RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 71988418 753 FGISLSRLVQRE--RRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIPDTNVIACLI 830
Cdd:cd04379   1 FGVPLSRLVEREgeSRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 831 KDFLRELPEPLISPQIHGMLLEAASVALPNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSL 910
Cdd:cd04379  81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 71988418 911 IFAPLLFFCLDTFSPYTISPTSKMAAVRTLDINQASSSLQMILSIWP 957
Cdd:cd04379 161 CFGPVLMFCSQEFSRYGISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418    617 ILYVHIVEGRGLKIpeKQKGLTEEMYCVLEVDEQ--HRARTGVSTIEQKFKWRETFHIDVVNATVSN--FFVYSWHPQFR 692
Cdd:smart00239   1 TLTVKIISARNLPP--KDKGGKSDPYVKVSLDGDpkEKKKTKVVKNTLNPVWNETFEFEVPPPELAEleIEVYDKDRFGR 78

                           90
                   ....*....|...
gi 71988418    693 HKLCHKGSLKLLE 705
Cdd:smart00239  79 DDFIGQVTIPLSD 91

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 71988418 753 FGISLSRLVQRE--RRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIPDTNVIACLI 830
Cdd:cd04379   1 FGVPLSRLVEREgeSRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 831 KDFLRELPEPLISPQIHGMLLEAASVALPNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSL 910
Cdd:cd04379  81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 71988418 911 IFAPLLFFCLDTFSPYTISPTSKMAAVRTLDINQASSSLQMILSIWP 957
Cdd:cd04379 161 CFGPVLMFCSQEFSRYGISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 122 QLVEIIKKPGQSLGLYLREGNGKDRSDGVFVSRFGDNSeLAKYGEVMRPGDEILTINNVEVSMMSIDDVVLILSIPRRLL 201
Cdd:cd06718   1 RRVELIKPPGKPLGFYIRDGNGVERVPGIFISRLVLGS-LADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMVAPTRLI 79

                ....*
gi 71988418 202 LRIRY 206
Cdd:cd06718  80 ITVKP 84

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418    122 QLVEIIKKPGQsLGLYLREGngKDRSDGVFVSRFGDNSELAKYGevMRPGDEILTINNVEVSMMSIDDVVLIL-SIPRRL 200
Cdd:smart00228   3 RLVELEKGGGG-LGFSLVGG--KDEGGGVVVSSVVPGSPAAKAG--LRVGDVILEVNGTSVEGLTHLEAVDLLkKAGGKV 77

                   ....*...
gi 71988418    201 LLRIRYSK 208
Cdd:smart00228  78 TLTVLRGG 85

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 618 LYVHIVEGRGLKIPEKQKglTEEMYCVLEVDEQHRARTGVSTIEQKFKWRETFHIDVVNATVSN--FFVYSWHPQFRHKL 695
Cdd:cd00030   1 LRVTVIEARNLPAKDLNG--KSDPYVKVSLGGKQKFKTKVVKNTLNPVWNETFEFPVLDPESDTltVEVWDKDRFSKDDF 78

C-terminal processing protease CtpA/Prc, contains a PDZ domain [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71988418 134 LGLYLREGNGKdrsdgVFVSRFGDNSELAKYGevMRPGDEILTINNVEVSMMSIDDVVLIL 194
Cdd:COG0793  62 LGAELGEEDGK-----VVVVSVIPGSPAEKAG--IKPGDIILAIDGKSVAGLTLDDAVKLL 115

RhoGAP_SYD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in SYD-1_like proteins. Syd-1, first identified and best studied in C.elegans, has been shown to play an important role in neuronal development by specifying axonal properties. 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 71988418 753 FGISLSRLVQRE--RRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIPDTNVIACLI 830
Cdd:cd04379   1 FGVPLSRLVEREgeSRDVPIVLQKCVQEIERRGLDVIGLYRLCGSAAKKKELRDAFERNSAAVELSEELYPDINVITGVL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 831 KDFLRELPEPLISPQIHGMLLEAASVALPNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSL 910
Cdd:cd04379  81 KDYLRELPEPLITPQLYEMVLEALAVALPNDVQTNTHLTLSIIDCLPLSAKATLLLLLDHLSLVLSNSERNKMTPQNLAV 160

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 71988418 911 IFAPLLFFCLDTFSPYTISPTSKMAAVRTLDINQASSSLQMILSIWP 957
Cdd:cd04379 161 CFGPVLMFCSQEFSRYGISPTSKMAAVSTVDFKQHIEVLHYLLQIWP 207

