Regulator of G-protein signalling DHEX domain; This domain is found in RGS9 (Class C) regulator of G-protein signalling (RGS) protein present in Mus musculus. RGS proteins attenuate heterotrimeric G-protein signalling by enhancing the intrinsic GTPase activity of G-alpha subunits and are vital for proper signal transduction kinetics. The domain is referred to as DEP helical extension (DHEX) because it is located next to N-terminal Dishevelled/Egl-10/Pleckstrin homology (DEP) domain. Both the DEP and DHEX domains are necessary, but not sufficient, to bind anchoring proteins such as RGS9 anchor protein. DHEX has no close structural homologs. This domain is also found in regulator of G-protein signaling 7 (RGS7), the crystal structure of which has been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 116 PYFWPSNCWEPENTDYAIYLCKRTMQNKARLElaDYEAENLARLQRAFARKWEFIFMQAEAQVKIDRKKDKTERKILDSQ 195
Cdd:pfam18148   1 PYFWPSQAWEPENTDYAIYLAKRNMRNKQRLE--EYEKEAYNKLQKKLNYKWDFIIMQAEEQYKVGKERNKADRYILDSQ 78

                          90       100
                  ....*....|....*....|..
gi 1632519259 196 ERAFWDVHRPVPGCVNTTEMDI 217
Cdd:pfam18148  79 ERAFWLVHRPPPGQVNVLEYGI 100

G protein gamma subunit-like motifs;

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1632519259  258 KEDIRKQITFLNAQIDRHCLKMSKVAESLIAYTEQYVEYDPLITPAEPS-NPWISDDVALWDI 319
Cdd:smart00224   1 KDQLRKEVEQLRKELSRERIKVSKAAEELLAYCEQHAEEDPLLTGPPPSkNPFIEDKTSCWIL 63

Regulator of G-protein signalling DHEX domain; This domain is found in RGS9 (Class C) regulator of G-protein signalling (RGS) protein present in Mus musculus. RGS proteins attenuate heterotrimeric G-protein signalling by enhancing the intrinsic GTPase activity of G-alpha subunits and are vital for proper signal transduction kinetics. The domain is referred to as DEP helical extension (DHEX) because it is located next to N-terminal Dishevelled/Egl-10/Pleckstrin homology (DEP) domain. Both the DEP and DHEX domains are necessary, but not sufficient, to bind anchoring proteins such as RGS9 anchor protein. DHEX has no close structural homologs. This domain is also found in regulator of G-protein signaling 7 (RGS7), the crystal structure of which has been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 116 PYFWPSNCWEPENTDYAIYLCKRTMQNKARLElaDYEAENLARLQRAFARKWEFIFMQAEAQVKIDRKKDKTERKILDSQ 195
Cdd:pfam18148   1 PYFWPSQAWEPENTDYAIYLAKRNMRNKQRLE--EYEKEAYNKLQKKLNYKWDFIIMQAEEQYKVGKERNKADRYILDSQ 78

                          90       100
                  ....*....|....*....|..
gi 1632519259 196 ERAFWDVHRPVPGCVNTTEMDI 217
Cdd:pfam18148  79 ERAFWLVHRPPPGQVNVLEYGI 100

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 1632519259  336 SFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQP-LQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNV 414
Cdd:smart00315   1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEdDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1632519259  415 KDGG--RYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 450
Cdd:smart00315  81 ESEEppPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

Domain found in Dishevelled, Egl-10, and Pleckstrin; Domain of unknown function present in signalling proteins that contain PH, rasGEF, rhoGEF, rhoGAP, RGS, PDZ domains. DEP domain in Drosophila dishevelled is essential to rescue planar polarity defects and induce JNK signalling (Cell 94, 109-118).

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1632519259   41 TGGVPIRTVKSFLSKIPSVVTGTDIVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISD-HVLTMKDDGTFYRFQ 114
Cdd:smart00049   2 ETGLKLRDRKYFLKTYPNCFTGSELVDWLMDNLEIIDREEAVHLGQLLLDEGLIHHVNGpNKHTFKDSKALYRFT 76

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1632519259  43 GVPIRTVKSFLSKIPSVVTGTDIVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTFYRF 113
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHGLFKDSYYFYRF 71

