C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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 1982469649   61 GQLKLSIEVRGRTLVLHVMEAKGLMGSECRACDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 140
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1982469649  141 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 180
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIVN-QKEISGWYYL 119

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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 1982469649   61 GQLKLSIEVRGRTLVLHVMEAKGLMGSECRACDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 140
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1982469649  141 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 180
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIVN-QKEISGWYYL 119

Regulator of G protein signalling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   881 SLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENL 960
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100       110
                    ....*....|....*....|....*....|....*..
gi 1982469649   961 QN--ITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:smart00315   81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLR 117

C2 domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   73 TLVLHVMEAKGLMGSE-CRACDSYVKMSIVpdaDWKCRQKTKTVPDSKNPVFHEHFVFPVQEEdEQKRLLVTVWNRERNS 151
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDgNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                           90       100
                   ....*....|....*....|....*....
gi 1982469649  152 RqSELIGCMSFGVKSLLSlDKEISGWYYL 180
Cdd:pfam00168   78 R-DDFIGEVRIPLSELDS-GEGLDGWYPL 104

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 1982469649   222 KQLKITIPRGSDGFGFTIC----CDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEIILL 297
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                    ...
gi 1982469649   298 VWR 300
Cdd:smart00228   81 VLR 83

Periplasmic serine protease, S1-C subfamily, contain C-terminal PDZ domain [Posttranslational modification, protein turnover, chaperones];

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1982469649  245 VRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKcvELAHEIRNCP--TEIILLVWR 300
Cdd:COG0265    203 VLVARVEPGSPAAKAGLRPGDVILAVDGKPVTSAR--DLQRLLASLKpgDTVTLTVLR 258

periplasmic serine protease, Do/DeqQ family; This family consists of a set proteins various designated DegP, heat shock protein HtrA, and protease DO. The ortholog in Pseudomonas aeruginosa is designated MucD and is found in an operon that controls mucoid phenotype. This family also includes the DegQ (HhoA) paralog in E. coli which can rescue a DegP mutant, but not the smaller DegS paralog, which cannot. Members of this family are located in the periplasm and have separable functions as both protease and chaperone. Members have a trypsin domain and two copies of a PDZ domain. This protein protects bacteria from thermal and other stresses and may be important for the survival of bacterial pathogens.// The chaperone function is dominant at low temperatures, whereas the proteolytic activity is turned on at elevated temperatures. [Protein fate, Protein folding and stabilization, Protein fate, Degradation of proteins, peptides, and glycopeptides]

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1982469649  247 VQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKcvELAHEIRNCP--TEIILLVWR 300
Cdd:TIGR02037  261 VAQVLPGSPAEKAGLKAGDVITSVNGKPISSFA--DLRRAIGTLKpgKKVTLGILR 314

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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 1982469649   61 GQLKLSIEVRGRTLVLHVMEAKGLMGSECRACDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 140
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1982469649  141 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 180
Cdd:cd08685     81 LVTVWNKLSKSRDSGLLGCMSFGVKSIVN-QKEISGWYYL 119

Regulator of G protein signaling (RGS) domain found in the RGS8 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS8 protein. RGS8 is a member of R4/RGS subfamily of RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS8 is involved in G-protein-gated potassium channels regulation and predominantly expressed in the brain. RGS8 also is selectively expressed in the hematopoietic system (NK cells).

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  871 TPEEALKWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDS 950
Cdd:cd08711      1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1982469649  951 YTREHTKENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08711     81 QTREATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMYLD 125

Regulator of G protein signaling (RGS) domain found in the RGS5 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS5 protein. RGS5 is member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Two splice isoforms of RGS5 has been found: RGS5L (long) which is expressed in smooth muscle cells (pericytes) and heart and RGS5S (short) which is highly expressed in the ciliary body of the eye, kidney, brain, spleen, skeletal muscle, and small intestine. Outside of the GPCR pathway, RGS5 interacts with the 14-3-3 protein.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  882 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 961
Cdd:cd08717      1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLV 80

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1982469649  962 NITRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 993
Cdd:cd08717     81 EPSSSSFDLAQKRIFALMEKDSLPRFVRSEFY 112

