GNAS2_HUMAN
ID GNAS2_HUMAN Reviewed; 394 AA.
AC P63092; A6NI00; E1P5G5; P04895; Q12927; Q14433; Q32P26; Q5JWD2; Q5JWD4;
AC Q5JWD5; Q6NR75; Q6NXS0; Q8TBC0; Q96H70;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Guanine nucleotide-binding protein G(s) subunit alpha isoforms short;
DE AltName: Full=Adenylate cyclase-stimulating G alpha protein;
GN Name=GNAS; Synonyms=GNAS1, GSP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
RC TISSUE=Liver;
RX PubMed=3093273; DOI=10.1016/0014-5793(86)81336-9;
RA Mattera R., Codina J., Crozat A., Kidd V., Woo S.L.C., Birnbaumer L.;
RT "Identification by molecular cloning of two forms of the alpha-subunit of
RT the human liver stimulatory (GS) regulatory component of adenylyl
RT cyclase.";
RL FEBS Lett. 206:36-42(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GNAS-1).
RX PubMed=3131741; DOI=10.1093/nar/16.8.3585;
RA Harris B.A.;
RT "Complete cDNA sequence of a human stimulatory GTP-binding protein alpha
RT subunit.";
RL Nucleic Acids Res. 16:3585-3585(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS
RP GNAS-1 AND GNAS-2).
RX PubMed=3127824; DOI=10.1073/pnas.85.7.2081;
RA Kozasa T., Itoh H., Tsukamoto T., Kaziro Y.;
RT "Isolation and characterization of the human Gs alpha gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2081-2085(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GNAS-1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1; 3 AND 4).
RC TISSUE=Bone marrow, Brain, Muscle, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-394 (ISOFORMS GNAS-1 AND 4).
RX PubMed=3024154; DOI=10.1073/pnas.83.23.8893;
RA Bray P., Carter A., Simons C., Guo V., Puckett C., Kamholz J., Spiegel A.,
RA Nirenberg M.;
RT "Human cDNA clones for four species of G alpha s signal transduction
RT protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8893-8897(1986).
RN [10]
RP PROTEIN SEQUENCE OF 187-199 AND 308-317.
RC TISSUE=Adipocyte;
RX PubMed=15242332; DOI=10.1042/bj20040647;
RA Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.;
RT "Vectorial proteomics reveal targeting, phosphorylation and specific
RT fragmentation of polymerase I and transcript release factor (PTRF) at the
RT surface of caveolae in human adipocytes.";
RL Biochem. J. 383:237-248(2004).
RN [11]
RP FUNCTION.
RX PubMed=12391161; DOI=10.1128/mcb.22.22.7942-7952.2002;
RA Pak Y., Pham N., Rotin D.;
RT "Direct binding of the beta1 adrenergic receptor to the cyclic AMP-
RT dependent guanine nucleotide exchange factor CNrasGEF leads to Ras
RT activation.";
RL Mol. Cell. Biol. 22:7942-7952(2002).
RN [12]
RP INTERACTION WITH ADCY5 AND ADCY6, AND FUNCTION.
RX PubMed=17110384; DOI=10.1074/jbc.m607522200;
RA Gao X., Sadana R., Dessauer C.W., Patel T.B.;
RT "Conditional stimulation of type V and VI adenylyl cyclases by G protein
RT betagamma subunits.";
RL J. Biol. Chem. 282:294-302(2007).
RN [13]
RP INTERACTION WITH CRY1.
RX PubMed=20852621; DOI=10.1038/nm.2214;
RA Zhang E.E., Liu Y., Dentin R., Pongsawakul P.Y., Liu A.C., Hirota T.,
RA Nusinow D.A., Sun X., Landais S., Kodama Y., Brenner D.A., Montminy M.,
RA Kay S.A.;
RT "Cryptochrome mediates circadian regulation of cAMP signaling and hepatic
RT gluconeogenesis.";
RL Nat. Med. 16:1152-1156(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP PALMITOYLATION AT CYS-3.
RX PubMed=21044946; DOI=10.1194/jlr.d011106;
RA Forrester M.T., Hess D.T., Thompson J.W., Hultman R., Moseley M.A.,
RA Stamler J.S., Casey P.J.;
RT "Site-specific analysis of protein S-acylation by resin-assisted capture.";
RL J. Lipid Res. 52:393-398(2011).
RN [17]
RP INTERACTION WITH GAS2L2, AND MUTAGENESIS OF GLN-227 AND ASP-295.
RX PubMed=23994616; DOI=10.1016/j.bbamcr.2013.08.009;
RA Wu Y.C., Lai H.L., Chang W.C., Lin J.T., Liu Y.J., Chern Y.;
RT "A novel Galphas-binding protein, Gas-2 like 2, facilitates the signaling
RT of the A2A adenosine receptor.";
RL Biochim. Biophys. Acta 1833:3145-3154(2013).
RN [18]
RP INTERACTION WITH SASH1.
RX PubMed=23333244; DOI=10.1016/j.cellsig.2012.12.025;
RA Zhou D., Wei Z., Deng S., Wang T., Zai M., Wang H., Guo L., Zhang J.,
RA Zhong H., He L., Xing Q.;
RT "SASH1 regulates melanocyte transepithelial migration through a novel
RT Galphas-SASH1-IQGAP1-E-cadherin dependent pathway.";
RL Cell. Signal. 25:1526-1538(2013).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [20]
RP INTERACTION WITH ADCY5, AND FUNCTION.
RX PubMed=26206488; DOI=10.1124/mol.115.099556;
RA Brand C.S., Sadana R., Malik S., Smrcka A.V., Dessauer C.W.;
RT "Adenylyl cyclase 5 regulation by Gbetagamma involves isoform specific use
RT of multiple interaction sites.";
RL Mol. Pharmacol. 88:758-767(2015).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [22]
RP VARIANTS AHO PRO-99 AND CYS-165.
RX PubMed=8388883; DOI=10.1210/jcem.76.6.8388883;
RA Miric A., Vechio J.D., Levine M.A.;
RT "Heterogeneous mutations in the gene encoding the alpha-subunit of the
RT stimulatory G protein of adenylyl cyclase in Albright hereditary
RT osteodystrophy.";
RL J. Clin. Endocrinol. Metab. 76:1560-1568(1993).
RN [23]
RP VARIANT MAS HIS-201.
RX PubMed=1594625; DOI=10.1073/pnas.89.11.5152;
RA Schwindinger W.F., Francomano C.A., Levine M.A.;
RT "Identification of a mutation in the gene encoding the alpha subunit of the
RT stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5152-5156(1992).
RN [24]
RP VARIANTS MAS CYS-201 AND HIS-201.
RX PubMed=1944469; DOI=10.1056/nejm199112123252403;
RA Weinstein L.S., Shenker A., Gejman P.V., Merino M.J., Friedman E.,
RA Spiegel A.M.;
RT "Activating mutations of the stimulatory G protein in the McCune-Albright
RT syndrome.";
RL N. Engl. J. Med. 325:1688-1695(1991).
RN [25]
RP VARIANTS SOMATOTROPHINOMA CYS-201; HIS-201 AND ARG-227.
RX PubMed=2549426; DOI=10.1038/340692a0;
RA Landis C.A., Masters S.B., Spada A., Pace A.M., Bourne H.R., Vallar L.;
RT "GTPase inhibiting mutations activate the alpha chain of Gs and stimulate
RT adenylyl cyclase in human pituitary tumours.";
RL Nature 340:692-696(1989).
RN [26]
RP VARIANT AHO HIS-385.
RX PubMed=7523385; DOI=10.1016/s0021-9258(18)47261-4;
RA Schwindinger W.F., Miric A., Zimmerman D., Levine M.A.;
RT "A novel Gs alpha mutant in a patient with Albright hereditary
RT osteodystrophy uncouples cell surface receptors from adenylyl cyclase.";
RL J. Biol. Chem. 269:25387-25391(1994).