PDZ domain of partitioning defective 6 (Par6), Drosophila Rho GTPase-activating protein 100F (RhoGAP100F), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of Par6 (also known as PAR6 or Par-6), RhoGAP100F, and related domains. Par6 is part of a conserved machinery that directs metazoan cell polarity, a process necessary for the function of diverse cell types. Par6 forms a cell polarity-regulatory complex with atypical protein kinase C (aPKC) and Par3. Par6 can also directly associate with PALS1 (proteins associated with Lin7, also known as Stardust) providing a link between the Par3/aPKC/Par6 complex and the PALS1-PATJ (protein-associated TJ) complex. Binding partners of the Par6-PDZ domain include Par3, PALS1/Stardust; leucine-rich repeat-containing protein netrin-G ligand-2 (NGL-2), human crumbs (CRB3) involve in the morphogenesis of the tight junctions in mammalian epithelial cells, and PAR-6 co-operates with the Par6 semi-CRIB domain to bind CDC42. CDC42 regulates the Par6 PDZ domain through an allosteric CRIB-PDZ transition. Drosophila RhoGAP100F, also known as synapse defective protein 1 homolog (syd-1 homolog), is a GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound form. The RhoGAP100F-PDZ domain binds the neurexin C terminus to control synapse formation at the Drosophila neuromuscular junction. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This Par6-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 122 QLVEIIKKPGQSLGLYLREGNGKDRSDGVFVSRFGDNSeLAKYGEVMRPGDEILTINNVEVSMMSIDDVVLILSIPRRLL 201
Cdd:cd06718   1 RRVELIKPPGKPLGFYIRDGNGVERVPGIFISRLVLGS-LADSTGLLAVGDEILEVNGVEVTGKSLDDVTDMMVAPTRLI 79

                ....*
gi 71988418 202 LRIRY 206
Cdd:cd06718  80 ITVKP 84

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 71988418 769 PIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESnplGTELAAESIPDTNVIACLIKDFLRELPEPLISPQIHG 848
Cdd:cd00159   1 PLIIEKCIEYLEKNGLNTEGIFRVSGSASKIEELKKKFDR---GEDIDDLEDYDVHDVASLLKLYLRELPEPLIPFELYD 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 849 MLLEAASValpNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIFAPLLFFCLDTFSPYTI 928
Cdd:cd00159  78 EFIELAKI---EDEEERIEALKELLKSLPPENRDLLKYLLKLLHKISQNSEVNKMTASNLAIVFAPTLLRPPDSDDELLE 154

                       170
                ....*....|....*
gi 71988418 929 SPTSKMAAVRTLDIN 943
Cdd:cd00159 155 DIKKLNEIVEFLIEN 169

RhoGAP_myosin_IXB: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXB. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons 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 71988418 753 FGISLSRLVQrERRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELaaESIPdTNVIACLIKD 832
Cdd:cd04407   1 FGVRVGSLTS-NKTSVPIVLEKLLEHVEMHGLYTEGIYRKSGSANRMKELHQLLQADPENVKL--ENYP-IHAITGLLKQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 833 FLRELPEPLISPQIHGMLLEAasVALPnDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIF 912
Cdd:cd04407  77 WLRELPEPLMTFAQYNDFLRA--VELP-EKQEQLQAIYRVLEQLPTANHNTLERLIFHLVKVALEEDVNRMSPNALAIVF 153

                       170
                ....*....|....*
gi 71988418 913 APLLFFCLDTFSPYT 927
Cdd:cd04407 154 APCLLRCPDSSDPLT 168

RhoGAP_fRGD1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of fungal RGD1-like proteins. Yeast Rgd1 is a GAP protein for Rho3 and Rho4 and plays a role in low-pH response. 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 71988418 753 FGISLSRLVQRERRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTEL--AAESIPDTNVIACLI 830
Cdd:cd04398   1 FGVPLEDLILREGDNVPNIVYQCIQAIENFGLNLEGIYRLSGNVSRVNKLKELFDKDPLNVLLisPEDYESDIHSVASLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 831 KDFLRELPEPLISPQIHGMLLEAASValpNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSL 910
Cdd:cd04398  81 KLFFRELPEPLLTKALSREFIEAAKI---EDESRRRDALHGLINDLPDANYATLRALMFHLARIKEHESVNRMSVNNLAI 157

