Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 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). 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 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. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 474
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1191017958 475 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd08713    81 NPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 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). 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 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. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 474
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1191017958 475 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd08713    81 NPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

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 1191017958  394 SLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNL 473
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1191017958  474 QS--VTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 509
Cdd:smart00315  81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  25 SPPSKEPSPGQELPPGQDLPPNKDSPSGQEPAPSQePLSSKDSATSEGSPPGPDAPPSKDVPPCQEPPPAqdLSPCQDLP 104
Cdd:pfam03154 327 TPPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTT-PIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPA--LKPLSSLS 403

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191017958 105 AGQEPLPHQDPL-LTKDLPAIQESPTRD--LPPCQDLPPSQVSLPakaltedtmSSGDLLAATGDPPAAPRP 173
Cdd:pfam03154 404 THHPPSAHPPPLqLMPQSQQLPPPPAQPpvLTQSQSLPPPAASHP---------PTSGLHQVPSQSPFPQHP 466

Regulator of G protein signaling (RGS) domain found in the RGS3 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS3 protein. RGS3 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). 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 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. RGS3 induces apoptosis when overexpressed and is involved in cell migration through interaction with the Ephrin receptor. RGS3 exits as several splice isoforms and interacts with neuroligin, estrogen receptor-alpha, and 14-3-3 outside of the GPCR pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 474
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1191017958 475 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd08713    81 NPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

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 1191017958 384 TSEEALKWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDS 463
Cdd:cd08711     1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1191017958 464 YTREHTKDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
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 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 474
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNLV 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1191017958 475 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 506
Cdd:cd08717    81 EPSSSSFDLAQKRIFALMEKDSLPRFVRSEFY 112

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 1191017958  394 SLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNL 473
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1191017958  474 QS--VTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 509
Cdd:smart00315  81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

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 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ 474
Cdd:cd08712     1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1191017958 475 SVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
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 1191017958 399 LVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKK-VKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNLQ--S 475
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKtTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEepY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1191017958 476 VTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd07440    81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

Regulator of G protein signaling (RGS) domain found in the RGS20 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS20 protein (also known as RGSZ1), 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). 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 the RGS domain, which accelerates GTPase activity of the alpha subunit by hydrolysis of GTP to GDP resulting in reassociation of the alpha-subunit with the beta-gamma-dimer and inhibition of downstream activity. 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. The RZ subfamily of RGS proteins include RGS17, RGS19 (former GAIP), and the splice variant of RGS20, Ret-RGS. RGS20 is expressed exclusively in brain, with the highest concentrations in the temporal lobe and the caudate nucleus and may play a role in signaling regulation in these brain regions. RGS20 acts as a GAP of both G-alpha-z and G-alpha-I and controls signaling in the mu opioid receptor pathway.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 379 KSFKPTSEEALKWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKE 458
Cdd:cd08746    38 ESPKPTLEEVCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKKEANKSVIEEKARIIYEDYISILSPKE 117

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1191017958 459 VNLDSYTREHTKDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd08746   118 VSLDSRVREVINRNMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

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 1191017958 390 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVkSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 469
Cdd:cd08705     4 RWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYG-PQSQVPEKVQEIYQEFLAPGAPSWINIDSKTMEIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1191017958 470 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 508
Cdd:cd08705    83 LKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G protein signaling (RGS) domain found in the RGS19 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS19 protein (also known as GAIP), 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). 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, resulting in a reassociation of the alpha-subunit with the beta-gamma-dimer and an inhibition of downstream activity. 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. The RZ subfamily of RGS proteins includes RGS17, RGS20, and its splice variant Ret-RGS. RGS19 participates in regulation of dopamine receptor D2R and D3R, as well as beta-adrenergic receptors .

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 391 WGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTK 470
Cdd:cd08745     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKAEANKHVIDEKARLIYEDYISILSPKEVSLDSRVREGIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1191017958 471 DNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 506
Cdd:cd08745    81 RKMQEPSSHTFDDAQLQIYTLMHRDSYPRFLNSPIY 116

Regulator of G protein signaling (RGS) domain found in the RGS6 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS6 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). Other members of the R7 subfamily (Neuronal RGS) include: RGS7, RGS9, 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. RGS6 exists in multiple splice isoforms with identical RGS domains, but possess complete or incomplete GGL domains and distinct N- and C-terminal domains. RGS6 interacts with SCG10, a neuronal growth-associated protein and therefore regulates neuronal differentiation. Another RGS6-binding protein is DMAP1, a component of the Dnmt1 complex involved in repression of newly replicated genes. Mutations of a critical residue required for interaction of RGS6 protein with G proteins did not affect the ability of RGS6 to interact with both SCG10 and DMAP1. 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 390 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVKSQsKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 469
Cdd:cd08737     5 RWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQ-DVAKRVEEIWQEFLAPGAPSAINLDSHSYEKT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1191017958 470 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDLI 510
Cdd:cd08737    84 SQNVKDPGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDLL 124