RN [27]
RP CHARACTERIZATION OF VARIANT PHP1A SER-366.
RX PubMed=8072545; DOI=10.1038/371164a0;
RA Iiri T., Herzmark P., Nakamoto J.M., van Dop C., Bourne H.R.;
RT "Rapid GDP release from Gs alpha in patients with gain and loss of
RT endocrine function.";
RL Nature 371:164-168(1994).
RN [28]
RP VARIANT NON-MAS ENDOCRINE TUMORS LEU-201.
RX PubMed=7751320; DOI=10.1007/bf01366965;
RA Gorelov V.N., Dumon K., Barteneva N.S., Palm D., Roher H.-D.,
RA Goretzki P.E.;
RT "Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs
RT alpha gene.";
RL J. Cancer Res. Clin. Oncol. 121:219-224(1995).
RN [29]
RP VARIANT PITUITARY ADENOMA HIS-227.
RX PubMed=7737262; DOI=10.1111/j.1365-2362.1995.tb01537.x;
RA Williamson E.A., Ince P.G., Harrison D., Kendall-Taylor P., Harris P.E.;
RT "G-protein mutations in human pituitary adrenocorticotrophic hormone-
RT secreting adenomas.";
RL Eur. J. Clin. Invest. 25:128-131(1995).
RN [30]
RP VARIANT PITUITARY TUMOR SER-201.
RX PubMed=8766942; DOI=10.1530/eje.0.1340720;
RA Yang I., Park S., Ryu M., Woo J., Kim S., Kim J., Kim Y., Choi Y.;
RT "Characteristics of gsp-positive growth hormone-secreting pituitary tumors
RT in Korean acromegalic patients.";
RL Eur. J. Endocrinol. 134:720-726(1996).
RN [31]
RP CHARACTERIZATION OF VARIANT AHO HIS-231, AND FUNCTION.
RX PubMed=8702665; DOI=10.1074/jbc.271.33.19653;
RA Farfel Z., Iiri T., Shapira H., Roitman A., Mouallem M., Bourne H.R.;
RT "Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region
RT of Gsalpha impairs receptor stimulation.";
RL J. Biol. Chem. 271:19653-19655(1996).
RN [32]
RP VARIANT POLYOSTOTIC FIBROUS DYSPLASIA SER-201.
RX PubMed=9267696; DOI=10.1016/s8756-3282(97)00107-5;
RA Candeliere G.A., Roughley P.J., Glorieux F.H.;
RT "Polymerase chain reaction-based technique for the selective enrichment and
RT analysis of mosaic arg201 mutations in G alpha s from patients with fibrous
RT dysplasia of bone.";
RL Bone 21:201-206(1997).
RN [33]
RP VARIANT AHO ARG-250.
RX PubMed=9328353; DOI=10.1210/mend.11.11.0013;
RA Warner D.R., Gejman P.V., Collins R.M., Weinstein L.S.;
RT "A novel mutation adjacent to the switch III domain of G(S alpha) in a
RT patient with pseudohypoparathyroidism.";
RL Mol. Endocrinol. 11:1718-1727(1997).
RN [34]
RP CHARACTERIZATION OF VARIANT AHO HIS-231.
RX PubMed=9159128; DOI=10.1073/pnas.94.11.5656;
RA Iiri T., Farfel Z., Bourne H.R.;
RT "Conditional activation defect of a human Gsalpha mutant.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:5656-5661(1997).
RN [35]
RP VARIANT AHO TRP-258, MUTAGENESIS OF ARG-258, AND CHARACTERIZATION OF
RP VARIANT AHO TRP-258.
RX PubMed=9727013; DOI=10.1074/jbc.273.37.23976;
RA Warner D.R., Weng G., Yu S., Matalon R., Weinstein L.S.;
RT "A novel mutation in the switch 3 region of Gs-alpha in a patient with
RT Albright hereditary osteodystrophy impairs GDP binding and receptor
RT activation.";
RL J. Biol. Chem. 273:23976-23983(1998).
RN [36]
RP VARIANT MAS GLY-201.
RX PubMed=10571700; DOI=10.1359/jbmr.1999.14.11.1987;
RA Riminucci M., Fisher L.W., Majolagbe A., Corsi A., Lala R., De Sanctis C.,
RA Robey P.G., Bianco P.;
RT "A novel GNAS1 mutation, R201G, in McCune-albright syndrome.";
RL J. Bone Miner. Res. 14:1987-1989(1999).
RN [37]
RP MUTAGENESIS OF GLN-170 AND ARG-258.
RX PubMed=10200251; DOI=10.1073/pnas.96.8.4268;
RA Warner D.R., Weinstein L.S.;
RT "A mutation in the heterotrimeric stimulatory guanine nucleotide binding
RT protein alpha-subunit with impaired receptor-mediated activation because of
RT elevated GTPase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4268-4272(1999).
RN [38]
RP INVOLVEMENT IN PHP1B.
RX PubMed=11067869; DOI=10.1172/jci10431;
RA Liu J., Litman D., Rosenberg M.J., Yu S., Biesecker L.G., Weinstein L.S.;
RT "A GNAS1 imprinting defect in pseudohypoparathyroidism type IB.";
RL J. Clin. Invest. 106:1167-1174(2000).
RN [39]
RP INVOLVEMENT IN PHP1B.
RX PubMed=11294659; DOI=10.1086/320117;
RA Bastepe M., Lane A.H., Jueppner H.;
RT "Paternal uniparental isodisomy of chromosome 20q -- and the resulting
RT changes in GNAS1 methylation -- as a plausible cause of
RT pseudohypoparathyroidism.";
RL Am. J. Hum. Genet. 68:1283-1289(2001).
RN [40]
RP INVOLVEMENT IN PHP1B, VARIANT ILE-382 DEL, AND CHARACTERIZATION OF VARIANT
RP ILE-382 DEL.
RX PubMed=11029463; DOI=10.1074/jbc.m006032200;
RA Wu W.-I., Schwindinger W.F., Aparicio L.F., Levine M.A.;
RT "Selective resistance to parathyroid hormone caused by a novel uncoupling
RT mutation in the carboxyl terminus of G alpha(s). A cause of
RT pseudohypoparathyroidism type Ib.";
RL J. Biol. Chem. 276:165-171(2001).
RN [41]
RP VARIANT AHO HIS-231.
RX PubMed=11450852; DOI=10.1007/s100380170062;
RA Ishikawa Y., Tajima T., Nakae J., Nagashima T., Satoh K., Okuhara K.,
RA Fujieda K.;
RT "Two mutations of the Gsalpha gene in two Japanese patients with sporadic
RT pseudohypoparathyroidism type Ia.";
RL J. Hum. Genet. 46:426-430(2001).
RN [42]
RP VARIANT AHO LEU-115.
RX PubMed=11600516; DOI=10.1210/jcem.86.10.7946;
RA Ahrens W., Hiort O., Staedt P., Kirschner T., Marschke C., Kruse K.;
RT "Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy.";
RL J. Clin. Endocrinol. Metab. 86:4630-4634(2001).
RN [43]
RP VARIANTS PHP1A ASN-156; MET-159 AND LYS-280.
RX PubMed=11788646; DOI=10.1210/jcem.87.1.8133;
RA Linglart A., Carel J.-C., Garabedian M., Le T., Mallet E., Kottler M.-L.;
RT "GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype
RT relationship and evidence of the maternal transmission of the hormonal
RT resistance.";
RL J. Clin. Endocrinol. Metab. 87:189-197(2002).
RN [44]
RP VARIANT PHP1A GLY-280.
