMTESHLMVTSQTLRLIDPQTQ-VSRACF--ELTSVTQFAAhq 515
Cdd:cd13161     4 FEAKYLGSVPVKEPKGNDVVMAAVKRLKDLKL-----KPKPVVLVVSSEGIRVVERLTGeVLTNVPikDISFVTVDPK-- 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1039732723 516 eNKRLVGFVIRvpestgEESLST---YIFESNSEGEKICYAIN 555
Cdd:cd13161    77 -DKKLFAFISH------DPRLGRitcHVFRCKRGAQEICDTIA 112