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 2006339209  56 GQLKLSIEVRGRTLVLHVMEAKGLMGTECRECDSYVKMSIVPDADRRCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 135
Cdd:cd08685     1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2006339209 136 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 175
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 2006339209  56 GQLKLSIEVRGRTLVLHVMEAKGLMGTECRECDSYVKMSIVPDADRRCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 135
Cdd:cd08685     1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2006339209 136 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 175
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 2006339209  874 SLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENL 953
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 2006339209  954 QN--VTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
Cdd:smart00315  81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLR 117

C2 domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2006339209  68 TLVLHVMEAKGLMGTE-CRECDSYVKMSIVpdaDRRCRQKTKTVPDSKNPVFHEHFVFPVQEEdEQKRLLVTVWNRERNS 146
Cdd:pfam00168   2 RLTVTVIEAKNLPPKDgNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDP-ENAVLEIEVYDYDRFG 77

                          90       100
                  ....*....|....*....|....*....
gi 2006339209 147 RqSELIGCMSFGVKSLLSlDKEISGWYYL 175
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 2006339209  217 QQLKITIPRGTDGFGFTIC----CDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEIILL 292
Cdd:smart00228   1 EPRLVELEKGGGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLT 80

                   ...
gi 2006339209  293 VWR 295
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 2006339209 240 VRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKcvELAHEIRNCP--TEIILLVWR 295
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 2006339209 242 VQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKcvELAHEIRNCP--TEIILLVWR 295
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 2006339209  56 GQLKLSIEVRGRTLVLHVMEAKGLMGTECRECDSYVKMSIVPDADRRCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQKRL 135
Cdd:cd08685     1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2006339209 136 LVTVWNRERNSRQSELIGCMSFGVKSLLSlDKEISGWYYL 175
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 2006339209 864 TPEEALKWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDS 943
Cdd:cd08711     1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2006339209 944 YTREHTKENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 954
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLV 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 2006339209 955 NVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 986
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 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 954
Cdd:cd08710     1 FDLLLNSKNGVAAFHAFLKTEFSEENLEFWLACEEFKKIRSATKLASRAHHIFEEFIRSEAPKEVNIDHETRELTRTNLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2006339209 955 NVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 954
Cdd:cd08712     1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2006339209 955 NVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 879 LLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIK-SQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQN-- 955
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTsSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEpy 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2006339209 956 VTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 871 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTK 950
Cdd:cd08718     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKKEANKHVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2006339209 951 ENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 986
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 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQsKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 954
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD-LLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIK 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2006339209 955 NVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLDI 989
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 2006339209 870 KWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKiKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHT 949
Cdd:cd08705     4 RWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKY-GPQSQVPEKVQEIYQEFLAPGAPSWINIDSKTMEIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2006339209 950 KENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSyTREHTKENLQ 954
Cdd:cd08706     1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIPDKKQLVQEAREIYDTFLSSKASSPVNIDS-QAQLAEEMLE 79

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2006339209 955 NVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209 871 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHTK 950
Cdd:cd08744     1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKVIEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2006339209 951 ENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 986
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 2006339209  55 KGQLKLSIEVRGRTLVLHVMEAKGL--MGTECREcDSYVKMSIVPDADRRCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQ 132
Cdd:cd04026     1 RGRIYLKISVKDNKLTVEVREAKNLipMDPNGLS-DPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2006339209 133 KRLLVTVWNRERNSRqSELIGCMSFGVKSLlsLDKEISGWYYLLGQDLGRTKH 185
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 2006339209 870 KWGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKkIKSQSKMVSKAKKIFAEYIAIQSCKEVNLDSYTREHT 949
Cdd:cd08739     4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLK-YGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMDIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 2006339209 950 KENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLY 986
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 2006339209 871 WGDSLEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQ--SKMVSKAKKIFAEYIAIQSCKEVNLDSYTReH 948
Cdd:cd08743     7 WAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIPASdtQQLAQEARKIYNEFLSSSSQSPVNIDQQAW-I 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2006339209 949 TKENLQNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYLD 988
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 2006339209  69 LVLHVMEAKGLMGTECRE-CDSYVKMSIvpdaDRRCRQKTKTVPDSKNPVFHEHFVFPVQEEDEQkRLLVTVWNRERNSR 147
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGkSDPYVKVSL----GGKQKFKTKVVKNTLNPVWNETFEFPVLDPESD-TLTVEVWDKDRFSK 75