RX PubMed=11926205; DOI=10.1515/jpem.2002.15.3.259;
RA Lim S.H., Poh L.K., Cowell C.T., Tey B.H., Loke K.Y.;
RT "Mutational analysis of the GNAS1 exons encoding the stimulatory G protein
RT in five patients with pseudohypoparathyroidism type 1a.";
RL J. Pediatr. Endocrinol. Metab. 15:259-268(2002).
RN [45]
RP INVOLVEMENT IN PHP1B.
RX PubMed=12858292; DOI=10.1086/377136;
RA Jan de Beur S., Ding C., Germain-Lee E., Cho J., Maret A., Levine M.A.;
RT "Discordance between genetic and epigenetic defects in
RT pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal
RT imprinting at GNAS1.";
RL Am. J. Hum. Genet. 73:314-322(2003).
RN [46]
RP VARIANTS AHO ILE-242; SER-246 AND VAL-259.
RX PubMed=12624854; DOI=10.1086/374566;
RA Rickard S.J., Wilson L.C.;
RT "Analysis of GNAS1 and overlapping transcripts identifies the parental
RT origin of mutations in patients with sporadic Albright hereditary
RT osteodystrophy and reveals a model system in which to observe the effects
RT of splicing mutations on translated and untranslated messenger RNA.";
RL Am. J. Hum. Genet. 72:961-974(2003).
RN [47]
RP VARIANT PHP1A ASN-338.
RX PubMed=12656668; DOI=10.1530/eje.0.1480463;
RA Pohlenz J., Ahrens W., Hiort O.;
RT "A new heterozygous mutation (L338N) in the human Gsalpha (GNAS1) gene as a
RT cause for congenital hypothyroidism in Albright's hereditary
RT osteodystrophy.";
RL Eur. J. Endocrinol. 148:463-468(2003).
RN [48]
RP VARIANTS AIMAH1 HIS-201 AND SER-201.
RX PubMed=12727968; DOI=10.1210/jc.2002-021362;
RA Fragoso M.C.B.V., Domenice S., Latronico A.C., Martin R.M., Pereira M.A.A.,
RA Zerbini M.C.N., Lucon A.M., Mendonca B.B.;
RT "Cushing's syndrome secondary to adrenocorticotropin-independent
RT macronodular adrenocortical hyperplasia due to activating mutations of
RT GNAS1 gene.";
RL J. Clin. Endocrinol. Metab. 88:2147-2151(2003).
RN [49]
RP INVOLVEMENT IN PHP1B.
RX PubMed=14561710; DOI=10.1172/jci200319159;
RA Bastepe M., Froehlich L.F., Hendy G.N., Indridason O.S., Josse R.G.,
RA Koshiyama H., Koerkkoe J., Nakamoto J.M., Rosenbloom A.L., Slyper A.H.,
RA Sugimoto T., Tsatsoulis A., Crawford J.D., Jueppner H.;
RT "Autosomal dominant pseudohypoparathyroidism type Ib is associated with a
RT heterozygous microdeletion that likely disrupts a putative imprinting
RT control element of GNAS.";
RL J. Clin. Invest. 112:1255-1263(2003).
RN [50]
RP VARIANT POH ARG-281.
RX PubMed=14723729; DOI=10.1111/j.1365-2230.2004.01439.x;
RA Chan I., Hamada T., Hardman C., McGrath J.A., Child F.J.;
RT "Progressive osseous heteroplasia resulting from a new mutation in the
RT GNAS1 gene.";
RL Clin. Exp. Dermatol. 29:77-80(2004).
RN [51]
RP INVOLVEMENT IN PHP1B.
RX PubMed=15800843; DOI=10.1086/429932;
RA Linglart A., Gensure R.C., Olney R.C., Jueppner H., Bastepe M.;
RT "A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type
RT Ib redefines the boundaries of a cis-acting imprinting control element of
RT GNAS.";
RL Am. J. Hum. Genet. 76:804-814(2005).
RN [52]
RP VARIANT AHO/PHP1A SER-106.
RX PubMed=15817905; DOI=10.1530/eje.1.01879;
RA Riepe F.G., Ahrens W., Krone N., Foelster-Holst R., Brasch J.,
RA Sippell W.G., Hiort O., Partsch C.-J.;
RT "Early manifestation of calcinosis cutis in pseudohypoparathyroidism type
RT Ia associated with a novel mutation in the GNAS gene.";
RL Eur. J. Endocrinol. 152:515-519(2005).
RN [53]
RP INVOLVEMENT IN PHP1B.
RX PubMed=15592469; DOI=10.1038/ng1487;
RA Bastepe M., Froehlich L.F., Linglart A., Abu-Zahra H.S., Tojo K.,
RA Ward L.M., Jueppner H.;
RT "Deletion of the NESP55 differentially methylated region causes loss of
RT maternal GNAS imprints and pseudohypoparathyroidism type Ib.";
RL Nat. Genet. 37:25-27(2005).
RN [54]
RP VARIANTS PHP1C ARG-388 AND LYS-392, CHARACTERIZATION OF VARIANTS PHP1C
RP ARG-388 AND LYS-392, AND FUNCTION.
RX PubMed=21488135; DOI=10.1002/humu.21489;
RA Thiele S., de Sanctis L., Werner R., Grotzinger J., Aydin C., Juppner H.,
RA Bastepe M., Hiort O.;
RT "Functional characterization of GNAS mutations found in patients with
RT pseudohypoparathyroidism type Ic defines a new subgroup of
RT pseudohypoparathyroidism affecting selectively Gsalpha-receptor
RT interaction.";
RL Hum. Mutat. 32:653-660(2011).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) function as
CC transducers in numerous signaling pathways controlled by G protein-
CC coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the
CC activation of adenylyl cyclases, resulting in increased levels of the
CC signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS
CC functions downstream of several GPCRs, including beta-adrenergic
CC receptors (PubMed:21488135). Stimulates the Ras signaling pathway via
CC RAPGEF2 (PubMed:12391161). {ECO:0000269|PubMed:12391161,
CC ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:21488135,
CC ECO:0000269|PubMed:26206488, ECO:0000269|PubMed:8702665}.
CC -!- SUBUNIT: Heterotrimeric G proteins are composed of 3 units; alpha, beta
CC and gamma. The alpha chain contains the guanine nucleotide binding
CC site. Interacts with CRY1; the interaction may block GPCR-mediated
CC regulation of cAMP concentrations (PubMed:20852621). Interacts with
CC ADCY5 and stimulates its adenylyl cyclase activity (PubMed:17110384,
CC PubMed:26206488). Interacts with ADCY6 and stimulates its adenylyl
CC cyclase activity (PubMed:17110384). Interacts with ADCY2 (By
CC similarity). Interaction with SASH1 (PubMed:23333244). Interacts with
CC GAS2L2 (PubMed:23994616). {ECO:0000250|UniProtKB:P04896,
CC ECO:0000269|PubMed:17110384, ECO:0000269|PubMed:20852621,
CC ECO:0000269|PubMed:23333244, ECO:0000269|PubMed:23994616}.
