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 1734338888 685 SFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAA 764
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADP-DEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIREN 79

                          90       100
                  ....*....|....*....|....*.
gi 1734338888 765 VEAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:pfam00615  80 LEKEPTRDLFDEAQAEVYELMEKDSY 105

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 1734338888 685 SFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAA 764
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADP-DEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIREN 79

                          90       100
                  ....*....|....*....|....*.
gi 1734338888 765 VEAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:pfam00615  80 LEKEPTRDLFDEAQAEVYELMEKDSY 105

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 1734338888 687 ESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTqKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAVE 766
Cdd:cd08713     2 EKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMAS-RAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100
                  ....*....|....*....|....
gi 1734338888 767 AGCKpDTFALAQSRVEQLMSKDSY 790
Cdd:cd08713    81 NPTR-GCFDLAQKRIYGLMEKDSY 103

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734338888 355 PDECYRTRLVTNCNSPSFDESFYFTFSENcVRDLLIVTVyeMDSNNAeKKRILGCMTFPVSRI 417
Cdd:cd04036    33 SDEKKRTKTIKNSINPVWNETFEFRIQSQ-VKNVLELTV--MDEDYV-MDDHLGTVLFDVSKL 91

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 1734338888 685 SFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAA 764
Cdd:pfam00615   1 SFDSLLEDQPGRRLFRQFLESEFSEENLEFWLACEEFKKADP-DEERLKKAKEIYNEFLAPGSPKEINLDSDLREEIREN 79

                          90       100
                  ....*....|....*....|....*.
gi 1734338888 765 VEAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:pfam00615  80 LEKEPTRDLFDEAQAEVYELMEKDSY 105

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 1734338888 687 ESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTqKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAVE 766
Cdd:cd08713     2 EKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMAS-RAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100
                  ....*....|....*....|....
gi 1734338888 767 AGCKpDTFALAQSRVEQLMSKDSY 790
Cdd:cd08713    81 NPTR-GCFDLAQKRIYGLMEKDSY 103

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 1734338888 690 LNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAVEA-G 768
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKTTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEEpY 80

                          90       100
                  ....*....|....*....|..
gi 1734338888 769 CKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd07440    81 PDPDCFDEAQEHILNLLEKDSY 102

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 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTqKAIEIYSEFVAEHSPKEVNLDSDTRAAT-KAA 764
Cdd:cd08717     1 LDKLLQNSYGLASFKSFLKSEFSEENIEFWEACEDYKKTKSPLKMAT-KAKKIYEEFIQTEAPKEVNIDHFTKDVTmKNL 79

                          90       100
                  ....*....|....*....|....*.
gi 1734338888 765 VEAgcKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08717    80 VEP--SSSSFDLAQKRIFALMEKDSL 103

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 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAV 765
Cdd:cd08706     1 FERLLQDPVGVKYFTEFLKKEFSEENILFWQACEKFKKIPD-KKQLVQEAREIYDTFLSSKASSPVNIDSQAQLAEEMLE 79

                          90       100
                  ....*....|....*....|....*
gi 1734338888 766 EAgcKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08706    80 EP--HPDMFQKQQLQIFNLMKFDSY 102

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 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTqKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAV 765
Cdd:cd08714     1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSKLSP-KARKIYEEFISVQATKEVNLDSCTREETSRNM 79

                          90       100
                  ....*....|....*....|....*
gi 1734338888 766 EAgCKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08714    80 LE-PTISCFDEAQKKIFTLMEKDSY 103

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 1734338888 682 WEISFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKmKDGKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAAT 761
Cdd:cd08745     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKA-EANKHVIDEKARLIYEDYISILSPKEVSLDSRVREGI 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1734338888 762 KAAVEagcKPD--TFALAQSRVEQLMSKDSY 790
Cdd:cd08745    80 NRKMQ---EPSshTFDDAQLQIYTLMHRDSY 107

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 1734338888 689 LLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTqKAIEIYSEFVAEHSPKEVNLDSDTR-AATKAAVEA 767
Cdd:cd08723     1 LLANQAGLDAFRTFLKSEFSEENVEFWLACEDFKKTKSSTEIAL-KAQMIYSEFIQADAPKEINIDFHTRdLISQNISEP 79

