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 353731086   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  81 TEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGF 160
Cdd:cd07632  105 TEVSTLKDLFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGY 184

                        170       180       190
                 ....*....|....*....|....*....|.
gi 353731086 161 AHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 191
Cdd:cd07632  185 THGQINFFKKGAELFSKKLDSFLSSVSDMNQ 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 353731086 209 QELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 288
Cdd:cd13247    1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 353731086 289 AVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQ 333
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 353731086   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  81 TEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGF 160
Cdd:cd07632  105 TEVSTLKDLFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGY 184

                        170       180       190
                 ....*....|....*....|....*....|.
gi 353731086 161 AHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 191
Cdd:cd07632  185 THGQINFFKKGAELFSKKLDSFLSSVSDMNQ 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 353731086 209 QELLSVDESVYTPDSDVAAPQINRNLIQKAGYLNLRNKTGLVTTTWERLYFFTQGGNLMCQPRGAVAGGLIQDLDNCSVM 288
Cdd:cd13247    1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 353731086 289 AVDCEDRRYCFQITTPNGKSGIILQAESRKENEEWICAINNISRQ 333
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 353731086   451 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENK 530
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 353731086   531 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 566
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  235 IQKAGYLnlRNKTGLVTTTWERLYFFTQGGNL-MCQPRGAVAGGLIQ---DLDNCSVMAVDCED---RRYCFQITTP--N 305
Cdd:pfam00169   1 VVKEGWL--LKKGGGKKKSWKKRYFVLFDGSLlYYKDDKSGKSKEPKgsiSLSGCEVVEVVASDspkRKFCFELRTGerT 78

                          90       100
                  ....*....|....*....|....*..
gi 353731086  306 GKSGIILQAESRKENEEWICAINNISR 332
Cdd:pfam00169  79 GKRTYLLQAESEEERKDWIKAIQSAIR 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 353731086   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07632   25 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVLHSELAKQLADTMVLPIIQFREKDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  81 TEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGF 160
Cdd:cd07632  105 TEVSTLKDLFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSLQYYCALNALQYRKRVAMLEPMLGY 184

                        170       180       190
                 ....*....|....*....|....*....|.
gi 353731086 161 AHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 191
Cdd:cd07632  185 THGQINFFKKGAELFSKKLDSFLSSVSDMNQ 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 353731086 439 FPEAEDSLLQQMFIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIFRMTESHLMVTSQSLRLIDPQTQVSRANFELT 518
Cdd:cd13158    1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 353731086 519 SVTQFAAHQENKRLVGFVIRVPESTGEE-SLSTYIFESNSEGEKICYAINLGKEI 572
Cdd:cd13158   81 DVVQFAAHQENKRLFGFVVRTPEGDGEEpSFSCYVFESNTEGEKICDAIALAKQI 135

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086   1 MQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDL 80
Cdd:cd07631   25 MHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDL 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  81 TEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGF 160
Cdd:cd07631  105 KEILTLKEVFQIASNDHDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGY 184

                        170       180       190
                 ....*....|....*....|....*....|.
gi 353731086 161 AHGQINFFKKGAEMFSKRMDSFLSSVADMVQ 191
Cdd:cd07631  185 MQAQISFFKMGSENLNEQLEEFLTNIGTSVQ 215

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 353731086   2 QRVYGAQNEMCLATQQLSKQLLAYEKQnfALGKGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLT 81
Cdd:cd07307   17 KKLLDSLKELPAAAEKLSEALQELGKE--LPDLSNTDLGEALEKFGKIQKELEEFRDQLEQKLENKVIEPLKEYLKKDLK 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  82 EVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFA 161
Cdd:cd07307   95 EIKKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKLEEKRKELFLSLLLSFI 174

                        170
                 ....*....|....*.
gi 353731086 162 HGQINFFKKGAEMFSK 177
Cdd:cd07307  175 EAQSEFFKEVLKILEQ 190

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 353731086   7 AQNEMCLATQQLSKQLLAYEKQNFALGKGDEE--VISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVS 84
Cdd:cd07635   31 ATKSLSAAQRKFAHSLRDFKFEFIGDAETDDErcIDASLQEFSNFLKNLEEQREIMALNVTETLIKPLERFRKEQLGAVK 110