CC -!- INTERACTION:
CC P63092; O89053: Coro1a; Xeno; NbExp=2; IntAct=EBI-1047114, EBI-6665847;
CC P63092-2; P42866: Oprm1; Xeno; NbExp=2; IntAct=EBI-7607528, EBI-5282656;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P63094};
CC Lipid-anchor {ECO:0000250|UniProtKB:P63094}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=Gnas-1; Synonyms=Alpha-S2, GNASl, Alpha-S-long;
CC IsoId=P63092-1, P04895-1;
CC Sequence=Displayed;
CC Name=Gnas-2; Synonyms=Alpha-S1, GNASs, Alpha-S-short;
CC IsoId=P63092-2, P04895-2;
CC Sequence=VSP_001833, VSP_001834;
CC Name=3;
CC IsoId=P63092-3; Sequence=VSP_026616, VSP_026617;
CC Name=XLas-1;
CC IsoId=Q5JWF2-1; Sequence=External;
CC Name=XLas-2;
CC IsoId=Q5JWF2-2; Sequence=External;
CC Name=XLas-3;
CC IsoId=Q5JWF2-3; Sequence=External;
CC Name=Nesp55;
CC IsoId=O95467-1; Sequence=External;
CC Name=4;
CC IsoId=P63092-4; Sequence=VSP_047325;
CC -!- DISEASE: Albright hereditary osteodystrophy (AHO) [MIM:103580]: A
CC disorder characterized by short stature, obesity, round facies,
CC brachydactyly and subcutaneous calcification. It is often associated
CC with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.
CC {ECO:0000269|PubMed:11450852, ECO:0000269|PubMed:11600516,
CC ECO:0000269|PubMed:12624854, ECO:0000269|PubMed:15817905,
CC ECO:0000269|PubMed:7523385, ECO:0000269|PubMed:8388883,
CC ECO:0000269|PubMed:8702665, ECO:0000269|PubMed:9159128,
CC ECO:0000269|PubMed:9328353, ECO:0000269|PubMed:9727013}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Pseudohypoparathyroidism 1A (PHP1A) [MIM:103580]: A disorder
CC characterized by end-organ resistance to parathyroid hormone,
CC hypocalcemia and hyperphosphatemia. It is commonly associated with
CC Albright hereditary osteodystrophy whose features are short stature,
CC obesity, round facies, short metacarpals and ectopic calcification.
CC {ECO:0000269|PubMed:11788646, ECO:0000269|PubMed:11926205,
CC ECO:0000269|PubMed:12656668, ECO:0000269|PubMed:8072545}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: McCune-Albright syndrome (MAS) [MIM:174800]: Characterized by
CC polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of
CC endocrine disorders, including precocious puberty, hyperthyroidism,
CC hypercortisolism, growth hormone excess, and hyperprolactinemia. The
CC mutations producing MAS lead to constitutive activation of GS alpha.
CC {ECO:0000269|PubMed:10571700, ECO:0000269|PubMed:1594625,
CC ECO:0000269|PubMed:1944469, ECO:0000269|PubMed:7751320}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Progressive osseous heteroplasia (POH) [MIM:166350]: Rare
CC autosomal dominant disorder characterized by extensive dermal
CC ossification during childhood, followed by disabling and widespread
CC heterotopic ossification of skeletal muscle and deep connective tissue.
CC {ECO:0000269|PubMed:14723729}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1)
CC [MIM:219080]: A rare adrenal defect characterized by multiple,
CC bilateral, non-pigmented, benign, adrenocortical nodules. It results in
CC excessive production of cortisol leading to ACTH-independent Cushing
CC syndrome. Clinical manifestations of Cushing syndrome include facial
CC and truncal obesity, abdominal striae, muscular weakness, osteoporosis,
CC arterial hypertension, diabetes. {ECO:0000269|PubMed:12727968}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder
CC characterized by end-organ resistance to parathyroid hormone,
CC hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack
CC developmental defects characteristic of Albright hereditary
CC osteodystrophy, and typically show no other endocrine abnormalities
CC besides resistance to PTH. {ECO:0000269|PubMed:11029463,
CC ECO:0000269|PubMed:11067869, ECO:0000269|PubMed:11294659,
CC ECO:0000269|PubMed:12858292, ECO:0000269|PubMed:14561710,
CC ECO:0000269|PubMed:15592469, ECO:0000269|PubMed:15800843}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. Most affected individuals have defects in methylation of the
CC gene. In some cases microdeletions involving the STX16 appear to cause
CC loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal
CC uniparental isodisomy have also been observed.
CC -!- DISEASE: GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is
CC characterized by increased trauma-related bleeding tendency, prolonged
CC bleeding time, brachydactyly and intellectual disability. Both the XLas
CC isoforms and the ALEX protein are mutated which strongly reduces the
CC interaction between them and this may allow unimpeded activation of the
CC XLas isoforms. Note=The disease is caused by variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: A disorder
CC characterized by end-organ resistance to parathyroid hormone,
CC hypocalcemia and hyperphosphatemia. It is commonly associated with
CC Albright hereditary osteodystrophy whose features are short stature,
CC obesity, round facies, short metacarpals and ectopic calcification.
CC {ECO:0000269|PubMed:21488135}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the ALEX protein from an overlapping reading frame.
CC -!- MISCELLANEOUS: The GNAS locus is imprinted in a complex manner, giving
CC rise to distinct paternally, maternally and biallelically expressed
CC proteins. The XLas isoforms are paternally derived, the Gnas isoforms
CC are biallelically derived and the Nesp55 isoforms are maternally
CC derived.
CC -!- SIMILARITY: Belongs to the G-alpha family. G(s) subfamily.
CC {ECO:0000305}.
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DR EMBL; X04408; CAA27996.1; -; mRNA.
DR EMBL; X04409; CAA27997.1; -; mRNA.
DR EMBL; M21142; AAA53147.1; -; Genomic_DNA.
DR EMBL; M21139; AAA53147.1; JOINED; Genomic_DNA.
DR EMBL; M21740; AAA53147.1; JOINED; Genomic_DNA.
DR EMBL; M21140; AAA53147.1; JOINED; Genomic_DNA.
DR EMBL; M21741; AAA53147.1; JOINED; Genomic_DNA.
DR EMBL; M21141; AAA53147.1; JOINED; Genomic_DNA.
DR EMBL; M21142; AAA53146.1; -; Genomic_DNA.
DR EMBL; M21139; AAA53146.1; JOINED; Genomic_DNA.
DR EMBL; M21740; AAA53146.1; JOINED; Genomic_DNA.
DR EMBL; M21140; AAA53146.1; JOINED; Genomic_DNA.
DR EMBL; M21741; AAA53146.1; JOINED; Genomic_DNA.
DR EMBL; M21141; AAA53146.1; JOINED; Genomic_DNA.
DR EMBL; M21142; AAA53148.1; -; Genomic_DNA.
DR EMBL; M21139; AAA53148.1; JOINED; Genomic_DNA.
DR EMBL; M21141; AAA53148.1; JOINED; Genomic_DNA.
DR EMBL; M21740; AAA53148.1; JOINED; Genomic_DNA.
DR EMBL; M21741; AAA53148.1; JOINED; Genomic_DNA.
DR EMBL; M21142; AAA53149.1; -; Genomic_DNA.
DR EMBL; M21139; AAA53149.1; JOINED; Genomic_DNA.
DR EMBL; M21740; AAA53149.1; JOINED; Genomic_DNA.
DR EMBL; M21741; AAA53149.1; JOINED; Genomic_DNA.
DR EMBL; M21141; AAA53149.1; JOINED; Genomic_DNA.
DR EMBL; U12466; AAB60334.2; -; Genomic_DNA.
DR EMBL; X07036; CAA30084.1; -; mRNA.
DR EMBL; AF493897; AAM12611.1; -; mRNA.
DR EMBL; AF493898; AAM12612.1; -; mRNA.
DR EMBL; BT009905; AAP88907.1; -; mRNA.
DR EMBL; AL109840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121917; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL132655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75468.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75460.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75463.1; -; Genomic_DNA.
DR EMBL; BC002722; AAH02722.1; -; mRNA.
DR EMBL; BC008855; AAH08855.1; -; mRNA.
DR EMBL; BC066923; AAH66923.1; -; mRNA.
DR EMBL; BC022875; AAH22875.1; -; mRNA.
DR EMBL; BC104928; AAI04929.1; -; mRNA.
DR EMBL; BC108315; AAI08316.2; -; mRNA.