GGL domain; G-protein gamma like domains (GGL) are found in the gamma subunit of the heterotrimeric G protein complex and in regulators of G protein signaling (RGS) proteins. It is also found fused to an inactive Galpha in the Dictyostelium protein gbqA. G-gamma likely shares a common origin with the helical N-terminal unit of G-beta. All organizms that posses a G-beta possess a G-gamma.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1632519259 255 KTTKEDIRKQITFLNAQIDRHCLKMSKVAESLIAYTEQYVEYDPLIT----PAEPSNPWISDDVALWD 318
Cdd:pfam00631   1 KQLKLKLKREIEQLREELKRERIKVSKACEELIDYCEQRSTKDPLLPgvwgPPAGENPWREDDGCCWI 68

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 1632519259 329 RVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08705     1 RVKRWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYGPQSQVPEKVQEIYQEFLAPGAPSWINIDSKTME 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1632519259 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08705    81 ITLKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

Regulator of G-protein signalling DHEX domain; This domain is found in RGS9 (Class C) regulator of G-protein signalling (RGS) protein present in Mus musculus. RGS proteins attenuate heterotrimeric G-protein signalling by enhancing the intrinsic GTPase activity of G-alpha subunits and are vital for proper signal transduction kinetics. The domain is referred to as DEP helical extension (DHEX) because it is located next to N-terminal Dishevelled/Egl-10/Pleckstrin homology (DEP) domain. Both the DEP and DHEX domains are necessary, but not sufficient, to bind anchoring proteins such as RGS9 anchor protein. DHEX has no close structural homologs. This domain is also found in regulator of G-protein signaling 7 (RGS7), the crystal structure of which has been solved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 116 PYFWPSNCWEPENTDYAIYLCKRTMQNKARLElaDYEAENLARLQRAFARKWEFIFMQAEAQVKIDRKKDKTERKILDSQ 195
Cdd:pfam18148   1 PYFWPSQAWEPENTDYAIYLAKRNMRNKQRLE--EYEKEAYNKLQKKLNYKWDFIIMQAEEQYKVGKERNKADRYILDSQ 78

                          90       100
                  ....*....|....*....|..
gi 1632519259 196 ERAFWDVHRPVPGCVNTTEMDI 217
Cdd:pfam18148  79 ERAFWLVHRPPPGQVNVLEYGI 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 336 SFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD-VAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNV 414
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADPDEeRLKKAKEIYNEFLAPGSPKEINLDSDLREEIRENL 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1632519259 415 KDG-GRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 450
Cdd:pfam00615  81 EKEpTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

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 1632519259 329 RVKRWGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08739     1 RVERWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLKYGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1632519259 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08739    81 ITVKGLKHPHRYVLDAAQTHIYMLMKKDSYARYLKSPIYKE 121

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 1632519259 341 LKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD--VAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKDGG 418
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDeeLKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEPY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1632519259 419 --RYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd07440    81 pdPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 1632519259 338 DEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKD 416
Cdd:cd08713     2 EKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKiKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQN 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1632519259 417 GGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08713    82 PTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

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 1632519259 333 WGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVakrVEE----IWQEFLAPGAPSAINLDSHSYE 408
Cdd:cd08718     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKKEANKHV---IEEkarlIYEDYISILSPKEVSLDSRVRE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1632519259 409 ITSQNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08718    78 VINRNMLEPSPHTFDDAQLQIYTLMHRDSYPRFLNSAIYKS 118

Regulator of G protein signaling (RGS) domain found in the RGS2 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS2 protein. RGS2 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. RGS2 plays important roles in the regulation of blood pressure and the pathogenesis of human hypertension, as well as in bone formation in osteoblasts. Outside of the GPCR pathway RGS2 interacts with calmodulin, beta- COP, tubulin, PKG1-alpha, and TRPV6.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVK 415
Cdd:cd08709     1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKtKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1632519259 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08709    81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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 1632519259 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKD 416
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESDLLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIKA 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1632519259 417 GGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQDL 450
Cdd:cd08715    81 PTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 114

Regulator of G protein signaling (RGS) domain found in the RGS21 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part RGS21 protein, a member of 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. As a major G-protein regulator, RGS domain containing proteins are involved in many crucial cellular processes. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, apoptosis, and cell proliferation, as well as modulation of cardiac development. RGS21 is a member of the R4/RGS subfamily and its mRNA was detected only in sensory taste cells that express sweet taste receptors and the taste G-alpha subunit, gustducin, suggesting a potential role in regulating taste transduction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 340 ILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK-QPLQDVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKDGG 418
Cdd:cd08723     1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKKtKSSTEIALKAQMIYSEFIQADAPKEINIDFHTRDLISQNISEPT 80

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1632519259 419 RYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08723    81 LKCFDEAQSLIYCLMAKDSFPRFLKSEVYKK 111