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  85 TLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQ 164
Cdd:cd07635  111 EEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQ-EADVQVEQNRQHFYELSLEYVCKLQEIQERKKFECVEPMLSFFQGV 189

                        170
                 ....*....|
gi 353731086 165 INFFKKGAEM 174
Cdd:cd07635  190 FTFYHQGYEL 199

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 353731086 237 KAGYLNLRnkTGLVTTTWERLYFFTQGGNLMC----QPRGAVAGGLIQDLDNCSVMAVDCEDRRYCFQITTPNGKSgIIL 312
Cdd:cd00821    1 KEGYLLKR--GGGGLKSWKKRWFVLFEGVLLYykskKDSSYKPKGSIPLSGILEVEEVSPKERPHCFELVTPDGRT-YYL 77

                         90
                 ....*....|....*
gi 353731086 313 QAESRKENEEWICAI 327
Cdd:cd00821   78 QADSEEERQEWLKAL 92

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 353731086   451 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHNIfRMTESHLMVTSQSLRLIDPQTQVSRANFELTSVTQFAAHQENK 530
Cdd:smart00462   6 FRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGPDDL 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 353731086   531 RLVGFVIRVPestGEESLSTYIFESNSEGEKICYAI 566
Cdd:smart00462  85 DVFGYIARDP---GSSRFACHVFRCEKAAEDIALAI 117

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086   6 GAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEV--ISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEV 83
Cdd:cd07634   30 GALRNLSMAVQKFSQSLQDFQFECIGDAETDDEIsiAQSLKEFARLLIAVEEERRRLIQNANDVLIAPLEKFRKEQIGAA 109

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  84 STLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKTEVgKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHG 163
Cdd:cd07634  110 KDGKKKFDKESEKYYSILEKHLNLSAKKKESHLQRAD-TQIDREHQNFYEASLEYVFKIQEVQEKKKFEFVEPLLAFLQG 188

                        170
                 ....*....|.
gi 353731086 164 QINFFKKGAEM 174
Cdd:cd07634  189 LFTFYHEGYEL 199

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 353731086   9 NEMCLATQQLSKQLLAYEK--QNFAL---GKG---DEEVIS-TLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKD 79
Cdd:cd07602   26 KNLISATKNLSKAQRSFAQtlQNFKFeciGETqtdDEIEIAeSLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRKEQ 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  80 LTEVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIG 159
Cdd:cd07602  106 IGGAKEEKKKFDKETEKFCSSLEKHLNLSTKKKENQLQ-EADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFVETLLS 184

                        170
                 ....*....|....*.
gi 353731086 160 FAHGQINFFKKGAEMF 175
Cdd:cd07602  185 FMYGWLTFYHQGHEVA 200

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  34 KGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGLASNEHDLSMAKYSRLPKKKEN 113
Cdd:cd07637   54 KKDEMISECLDKFGDSLQEMVNYHMILFDQAQRSVRQQLHSFVKEDVRKFKETKKQFDKVREDLEIALVKNAQAPRHKPH 133

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 353731086 114 EkVKTEVGKEVAAARRKQHLSsLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKG 171
Cdd:cd07637  134 E-VEEATSTLTITRKCFRHLA-LDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQG 189

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 353731086  14 ATQQLSKQLLAYEKQNFALGKGDEE--VISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVSTLKDLFG 91
Cdd:cd07636   38 AKRKFADSLNEFKFQCIGDAETDDEicIARSLQEFAAVLRNLEDERTRMIENASEVLITPLEKFRKEQIGAAKEAKKKYD 117

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  92 LASNEHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKG 171
Cdd:cd07636  118 KETEKYCAVLEKHLNLSSKKKESQLH-EADSQVDLVRQHFYEVSLEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHG 196

                 ...
gi 353731086 172 AEM 174
Cdd:cd07636  197 YEL 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 353731086 237 KAGYLNlrnKTGLVTTTWERLYFFTQGgNLMC--------QPRGAVAggliqdLDNCSVMAVDCEDRrYCFQITTPNGKS 308
Cdd:cd13288   10 KEGYLW---KKGERNTSYQKRWFVLKG-NLLFyfekkgdrEPLGVIV------LEGCTVELAEDAEP-YAFAIRFDGPGA 78