DR EMBL; M14631; AAA52583.1; -; mRNA.
DR CCDS; CCDS13472.1; -.
DR CCDS; CCDS42892.1; -. [P63092-3]
DR CCDS; CCDS46623.1; -. [P63092-4]
DR CCDS; CCDS46624.1; -. [P63092-2]
DR PIR; B31927; RGHUA2.
DR PIR; C31927; RGHUA1.
DR RefSeq; NP_000507.1; NM_000516.5. [P63092-1]
DR RefSeq; NP_001070956.1; NM_001077488.3. [P63092-4]
DR RefSeq; NP_001070957.1; NM_001077489.3. [P63092-3]
DR RefSeq; NP_001070958.1; NM_001077490.2.
DR RefSeq; NP_001296769.1; NM_001309840.1.
DR RefSeq; NP_536350.2; NM_080425.3.
DR RefSeq; NP_536351.1; NM_080426.3. [P63092-2]
DR PDB; 5G53; X-ray; 3.40 A; C/D=26-60, C/D=204-394.
DR PDB; 5UZ7; EM; 4.10 A; A=1-394.
DR PDB; 5VAI; EM; 4.10 A; A=1-394.
DR PDB; 6AU6; X-ray; 1.70 A; A=7-394.
DR PDB; 6B3J; EM; 3.30 A; A=1-394.
DR PDB; 6E3Y; EM; 3.30 A; A=1-394.
DR PDB; 6E67; X-ray; 3.70 A; A/B=381-393.
DR PDB; 6EG8; X-ray; 2.80 A; I/J/K/L=4-394.
DR PDB; 6GDG; EM; 4.11 A; D=6-64, D=204-394.
DR PDB; 6LI3; EM; 3.32 A; A=6-64, A=204-394.
DR PDB; 6LMK; EM; 3.70 A; A=1-394.
DR PDB; 6LPB; EM; 3.90 A; A=5-394.
DR PDB; 6M1H; EM; 3.60 A; F=1-394.
DR PDB; 6M1I; EM; 3.50 A; F=1-394.
DR PDB; 6NI3; EM; 3.80 A; A=1-394.
DR PDB; 6NIY; EM; 3.34 A; A=1-394.
DR PDB; 6ORV; EM; 3.00 A; AP=1-394.
DR PDB; 6P9X; EM; 2.91 A; A=1-394.
DR PDB; 6P9Y; EM; 3.01 A; A=1-394.
DR PDB; 6PB0; EM; 3.00 A; A=1-67, A=208-394.
DR PDB; 6PB1; EM; 2.80 A; A=1-67, A=208-394.
DR PDB; 6UUN; EM; 3.00 A; A=1-394.
DR PDB; 6UUS; EM; 2.40 A; A=1-394.
DR PDB; 6UVA; EM; 2.30 A; A=1-394.
DR PDB; 6VCB; EM; 3.30 A; A=1-394.
DR PDB; 6VN7; EM; 3.20 A; A=1-394.
DR PDB; 6WHC; EM; 3.40 A; A=1-394.
DR PDB; 6WI9; EM; 4.30 A; A=1-394.
DR PDB; 6WPW; EM; 3.10 A; C=1-394.
DR PDB; 6WZG; EM; 2.30 A; A=1-394.
DR PDB; 6X18; EM; 2.10 A; A=1-394.
DR PDB; 6X19; EM; 2.10 A; A=1-394.
DR PDB; 6X1A; EM; 2.50 A; A=1-394.
DR PDB; 6XOX; EM; 3.10 A; A=27-394.
DR PDB; 7AUE; EM; 2.97 A; A=1-394.
DR PDB; 7BB6; EM; 4.20 A; E=1-394.
DR PDB; 7BB7; EM; 4.40 A; E=1-394.
DR PDB; 7BPH; X-ray; 1.57 A; A=7-394.
DR PDB; 7BW0; EM; 3.90 A; A=26-394.
DR PDB; 7BZ2; EM; 3.82 A; A=1-394.
DR PDB; 7C2E; EM; 4.20 A; A=1-394.
DR PDB; 7CFM; EM; 3.00 A; A=1-394.
DR PDB; 7CFN; EM; 3.00 A; A=1-394.
DR PDB; 7CKW; EM; 3.22 A; A=1-394.
DR PDB; 7CKX; EM; 3.54 A; A=1-394.
DR PDB; 7CKY; EM; 3.20 A; A=1-394.
DR PDB; 7CKZ; EM; 3.10 A; A=1-394.
DR PDB; 7CRH; EM; 3.30 A; A=1-394.
DR PDB; 7CX2; EM; 2.80 A; A=1-394.
DR PDB; 7CX3; EM; 2.80 A; A=1-394.
DR PDB; 7CX4; EM; 2.90 A; A=1-394.
DR PDB; 7CZ5; EM; 2.60 A; A=1-394.
DR PDB; 7D3S; EM; 2.90 A; A=5-394.
DR PDB; 7D7M; EM; 3.30 A; D=5-64, D=204-394.
DR PDB; 7DH5; EM; 3.16 A; A=5-64, A=204-394.
DR PDB; 7DHI; EM; 3.26 A; A=1-394.
DR PDB; 7DHR; EM; 3.80 A; A=1-394.
DR PDB; 7DUQ; EM; 2.50 A; A=1-394.
DR PDB; 7DUR; EM; 3.30 A; A=1-394.
DR PDB; 7DW9; EM; 2.60 A; A=27-67, A=205-251, A=266-394.
DR PDB; 7E14; EM; 2.90 A; A=1-394.
DR PDB; 7E5E; X-ray; 1.95 A; A/B/C/D=35-394.
DR PDB; 7EVM; EM; 2.50 A; A=1-394.
DR PDB; 7EVW; EM; 3.22 A; A=6-394.
DR PDB; 7EZK; EM; 3.10 A; A=27-67, A=205-251, A=266-394.
DR PDB; 7F16; EM; 2.80 A; A=1-394.
DR PDB; 7F4F; EM; 2.90 A; A=27-67, A=205-251, A=266-394.
DR PDB; 7F4I; EM; 3.10 A; A=27-67, A=205-251, A=266-394.
DR PDB; 7F53; EM; 3.00 A; A=1-394.
DR PDB; 7F54; EM; 3.00 A; A=1-394.
DR PDB; 7F55; EM; 3.10 A; A=1-394.
DR PDB; 7F58; EM; 3.10 A; A=1-394.
DR PDB; 7JOZ; X-ray; 3.80 A; A=1-394.
DR PDB; 7JV5; EM; 3.00 A; A=2-394.
DR PDB; 7JVP; EM; 2.90 A; A=2-394.
DR PDB; 7JVQ; EM; 3.00 A; A=1-394.
DR PDB; 7KH0; EM; 2.80 A; A=27-394.
DR PDB; 7KI0; EM; 2.50 A; A=1-394.
DR PDB; 7KI1; EM; 2.50 A; A=1-394.
DR PDB; 7LCI; EM; 2.90 A; A=1-394.
DR PDB; 7LJC; EM; 3.00 A; A=1-394.
DR PDB; 7LJD; EM; 3.20 A; A=1-394.
DR PDB; 7LLL; EM; 3.70 A; A=1-394.
DR PDB; 7LLY; EM; 3.30 A; A=1-394.
DR PDB; 7MBX; EM; 1.95 A; A=1-394.
DR PDB; 7P02; EM; 2.87 A; A=204-251, A=266-394.
DR PDB; 7PIU; EM; 2.58 A; A=1-394.
DR PDB; 7PIV; EM; 2.86 A; A=1-394.
DR PDB; 7RA3; EM; 3.24 A; A=27-394.
DR PDB; 7RBT; EM; 3.08 A; A=26-394.