Regulator of G protein signaling (RGS) domain found in the RGS16 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS16 protein. RGS16 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS16 is a member of the R4/RGS subfamily and interacts with neuronal G-alpha0. RGS16 expression is upregulated by IL-17 of the NF-kappaB signaling pathway in autoimmune B cells.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  882 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 961
Cdd:cd08710      1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIRSATKLASRAHHIFEEFIRSEAPKEVNIDHETRELTRTNLQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1982469649  962 NITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08710     81 AATTSCFDVAQGKTRTLMEKDSYPRFLKSPAYRD 114

Regulator of G protein signaling (RGS) domain found in the RGS18 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS18 protein. RGS18 is a member of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS18 is a member of the R4/RGS subfamily and is expressed predominantly in osteoclasts where it acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway. RANKL (receptor activator of nuclear factor B ligand) stimulates osteoclastogenesis by inhibiting expression of RGS18.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  882 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 961
Cdd:cd08712      1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1982469649  962 NITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08712     81 QPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIYLD 114

Regulator of G protein signaling (RGS) domain superfamily; The RGS domain is an essential part of the Regulator of G-protein Signaling (RGS) protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. While inactive, G-alpha-subunits bind GDP, which is released and replaced by GTP upon agonist activation. GTP binding leads to dissociation of the alpha-subunit and the beta-gamma-dimer, allowing them to interact with effectors molecules and propagate signaling cascades associated with cellular growth, survival, migration, and invasion. Deactivation of the G-protein signaling controlled by the RGS domain accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in the reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins are also involved in apoptosis and cell proliferation, as well as modulation of cardiac development. Several RGS proteins can fine-tune immune responses, while others play important roles in neuronal signals modulation. Some RGS proteins are principal elements needed for proper vision.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  886 LLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIK-SQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQN-- 962
Cdd:cd07440      1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTsSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEpy 80

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1982469649  963 ITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd07440     81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RZ protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling is controlled by RGS domains, which accelerate GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, which results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The RZ subfamily of RGS proteins includes RGS17, RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  878 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTK 957
Cdd:cd08718      1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKKEANKHVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1982469649  958 ENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 993
Cdd:cd08718     81 RNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIY 116

Regulator of G protein signaling (RGS) domain found in the RGS1 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS1 protein. RGS1 is a member of the R4/RGS subfamily of the RGS family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha subunits. The RGS domain controls G-protein signaling by accelerating the GTPase activity of the G-alpha subunit which leads to G protein deactivation and promotes desensitization. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS 1 is expressed predominantly in hematopoietic compartments, including T and B lymphocytes, and may play a major role in chemokine-mediated homing of lymphocytes to secondary lymphoid organs. In addition, RGS1 interacts with calmodulin and 14-3-3 protein outside of the GPCR pathway.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  882 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQsKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 961
Cdd:cd08715      1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD-LLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIK 79

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1982469649  962 NITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLDI 996
Cdd:cd08715     80 APTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 114

Regulator of G protein signaling (RGS) domain found in the R7 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R7 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R7 subfamily includes RGS6, RGS7, RGS9, and RGS11, all of which, in humans, are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes. In addition, R7 proteins were found to bind many other proteins outside of the G protein signaling pathways including: m-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, guanylyl cyclase, among others.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  877 KWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKiKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHT 956
Cdd:cd08705      4 RWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKY-GPQSQVPEKVQEIYQEFLAPGAPSWINIDSKTMEIT 82

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1982469649  957 KENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08705     83 LKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling (RGS) domain found in the R12 subfamily of proteins; The RGS (Regulator of G-protein Signaling) domain is an essential part of the R12 (Neuronal RGS) protein subfamily of the RGS protein family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RGS proteins play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of G-protein signaling, controlled by RGS domain, accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP that results in reassociation of the alpha-subunit with the beta-gamma-dimer and thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. The R12 RGS subfamily includes RGS10, RGS12 and RGS14 all of which are highly selective for G-alpha-i1 over G-alpha-q.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  882 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSyTREHTKENLQ 961
Cdd:cd08706      1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIPDKKQLVQEAREIYDTFLSSKASSPVNIDS-QAQLAEEMLE 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1982469649  962 NITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08706     80 EPHPDMFQKQQLQIFNLMKFDSYSRFLKSPLYQQ 113

