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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08713    81 NPTRGCFDLAQKRIYGLMEKDSYPRFLRSDLYQD 114

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980    1 MSREPGICDPYVKVSLIPEDSQLPCQTTQIIPDCRDPAFHEHFFFPVPEEGDQKRLLVTVWNRASETRQHTLIGCMSFGV 80
Cdd:cd08685    25 RSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRLLVTVWNKLSKSRDSGLLGCMSFGV 104

                          90
                  ....*....|....*.
gi 568926980   81 RSLLtPDKEISGWYYL 96
Cdd:cd08685   105 KSIV-NQKEISGWYYL 119

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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
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 568926980    960 SLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENL 1039
Cdd:smart00315    1 SLESLLSDPIGRLLFREFLESEFSEENLEFWLAVEEFKKAEDDEERIAKAREIYDKFLSPNAPKEVNLDSDLREKIEENL 80

                            90       100       110
                    ....*....|....*....|....*....|....*...
gi 568926980   1040 QS--ITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 1075
Cdd:smart00315   81 ESeePPPDLFDEAQREVYELLEKDSFPRFLESDYYLRF 118

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980    1 MSREPGICDPYVKVSLIPEDSQLPCQTTQIIPDCRDPAFHEHFFFPVPEEGDQKRLLVTVWNRASETRQHTLIGCMSFGV 80
Cdd:cd08685    25 RSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFDVNERDYQKRLLVTVWNKLSKSRDSGLLGCMSFGV 104

                          90
                  ....*....|....*.
gi 568926980   81 RSLLtPDKEISGWYYL 96
Cdd:cd08685   105 KSIV-NQKEISGWYYL 119

Domain present in PSD-95, Dlg, and ZO-1/2; Also called DHR (Dlg homologous region) or GLGF (relatively well conserved tetrapeptide in these domains). Some PDZs have been shown to bind C-terminal polypeptides; others appear to bind internal (non-C-terminal) polypeptides. Different PDZs possess different binding specificities.

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568926980    138 ITIRRGKDGFGFTIC----CDSPVRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLVWR 212
Cdd:smart00228    5 VELEKGGGGLGFSLVggkdEGGGVVVSSVVPGSPAAKAGLRVGDVILEVNGTSVEGLTHLEAVDLLKKAGGKVTLTVLR 83

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 568926980   536 PGAEEPAPSKNPSPGQELPPGqdlPPSKDPSPSQELPagqDLPPSKDPSPSQELPAGQDLPPSKDPSPSQELPVGQDLPP 615
Cdd:pfam03154  292 PVPPQPFPLTPQSSQSQVPPG---PSPAAPGQSQQRI---HTPPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIPQ 365

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980   616 RKDSSGQEAAPGPESPSSEDI-ATCPKPPQ-SPETSTSKDSPPGQGSSPTTELPSCQGLPAgqeSTSQDPLLSQEPPVIP 693
Cdd:pfam03154  366 LPNPQSHKHPPHLSGPSPFQMnSNLPPPPAlKPLSSLSTHHPPSAHPPPLQLMPQSQQLPP---PPAQPPVLTQSQSLPP 442

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 568926980   694 ESSasvqkrlpSQESPSSLGSLPEKDLAEQT--ISSGEPPVATGAVLPASRPN 744
Cdd:pfam03154  443 PAA--------SHPPTSGLHQVPSQSPFPQHpfVPGGPPPITPPSGPPTSTSS 487

PDZ domain; PDZ domains are found in diverse signaling proteins.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980   137 QITIRRGKDG-FGFTI-----CCDSPVRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLV 210
Cdd:pfam00595    1 QVTLEKDGRGgLGFSLkggsdQGDPGIFVSEVLPGGAAEAGGLKVGDRILSINGQDVENMTHEEAVLALKGSGGKVTLTI 80

                   .
gi 568926980   211 W 211
Cdd:pfam00595   81 L 81

pneumococcal surface protein PspC, LPXTG-anchored form; The pneumococcal surface protein PspC, as described in Streptococcus pneumoniae, is a repetitive and highly variable protein, recognized by a conserved N-terminal domain and also by genomic location. This form, subgroup 2, is anchored covalently after cleavage by sortase at a C-terminal LPXTG site. The other form, subgroup 1, has variable numbers of a choline-binding repeat in the C-terminal region, and is also known as choline-binding protein A.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980  534 KGPGAEEPAPSKNPSPGQELPPGQDLPPSKDPSPSQELPAGQDLPPSKDPSPsqELPAGQDLP-PSKDPSPSQELPVGQ- 611
Cdd:NF033839  290 KKPSAPKPGMQPSPQPEKKEVKPEPETPKPEVKPQLEKPKPEVKPQPEKPKP--EVKPQLETPkPEVKPQPEKPKPEVKp 367

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980  612 -------DLPPRKDSSGQEAAPGPESPSSE--DIATCPKPPQSPETSTSKDSPPGQGSSPTTEL--------PSCQGLPA 674
Cdd:NF033839  368 qpekpkpEVKPQPETPKPEVKPQPEKPKPEvkPQPEKPKPEVKPQPEKPKPEVKPQPEKPKPEVkpqpekpkPEVKPQPE 447