DR PDB; 7RG9; EM; 3.20 A; A=26-394.
DR PDB; 7RMH; EM; 3.10 A; A=6-64, A=204-394.
DR PDB; 7RTB; EM; 2.14 A; A=1-394.
DR PDB; 7S1M; EM; 2.41 A; A=1-394.
DR PDB; 7S3I; EM; 2.51 A; A=1-394.
DR PDB; 7TYF; EM; 2.20 A; A=1-394.
DR PDB; 7TYH; EM; 3.30 A; A=1-394.
DR PDB; 7TYI; EM; 3.30 A; A=1-394.
DR PDB; 7TYL; EM; 3.30 A; A=1-394.
DR PDB; 7TYN; EM; 2.60 A; A=1-394.
DR PDB; 7TYO; EM; 2.70 A; A=1-394.
DR PDB; 7TYW; EM; 3.00 A; A=1-394.
DR PDB; 7TYX; EM; 2.55 A; A=1-394.
DR PDB; 7TYY; EM; 3.00 A; A=1-394.
DR PDB; 7TZF; EM; 2.40 A; A=1-394.
DR PDB; 7V35; EM; 3.40 A; A=1-394.
DR PDB; 7V9M; EM; 3.29 A; A=1-394.
DR PDB; 7VBH; EM; 3.00 A; A=1-394.
DR PDB; 7VBI; EM; 3.00 A; A=12-394.
DR PDB; 7VUH; EM; 3.22 A; A=5-64, A=204-371.
DR PDB; 7VUI; EM; 3.30 A; A=5-64, A=204-371.
DR PDB; 7VUJ; EM; 3.80 A; A=5-64, A=204-371.
DR PDBsum; 5G53; -.
DR PDBsum; 5UZ7; -.
DR PDBsum; 5VAI; -.
DR PDBsum; 6AU6; -.
DR PDBsum; 6B3J; -.
DR PDBsum; 6E3Y; -.
DR PDBsum; 6E67; -.
DR PDBsum; 6EG8; -.
DR PDBsum; 6GDG; -.
DR PDBsum; 6LI3; -.
DR PDBsum; 6LMK; -.
DR PDBsum; 6LPB; -.
DR PDBsum; 6M1H; -.
DR PDBsum; 6M1I; -.
DR PDBsum; 6NI3; -.
DR PDBsum; 6NIY; -.
DR PDBsum; 6ORV; -.
DR PDBsum; 6P9X; -.
DR PDBsum; 6P9Y; -.
DR PDBsum; 6PB0; -.
DR PDBsum; 6PB1; -.
DR PDBsum; 6UUN; -.
DR PDBsum; 6UUS; -.
DR PDBsum; 6UVA; -.
DR PDBsum; 6VCB; -.
DR PDBsum; 6VN7; -.
DR PDBsum; 6WHC; -.
DR PDBsum; 6WI9; -.
DR PDBsum; 6WPW; -.
DR PDBsum; 6WZG; -.
DR PDBsum; 6X18; -.
DR PDBsum; 6X19; -.
DR PDBsum; 6X1A; -.
DR PDBsum; 6XOX; -.
DR PDBsum; 7AUE; -.
DR PDBsum; 7BB6; -.
DR PDBsum; 7BB7; -.
DR PDBsum; 7BPH; -.
DR PDBsum; 7BW0; -.
DR PDBsum; 7BZ2; -.
DR PDBsum; 7C2E; -.
DR PDBsum; 7CFM; -.
DR PDBsum; 7CFN; -.
DR PDBsum; 7CKW; -.
DR PDBsum; 7CKX; -.
DR PDBsum; 7CKY; -.
DR PDBsum; 7CKZ; -.
DR PDBsum; 7CRH; -.
DR PDBsum; 7CX2; -.
DR PDBsum; 7CX3; -.
DR PDBsum; 7CX4; -.
DR PDBsum; 7CZ5; -.
DR PDBsum; 7D3S; -.
DR PDBsum; 7D7M; -.
DR PDBsum; 7DH5; -.
DR PDBsum; 7DHI; -.
DR PDBsum; 7DHR; -.
DR PDBsum; 7DUQ; -.
DR PDBsum; 7DUR; -.
DR PDBsum; 7DW9; -.
DR PDBsum; 7E14; -.
DR PDBsum; 7E5E; -.
DR PDBsum; 7EVM; -.
DR PDBsum; 7EVW; -.
DR PDBsum; 7EZK; -.
DR PDBsum; 7F16; -.
DR PDBsum; 7F4F; -.
DR PDBsum; 7F4I; -.
DR PDBsum; 7F53; -.
DR PDBsum; 7F54; -.
DR PDBsum; 7F55; -.
DR PDBsum; 7F58; -.
DR PDBsum; 7JOZ; -.
DR PDBsum; 7JV5; -.
DR PDBsum; 7JVP; -.
DR PDBsum; 7JVQ; -.
DR PDBsum; 7KH0; -.
DR PDBsum; 7KI0; -.
DR PDBsum; 7KI1; -.
DR PDBsum; 7LCI; -.
DR PDBsum; 7LJC; -.
DR PDBsum; 7LJD; -.
DR PDBsum; 7LLL; -.
DR PDBsum; 7LLY; -.
DR PDBsum; 7MBX; -.
DR PDBsum; 7P02; -.
DR PDBsum; 7PIU; -.
DR PDBsum; 7PIV; -.
DR PDBsum; 7RA3; -.
DR PDBsum; 7RBT; -.
DR PDBsum; 7RG9; -.
DR PDBsum; 7RMH; -.
DR PDBsum; 7RTB; -.
DR PDBsum; 7S1M; -.
DR PDBsum; 7S3I; -.
DR PDBsum; 7TYF; -.
DR PDBsum; 7TYH; -.
DR PDBsum; 7TYI; -.
DR PDBsum; 7TYL; -.
DR PDBsum; 7TYN; -.
DR PDBsum; 7TYO; -.
DR PDBsum; 7TYW; -.
DR PDBsum; 7TYX; -.
DR PDBsum; 7TYY; -.
DR PDBsum; 7TZF; -.
DR PDBsum; 7V35; -.
DR PDBsum; 7V9M; -.
DR PDBsum; 7VBH; -.
DR PDBsum; 7VBI; -.
DR PDBsum; 7VUH; -.
DR PDBsum; 7VUI; -.
DR PDBsum; 7VUJ; -.
DR AlphaFoldDB; P63092; -.
DR SMR; P63092; -.
DR BioGRID; 109040; 213.
DR CORUM; P63092; -.
DR IntAct; P63092; 57.
DR MINT; P63092; -.
DR ChEMBL; CHEMBL4377; -.
DR DrugBank; DB06843; 2',5'-DIDEOXY-ADENOSINE 3'-MONOPHOSPHATE.
DR DrugBank; DB02587; Colforsin.
DR TCDB; 8.A.92.1.1; the g-protein AlphaBetaGama complex (gpc) family.
DR iPTMnet; P63092; -.
DR PhosphoSitePlus; P63092; -.
DR SwissPalm; P63092; -.
DR BioMuta; GNAS; -.
DR DMDM; 52000961; -.
DR EPD; P63092; -.
DR jPOST; P63092; -.
DR MassIVE; P63092; -.
DR MaxQB; P63092; -.
DR PeptideAtlas; P63092; -.
DR PRIDE; P63092; -.
DR ProteomicsDB; 1235; -.
DR ProteomicsDB; 57472; -.
DR ProteomicsDB; 57473; -. [P63092-2]
DR ProteomicsDB; 57474; -. [P63092-3]
DR Antibodypedia; 4152; 809 antibodies from 44 providers.
DR DNASU; 2778; -.
