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 198278482  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07634    1 RERLQCHEIELERTNKFIKELIKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAK----------------------------------ADSQIGREHQNFYEAS 144
Cdd:cd07634   81 EERRRLIQNANDVLIAPLEKFRKEQIGAAKdgkkkfdkesekyysilekhlnlsakkkeshlqrADTQIDREHQNFYEAS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 198278482 145 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 191
Cdd:cd07634  161 LEYVFKIQEVQEKKKFEFVEPLLAFLQGLFTFYHEGYELAQEFAPYK 207

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity 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. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 198278482 787 QAQAMYSCKAEHSHELSFPQGAIFSNVHPSVEPGWLKATYEGRTGLVPENYVVFL 841
Cdd:cd12066    1 QAKAMYSCKAEHSHELSFPQGAIFSNVYPSVEPGWLKATYEGKTGLVPENYVVFL 55

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 198278482  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07634    1 RERLQCHEIELERTNKFIKELIKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAK----------------------------------ADSQIGREHQNFYEAS 144
Cdd:cd07634   81 EERRRLIQNANDVLIAPLEKFRKEQIGAAKdgkkkfdkesekyysilekhlnlsakkkeshlqrADTQIDREHQNFYEAS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 198278482 145 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 191
Cdd:cd07634  161 LEYVFKIQEVQEKKKFEFVEPLLAFLQGLFTFYHEGYELAQEFAPYK 207

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 198278482 233 TMEGYLYVQEKRPLGFTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvTGSPEMFKLKSCIRRKTDSIDKRFCFDIEVV 312
Cdd:cd01249    1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGK-----LGTTEVVTLKSCVRRKTDSIDRRFCFDIEVV 75

                         90       100       110
                 ....*....|....*....|....*....|
gi 198278482 313 ERHGIITLQAFSEANRKLWLEAMDGKEPIY 342
Cdd:cd01249   76 DRPTVLTLQALSEEDRKLWLEAMDGKEPIY 105

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  363 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfSPKSPPDMDIDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 442
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELRE---AFDRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 198278482  443 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMR 508
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145

Src homology 3 domains; Src homology 3 (SH3) domains bind to target proteins through sequences containing proline and hydrophobic amino acids. Pro-containing polypeptides may bind to SH3 domains in 2 different binding orientations.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 198278482   784 SGRQAQAMYSCKAEHSHELSFPQGAIFSnVHPSVEPGWLKATYE-GRTGLVPENYV 838
Cdd:smart00326   1 EGPQVRALYDYTAQDPDELSFKKGDIIT-VLEKSDDGWWKGRLGrGKEGLFPSNYV 55

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 198278482   233 TMEGYLYVQEKRPLGfTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvtgsPEMFKLKSCIRR---KTDSIDKRFCFDI 309
Cdd:smart00233   2 IKEGWLYKKSGGGKK-SWKKRYFVLFNSTLLYYKSKKDKKSYKP--------KGSIDLSGCTVReapDPDSSKKPHCFEI 72

                           90       100
                   ....*....|....*....|....*.
gi 198278482   310 EVVERHgIITLQAFSEANRKLWLEAM 335
Cdd:smart00233  73 KTSDRK-TLLLQAESEEEREKWVEAL 97

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 198278482  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07634    1 RERLQCHEIELERTNKFIKELIKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAK----------------------------------ADSQIGREHQNFYEAS 144
Cdd:cd07634   81 EERRRLIQNANDVLIAPLEKFRKEQIGAAKdgkkkfdkesekyysilekhlnlsakkkeshlqrADTQIDREHQNFYEAS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 198278482 145 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 191
Cdd:cd07634  161 LEYVFKIQEVQEKKKFEFVEPLLAFLQGLFTFYHEGYELAQEFAPYK 207

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 198278482  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07636    1 RERLKSHEAELDKTNKFIKELIKDGKSLIAALKNLSSAKRKFADSLNEFKFQCIGDAETDDEICIARSLQEFAAVLRNLE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAK----------------------------------ADSQIGREHQNFYEAS 144
Cdd:cd07636   81 DERTRMIENASEVLITPLEKFRKEQIGAAKeakkkydketekycavlekhlnlsskkkesqlheADSQVDLVRQHFYEVS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 198278482 145 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 191
Cdd:cd07636  161 LEYVFKVQEVQERKMFEFVEPLLAFLQGLFTFYHHGYELAKDFSDFK 207