                          90       100
                  ....*....|....*....|....*...
gi 2006339209 148 QsELIGCMSFGVKSLLSLDKEISGWYYL 175
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 2006339209  55 KGQLKLSIEVRGRTLVLHVMEAKGLMGTECRECDSYVKMSIVPDADRRCRQKTKTVPDSKNPVFHEHFV---FPVqEEDE 131
Cdd:cd08381     1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVydgLPV-EDLQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2006339209 132 QKRLLVTVWNRERnSRQSELIGCMSFGVKSLLsLDKEISGWYYL 175
Cdd:cd08381    80 QRVLQVSVWSHDS-LVENEFLGGVCIPLKKLD-LSQETEKWYPL 121

Regulator of G protein signaling (RGS) domain found in the Axin protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the Axin protein. Axin is a member of the RA/RGS 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. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, and skeletal and muscle development. The RGS domain of Axin is specifically interacts with the heterotrimeric G-alpha12 protein, but not with closely related G-alpha13, and provides a unique tool to regulate G-alpha12-mediated signaling processes. The RGS domain of Axin also interacts with the tumor suppressor protein APC (Adenomatous Polyposis Coli) in order to control the cytoplasmic level of the proto-oncogene, beta-catenin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2006339209 875 LEKLLLHKYGLAAFRAFLRTEFSEENLEFWLACEEFKKIKSQSKMVSK-AKKIFAEYIAIQSCKEVNLDSYTREHTKENL 953
Cdd:cd08707     1 LHSLLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMSDSEEKRSKlAKAIYRRYIKDNGIVSRQLKPATKSFIKECI 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2006339209 954 --QNVTRSCFDLAQKRIYGLMEKDSYPRFLRSDLYL 987
Cdd:cd08707    81 kkQQLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYL 116

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 2006339209  55 KGQLKLSI-----EVRGRTL-------VLHVM--EAKGLMGTECREC-DSYVKMSIVPDADRRCRQKTKTVPDSKNPVFH 119
Cdd:cd04020     1 RGELKVALkyvppESEGALKskkpstgELHVWvkEAKNLPALKSGGTsDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2006339209 120 EHFVFP-VQEEDEQKRLL-VTVWNRERNSrQSELIGCMSFGVKSLLSL----------DKEISGW 172
Cdd:cd04020    81 HTFVYDgVSPEDLSQACLeLTVWDHDKLS-SNDFLGGVRLGLGTGKSYgqavdwmdstGEEILLW 144

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 2006339209 220 KITIPRG-TDGFGFTIC----CDSPVRVQAVDSGGPAEKAG-LQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEIILLV 293
Cdd:cd00136     1 TVTLEKDpGGGLGFSIRggkdGGGGIFVSRVEPGGPAARDGrLRVGDRILEVNGVSLEGLTHEEAVELLKSAGGEVTLTV 80

PDZ domain of rhophilin-1, rhophilin-2, and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain of rhophilin-1, rhophilin-2, and related domains. Rhophilin-1 (RHPN1, also known as GTP-Rho-binding protein 1) and rhophilin-2 (RHPN2, also known as GTP-Rho-binding protein 2) are Rho-GTP binding proteins involved in cytoskeletal dynamics. Rhophilin-2 inhibits RhoA's activity to induce F-actin stress fibers. 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 rhophilin-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 2006339209 220 KITIPRGTDGFGFTICCDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPVEHWKCVELAHEIRNCPTEII 290
Cdd:cd06712     3 TVHLTKEEGGFGFTLRGDSPVQVASVDPGSCAAEAGLKEGDYIVSVGGVDCKWSKHSEVVKLLKSAGEEGL 73

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. 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 delphilin-like family PDZ2 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 2006339209 221 ITIPRGTDGFGFTICCDSPVRVQAVDSGGPAEKAGLQQLDTVLQLNEQPV---EHWKCVELAHEIRNCPT 287
Cdd:cd06744     2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGLDVrncSHDKVVSLLQGSGSMPT 71