Regulator of G protein signaling (RGS) domain found in the RGS17 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS17 protein, a member of the RZ subfamily of the RGS protein family. They are a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, the RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS proteins play critical regulatory roles as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP, results in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. The RZ subfamily of RGS proteins includes RGS19 (former GAIP), RGS20, and its splice variant Ret-RGS. RGS17 is a relatively non-selective GAP for G-alpha-z and other G-alpha-i/o proteins. RGS17 blocks dopamine receptor-mediated inhibition of cAMP accumulation; it also blocks thyrotropin releasing hormone-stimulated Ca++ mobilization. RGS17, like other members of RZ subfamily, can act either as a GAP or as G-protein effector antogonist.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  878 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTK 957
Cdd:cd08744      1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1982469649  958 ENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 993
Cdd:cd08744     81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIY 116

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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. Members here have a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   60 KGQLKLSIEVRGRTLVLHVMEAKGL--MGSECRAcDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQ 137
Cdd:cd04026      1 RGRIYLKISVKDNKLTVEVREAKNLipMDPNGLS-DPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1982469649  138 KRLLVTVWNRERNSRqSELIGCMSFGVKSLlsLDKEISGWYYLLGEDLGRTKH 190
Cdd:cd04026     80 RRLSIEVWDWDRTTR-NDFMGSLSFGVSEL--IKMPVDGWYKLLNQEEGEYYN 129

Regulator of G protein signaling (RGS) domain found in the RGS9 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS9 protein, a member of R7 subfamily of the RGS protein family. RGS is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. Other members of the R7 subfamily (Neuronal RGS) include: RGS6, RGS7, and RGS11, all of which are expressed predominantly in the nervous system, form an obligatory complex with G-beta-5, and play important roles in the regulation of crucial neuronal processes such as vision and motor control. Additionally they have been implicated in many neurological conditions such as anxiety, schizophrenia, and drug dependence. RGS9 forms constitutive complexes with G-beta-5 subunit and controls such fundamental functions as vision and behavior. RGS9 exists in two splice isoforms: RGS9-1 which regulates phototransduction in rods and cones and RGS9-2 which regulates dopamine and opioid signaling in the basal ganglia. In addition, RGS9 was found to bind many other proteins outside of G protein signaling pathways including: mu-opioid receptor, beta-arrestin, alpha-actinin-2, NMDAR, polycystin, spinophilin, and guanylyl cyclase, among others.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  877 KWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKkIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHT 956
Cdd:cd08739      4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLK-YGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMDIT 82

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1982469649  957 KENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 993
Cdd:cd08739     83 VKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIY 119

Regulator of G protein signaling (RGS) domain found in the RGS14 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS14 protein. RGS14 is a member of the RA/RGS subfamily of RGS proteins family, a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes such as regulation of intracellular trafficking, glial differentiation, embryonic axis formation, skeletal and muscle development, and cell migration during early embryogenesis. RGS14 belong to the R12 RGS subfamily, which includes RGS10 and RGS12, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS14 binds and regulates the subcellular localization and activities of H-Ras and Raf kinases in cells and thereby integrates G protein and Ras/Raf signaling pathways.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649  878 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQ--SKMVSKAKKIFAEYIAIQSCKEVNLDSYTReH 955
Cdd:cd08743      7 WAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASdtQQLAQEARKIYNEFLSSSSQSPVNIDQQAW-I 85

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1982469649  956 TKENLQNITRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 995
Cdd:cd08743     86 GEDMLATPSPDMFRAQQLQIFNLMKFDSYARFVKSPLYQD 125

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 1982469649   74 LVLHVMEAKGLMGSEC-RACDSYVKMSIVPdadwKCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQkRLLVTVWNRERNSR 152
Cdd:cd00030      1 LRVTVIEARNLPAKDLnGKSDPYVKVSLGG----KQKFKTKVVKNTLNPVWNETFEFPVLDPESD-TLTVEVWDKDRFSK 75