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 198278482  19 RERLQCHEIELERTNKFIKELLKDGSLLIGALRNLSMAVQKFSQSLQDFQFECIGDAETDDEISIAQSLKEFARLLIAVE 98
Cdd:cd07635    1 RERIRAHEAELERTNRFIKELLKDGKNLIAATKSLSAAQRKFAHSLRDFKFEFIGDAETDDERCIDASLQEFSNFLKNLE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  99 EERRRLIQNANDVLIAPLEKFRKEQIGAAK----------------------------------ADSQIGREHQNFYEAS 144
Cdd:cd07635   81 EQREIMALNVTETLIKPLERFRKEQLGAVKeekkkfdketeknysllekhlnlsakkkepqlqeADVQVEQNRQHFYELS 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 198278482 145 LEYVFKIQEVQEKKKFEFVEPLLSFLQGLFTFYHEGYELAQEFAPYK 191
Cdd:cd07635  161 LEYVCKLQEIQERKKFECVEPMLSFFQGVFTFYHQGYELAKDFNHYK 207

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 198278482 233 TMEGYLYVQEKRPLGFTWTKHYCTYDKGSKMFTMSVSDVKASGKmnglvTGSPEMFKLKSCIRRKTDSIDKRFCFDIEVV 312
Cdd:cd01249    1 TKEGYLYLQEKKPLGSTWTKHYCTYRKESKMFTMIPYNQQSSGK-----LGTTEVVTLKSCVRRKTDSIDRRFCFDIEVV 75

                         90       100       110
                 ....*....|....*....|....*....|
gi 198278482 313 ERHGIITLQAFSEANRKLWLEAMDGKEPIY 342
Cdd:cd01249   76 DRPTVLTLQALSEEDRKLWLEAMDGKEPIY 105

RhoGAP: GTPase-activator protein (GAP) for Rho-like GTPases; GAPs towards Rho/Rac/Cdc42-like small GTPases. Small GTPases (G proteins) cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when bound to GDP. The Rho family of small G proteins, which includes Cdc42Hs, activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. G proteins generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude. The RhoGAPs are one of the major classes of regulators of Rho G proteins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 363 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTtFSPKSPPDmdiDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 442
Cdd:cd00159    3 IIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKK-FDRGEDID---DLEDYDVHDVASLLKLYLRELPEPLIPFELYDE 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 443 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMMNIKF 522
Cdd:cd00159   79 FIELAKIEDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLEDIKK 158

                        170
                 ....*....|.
gi 198278482 523 QNIVVEILIEH 533
Cdd:cd00159  159 LNEIVEFLIEN 169

RhoGAP domain; GTPase activator proteins towards Rho/Rac/Cdc42-like small GTPases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482  363 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfSPKSPPDMDIDIELWDNKTITSGLKNYLRCLAEPLMTYKLHKD 442
Cdd:pfam00620   3 IVRKCVEYLEKRGLDTEGIFRVSGSASRIKELRE---AFDRGPDVDLDLEEEDVHVVASLLKLFLRELPEPLLTFELYEE 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 198278482  443 FIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMR 508
Cdd:pfam00620  80 FIEAAKLPDEEERLEALRELLRKLPPANRDTLRYLLAHLNRVAQNSDVNKMNAHNLAIVFGPTLLR 145

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase 3; GRAF3 is also called Rho GTPase activating protein 42 (ARHGAP42) or ARHGAP10-like. Though its function has not been characterized, it may be a GAP with activity towards RhoA and Cdc42, based on its similarity 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. The SH3 domain of GRAF and GRAF2 binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 198278482 787 QAQAMYSCKAEHSHELSFPQGAIFSNVHPSVEPGWLKATYEGRTGLVPENYVVFL 841
Cdd:cd12066    1 QAKAMYSCKAEHSHELSFPQGAIFSNVYPSVEPGWLKATYEGKTGLVPENYVVFL 55

RhoGAP_ARHGAP21: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP21-like proteins. ArhGAP21 is a multi-domain protein, containing RhoGAP, PH and PDZ domains, and is believed to play a role in the organization of the cell-cell junction complex. It has been shown to function as a GAP of Cdc42 and RhoA, and to interact with alpha-catenin and Arf6. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 363 FVRKCIQAVEMRGITILGLYRIGGVN---SKVQKLMNttfspKSPPDMDIDIELW-DNKTITSGLKNYLRCLAEPLMTYK 438
Cdd:cd04395   21 IVEVCCNIVEARGLETVGIYRVPGNNaaiSALQEELN-----RGGFDIDLQDPRWrDVNVVSSLLKSFFRKLPEPLFTNE 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 439 LHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMM 518
Cdd:cd04395   96 LYPDFIEANRIEDPVERLKELRRLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTLVRTSDDNMETMV 175

                        170       180
                 ....*....|....*....|.
gi 198278482 519 -NIKFQNIVVEILIEHYEKIF 538
Cdd:cd04395  176 tHMPDQCKIVETLIQHYDWFF 196

RhoGAP_MgcRacGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in MgcRacGAP proteins. MgcRacGAP plays an important dual role in cytokinesis: i) it is part of centralspindlin-complex, together with the mitotic kinesin MKLP1, which is critical for the structure of the central spindle by promoting microtuble bundling. ii) after phosphorylation by aurora B MgcRacGAP becomes an effective regulator of RhoA and plays an important role in the assembly of the contractile ring and the initiation of cytokinesis. MgcRacGAP-like proteins contain a N-terminal C1-like domain, and a C-terminal RhoGAP domain. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 363 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNTTFSPKSPPDM-DIDIElwdnkTITSGLKNYLRCLAEPLMTYKLHK 441
Cdd:cd04382   20 LIVHCVNEIEARGLTEEGLYRVSGSEREVKALKEKFLRGKTVPNLsKVDIH-----VICGCLKDFLRSLKEPLITFALWK 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 442 DFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSlHSQQNLMTISNLGVIFGPTLM---RAQEETVAAMM 518
Cdd:cd04382   95 EFMEAAEILDEDNSRAALYQAISELPQPNRDTLAFLILHLQRVA-QSPECKMDINNLARVFGPTIVgysVPNPDPMTILQ 173

                        170
                 ....*....|....
gi 198278482 519 NIKFQNIVVEILIE 532
Cdd:cd04382  174 DTVRQPRVVERLLE 187

RhoGAP-p50rhoGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p50RhoGAP-like proteins; p50RhoGAP, also known as RhoGAP-1, contains a C-terminal RhoGAP domain and an N-terminal Sec14 domain which binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3). It is ubiquitously expressed and preferentially active on Cdc42. This subgroup also contains closely related ARHGAP8. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 364 VRKCIQAVEMRGITILGLYRIGG---VNSKVQKLMNTtfspksppDMDIDIELWDNKTITSG-LKNYLRCLAEPLMTYKL 439
Cdd:cd04404   27 VRETVEYLQAHALTTEGIFRRSAntqVVKEVQQKYNM--------GEPVDFDQYEDVHLPAViLKTFLRELPEPLLTFDL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 440 HkDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRA--QEETVAAM 517
Cdd:cd04404   99 Y-DDIVGFLNVDKEERVERVKQLLQTLPEENYQVLKYLIKFLVQVSAHSDQNKMTNSNLAVVFGPNLLWAkdASMSLSAI 177

                        170       180
                 ....*....|....*....|.
gi 198278482 518 MNIkfqNIVVEILIEHYEKIF 538
Cdd:cd04404  178 NPI---NTFTKFLLDHQDEIF 195

RhoGAP_GMIP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of GMIP (Gem interacting protein) and PARG1 (PTPL1-associated RhoGAP1). GMIP plays important roles in neurite growth and axonal guidance, and interacts with Gem, a member of the RGK subfamily of the Ras small GTPase superfamily, through the N-terminal half of the protein. GMIP contains a C-terminal RhoGAP domain. GMIP inhibits RhoA function, but is inactive towards Rac1 and Cdc41. PARG1 interacts with Rap2, also a member of the Ras small GTPase superfamily whose exact function is unknown, and shows strong preference for Rho. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 364 VRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNT--------TFSPKSPPDmdidielwdnktITSGLKNYLRCLAEPLM 435
Cdd:cd04378   20 IKKCTSEIENRALGVQGIYRVSGSKARVEKLCQAfengkdlvELSELSPHD------------ISSVLKLFLRQLPEPLI 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 436 TYKLHKDFIIAVK--------------SDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVI 501
Cdd:cd04378   88 LFRLYNDFIALAKeiqrdteedkapntPIEVNRIIRKLKDLLRQLPASNYNTLQHLIAHLYRVAEQFEENKMSPNNLGIV 167