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 568926980  675 GQESTSQDPLLSQEPPVIPESSASVQKRLPSQESPSSLGSLPEKD 719
Cdd:NF033839  448 KPKPEVKPQPETPKPEVKPQPEKPKPEVKPQPEKPKPDNSKPQAD 492

LPXTG-anchored collagen-like adhesin Scl2/SclB; SclB (or Scl2 - streptococcal collagen-like protein 2) is an LPXTG-anchored surface-anchored adhesin with a variable-length region of triple helix-forming collagen-like Gly-Xaa-Xaa repeats.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980  534 KGPGAEEPAPSKNPSPGQELPPGQDLPPSKDPSPSQELPAGQDLPPSKDPSPSQELPAGQDLP---PSKDPSPSQELPVG 610
Cdd:NF038329  247 DGPQGPDGPAGKDGPRGDRGEAGPDGPDGKDGERGPVGPAGKDGQNGKDGLPGKDGKDGQNGKdglPGKDGKDGQPGKDG 326

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568926980  611 QDLPPRKDSS-GQEAAPGPESPSSEDIAT-CPKPPQSPetSTSKDsppgqgSSPTTELPSCQGL 672
Cdd:NF038329  327 LPGKDGKDGQpGKPAPKTPEVPQKPDTAPhTPKTPQIP--GQSKD------VTPAPQNPSNRGL 382

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

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 568926980   157 VRVQAVDSGGPAERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIILLVWR 212
Cdd:TIGR02037  364 VVVTKVVSGSPAARAGLQPGDVILSVNQQPVSSVAELRKVLARAKKGGRVALLILR 419

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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08713     1 LEKLLLHKYGLAVFRAFLQTEFSEENLEFWLACEEYKKIKSQSKMASRAKKIFAEYIAIQSCKEVNLDSYTREHTKENLQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
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 568926980  950 TSEEALKWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDS 1029
Cdd:cd08711     1 STEEATRWADSFDVLLSHKYGVAAFRAFLKTEFSEENLEFWLACEEFKKTRSTAKLVSKAHRIFEEFVDVQAPREVNIDF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 568926980 1030 YTREHTKENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08711    81 QTREATRKNLQEPSLTCFDQAQGKVHSLMEKDSYPRFLRSKMYLD 125

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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08714     1 LENLINHECGLAAFKAFLKSEYSEENIDFWVSCEDYKKTKSPSKLSPKARKIYEEFISVQATKEVNLDSCTREETSRNML 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08714    81 EPTISCFDEAQKKIFTLMEKDSYRRFLKSRFYLD 114

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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08709     1 FDELLASKYGVAAFRAFLKSEFSEENIEFWLACEDFKKTKSPQKLTSKAKKIYTDFIEKEAPKEINIDFQTKTLIAQNIQ 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08709    81 EATSGCFTAAQKRVYSLMENNSYPRFLESEFYQE 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08712     1 FDKLLSHKDGLEAFTRFLKTEFSEENIEFWIACEDYKKSKTPQQIHLKAKAIYEKFIQTDAPKEVNLDFHTKEVTTNSIE 80

                          90       100       110
                  ....*....|....*....|....*....|....
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08712    81 QPTLTSFDAAQSRVYQLMEQDSYPRFLKSDIYLD 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 568926980  961 LEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQsKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ 1040
Cdd:cd08715     1 LEKLLASQTGQNVFRSFLKSEFSEENIEFWLACEDYKKTESD-LLPCKAEEIYKEFVQSDAAKQINIDFRTRESTAKKIK 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 568926980 1041 SITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDL 1075
Cdd:cd08715    80 APTPTCFDEAQKVIYILMERDSYPRFLKSDIYLNL 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 568926980  965 LLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKK-VKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTKENLQ--S 1041
Cdd:cd07440     1 LRDPYGLEYFRQFLKSEHCEENLEFWLAVEKFKKtTSSDEELKSKAKEIYDKYISKDAPKEINIPESIREEIEENLEepY 80

                          90       100       110
                  ....*....|....*....|....*....|...
gi 568926980 1042 ITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd07440    81 PDPDCFDEAQEHILNLLEKDSYPRFLKSDLYLK 113

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 568926980  956 KWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVkSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHT 1035
Cdd:cd08705     4 RWGFSFSELLKDPVGREQFLKFLEKEFSGENLRFWEACQDLKYG-PQSQVPEKVQEIYQEFLAPGAPSWINIDSKTMEIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568926980 1036 KENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08705    83 LKNLKDPHRYTFDAAQEHIYMLMKKDSYPRFLRSDIYKE 121

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 568926980  945 KSFKPTSEEALKWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKE 1024
Cdd:cd08746    38 ESPKPTLEEVCAWGQSFDKLMLTPAGRNAFREFLRTEFSEENMLFWMACEELKKEANKSVIEEKARIIYEDYISILSPKE 117