                ....*..
gi 71988418 911 IFAPLLF 917
Cdd:cd04398 158 IWGPTLM 164

RhoGAP_myosin_IXA: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in myosins IXA. Class IX myosins contain a characteristic head domain, a neck domain and a tail domain which contains a C6H2-zinc binding motif and a Rho-GAP domain. Class IX myosins are single-headed, processive myosins that are partly cytoplasmic, and partly associated with membranes and the actin cytoskeleton. Class IX myosins are implicated in the regulation of neuronal morphogenesis and function of sensory systems, like the inner ear. There are two major isoforms, myosin IXA and IXB with several splice variants, which are both expressed in developing neurons. 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 71988418 753 FGISLSRLVQRERrDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIpdtNVIACLIKD 832
Cdd:cd04406   1 FGVELSRLTSEDR-SVPLVVEKLINYIEMHGLYTEGIYRKSGSTNKIKELRQGLDTDANSVNLDDYNI---HVIASVFKQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 833 FLRELPEPLISPQIHGMLLEAASValpNDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIF 912
Cdd:cd04406  77 WLRDLPNPLMTFELYEEFLRAMGL---QERRETVRGVYSVIDQLSRTHLNTLERLIFHLVRIALQEETNRMSANALAIVF 153

                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 71988418 913 APLLFFCLDTFSPytisptskMAAVRtlDINQASSSLQMIL 953
Cdd:cd04406 154 APCILRCPDTTDP--------LQSVQ--DISKTTTCVELIV 184

RhoGAP_ARAP: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in ARAPs. ARAPs (also known as centaurin deltas) contain, besides the RhoGAP domain, an Arf GAP, ankyrin repeat ras-associating, and PH domains. Since their ArfGAP activity is PIP3-dependent, ARAPs are considered integration points for phosphoinositide, Arf and Rho signaling. 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 71988418 762 QRERRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTEL--AAESIPDtnvIACLIKDFLRELPE 839
Cdd:cd04385   9 QLTDNDIPVIVDKCIDFITQHGLMSEGIYRKNGKNSSVKKLLEAFRKDARSVQLreGEYTVHD---VADVLKRFLRDLPD 85

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71988418 840 PLISPQIHGMLLEAASVALPND-VQTNRHLvlkiIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIFAPLLF 917
Cdd:cd04385  86 PLLTSELHAEWIEAAELENKDErIARYKEL----IRRLPPINRATLKVLIGHLYRVQKHSDENQMSVHNLALVFGPTLF 160

RhoGAP_Bcr: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of Bcr (breakpoint cluster region protein)-like proteins. Bcr is a multidomain protein with a variety of enzymatic functions. It contains a RhoGAP and a Rho GEF domain, a Ser/Thr kinase domain, an N-terminal oligomerization domain, and a C-terminal PDZ binding domain, in addition to PH and C2 domains. Bcr is a negative regulator of: i) RacGTPase, via the Rho GAP domain, ii) the Ras-Raf-MEK-ERK pathway, via phosphorylation of the Ras binding protein AF-6, and iii) the Wnt signaling pathway through binding beta-catenin. Bcr can form a complex with beta-catenin and Tcf1. The Wnt signaling pathway is involved in cell proliferation, differentiation, and cell renewal. Bcr was discovered as a fusion partner of Abl. The Bcr-Abl fusion is characteristic for a large majority of chronic myelogenous leukemias (CML). 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 71988418 753 FGISLSRLVQRERRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIpDTNVIACLIKD 832
Cdd:cd04387   1 FGVKISTVTKRERSKVPYIVRQCVEEVERRGMEEVGIYRISGVATDIQALKAAFDTNNKDVSVMLSEM-DVNAIAGTLKL 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 833 FLRELPEPLISPQIHGMLLEAASVAlpnDVQTNRHLVLKIIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIF 912
Cdd:cd04387  80 YFRELPEPLFTDELYPNFAEGIALS---DPVAKESCMLNLLLSLPDPNLVTFLFLLHHLKRVAEREEVNKMSLHNLATVF 156

                ....
gi 71988418 913 APLL 916
Cdd:cd04387 157 GPTL 160

RhoGAP-ARHGAP11A: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP11A-like proteins. The mouse homolog of human ArhGAP11A has been detected as a gene exclusively expressed in immature ganglion cells, potentially playing a role in retinal development. The exact function of ArhGAP11A is unknown. 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 71988418 752 VFGISLSRLVQR---ERRDTPIVLTRLIQEIEKRgVDYSGLYVLCGSVEKKKMLRAELESNplGTELAAESIPDtnvIAC 828
Cdd:cd04394   1 VFGVPLHSLPHStvpEYGNVPKFLVDACTFLLDH-LSTEGLFRKSGSVVRQKELKAKLEGG--EACLSSALPCD---VAG 74