                          90       100
                  ....*....|....*....|...
gi 1734338888 768 GCKpdTFALAQSRVEQLMSKDSY 790
Cdd:cd08723    80 TLK--CFDEAQSLIYCLMAKDSF 100

Regulator of G protein signaling (RGS) domain found in the RGS10 protein; RGS (Regulator of G-protein Signaling) domain is an essential part of the RGS10 protein. RGS10 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. RGS10 belong to the R12 RGS subfamily, which includes RGS12 and RGS14, all of which are highly selective for G-alpha-i1 over G-alpha-q. RGS10 exists in 2 splice isoforms. RGS10A is specifically expressed in osteoclasts and is a key component in the RANKL signaling mechanism for osteoclast differentiation, whereas RGS10B expressed in brain and in immune tissues and has been implicated in diverse processes including: promoting of dopaminergic neuron survival via regulation of the microglial inflammatory response, modulation of presynaptic and postsynaptic G-protein signalling, as well as a possible role in regulation of gene expression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKAAV 765
Cdd:cd08741     1 LENLLEDPEGVKRFREFLKKEFSEENVLFWLACEDFKKMQD-KTQMQEKAKEIYMTFLSSKASSQVNVEGQSRLNEKILE 79

                          90       100
                  ....*....|....*....|....*
gi 1734338888 766 EAgcKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08741    80 EP--HPLMFQKLQDQIFNLMKYDSY 102

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 1734338888 679 VRQWEISFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKM-KDGKKSTTQKAIEIYSEFVAEHSPKEVNLDSdt 757
Cdd:cd08743     4 VASWAVSFERLLQDPLGVEYFTEFLKKEFSAENVNFWKACERFQQIpASDTQQLAQEARKIYNEFLSSSSQSPVNIDQ-- 81

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1734338888 758 RAATKAAVEAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08743    82 QAWIGEDMLATPSPDMFRAQQLQIFNLMKFDSY 114

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 1734338888 679 VRQWEISFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTQKaiEIYSEFVAEHSPKEVNLDSDTR 758
Cdd:cd08740     3 VERWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRYGEQSKIPELVD--SVYQQFLAPGATRWVNIDSKTM 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1734338888 759 AATkaaVEAGCKPDTFAL--AQSRVEQLMSKDSY 790
Cdd:cd08740    81 ERT---LEGLKQPHRYVLddAQMHIYMLMKKDSY 111

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 1734338888 682 WEISFESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDgKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAAT 761
Cdd:cd08744     1 WSQNFDKMMKTPAGRNLFREFLRTEYSEENLLFWLACEDLKKEQN-KKVIEEKARLIYEDYISILSPKEVSLDSRVREVI 79

                          90       100
                  ....*....|....*....|....*....
gi 1734338888 762 KAAVeAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08744    80 NRNL-LDPNPHMYEDAQLQIYTLMHRDSF 107

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 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKD-GKKSTTQKAIEIYSEFVAEHSPKEVNLDSDTRAATKaa 764
Cdd:cd08742     1 FERLLQDPVGVRYFSEFLRKEFSEENILFWQACEYFNHVPAhDKKELSYRAREIFSKFLCSKATTPVNIDSQAQLADD-- 78

                          90       100
                  ....*....|....*....|....*.
gi 1734338888 765 VEAGCKPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08742    79 ILNAPHPDMFKEQQLQIFNLMKFDSY 104

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 1734338888 688 SLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKMKDGKKSTTQKAIEIYSEFVAEHSPKEVnldsDTRAATKAAVeA 767
Cdd:cd08707     3 SLLDDQDGIELFRTYLEQEGCADLLDFWFACNGFRKMSDSEEKRSKLAKAIYRRYIKDNGIVSR----QLKPATKSFI-K 77

                          90       100
                  ....*....|....*....|....*....
gi 1734338888 768 GC------KPDTFALAQSRVEQLMSKDSY 790
Cdd:cd08707    78 ECikkqqlDPAMFDQAQTEIQTTMEENTY 106