                        170       180       190
                 ....*....|....*....|....*....|....*.
gi 198278482 502 FGPTLMR----AQEETVAAMMNIKFQNIVVEILIEH 533
Cdd:cd04378  168 FGPTLIRprpgDADVSLSSLVDYGYQARLVEFLITN 203

RhoGAP_CdGAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of CdGAP-like proteins; CdGAP contains an N-terminal RhoGAP domain and a C-terminal proline-rich region, and it is active on both Cdc42 and Rac1 but not RhoA. CdGAP is recruited to focal adhesions via the interaction with the scaffold protein actopaxin (alpha-parvin). Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 351 KEEMYLNeAGFNF---VRKCIQAVEMRGItILGLYRIGGVNSKVQKLmNTTFSPKSPPDMDIDIELWDNKTITSGLKNYL 427
Cdd:cd04384    7 LTEHLLN-SGQDVpqvLKSCTEFIEKHGI-VDGIYRLSGIASNIQRL-RHEFDSEQIPDLTKDVYIQDIHSVSSLCKLYF 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 428 RCLAEPLMTYKLHKDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLM 507
Cdd:cd04384   84 RELPNPLLTYQLYEKFSEAVSAASDEERLEKIHDVIQQLPPPHYRTLEFLMRHLSRLAKYCSITNMHAKNLAIVWAPNLL 163

                        170       180       190
                 ....*....|....*....|....*....|..
gi 198278482 508 RAQE------ETVAAMMNIKFQNIVVEILIEH 533
Cdd:cd04384  164 RSKQiesacfSGTAAFMEVRIQSVVVEFILNH 195

RhoGAP_p190: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of p190-like proteins. p190, also named RhoGAP5, plays a role in neuritogenesis and axon branch stability. p190 shows a preference for Rho, over Rac and Cdc42, and consists of an N-terminal GTPase domain and a C-terminal GAP domain. The central portion of p190 contains important regulatory phosphorylation sites. Small GTPases cluster into distinct families, and all act as molecular switches, active in their GTP-bound form but inactive when GDP-bound. The Rho family of GTPases activates effectors involved in a wide variety of developmental processes, including regulation of cytoskeleton formation, cell proliferation and the JNK signaling pathway. GTPases generally have a low intrinsic GTPase hydrolytic activity but there are family-specific groups of GAPs that enhance the rate of GTP hydrolysis by several orders of magnitude.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 363 FVRKCIQAVEMRGITILGLYRIGGVNSKVQKLMNttfspKSPPDMDIDIELWDN--KTITSGLKNYLRCLAEPLMTYKLH 440
Cdd:cd04373   18 FLEKCVEFIEATGLETEGIYRVSGNKTHLDSLQK-----QFDQDHNLDLVSKDFtvNAVAGALKSFFSELPDPLIPYSMH 92

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198278482 441 KDFIIAVKSDDQNYRVEAVHALVHKLPEKNREMLDILIKHLLKVSLHSQQNLMTISNLGVIFGPTLMRAQEETVAAMMNI 520
Cdd:cd04373   93 LELVEAAKINDREQRLHALKELLKKFPPENFDVFKYVITHLNKVSQNSKVNLMTSENLSICFWPTLMRPDFTSMEALSAT 172

                        170
                 ....*....|.
gi 198278482 521 KFQNIVVEILI 531
Cdd:cd04373  173 RIYQTIIETFI 183

Src Homology 3 domain of GTPase Regulator Associated with Focal adhesion kinase; GRAF, also called Rho GTPase activating protein 26 (ARHGAP26), Oligophrenin-1-like (OPHN1L) or GRAF1, 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. It is essential for the major clathrin-independent endocytic pathway mediated by pleiomorphic membranes. GRAF contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, a Rho GAP domain, and a C-terminal SH3 domain. The SH3 domain of GRAF binds PKNbeta, a target of the small GTPase Rho. SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of signal pathway components and mediate multiprotein complex assemblies.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 198278482 786 RQAQAMYSCKAEHSHELSFPQGAIFSNVHPSVEPGWLKATYEGRTGLVPENYVVFL 841
Cdd:cd12064    1 RKAKALYACKAEHDSELSFTAGTVFDNVHPSQEPGWLEGTLNGKTGLIPENYVEFL 56