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 6912242   20 RSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 99
Cdd:cd07631   1 RSLLGVFEEDAAAISNYFNQLFQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  100 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMM 179
Cdd:cd07631  81 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMM 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6912242  180 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLANIGTSVQ 234
Cdd:cd07631 161 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLTNIGTSVQ 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 6912242  252 EDLEVASDPLYVPDPDPTKFPVNRNLTRKAGYLNARNKTGLVSSTWDRQFYFTQGGNLMSQARGDVAGGLAMDIDNCSVM 331
Cdd:cd13247   1 EELSSSADYFYEGDPDETQAAPNRNLTQKAGYLFIRSKTGLVTNKWDRTYFFTQGGNLMSQPRDEVAGSLVLDLDNCSVQ 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 6912242  332 AVDCEDRRYCFQITSFDGKKSSILQAESKKDHEEWICTINNISKQ 376
Cdd:cd13247  81 AADCEDRRNVFQITSPDGKKAIVLQAESKKDYEEWIATINNISQQ 125

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 6912242   20 RSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 99
Cdd:cd07631   1 RSLLGVFEEDAAAISNYFNQLFQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  100 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMM 179
Cdd:cd07631  81 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMM 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6912242  180 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLANIGTSVQ 234
Cdd:cd07631 161 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLTNIGTSVQ 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 6912242  490 KSETEDSILHQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNIFRMTESHLLVTCDCLKLIDPQTQVTRLTFPLP 569
Cdd:cd13158   1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 6912242  570 CVVLYATHQENKRLFGFVLRTSSGRSESNlSSVCYIFESNNEGEKICDSVGLAKQI 625
Cdd:cd13158  81 DVVQFAAHQENKRLFGFVVRTPEGDGEEP-SFSCYVFESNTEGEKICDAIALAKQI 135

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 6912242     499 HQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNIfRMTESHLLVTCDCLKLIDPQTQVTRLTFPLPCVVLYATHQ 578
Cdd:smart00462   3 GVSFRVKYLGSVEVPEARGLQVVQEAIRKLRAAQGSEKK-EPQKVILSISSRGVKLIDEDTKAVLHEHPLRRISFCAVGP 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 6912242     579 ENKRLFGFVLRTSSGRSESnlssvCYIFESNNEGEKICDSVGLAKQIALHAELDRR 634
Cdd:smart00462  82 DDLDVFGYIARDPGSSRFA-----CHVFRCEKAAEDIALAIGQAFQLAYELKLKAR 132

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242     278 TRKAGYLnaRNKTGLVSSTWDRQFYFTQGGNLM----SQARGDVAGGLAMDIDNCSVMAVDCED---RRYCFQITSFDGK 350
Cdd:smart00233   1 VIKEGWL--YKKSGGGKKSWKKRYFVLFNSTLLyyksKKDKKSYKPKGSIDLSGCTVREAPDPDsskKPHCFEIKTSDRK 78

                           90       100
                   ....*....|....*....|....*
gi 6912242     351 kSSILQAESKKDHEEWICTINNISK 375
Cdd:smart00233  79 -TLLLQAESEEEREKWVEALRKAIA 102

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 6912242   20 RSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 99
Cdd:cd07631   1 RSLLGVFEEDAAAISNYFNQLFQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  100 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMM 179
Cdd:cd07631  81 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKRRENEKVKYEVTEDVYTSRKKQHQTMM 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6912242  180 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLANIGTSVQ 234
Cdd:cd07631 161 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLTNIGTSVQ 215

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 6912242   20 RSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGGDDEVMSSTLQQFSKVIDELSSC 99
Cdd:cd07632   1 RSLLSVFEEDAGTLTDYTNQLLQAMQRVYGAQNEMCLATQQLSKQLLAYEKQNFALGKGDEEVISTLQYFAKVVDELNVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  100 HAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMM 179
Cdd:cd07632  81 HSELAKQLADTMVLPIIQFREKDLTEVSTLKDLFGIASNEHDLSMAKYSRLPKKRENEKVKAEVAKEVAYSRRKQHLSSL 160

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 6912242  180 HYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEEFLANIGTSVQ 234
Cdd:cd07632 161 QYYCALNALQYRKRVAMLEPMLGYTHGQINFFKKGAELFSKKLDSFLSSVSDMNQ 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 6912242  490 KSETEDSILHQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNIFRMTESHLLVTCDCLKLIDPQTQVTRLTFPLP 569
Cdd:cd13158   1 SSEDEDSLLQQLFIVRFLGSMEVKSDRTSEVIYEAMRQVLAARAIHNIFRMTESHLLVTSDCLRLIDPQTQVTRARFPLA 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 6912242  570 CVVLYATHQENKRLFGFVLRTSSGRSESNlSSVCYIFESNNEGEKICDSVGLAKQI 625
Cdd:cd13158  81 DVVQFAAHQENKRLFGFVVRTPEGDGEEP-SFSCYVFESNTEGEKICDAIALAKQI 135