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 1632519259 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK--QPLQdVAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNV 414
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKtkSPLK-MATKAKKIYEEFIQTEAPKEVNIDHFTKDVTMKNL 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1632519259 415 KDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08717    80 VEPSSSSFDLAQKRIFALMEKDSLPRFVRSEFYQE 114

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 1632519259 333 WGFSFDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDV-AKRVEEIWQEFLAPGAPSAINLDSHSYEITS 411
Cdd:cd08744     1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQNKKViEEKARLIYEDYISILSPKEVSLDSRVREVIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1632519259 412 QNVKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQ 448
Cdd:cd08744    81 RNLLDPNPHMYEDAQLQIYTLMHRDSFPRFLNSQIYK 117

Regulator of G protein signaling (RGS) domain found in the RGS4 protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS4 protein. RGS4 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. RGS4 is expressed widely in brain including prefrontal cortex, striatum, locus coeruleus (LC), and hippocampus and has been implicated in regulation of opioid, cholinergic, and serotonergic signaling. Dysfunctions in RGS4 proteins are involved in etiology of Parkinson's disease, addiction, and schizophrenia. RGS4 also is up-regulated in the failing human heart. RGS4 interacts with many binding partners outside of GPCR pathways, including calmodulin, COP, Kir3, PIP, calcium/CaM, PA, ErbB3, and 14-3-3.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD-VAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVK 415
Cdd:cd08714     1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSkLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1632519259 416 DGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08714    81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

Domain found in Dishevelled, Egl-10, and Pleckstrin (DEP); The DEP domain is responsible for mediating intracellular protein targeting and regulation of protein stability in the cell. The DEP domain is present in a number of signaling molecules, including Regulator of G protein Signaling (RGS) proteins, and has been implicated in membrane targeting. New findings in yeast, however, demonstrate a major role for a DEP domain in mediating the interaction of an RGS protein to the C-terminal tail of a GPCR, thus placing RGS in close proximity with its substrate G protein alpha subunit.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1632519259  43 GVPIRTVKSFLSKIPSVVTGTDIVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTFYRF 113
Cdd:pfam00610   1 GVKLKDRRKHLKTYPNCFTGSEAVDWLMDNLEIITREEAVELGQLLLDQGLIHHVGDKHGLFKDSYYFYRF 71

DEP domain, named after Dishevelled, Egl-10, and Pleckstrin, where this domain was first discovered. The function of this domain is still not clear, but it is believed to be important for the membrane association of the signaling proteins in which it is present. New studies show that the DEP domain of Sst2, a yeast RGS protein is necessary and sufficient for receptor interaction.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259  31 DIITKMQDDKTGgVPIRTVKSFLSKIPSVVTGTDIVQWLMKNLSIEDPVEAIHLGSLIAAQGYIFPISDHVLTMKDDGTF 110
Cdd:cd04371     1 DLVRIMLDSDSG-VPIKDRKYHLKTYPNCFTGSELVDWLLDNLEAITREEAVELGQALLKHGLIHHVSDDKHTFRDSYAL 79

                  ..
gi 1632519259 111 YR 112
Cdd:cd04371    80 YR 81

Regulator of G protein signaling (RGS) domain found in the RGS12 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS12 protein. RGS12 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. RGS12 belong to the R12 RGS subfamily, which includes RGS10 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS12 exist in multiple splice variants: RGS12s (short) contains the core RGS/RBD/GoLoco domains, while RGS12L (long) has additional N-terminal PDZ and PTB domains. RGS12 splice variants show distinct expression patterns, suggesting that they have discrete functions during mouse embryogenesis. RGS12 also may play a critical role in coordinating Ras-dependent signals that are required for promoting and maintaining neuronal differentiation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 337 FDEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD---VAKRVEEIWQEFLAPGAPSAINLDSHSyEITSQN 413
Cdd:cd08742     1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAHDkkeLSYRAREIFSKFLCSKATTPVNIDSQA-QLADDI 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1632519259 414 VKDGGRYTFEDAQEHIYKLMKSDSYARFLRSNAYQD 449
Cdd:cd08742    80 LNAPHPDMFKEQQLQIFNLMKFDSYTRFLKSPLYQE 115

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 1632519259 338 DEILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKK--QPLQDVAKRVEE-----------------IWQEFLAPGAPS 398
Cdd:cd08708     3 DKILKDPGLRYLFREHLEKEFCEENLSFYLEVKEFLKkmTILSKLLDFKSSqaadedldreslaqayhIYNTYLAPGSPC 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1632519259 399 AINLDSHSYE-ITS--------QNV-----KDGGRYTFEDAQEHIYK-LMKSDSYARFLRSNAY 447
Cdd:cd08708    83 ELNIDHNLRNrITTimtekivgEDDsmaesLQGVEALFEEAQNAVFKpLMAGDSVPKFLKQPEY 146