DR Ensembl; ENST00000265620.11; ENSP00000265620.7; ENSG00000087460.29. [P63092-3]
DR Ensembl; ENST00000354359.12; ENSP00000346328.7; ENSG00000087460.29. [P63092-4]
DR Ensembl; ENST00000371085.8; ENSP00000360126.3; ENSG00000087460.29. [P63092-1]
DR Ensembl; ENST00000371095.7; ENSP00000360136.3; ENSG00000087460.29. [P63092-2]
DR GeneID; 2778; -.
DR KEGG; hsa:2778; -.
DR MANE-Select; ENST00000371085.8; ENSP00000360126.3; NM_000516.7; NP_000507.1.
DR UCSC; uc002yaa.4; human.
DR CTD; 2778; -.
DR DisGeNET; 2778; -.
DR GeneCards; GNAS; -.
DR GeneReviews; GNAS; -.
DR HGNC; HGNC:4392; GNAS.
DR HPA; ENSG00000087460; Low tissue specificity.
DR MalaCards; GNAS; -.
DR MIM; 103580; phenotype.
DR MIM; 139320; gene+phenotype.
DR MIM; 166350; phenotype.
DR MIM; 174800; phenotype.
DR MIM; 219080; phenotype.
DR MIM; 603233; phenotype.
DR MIM; 612462; phenotype.
DR neXtProt; NX_P63092; -.
DR OpenTargets; ENSG00000087460; -.
DR Orphanet; 189427; Cushing syndrome due to macronodular adrenal hyperplasia.
DR Orphanet; 57782; Mazabraud syndrome.
DR Orphanet; 562; McCune-Albright syndrome.
DR Orphanet; 93277; Monostotic fibrous dysplasia.
DR Orphanet; 93276; Polyostotic fibrous dysplasia.
DR Orphanet; 2762; Progressive osseous heteroplasia.
DR Orphanet; 79443; Pseudohypoparathyroidism type 1A.
DR Orphanet; 94089; Pseudohypoparathyroidism type 1B.
DR Orphanet; 79444; Pseudohypoparathyroidism type 1C.
DR Orphanet; 79445; Pseudopseudohypoparathyroidism.
DR PharmGKB; PA175; -.
DR VEuPathDB; HostDB:ENSG00000087460; -.
DR GeneTree; ENSGT00940000156300; -.
DR HOGENOM; CLU_014184_3_0_1; -.
DR OMA; QENRATC; -.
DR OrthoDB; 754573at2759; -.
DR PathwayCommons; P63092; -.
DR Reactome; R-HSA-163359; Glucagon signaling in metabolic regulation.
DR Reactome; R-HSA-164378; PKA activation in glucagon signalling.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-392851; Prostacyclin signalling through prostacyclin receptor.
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-420092; Glucagon-type ligand receptors.
DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-HSA-5610787; Hedgehog 'off' state.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P63092; -.
DR SIGNOR; P63092; -.
DR BioGRID-ORCS; 2778; 28 hits in 1092 CRISPR screens.
DR ChiTaRS; GNAS; human.
DR GenomeRNAi; 2778; -.
DR Pharos; P63092; Tbio.
DR Proteomes; UP000005640; Chromosome 20.
DR Bgee; ENSG00000087460; Expressed in type B pancreatic cell and 213 other tissues.
DR ExpressionAtlas; P63092; baseline and differential.
DR Genevisible; P63092; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005834; C:heterotrimeric G-protein complex; ISS:BHF-UCL.
DR GO; GO:0031224; C:intrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0010856; F:adenylate cyclase activator activity; ISS:UniProtKB.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:UniProtKB.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0060348; P:bone development; IDA:UniProtKB.
DR GO; GO:0071870; P:cellular response to catecholamine stimulus; ISS:BHF-UCL.
DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; ISS:BHF-UCL.
DR GO; GO:0050890; P:cognition; IDA:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IDA:UniProtKB.
DR GO; GO:0060789; P:hair follicle placode formation; IDA:UniProtKB.
DR GO; GO:0046907; P:intracellular transport; NAS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IDA:UniProtKB.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0007608; P:sensory perception of smell; TAS:UniProtKB.
DR CDD; cd00066; G-alpha; 1.
DR Gene3D; 1.10.400.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000367; Gprotein_alpha_S.
DR InterPro; IPR001019; Gprotein_alpha_su.
DR InterPro; IPR011025; GproteinA_insert.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10218; PTHR10218; 1.
DR Pfam; PF00503; G-alpha; 1.
DR PRINTS; PR00318; GPROTEINA.
DR PRINTS; PR00443; GPROTEINAS.
DR SMART; SM00275; G_alpha; 1.
DR SUPFAM; SSF47895; SSF47895; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51882; G_ALPHA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing; Cell membrane;
KW Cushing syndrome; Direct protein sequencing; Disease variant; Dwarfism;
KW GTP-binding; Isopeptide bond; Lipoprotein; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Obesity; Palmitate; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Transducer; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT CHAIN 2..394
FT /note="Guanine nucleotide-binding protein G(s) subunit
FT alpha isoforms short"
FT /id="PRO_0000203721"
FT DOMAIN 39..394
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 42..55
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 68..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..204
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 219..228
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 288..295
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 364..369
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT COMPBIAS 9..23
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 47..55
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 54
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 197..204
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 204
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 223..227
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 292..295
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 366
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT MOD_RES 201
FT /note="ADP-ribosylarginine; by cholera toxin"
FT /evidence="ECO:0000250"
FT MOD_RES 352
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT LIPID 2
FT /note="N-palmitoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:21044946"
FT CROSSLNK 300
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT VAR_SEQ 71..72
FT /note="EG -> DS (in isoform Gnas-2)"
FT /evidence="ECO:0000303|PubMed:3093273, ECO:0000303|Ref.4"
FT /id="VSP_001833"
FT VAR_SEQ 71
FT /note="E -> D (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026616"
FT VAR_SEQ 72..86
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026617"
FT VAR_SEQ 73..86
FT /note="Missing (in isoform Gnas-2)"
FT /evidence="ECO:0000303|PubMed:3093273, ECO:0000303|Ref.4"
FT /id="VSP_001834"
FT VAR_SEQ 86
FT /note="G -> GS (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:3024154"
FT /id="VSP_047325"
FT VARIANT 99
FT /note="L -> P (in AHO; dbSNP:rs137854531)"
FT /evidence="ECO:0000269|PubMed:8388883"
FT /id="VAR_003439"
FT VARIANT 106
FT /note="I -> S (in AHO/PHP1A)"
FT /evidence="ECO:0000269|PubMed:15817905"
FT /id="VAR_031872"
FT VARIANT 115
FT /note="P -> L (in AHO; dbSNP:rs137854539)"
FT /evidence="ECO:0000269|PubMed:11600516"
FT /id="VAR_017843"
FT VARIANT 156
FT /note="D -> N (in PHP1A)"
FT /evidence="ECO:0000269|PubMed:11788646"
FT /id="VAR_031873"
FT VARIANT 159
FT /note="V -> M (in PHP1A)"
FT /evidence="ECO:0000269|PubMed:11788646"
FT /id="VAR_031874"
FT VARIANT 165
FT /note="R -> C (in AHO; dbSNP:rs137854532)"
FT /evidence="ECO:0000269|PubMed:8388883"
FT /id="VAR_003440"
FT VARIANT 201
FT /note="R -> C (in MAS; also found in somatotrophinoma;