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242   29 DATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEKQRFPLGgdDEVMSSTLQQFSKVIDELSSCHAVLSTQLA 108
Cdd:cd07307   1 KLDELEKLLKKLIKDTKKLLDSLKELPAAAEKLSEALQELGKELPDLS--NTDLGEALEKFGKIQKELEEFRDQLEQKLE 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  109 DAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKYEVTEDVYTSRKKQHQTMMHYFCALNTL 188
Cdd:cd07307  79 NKVIEPLKEYLKKDLKEIKKRRKKLDKARLDYDAAREKLKKLRKKKKDSSKLAEAEEELQEAKEKYEELREELIEDLNKL 158

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 6912242  189 QYKKKIALLEPLLGYMQAQISFFKMGSENLNEQLEE 224
Cdd:cd07307 159 EEKRKELFLSLLLSFIEAQSEFFKEVLKILEQLLPY 194

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242   78 DDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKREND 157
Cdd:cd07603  55 DDSLVQNCLNKFIQALQEMNNFHTILLDQAQRTVSTQLQNFVKEDIKKVKESKKHFEKISDDLDNALVKNAQAPRSKPQE 134

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 6912242  158 kvkYEVTEDVYTSRKK--QHQTMMHYFCaLNTLQYKKKIALLEPLLGYMQAQISFFKMGSEnLNEQLEEFL 226
Cdd:cd07603 135 ---AEEATNILTATRScfRHTALDYVLQ-INVLQAKKRHEILSTLLSYMHAQFTFFHQGYD-LLEDLEPYM 200

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 6912242   36 YMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYekqRFPLGGDDEV-----MSSTLQQFSKVIDELSSCHAVLSTQLADA 110
Cdd:cd07635  17 FIKELLKDGKNLIAATKSLSAAQRKFAHSLRDF---KFEFIGDAETddercIDASLQEFSNFLKNLEEQREIMALNVTET 93

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  111 MMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKyEVTEDVYTSRKKQHQTMMHYFCALNTLQY 190
Cdd:cd07635  94 LIKPLERFRKEQLGAVKEEKKKFDKETEKNYSLLEKHLNLSAKKKEPQLQ-EADVQVEQNRQHFYELSLEYVCKLQEIQE 172

                       170       180
                ....*....|....*....|....*.
gi 6912242  191 KKKIALLEPLLGYMQAQISFFKMGSE 216
Cdd:cd07635 173 RKKFECVEPMLSFFQGVFTFYHQGYE 198

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 6912242   79 DEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDK 158
Cdd:cd07637  56 DEMISECLDKFGDSLQEMVNYHMILFDQAQRSVRQQLHSFVKEDVRKFKETKKQFDKVREDLEIALVKNAQAPRHKPHEV 135

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 6912242  159 vkYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNE 220
Cdd:cd07637 136 --EEATSTLTITRKCFRHLALDYVLQINVLQAKKKFEILDSMLSFMHAQYTFFQQGYSLLHE 195

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 6912242   79 DEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDK 158
Cdd:cd07638  56 DAVIETSLTKFSDTLQEMINYHTILFDQAQRSIKAQLQTFVKEDLRKFKDAKKQFDKVSEEKENALVKNAQVQRNKQHEV 135

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 6912242  159 vkYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSEnLNEQLEEFL 226
Cdd:cd07638 136 --EEATNILTATRKCFRHIALDYVLQINVLQSKRRSEILKSMLSFMYAHLTFFHQGYD-LFSELGPYM 200

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 6912242   78 DDE-VMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKREN 156
Cdd:cd07602  60 DDEiEIAESLKEFGRLIETVEDERDRMLENAEEQLIEPLEKFRKEQIGGAKEEKKKFDKETEKFCSSLEKHLNLSTKKKE 139

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 6912242  157 DKVKyEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNE 220
Cdd:cd07602 140 NQLQ-EADAQLDMERRNFHQASLEYVFKLQEVQERKKFEFVETLLSFMYGWLTFYHQGHEVAKD 202

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 6912242  279 RKAGYLNARNKTGLVS-STWDRQFYFTQGG----NLMSQARGDVAGGLAMDIDNCSVMAVDCEDRRYCFQITSFDgKKSS 353
Cdd:cd13280   1 EKSGWLYMKTSVGKPNrTIWVRRWCFVKNGvfgmLSLSPSKTYVEETDKFGVLLCSVRYAPEEDRRFCFEVKIFK-DISI 79

                        90       100
                ....*....|....*....|....*..
gi 6912242  354 ILQAESKKDHEEWICTINNiSKQIYLS 380
Cdd:cd13280  80 ILQAETLKELKSWLTVFEN-AKRYALQ 105

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 6912242  499 HQLFIVRFLGSMEVKSDDHPDVVYETMRQILAARAIHNI--FRMTESHLLVTCDCLKLIDPQTQVTRLTFPLPCVVLYAT 576
Cdd:cd01273  11 HVAYLVKFLGCTEVEQPKGTEVVKEAIRKLKFARQLKKSegAKLPKVELQISIDGVKIQDPKTKVIMHQFPLHRISFCAD 90