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 25 (SNX25) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX25 (Sorting Nexin 25) 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. SNX25 is a member of the Dopamine receptors (DAR) signalplex and regulates the trafficking of D1 and D2 DARs.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 340 ILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFL-APGAPsaINLDSHSY-EITSQNVKDG 417
Cdd:cd08720     1 ILANVFGRKYLSQFLERMDSQALIGFWEAVEELRSANKSEWHQLGAEIFYTFIvEPTAE--IKVDKSLRkRIEQFLLGDK 78

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1632519259 418 GRYTFEDAQEHIYKLMKSDSYARFLRSNAYQ 448
Cdd:cd08720    79 GPEVFYEVQENVVETLEEKYYPSFVVSDQYK 109

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 1632519259 340 ILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQD--VAKRVEEIWQEFLAPGAPSAINLDSHSYEITSQNVKDG 417
Cdd:cd08707     4 LLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMSDSEekRSKLAKAIYRRYIKDNGIVSRQLKPATKSFIKECIKKQ 83

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1632519259 418 --GRYTFEDAQEHIYKLMKSDSYARFLRSNAY 447
Cdd:cd08707    84 qlDPAMFDQAQTEIQTTMEENTYPSFLKSDIY 115

Regulator of G protein signaling (RGS) domain found in the Sorting Nexin 13 (SNX13) protein; The RGS (Regulator of G-protein Signaling) domain is an essential part of the SNX13 (Sorting Nexin 13) 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. The RGS-domain of SNX13 plays a major role through attenuation of Galphas-mediated signaling and regulates endocytic trafficking and degradation of the epidermal growth factor receptor. Snx13-null mice were embryonic lethal around midgestation which supports an essential role for SNX13 in mouse development and regulation of endocytosis dynamics.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259 340 ILKDQVGRDQFLRFLESEFSSENLRFWLAVQDLK---KQPLQDVAKRVEE------------------IWQEFLAPGAPS 398
Cdd:cd08719     1 ILVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRvsaEQQLSELHLRQRGgehqrsdvyemlraaalnIYDQYLSEKASP 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1632519259 399 AINLDSHSYEITSQ--NVKDGGRYTFEDAQEHIYKLMKSDS--YARFLRSNAY 447
Cdd:cd08719    81 RVPLDDSLVKKLLNrlRNDTPSDLWFDDIQQKVFDIMQEDErfYPAFKKSPAY 133

DEP (Dishevelled, Egl-10, and Pleckstrin) domain found in fungal RhoGAP (GTPase-activator protein) Rgd2-like proteins. Rgd2-like proteins share a common domain architecture, containing, beside the RhoGAP domain, a DEP and a FCH (Fes/CIP4 homology) domain. Yeast Rgd2 is a GAP protein for Cdc42 and Rho5.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632519259  35 KMQDDKtggVPIrtvksfLSKIPSVVTGTDIVQWLMKNLSIEDPVEAIHLGSLIAAQGYI 94
Cdd:cd04436    14 PLADYK---VPI------LGTYQNTSSGSEIVSWLQENMPEKDLDAAEAFGQDLLNQGFL 64

Regulator of G protein signaling (RGS) domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein; The RGS domain found in the Rho guanine nucleotide exchange factor (RhoGEF) protein subfamily of the RGS domain containing protein family, which is a diverse group of multifunctional proteins that regulate cellular signaling events downstream of G-protein coupled receptors (GPCRs). RhoGEFs link signals from heterotrimeric G-alpha12/13 protein-coupled receptors to Rho GTPase activation, leading to various cellular responses, such as actin reorganization and gene expression. The RGS domain of the RhoGEFs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. The RGS-GEFs subfamily includes the leukemia-associated RhoGEF (LARG), p115RhoGEF, and PDZ-RhoGEF. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. RGS proteins play critical regulatory role as GTPase activating proteins (GAPs) of the heterotrimeric G-protein G-alpha-subunits. 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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1632519259 350 FLRFLESEFSSENLRFWLAVQDLKKQPLQDVAKRVEEIWQEFLAPGAPSAINLD 403
Cdd:cd08736    10 FLHYVLSQFDPSPLLFYLITDLYKQGNPKDMRKWAYEIYSTFLEKNAPLKVKVP 63