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734338888  308 RLTLNVQNAAYFCSAARPTSVCSYVSAVLCHRPSsqsssssrqyrqrpdECYRTRLVTNCNSPSFDESFYFTFSENCVRD 387
Cdd:smart00239   1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPK---------------EKKKTKVVKNTLNPVWNETFEFEVPPPELAE 65

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1734338888  388 lLIVTVYEMDSNNaeKKRILGCMTFPVSRILKKASQVV 425
Cdd:smart00239  66 -LEIEVYDKDRFG--RDDFIGQVTIPLSDLLLGGRHEK 100

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1734338888 355 PDECYRTRLVTNCNSPSFDESFYFTFSENcVRDLLIVTVYemDSNNAEKKRILGCMTFPVSRILKK 420
Cdd:cd00030    30 GKQKFKTKVVKNTLNPVWNETFEFPVLDP-ESDTLTVEVW--DKDRFSKDDFLGEVEIPLSELLDS 92

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1734338888 360 RTRLVTNCNSPSFDESFYFTFSENCVRDLLIVTVYeMDSNNAEKKRILGCMTFPVSRILKK 420
Cdd:cd08685    51 KTSTVPDSANPLFHETFSFDVNERDYQKRLLVTVW-NKLSKSRDSGLLGCMSFGVKSIVNQ 110

Regulator of G protein signaling domain RGS_RGS22_3; The RGS (Regulator of G-protein Signaling) domain found in the RGS22 protein, a member of the RA/RGS 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 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. RGS22 contains at least 3 copies of the RGS domain in vertebrata and exists in multiple splicing variants. RGS22 is predominantly expressed in testis and believed to play an important role in spermatogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1734338888 686 FESLLNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKM--KDGKKStTQKAIEIYSEF 742
Cdd:cd08726     1 FQDLLHNRLELEFFRKFLEENSASMDLLCWLDIEQFRRIphTDNAKR-DEKAKEIKNKY 58

C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734338888 358 CYRTrlvtncNSPSFDESFYFtFSENCVRDLLIVTVYEMDSNNAekkriLGCMTFPVSRILKKASQVVGDPFP 430
Cdd:cd04050    39 KERT------NNPVWEEGFTF-LVRNPENQELEIEVKDDKTGKS-----LGSLTLPLSELLKEPDLTLDQPFP 99

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 1734338888 690 LNNKFGCALFRQFLKKEFSDENMDFWLECEEFKKM------------KDGKKSTTQ-------KAIEIYSEFVAEHSPKE 750
Cdd:cd08719     2 LVNNVALSYFIDFMQSVGGQAYLFFWLTVEGYRVSaeqqlselhlrqRGGEHQRSDvyemlraAALNIYDQYLSEKASPR 81

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1734338888 751 VNLDSDTRAATKAAVEAGCKPDT-FALAQSRVEQLMSKD 788
Cdd:cd08719    82 VPLDDSLVKKLLNRLRNDTPSDLwFDDIQQKVFDIMQED 120

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 2 (GRK2) and G protein-coupled receptor kinase 3 (GRK3); The RGS domain is an essential part of the GRK2 (G protein-coupled receptor kinases 2) and the GRK3 proteins, which are members of the beta-adrenergic receptor kinases subfamily. GRK2 and GRK3 are ubiquitously expressed and can phosphorylate many different GPCR. The C-terminus of GRK2 and 3 contains a plekstrin homology domain (PH) with binding sites for the membrane phospholipid PIP2 and free G#? subunits. These specific interactions could help to maintain a membrane-bound population of GRK2 prior to the agonist-dependent overt GRK2 translocation. GRK2 and GRK3 are members of the GRK kinase family which includes three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs 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. 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        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734338888 683 EISFESLLNNKFGCALFRQFLKKEfSDE---NMDFWLECEEFKKMkDGKKSTTQKAIEIYSEFVAehspKEvnLDSDTRA 759
Cdd:cd08747    23 EVTFDKIFNQKLGYLLFKDFCENV-SEEpvpQLKFYEEIKKYEKL-DTEEERIKKAREIYDNYIM----KE--LLSCSHP 94

                  ....*..
gi 1734338888 760 ATKAAVE 766
Cdd:cd08747    95 FSKSAVE 101