Regulator of G protein signaling (RGS) domain found in the RGS11 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS11 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 RGS9, 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. RGS11 is expressed exclusively in retinal ON-bipolar neurons in which it forms complexes with G-beta-5 and R7AP (RGS7 anchor protein ) and plays crucial roles in processing the light responses of retinal neurons.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 390 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 469
Cdd:cd08740     5 RWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY-GEQSKIPELVDSVYQQFLAPGATRWVNIDSKTMERT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1191017958 470 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDLINQ 512
Cdd:cd08740    84 LEGLKQPHRYVLDDAQMHIYMLMKKDSYPRFLKSDLYKNLLAE 126

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 1191017958 390 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKkVKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 469
Cdd:cd08739     4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLK-YGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMDIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1191017958 470 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 506
Cdd:cd08739    83 VKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIY 119

Regulator of G protein signaling (RGS) domain found in the RGS7 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS7 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. 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, RGS9, 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. R7 RGS proteins are key modulators of the pharmacological effects of drugs involved in the development of tolerance and addiction. In addition, RGS7 was found to bind a component of the synaptic fusion complex, snapin, and some other proteins outside of G protein signaling pathways.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 390 KWGESLEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHT 469
Cdd:cd08738     4 RWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYDKT 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1191017958 470 KDNLQSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 506
Cdd:cd08738    83 TQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 119

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 1191017958 395 LEKLLVHKYGLAVFQAFLRTEFSEENLEFWLACEDFKKVK-SQSKMASKAKKIFAEYIAIQACKEVNLDSYTREHTKDNL 473
Cdd:cd08707     1 LHSLLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMSdSEEKRSKLAKAIYRRYIKDNGIVSRQLKPATKSFIKECI 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1191017958 474 --QSVTRGCFDLAQKRIFGLMEKDSYPRFLRSDLYL 507
Cdd:cd08707    81 kkQQLDPAMFDQAQTEIQTTMEENTYPSFLKSDIYL 116

Regulator of G protein signaling (RGS) domain 2 found in the A-kinase anchoring protein, D-AKAP2; The RGS (Regulator of G-protein Signaling) domain is an essential part of the D-AKAP2 (A-kinase anchoring protein), a member 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 regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development. D-AKAP2 contains two RGS domains which play an important role in spatiotemporal localization of cAMP-dependent PKA (cyclic AMP-dependent protein kinase) that regulates many different signaling pathways by phosphorylation of target proteins. This cd contains the second RGS domain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 408 FQAFLRTEFSEENLEFWLACEDFKKV-----KSQSKMA--SKAKKIFAEYIAIQACKEVNLDSYTREHTKdnlQSVTRG- 479
Cdd:cd08721    11 FMEYMEQEGARNLLQFWLAADNFQSQlaakeGQYDGQQaqNDAMIIYDKYFSLQATEPLGFDDKTRLEVE---SNICREg 87

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1191017958 480 -----CFDLAQKRIFGLMEKDSYPRFLRSDLY 506
Cdd:cd08721    88 gplpsCFEAPLLQALTTLEQHYLPGFLSSQLY 119

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958   20 PGAEDSPPSKEPSPGQELPPGQDLPPNKDSPSGQEPAPSQEPLSSKdsATSEGSPPGPDAPPSKDVPPCQEPP--PAQDL 97
Cdd:PHA03247  2621 THAPDPPPPSPSPAANEPDPHPPPTVPPPERPRDDPAPGRVSRPRR--ARRLGRAAQASSPPQRPRRRAARPTvgSLTSL 2698

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958   98 SPCQDLPAGQEPLPH----QDPLLTKDLPAIQESPTRDLPPCQDLPPSQVSLPA---KALTEDTMSSGDLLAATGDPPAA 170
Cdd:PHA03247  2699 ADPPPPPPTPEPAPHalvsATPLPPGPAAARQASPALPAAPAPPAVPAGPATPGgpaRPARPPTTAGPPAPAPPAAPAAG 2778

                          170
                   ....*....|
gi 1191017958  171 PRPAFVIPEV 180
Cdd:PHA03247  2779 PPRRLTRPAV 2788

Regulator of G protein signaling (RGS) domain found in the FLBA (Fluffy Low BrlA) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the FLBA (Fluffy Low BrlA) protein. FLBA 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). 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 play a critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. Deactivation of the G-protein signaling controlled by the RGS domain accelerates the 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 thereby inhibition of downstream activity. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. The RGS domain of the FLBA protein antagonizes G protein signaling to block proliferation and allow development. It is required for control of mycelial proliferation and activation of asexual sporulation in yeast.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 408 FQAFLRTEFSEENLEFWLACEDFKK-----------VKSQSKMASKAKKIFAE-------YIAIQACKEVNLDSYTRE-- 467
Cdd:cd08708    15 FREHLEKEFCEENLSFYLEVKEFLKkmtilsklldfKSSQAADEDLDRESLAQayhiyntYLAPGSPCELNIDHNLRNri 94

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1191017958 468 ----------HTKDNLQSV--TRGCFDLAQKRIF-GLMEKDSYPRFLRSDLYL 507
Cdd:cd08708    95 ttimtekivgEDDSMAESLqgVEALFEEAQNAVFkPLMAGDSVPKFLKQPEYL 147