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 568926980 1025 VNLDSYTREHTKENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLD 1074
Cdd:cd08746   118 VSLDSRVREVINRNMLEPSQHTFDDAQLQIYTLMHRDSYPRFMNSAIYKN 167

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 568926980  957 WSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHTK 1036
Cdd:cd08745     1 WAQSFDKLMKSPAGRNVFREFLRTEYSEENMLFWLACEELKAEANKHVIDEKARLIYEDYISILSPKEVSLDSRVREGIN 80

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 568926980 1037 ENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1072
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 568926980  956 KWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKVKSQsKMAAKAKKIFAEFIAIQACKEVNLDSYTREHT 1035
Cdd:cd08737     5 RWGFSLDEVLKDPVGRDQFLRFLESEFSSENLRFWLAVQDLKKQPLQ-DVAKRVEEIWQEFLAPGAPSAINLDSHSYEKT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568926980 1036 KENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDLI 1076
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 568926980  956 KWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHT 1035
Cdd:cd08740     5 RWGFSFRELLNDPVGRKEFLDFLEKEFSAENLSFWEACEELRY-GEQSKIPELVDSVYQQFLAPGATRWVNIDSKTMERT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 568926980 1036 KENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLYLDLINQ 1078
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 568926980  956 KWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKkVKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHT 1035
Cdd:cd08739     4 RWAFNFSELIRDPKGRQSFQLFLKKEFSGENLGFWEACEDLK-YGDQSKVKEKAEEIYKLFLAPGARRWINIDGKTMDIT 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568926980 1036 KENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1072
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 568926980  956 KWSESLEKLLLHKYGLEVFQAFLRTEFSEENLEFWLACEDFKKvKSQSKMAAKAKKIFAEFIAIQACKEVNLDSYTREHT 1035
Cdd:cd08738     4 RWGFGMDEALKDPVGREQFLKFLESEFSSENLRFWLAVEDLKK-RPIREVPSRVQEIWQEFLAPGAPSAINLDSKSYDKT 82

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 568926980 1036 KENLQSITRGCFDLAQKRIFGLMEKDSYPRFLRSDLY 1072
Cdd:cd08738    83 TQNVKDPGRYTFEDAQEHIYKLMKSDSYPRFIRSSAY 119

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980    6 GICDPYVKVSLIPEDSQLPCQTTQIIPDCRDPAFHEHFFFPVPEEGDQKRLLVTVWNRASETRqHTLIGCMSFGVRSLLt 85
Cdd:cd04026    32 GLSDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFDLKPADKDRRLSIEVWDWDRTTR-NDFMGSLSFGVSELI- 109

                          90       100
                  ....*....|....*....|.
gi 568926980   86 pDKEISGWYYLLGEDLGRTKH 106
Cdd:cd04026   110 -KMPVDGWYKLLNQEEGEYYN 129

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980    6 GICDPYVKVSLIPEdsqlPCQTTQIIPDCRDPAFHEHFFFPVPEEGDQkRLLVTVWNRaSETRQHTLIGCMSFGVRSLLT 85
Cdd:cd00030    18 GKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFEFPVLDPESD-TLTVEVWDK-DRFSKDDFLGEVEIPLSELLD 91

                          90
                  ....*....|.
gi 568926980   86 PDKEISGWYYL 96
Cdd:cd00030    92 SGKEGELWLPL 102

PDZ domain 2 of delphilin (L-delphilin isoform), and related domains; PDZ (PSD-95 (Postsynaptic density protein 95), Dlg (Discs large protein), and ZO-1 (Zonula occludens-1)) domain 2 of delphilin (also known as glutamate receptor, ionotropic, delta 2-interacting protein 1, L-delphilin). Delphilin, a postsynaptic protein which it is selectively expressed at cerebellar Purkinje cells, links the glutamate receptor delta 2 subunit (GluRdelta2) with the actin cytoskeleton and various signaling molecules. Two alternatively spliced isoforms of delphilin have been characterized: L-delphilin has two PDZ domains, PDZ1 and PDZ2, and S-delphilin has a single PDZ domain (PDZ2). These two isoforms are differently palmitoylated and may be involved in controlling GluRdelta2 signaling in Purkinje cells. PDZ domains usually bind in a sequence-specific manner to short peptide sequences located at the C-terminal end of their partner proteins (known as PDZ binding motifs). The PDZ superfamily includes canonical PDZ domains as well as those with circular permutations and domain swapping mediated by beta-strands. This delphilin-like family PDZ2 domain is a canonical PDZ domain containing six beta-strands A-F and two alpha-helices (alpha-helix 1 and 2), arranged in the order: beta-strands A, B, C, alpha-helix 1, beta-strands D, E, alpha-helix 2 and beta-strand F

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568926980  138 ITIRRGKDGFGFTICCDSPVRVQAVDSGGPAERAGLQQLDTVLQLNE---RPVEHWKCVELAHEIRSCPS 204
Cdd:cd06744     2 VRVYRGNGSFGFTLRGHAPVYIESVDPGSAAERAGLKPGDRILFLNGldvRNCSHDKVVSLLQGSGSMPT 71