                         90       100
                 ....*....|....*....|
gi 353731086 309 GI-ILQAESRKENEEWICAI 327
Cdd:cd13288   79 RSyVLAAENQEDMESWMKAL 98

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  34 KGDEEVISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLTEVS-TLKDLFGLASNEHDLSMAKYSRlpKKKE 112
Cdd:cd07642   56 RDDPDLGSAFLKFSVFTKELTALFKNLVQNMNNIITFPLDSLLKGDLKGVKgDLKKPFDKAWKDYETKVTKIEK--EKKE 133

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 353731086 113 NEK----VKTEV-GKEVA----AARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFAHGQINFFKKG 171
Cdd:cd07642  134 HAKmhgmIRTEIsGAEIAeemeKERRFFQLQMCEYLLKVNEIKIKKGVDLLQNLIKYFHAQCNFFQDG 201

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086 235 IQKAGYLNLRNKTglvTTTWERLYFftqggnLMCQP--------RGAVAGGLIqDLDNCSV-----MAvDCEDRRYCFQI 301
Cdd:cd01233    6 VSKRGYLLFLEDA---TDGWVRRWV------VLRRPylhiysseKDGDERGVI-NLSTARVeyspdQE-ALLGRPNVFAV 74

                         90       100
                 ....*....|....*....|....*...
gi 353731086 302 TTPNgkSGIILQAESRKENEEWICAINN 329
Cdd:cd01233   75 YTPT--NSYLLQARSEKEMQDWLYAIDP 100

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086 451 FIVRFLGSMAVKTDSTTEVIYEAMRQVLAARAIHnifRMTESHLM-----VTSQSLRLIDPQTQVSRANFELTSVTQFAA 525
Cdd:cd01273   14 YLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLK---KSEGAKLPkvelqISIDGVKIQDPKTKVIMHQFPLHRISFCAD 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 353731086 526 HQENKRLVGFVIRVPEStgeESLSTYIFESNSEGEKICYAI 566
Cdd:cd01273   91 DKTDKRIFSFIAKDSES---EKHLCFVFDSEKLAEEITLTI 128

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086 235 IQKAGYLNLRNKtGLVTTTWERLYF-----------------FTQGGNLMCQPRGavagglIQDLDNCSVMAVDCEDRRY 297
Cdd:cd13281   12 VQLHGILWKKPF-GHQSAKWSKRFFiikegfllyysesekkdFEKTRHFNIHPKG------VIPLGGCSIEAVEDPGKPY 84

                         90       100
                 ....*....|....*....|....*..
gi 353731086 298 CFQITTPNGKSGIILQAESRKENEEWI 324
Cdd:cd13281   85 AISISHSDFKGNIILAADSEFEQEKWL 111

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086 236 QKAGYLNLR-NKTGLVTTTWeRLYFFTQGGNLMC---QPRGAVAG---------GLIQDLDncsvmavdcEDR---RYCF 299
Cdd:cd13277    4 VKEGYLLKRrKKTLGSTGGW-KLRYGVLDGNILElyeSRGGQLLEsiklrnaqiERQPNLP---------DDKygtRHGF 73

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 353731086 300 QITTPNGKSGI-----ILQAESRKENEEWICAINN 329
Cdd:cd13277   74 LINEHKKSGLSsttkyYLCAETDKERDEWVSALSE 108

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086   4 VYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEE--VISTLHYFSKVVDELNLLHTELAKQLADTMVLPIIQFREKDLT 81
Cdd:cd07633   28 LISAIKEYSSAVQKFSQTLQSFQFDFIGDTLTDDEinIAESFKEFAELLQEVEEERMMMVQNASDLLIKPLENFRKEQIG 107

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 353731086  82 EVSTLKDLFGLASNEHDLSMAKYSRLPKKKENEKVKtEVGKEVAAARRKQHLSSLQYYCALNALQYRKQMAMMEPMIGFA 161
Cdd:cd07633  108 FTKERKKKFEKDSEKFYSLLDRHVNLSSKKKESQLQ-EADLQVDKERQNFYESSLEYVYQIQEVQESKKFDVVEPVLAFL 186

                 .
gi 353731086 162 H 162
Cdd:cd07633  187 H 187