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  22 AEDSPPSKEPSPGQELPPGQDLPPNKDSPSGQEPAPSQEPLSSKDSATSEGSPPGPDAPPSKdVPPCQEPPPAQDLSPCQ 101
Cdd:PRK12323  395 AAPAPAAPPAAPAAAPAAAAAARAVAAAPARRSPAPEALAAARQASARGPGGAPAPAPAPAA-APAAAARPAAAGPRPVA 473

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958 102 DlPAGQEPLPHQdplltkdlPAIQESPT-RDLPPCQDLPPSQVSL--------PAKALTEDTMSSGDLLAATGDPPAAPR 172
Cdd:PRK12323  474 A-AAAAAPARAA--------PAAAPAPAdDDPPPWEELPPEFASPapaqpdaaPAGWVAESIPDPATADPDDAFETLAPA 544

                  ..
gi 1191017958 173 PA 174
Cdd:PRK12323  545 PA 546

DNA polymerase III subunit gamma/tau;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  20 PGAEDSPPSKEPSPGQELPPGQDLPPNKDSPSGQEPAPSQEPLSSKDSATSEGSPPGPDAPPSKDVPPC--QEPPPAQDL 97
Cdd:PRK07003  419 AATRAEAPPAAPAPPATADRGDDAADGDAPVPAKANARASADSRCDERDAQPPADSGSASAPASDAPPDaaFEPAPRAAA 498

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  98 SPCQDLPAGQEPLPHQDPlLTKDLPAIQESPTRDLP---PCQDLPPSQVSLPAKAL----------TEDTMSSGDLLA-- 162
Cdd:PRK07003  499 PSAATPAAVPDARAPAAA-SREDAPAAAAPPAPEARpptPAAAAPAARAGGAAAALdvlrnagmrvSSDRGARAAAAAkp 577

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1191017958 163 ----ATGDPPAAPRPAFVIPEVRLDSTYSQKAGA 192
Cdd:PRK07003  578 aaapAAAPKPAAPRVAVQVPTPRARAATGDAPPN 611

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958    1 MFETEADEKREMALEEGKGPGAEDSPPSKE-PSPGQELPPGQDLPPNKDSPSGQEPAPSQEPLSSKDSATSEGSPP---- 75
Cdd:PHA03307    42 QLVSDSAELAAVTVVAGAAACDRFEPPTGPpPGPGTEAPANESRSTPTWSLSTLAPASPAREGSPTPPGPSSPDPPpptp 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958   76 ---GPDAPPSKDVPPCQ-----EPPPAQDLSPCQDLPAGQEPLPHQDPLLTKDLPAIQESPTRDLPPCQDLPPSQVSLPA 147
Cdd:PHA03307   122 ppaSPPPSPAPDLSEMLrpvgsPGPPPAASPPAAGASPAAVASDAASSRQAALPLSSPEETARAPSSPPAEPPPSTPPAA 201

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1191017958  148 KALTEDTMSSGDLLAATGDPPAAPR-PAFVIPEVRLDSTYSQKAGAEQG 195
Cdd:PHA03307   202 ASPRPPRRSSPISASASSPAPAPGRsAADDAGASSSDSSSSESSGCGWG 250

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  25 SPPSKEPSPGQELPPGQDLPPNKDSPSGQEPAPSQePLSSKDSATSEGSPPGPDAPPSKDVPPCQEPPPAqdLSPCQDLP 104
Cdd:pfam03154 327 TPPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTT-PIPQLPNPQSHKHPPHLSGPSPFQMNSNLPPPPA--LKPLSSLS 403

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1191017958 105 AGQEPLPHQDPL-LTKDLPAIQESPTRD--LPPCQDLPPSQVSLPakaltedtmSSGDLLAATGDPPAAPRP 173
Cdd:pfam03154 404 THHPPSAHPPPLqLMPQSQQLPPPPAQPpvLTQSQSLPPPAASHP---------PTSGLHQVPSQSPFPQHP 466

DNA polymerase III subunits gamma and tau; Validated

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958   3 ETEADEKREMALEEGKGPGAEDSPPSKE--PSPGQELPP-----GQDLPPNKDSPSGQEPAPSQEPLSSKD-SATSEGSP 74
Cdd:PRK08691  386 EKETAAKKPQPRPEAETAQTPVQTASAAamPSEGKTAGPvsnqeNNDVPPWEDAPDEAQTAAGTAQTSAKSiQTASEAET 465

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1191017958  75 PGPD-------APPSKDVPPCQEPPPAQDLSPCQDLPAGQEPLPHQDPLLTKDLPAIqesPTRDLPP--CQDLPPSQVSL 145
Cdd:PRK08691  466 PPENqvsknkaADNETDAPLSEVPSENPIQATPNDEAVETETFAHEAPAEPFYGYGF---PDNDCPPedGAEIPPPDWEH 542

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1191017958 146 PAKALTEDTMSSGDLLAAT--GDP-PAAPRPAFVIPE-VRLDSTYSQKAGAEQ 194
Cdd:PRK08691  543 AAPADTAGGGADEEAEAGGigGNNtPSAPPPEFSTENwAAIVRHFARKLGAAQ 595