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 829 LIKDFLRELPEPLISPQIHGMLLEAASvaLPNDVQTNRHLVLkiIDCLqLSAK--NCLLLVLDHLSTVLCSSPHNGLTPT 906
Cdd:cd04394  75 LLKQFFRELPEPLLPYDLHEALLKAQE--LPTDEERKSATLL--LTCL-LPDEhvNTLRYFFSFLYDVAQRCSENKMDSS 149

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 71988418 907 RLSLIFAPLLFFC---LDTFSPYTISPTSKMAAVRTLDINQAS 946
Cdd:cd04394 150 NLAVIFAPNLFQSeegGEKMSSSTEKRLRLQAAVVQTLIDNAS 192

RhoGAP_ARHGAP18: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of ArhGAP18-like proteins. The function of ArhGAP18 is unknown. 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 71988418 752 VFGISLSRLVQRERRDT-----PIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIpDTNVI 826
Cdd:cd04391   1 LFGVPLSTLLERDQKKVpgskvPLIFQKLINKLEERGLETEGILRIPGSAQRVKFLCQELEAKFYEGTFLWDQV-KQHDA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 827 ACLIKDFLRELPEPLISPQihgmLLEA--ASVALPNDVQTNRHLVLKIIdCLQLSAKNCLLLVLDHLSTVLCSSPHNGLT 904
Cdd:cd04391  80 ASLLKLFIRELPQPLLTVE----YLPAfySVQGLPSKKDQLQALNLLVL-LLPEANRDTLKALLEFLQKVVDHEEKNKMN 154

                       170
                ....*....|....*
gi 71988418 905 PTRLSLIFAPLLFFC 919
Cdd:cd04391 155 LWNVAMIMAPNLFPP 169

canonical PDZ domain; Canonical PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain. PDZ domains usually bind to short specific peptide sequences located at the C-terminal end of their partner proteins known as PDZ binding motifs. These domains can also interact with internal peptide motifs and certain lipids, and can take part in a head-to-tail oligomerization with other PDZ domains. The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. The canonical PDZ domain contains six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 123 LVEIIKKPGQSLGLYLREGngKDRSDGVFVSRFGDNSELAKYGeVMRPGDEILTINNVEVSMMSIDDVV-LILSIPRRLL 201
Cdd:cd00136   1 TVTLEKDPGGGLGFSIRGG--KDGGGGIFVSRVEPGGPAARDG-RLRVGDRILEVNGVSLEGLTHEEAVeLLKSAGGEVT 77

                ....
gi 71988418 202 LRIR 205
Cdd:cd00136  78 LTVR 81

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 71988418 752 VFGISLSRLVQRERRDTPIVLTRLIQEIEKRGVdYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIPDTNVIACLIK 831
Cdd:cd04384   2 VFGCDLTEHLLNSGQDVPQVLKSCTEFIEKHGI-VDGIYRLSGIASNIQRLRHEFDSEQIPDLTKDVYIQDIHSVSSLCK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 832 DFLRELPEPLISPQIHGMLLEAASVAlpndvqTNRHLVLKIIDCLQLSAK---NCLLLVLDHLSTVLCSSPHNGLTPTRL 908
Cdd:cd04384  81 LYFRELPNPLLTYQLYEKFSEAVSAA------SDEERLEKIHDVIQQLPPphyRTLEFLMRHLSRLAKYCSITNMHAKNL 154

                ....*....
gi 71988418 909 SLIFAPLLF 917
Cdd:cd04384 155 AIVWAPNLL 163

RhoGAP_p85: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain present in the p85 isoforms of the regulatory subunit of the class IA PI3K (phosphatidylinositol 3'-kinase). This domain is also called Bcr (breakpoint cluster region protein) homology (BH) domain. Class IA PI3Ks are heterodimers, containing a regulatory subunit (p85) and a catalytic subunit (p110) and are activated by growth factor receptor tyrosine kinases (RTKs); this activation is mediated by the p85 subunit. p85 isoforms, alpha and beta, contain a C-terminal p110-binding domain flanked by two SH2 domains, an N-terminal SH3 domain, and a RhoGAP domain flanked by two proline-rich regions. 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 71988418 769 PIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKmLRAELESNPLGTELaaESIpDTNVIACLIKDFLRELPEPLISPQIHG 848
Cdd:cd04388  16 PPLLIKLVEAIEKKGLESSTLYRTQSSSSLTE-LRQILDCDAASVDL--EQF-DVAALADALKRYLLDLPNPVIPAPVYS 91