                           90       100
                   ....*....|....*....|....*...
gi 1982469649  153 QsELIGCMSFGVKSLLSLDKEISGWYYL 180
Cdd:cd00030     76 D-DFLGEVEIPLSELLDSGKEGELWLPL 102

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   60 KGQLKLSIEVRGRTLVLHVMEAKGLMGSECRACDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFV---FPVqEEDE 136
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVydgLPV-EDLQ 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1982469649  137 QKRLLVTVWNRERnSRQSELIGCMSFGVKSLLsLDKEISGWYYL 180
Cdd:cd08381     80 QRVLQVSVWSHDS-LVENEFLGGVCIPLKKLD-LSQETEKWYPL 121

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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. This cd contains the third C2 repeat, C2C, and has a type-II topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   59 GKGQLKLSIE---VRGRTLVLhVMEAKGLMG-SECRACDSYVKMSIVPDADWKCRQKTKTVPDSKNPVFHEHFVFPVQEE 134
Cdd:cd04030      1 PLGRIQLTIRyssQRQKLIVT-VHKCRNLPPcDSSDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLE 79

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1982469649  135 DEQKRLL-VTVWN-RERNSRQSELIGcmsfgvKSLLSLDKE-----ISGWYYL 180
Cdd:cd04030     80 ELKRRTLdVAVKNsKSFLSREKKLLG------QVLIDLSDLdlskgFTQWYDL 126

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   60 KGQLKLSI-----EVRGRTL-------VLHVM--EAKGLMGSECRAC-DSYVKMSIVPDADWKCRQKTKTVPDSKNPVFH 124
Cdd:cd04020      1 RGELKVALkyvppESEGALKskkpstgELHVWvkEAKNLPALKSGGTsDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1982469649  125 EHFVFP-VQEEDEQKRLL-VTVWNRERNSrQSELIGCMSFGVKSLLSL----------DKEISGW 177
Cdd:cd04020     81 HTFVYDgVSPEDLSQACLeLTVWDHDKLS-SNDFLGGVRLGLGTGKSYgqavdwmdstGEEILLW 144

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1982469649   61 GQLKLSIE--VRGRTLVLHVMEAKGLMG--SECRACDSYVKMSIVPDAdwKCRQKTKTVPDSKNPVFHEHFVFPVQEEDE 136
Cdd:cd08390      1 GRLWFSVQydLEEEQLTVSLIKARNLPPrtKDVAHCDPFVKVCLLPDE--RRSLQSKVKRKTQNPNFDETFVFQVSFKEL 78

                           90       100
                   ....*....|....*....|...
gi 1982469649  137 QKR-LLVTVWNRERNSRQSeLIG 158
Cdd:cd08390     79 QRRtLRLSVYDVDRFSRHC-IIG 100

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 1982469649   222 KQLKITIPRGSDGFGFTIC----CDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEIILL 297
Cdd:smart00228    1 EPRLVELEKGGGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                    ...
gi 1982469649   298 VWR 300
Cdd:smart00228   81 VLR 83

PDZ domain of DEP domain-containing mTOR-interacting protein (DEPTOR), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of DEPTOR, and related domains. DEPTOR (also known as DEP domain-containing protein 6, DEP6) is a regulatory protein of mTOR signaling; it is a negative regulator of both the mTORC1 and mTORC2 signaling pathways. DEPTOR's PDZ domain binds to mTOR's FAT domain to suppress mTOR's kinase activity. The DEPTOR PDZ domain also binds lysine-specific demethylase 4A (KDM4A), leucine-rich repeat containing 4 (LRRC4), p38gamma, and major intrinsically disordered Notch2-binding receptor 1 (MINAR1, also known as Ubtor). DEPTOR also interacts with salt-inducible kinase 3 (SIK3). 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 DEPTOR-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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1982469649  226 ITIPRGSDGFGFTICCDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEIILLV 298
Cdd:cd23067      2 LTIVGDAVGWGFVVRGSKPCHIQAVDPSGPAAAAGMKVCQFIVSVNGLNVLHMDHRTVSNLILTGPRTIVMEV 74