FT dbSNP:rs11554273)"
FT /evidence="ECO:0000269|PubMed:1944469,
FT ECO:0000269|PubMed:2549426"
FT /id="VAR_003442"
FT VARIANT 201
FT /note="R -> G (in MAS; dbSNP:rs11554273)"
FT /evidence="ECO:0000269|PubMed:10571700"
FT /id="VAR_017844"
FT VARIANT 201
FT /note="R -> H (in MAS and AIMAH1; also found in
FT somatotrophinoma; dbSNP:rs121913495)"
FT /evidence="ECO:0000269|PubMed:12727968,
FT ECO:0000269|PubMed:1594625, ECO:0000269|PubMed:1944469,
FT ECO:0000269|PubMed:2549426"
FT /id="VAR_003441"
FT VARIANT 201
FT /note="R -> L (in non-MAS endocrine tumors;
FT dbSNP:rs121913495)"
FT /evidence="ECO:0000269|PubMed:7751320"
FT /id="VAR_017845"
FT VARIANT 201
FT /note="R -> S (in AIMAH1; also found in pituitary tumor and
FT polyostotic fibrous dysplasia; dbSNP:rs11554273)"
FT /evidence="ECO:0000269|PubMed:12727968,
FT ECO:0000269|PubMed:8766942, ECO:0000269|PubMed:9267696"
FT /id="VAR_017846"
FT VARIANT 227
FT /note="Q -> H (in pituitary adenomas; also found in a
FT patient with severe Cushing syndrome; dbSNP:rs137854533)"
FT /evidence="ECO:0000269|PubMed:7737262"
FT /id="VAR_017847"
FT VARIANT 227
FT /note="Q -> R (in somatotrophinoma; dbSNP:rs121913494)"
FT /evidence="ECO:0000269|PubMed:2549426"
FT /id="VAR_003443"
FT VARIANT 231
FT /note="R -> H (in AHO; impairs the ability to mediate
FT hormonal stimulation; dbSNP:rs137854538)"
FT /evidence="ECO:0000269|PubMed:11450852,
FT ECO:0000269|PubMed:8702665, ECO:0000269|PubMed:9159128"
FT /id="VAR_017848"
FT VARIANT 242
FT /note="T -> I (in AHO)"
FT /evidence="ECO:0000269|PubMed:12624854"
FT /id="VAR_031875"
FT VARIANT 246
FT /note="F -> S (in AHO)"
FT /evidence="ECO:0000269|PubMed:12624854"
FT /id="VAR_031876"
FT VARIANT 250
FT /note="S -> R (in AHO; may alter guanine nucleotide binding
FT which could lead to thermolability and impaired function;
FT dbSNP:rs137854534)"
FT /evidence="ECO:0000269|PubMed:9328353"
FT /id="VAR_017849"
FT VARIANT 258
FT /note="R -> W (in AHO; defective GDP binding resulting in
FT increased thermolability and decreased activation;
FT dbSNP:rs137854535)"
FT /evidence="ECO:0000269|PubMed:9727013"
FT /id="VAR_015388"
FT VARIANT 259
FT /note="E -> V (in AHO)"
FT /evidence="ECO:0000269|PubMed:12624854"
FT /id="VAR_031877"
FT VARIANT 280
FT /note="R -> G (in PHP1A)"
FT /evidence="ECO:0000269|PubMed:11926205"
FT /id="VAR_031878"
FT VARIANT 280
FT /note="R -> K (in PHP1A)"
FT /evidence="ECO:0000269|PubMed:11788646"
FT /id="VAR_031879"
FT VARIANT 281
FT /note="W -> R (in POH)"
FT /evidence="ECO:0000269|PubMed:14723729"
FT /id="VAR_031880"
FT VARIANT 338
FT /note="K -> N (in PHP1A)"
FT /evidence="ECO:0000269|PubMed:12656668"
FT /id="VAR_031881"
FT VARIANT 366
FT /note="A -> S (in PHP1A; the patient also shows
FT testotoxicosis; constitutively activates adenylyl cyclase
FT in vitro; rapidly degraded at 37 degrees resulting in loss
FT of Gs activity; dbSNP:rs137854537)"
FT /evidence="ECO:0000269|PubMed:8072545"
FT /id="VAR_017850"
FT VARIANT 380
FT /note="R -> L (in dbSNP:rs8986)"
FT /id="VAR_049358"
FT VARIANT 382
FT /note="Missing (unable to interact with the receptor for
FT PTH)"
FT /evidence="ECO:0000269|PubMed:11029463"
FT /id="VAR_034744"
FT VARIANT 385
FT /note="R -> H (in AHO; uncouples receptors from adenylyl
FT cyclases)"
FT /evidence="ECO:0000269|PubMed:7523385"
FT /id="VAR_003444"
FT VARIANT 388
FT /note="L -> R (in PHP1C; significantly reduces receptor-
FT mediated activation; displays normal receptor-independent
FT activation; dbSNP:rs397514457)"
FT /evidence="ECO:0000269|PubMed:21488135"
FT /id="VAR_066387"
FT VARIANT 392
FT /note="E -> K (in PHP1C; significantly reduces receptor-
FT mediated activation; displays normal receptor-independent
FT activation; dbSNP:rs397514456)"
FT /evidence="ECO:0000269|PubMed:21488135"
FT /id="VAR_066388"
FT MUTAGEN 170
FT /note="Q->A: Increases GDP release but does not affect
FT receptor-mediated activation."
FT /evidence="ECO:0000269|PubMed:10200251"
FT MUTAGEN 227
FT /note="Q->L: Increases binding to GAS2L2; when associated
FT with N-295."
FT /evidence="ECO:0000269|PubMed:23994616"
FT MUTAGEN 258
FT /note="R->A: Increases GDP release and impairs receptor-
FT mediated activation; markedly elevated intrinsic GTPase
FT rate which will lead to more rapid inactivation."
FT /evidence="ECO:0000269|PubMed:10200251,
FT ECO:0000269|PubMed:9727013"
FT MUTAGEN 295
FT /note="D->N: Increases binding to GAS2L2; when associated
FT with L-227."
FT /evidence="ECO:0000269|PubMed:23994616"
FT CONFLICT 3
FT /note="C -> Y (in Ref. 8; AAH66923)"
FT /evidence="ECO:0000305"
FT CONFLICT 6
FT /note="N -> T (in Ref. 3; CAA30084)"
FT /evidence="ECO:0000305"
FT CONFLICT 72
FT /note="Missing (in Ref. 8; AAH66923)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="N -> D (in Ref. 8; AAH22875)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="E -> Q (in Ref. 9; AAA52583)"
FT /evidence="ECO:0000305"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:7CKZ"
FT HELIX 18..39
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:7BPH"
FT TURN 49..52
FT /evidence="ECO:0007829|PDB:7RTB"
FT HELIX 53..64
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 92..112
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 122..124
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 125..133
FT /evidence="ECO:0007829|PDB:7BPH"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 144..154
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 157..163
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 175..179
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 206..214
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 217..224
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:7CFM"
FT HELIX 228..237
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 250..254
FT /evidence="ECO:0007829|PDB:7BPH"
FT TURN 258..260
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 265..277
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 287..292
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 294..303
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:7CKZ"
FT HELIX 308..310
FT /evidence="ECO:0007829|PDB:7BPH"
FT HELIX 313..317
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 322..324
FT /evidence="ECO:0007829|PDB:7CZ5"
FT STRAND 328..330
FT /evidence="ECO:0007829|PDB:7KI0"
FT HELIX 332..349
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:6PB1"
FT TURN 354..356
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:7BPH"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:7CKZ"
FT HELIX 369..393
FT /evidence="ECO:0007829|PDB:7BPH"
SQ SEQUENCE 394 AA; 45665 MW; CD541181FC4412EF CRC64;
MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM
RILHVNGFNG EGGEEDPQAA RSNSDGEKAT KVQDIKNNLK EAIETIVAAM SNLVPPVELA
NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR ACYERSNEYQ LIDCAQYFLD
KIDVIKQADY VPSDQDLLRC RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND
VTAIIFVVAS SSYNMVIRED NQTNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK
VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST ASGDGRHYCY
PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL