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71988418 849 MLLEAASvalpnDVQTNR---HLVLKIIDCLQLSAKNCLLL--VLDHLSTVLCSSPHNGLTPTRLSLIFAPLLF 917
Cdd:cd04388  92 EMISRAQ-----EVQSSDeyaQLLRKLIRSPNLPHQYWLTLqyLLKHFFRLCQSSSKNLLSARALAEIFSPLLF 160

RhoGAP_PARG1: RhoGAP (GTPase-activator protein [GAP] for Rho-like small GTPases) domain of PARG1 (PTPL1-associated RhoGAP1). PARG1 was originally cloned as an interaction partner of PTPL1, an intracellular protein-tyrosine phosphatase. 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 71988418 753 FGISLSRLVQRERRDTPIVLTRLIQEIEKRGVDYSGLYVLCGSVEKKKMLRAELESnplGTELAAESIPDTNVIACLIKD 832
Cdd:cd04409   1 FGADFAQVAKKSPDGIPFIIKKCTSEIESRALCLKGIYRVNGAKSRVEKLCQAFEN---GKDLVELSELSPHDISNVLKL 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 833 FLRELPEPLISPQIHGMLLEAASVAL----------------PN-DVQTNRhLVLKIIDCL-QLSAKN--CLLLVLDHLS 892
Cdd:cd04409  78 YLRQLPEPLILFRLYNEFIGLAKESQhvnetqeakknsdkkwPNmCTELNR-ILLKSKDLLrQLPAPNynTLQFLIVHLH 156

                       170       180       190
                ....*....|....*....|....*....|....*..
gi 71988418 893 TVLCSSPHNGLTPTRLSLIFAPLLFFCLDTFSPYTIS 929
Cdd:cd04409 157 RVSEQAEENKMSASNLGIIFGPTLIRPRPTDATVSLS 193

PDZ domain of PDZ domain-containing protein 11, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of PDZD11, and related domains. PDZD11 (also known as ATPase-interacting PDZ protein, plasma membrane calcium ATPase-interacting single-PDZ protein, PMCA-interacting single-PDZ protein, PISP) is involved in the dynamic assembly of apical junctions (AJs). It is recruited by PLEKHA7 to AJs to promote the efficient junctional recruitment and stabilization of nectins, and the efficient early phases of assembly of AJs in epithelial cells. The PDZD11 PDZ domain binds nectin-1 and nectin-3. PDZD11 also binds to a PDZ binding motif located in the C-terminal tail of the human sodium-dependent multivitamin transporter, to the cytoplasmic tail of the Menkes copper ATPase ATP7A, and to the cytoplasmic tail of all plasma membrane Ca2+-ATPase b-splice variants. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This PDZD11-like family domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71988418 124 VEIIKKPGQSLGLYLRegNGKDRSDGVFVSRFGDNSELAKYGevMRPGDEILTINNVEVSMMSIDDVVLILSIPRRLLLR 203
Cdd:cd06752   3 VVLKRPPGEQLGFNIR--GGKASGLGIFISKVIPDSDAHRLG--LKEGDQILSVNGVDFEDIEHSEAVKVLKTAREIQMR 78

                ...
gi 71988418 204 IRY 206
Cdd:cd06752  79 VRY 81

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 71988418 779 IEKRGVDYSGLYVLCGSVEKKKMLRAELESNPLGTELAAESIPDTNVIACLIKDFLRELPEPLISPQIHGMLLEAASVAL 858
Cdd:cd04395  29 VEARGLETVGIYRVPGNNAAISALQEELNRGGFDIDLQDPRWRDVNVVSSLLKSFFRKLPEPLFTNELYPDFIEANRIED 108

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 71988418 859 PndvqTNRHLVLK-IIDCLQLSAKNCLLLVLDHLSTVLCSSPHNGLTPTRLSLIFAPLL 916
Cdd:cd04395 109 P----VERLKELRrLIHSLPDHHYETLKHLIRHLKTVADNSEVNKMEPRNLAIVFGPTL 163