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 6912242  577 HQENKRLFGFVLRTSSGRSESnlssvCYIFESNNEGEKICDSVGLAKQIA 626
Cdd:cd01273  91 DKTDKRIFSFIAKDSESEKHL-----CFVFDSEKLAEEITLTIGQAFDLA 135

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242  280 KAGYLNARNKTGLvSSTWDRQFY-FTQGGNLM------SQARGDVAGGLAMDIDNCSVMAVDCEDRRYCFQITSFDGKKS 352
Cdd:cd01249   2 KEGYLYLQEKKPL-GSTWTKHYCtYRKESKMFtmipynQQSSGKLGTTEVVTLKSCVRRKTDSIDRRFCFDIEVVDRPTV 80

                        90
                ....*....|....*
gi 6912242  353 SILQAESKKDHEEWI 367
Cdd:cd01249  81 LTLQALSEEDRKLWL 95

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 6912242  280 KAGYLNarnKTGLVSSTWDRQfYFTQGGNLM----SQARGDVAGGLAMDidNCSVMAVDCEDRrYCFQITsFDGK--KSS 353
Cdd:cd13288  10 KEGYLW---KKGERNTSYQKR-WFVLKGNLLfyfeKKGDREPLGVIVLE--GCTVELAEDAEP-YAFAIR-FDGPgaRSY 81

                        90
                ....*....|....
gi 6912242  354 ILQAESKKDHEEWI 367
Cdd:cd13288  82 VLAAENQEDMESWM 95

The Bin/Amphiphysin/Rvs (BAR) domain of ArfGAP with Coiled-coil, 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. ACAP1 (ArfGAP with Coiled-coil, ANK repeat and PH domain containing protein 1), also called centaurin beta-1, 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. ACAP1 also participates in the cargo sorting and recycling of the transferrin receptor and integrin beta1. It may also play a role in innate immune responses. ACAP1 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 6912242   75 LGGDDEVMSSTLQQFSKVIDELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKR 154
Cdd:cd07639  52 HGPKDPMMAECLEKFSDGLNHILDSHAELLEATQFSFKQQLQLLVKEDLRGFRDARKEFERGAESLEAALQHNAETPRRK 131

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 6912242  155 ENDKvkYEVTEDVYTSRKKQHQTMMHYFCALNTLQYKKKIALLEPLLGYMQAQISFFKMGSENLNE 220
Cdd:cd07639 132 AQEV--EEAAAALLGARATFRDRALDYALQINVIEDKKKFDILEFMLQLMEAQASFFQQGHEALSA 195

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 6912242   20 RSLLGVFEEDATAISNYMNQLYQAMHRIYDAQNELSAATHLTSKLLKEYEkqrFPLGGD----DEV-MSSTLQQFSKVID 94
Cdd:cd07633   1 RERLKCYEQELERTNKFIKDVIKDGNALISAIKEYSSAVQKFSQTLQSFQ---FDFIGDtltdDEInIAESFKEFAELLQ 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242   95 ELSSCHAVLSTQLADAMMFPITQFKERDLKEILTLKEVFQIASNDHDAAINRYSRLSKKRENDKVKyEVTEDVYTSRKKQ 174
Cdd:cd07633  78 EVEEERMMMVQNASDLLIKPLENFRKEQIGFTKERKKKFEKDSEKFYSLLDRHVNLSSKKKESQLQ-EADLQVDKERQNF 156

                       170       180       190
                ....*....|....*....|....*....|..
gi 6912242  175 HQTMMHYFCALNTLQYKKKIALLEPLLGYMQA 206
Cdd:cd07633 157 YESSLEYVYQIQEVQESKKFDVVEPVLAFLHS 188

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 6912242  501 LFIVRFLGSMEVKSDDHPDVVYEtmrqilAARAIHNIFRM-TESHLLVTCDCLKLIDPQTQVTRLTFPLPCVVLYATHQE 579
Cdd:cd13161   3 VFEAKYLGSVPVKEPKGNDVVMA------AVKRLKDLKLKpKPVVLVVSSEGIRVVERLTGEVLTNVPIKDISFVTVDPK 76

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 6912242  580 NKRLFGFVLRTSSGRSesnlsSVCYIFESNNEGEKICDSVGLAKQIA 626
Cdd:cd13161  77 DKKLFAFISHDPRLGR-----ITCHVFRCKRGAQEICDTIAEAFKAA 118

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 6912242    280 KAGYLnaRNKTGLVSSTWDRQFYFTQGGNLMSQARGDVAGGLA----MDIDNCSVMAVDCED---RRYCFQI--TSFDGK 350
Cdd:pfam00169   3 KEGWL--LKKGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSKEpkgsISLSGCEVVEVVASDspkRKFCFELrtGERTGK 80

                          90       100
                  ....*....|....*....|....*
gi 6912242    351 KSSILQAESKKDHEEWICTINNISK 375
Cdd:pfam00169  81 RTYLLQAESEEERKDWIKAIQSAIR 105