GNAS1_HUMAN
ID GNAS1_HUMAN Reviewed; 1037 AA.
AC Q5JWF2; A2A2S3; E1P5G3; O75684; O75685; Q5JW67; Q5JWF1; Q9NY42;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas;
DE AltName: Full=Adenylate cyclase-stimulating G alpha protein;
DE AltName: Full=Extra large alphas protein;
DE Short=XLalphas;
GN Name=GNAS; Synonyms=GNAS1 {ECO:0000303|PubMed:9707596};
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 [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 [2]
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 [3] {ECO:0000305, ECO:0000312|EMBL:CAB83215.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-689.
RX PubMed=10749992; DOI=10.1093/hmg/9.5.835;
RA Hayward B.E., Bonthron D.T.;
RT "An imprinted antisense transcript at the human GNAS1 locus.";
RL Hum. Mol. Genet. 9:835-841(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAA12165.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 197-1037 (ISOFORM XLAS-3).
RX PubMed=9707596; DOI=10.1073/pnas.95.17.10038;
RA Hayward B.E., Kamiya M., Strain L., Moran V., Campbell R., Hayashizaki Y.,
RA Bonthron D.T.;
RT "The human GNAS1 gene is imprinted and encodes distinct paternally and
RT biallelically expressed G proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10038-10043(1998).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAX51890.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 302-689.
RX PubMed=16110341; DOI=10.1371/journal.pgen.0010018;
RA Nekrutenko A., Wadhawan S., Goetting-Minesky P., Makova K.D.;
RT "Oscillating evolution of a mammalian locus with overlapping reading
RT frames: an XLalphas/ALEX relay.";
RL PLoS Genet. 1:197-204(2005).
RN [6]
RP INVOLVEMENT IN PHP1C.
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 [7] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=15148396; DOI=10.1073/pnas.0308758101;
RA Abramowitz J., Grenet D., Birnbaumer M., Torres H.N., Birnbaumer L.;
RT "XL alpha-s, the extra-long form of the alpha subunit of the Gs G protein,
RT is significantly longer than suspected, and so is its companion Alex.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:8366-8371(2004).
RN [8]
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 [9]
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 [10]
RP INVOLVEMENT IN PHP1B.
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-995, 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 [12]
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 [13]
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 [14]
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 [15] {ECO:0000305}
RP VARIANTS GNASHYP ASP-436;
RP PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459.
RX PubMed=11583302;
RA Freson K., Hoylaerts M.F., Jaeken J., Eyssen M., Arnout J., Vermylen J.,
RA Van Geet C.;
RT "Genetic variation of the extra-large stimulatory G protein alpha-subunit
RT leads to Gs hyperfunction in platelets and is a risk factor for bleeding.";
RL Thromb. Haemost. 86:733-738(2001).
RN [16]
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 [17] {ECO:0000305}
RP VARIANTS GNASHYP ASP-436;
RP PRO-ALA-ASP-PRO-ASP-SER-GLY-ALA-ALA-PRO-ASP-ALA-437 INS AND ARG-459.
RX PubMed=12719376; DOI=10.1093/hmg/ddg130;
RA Freson K., Jaeken J., Van Helvoirt M., de Zegher F., Wittevrongel C.,
RA Thys C., Hoylaerts M.F., Vermylen J., Van Geet C.;
RT "Functional polymorphisms in the paternally expressed XLalphas and its
RT cofactor ALEX decrease their mutual interaction and enhance receptor-
RT mediated cAMP formation.";
RL Hum. Mol. Genet. 12:1121-1130(2003).
RN [18]
RP INVOLVEMENT IN AIMAH1.
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 [19]
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 [20]
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 [21]
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 [22]
RP INTERACTION WITH MAGED2, AND SUBCELLULAR LOCATION.
RX PubMed=27120771; DOI=10.1056/nejmoa1507629;
RA Laghmani K., Beck B.B., Yang S.S., Seaayfan E., Wenzel A., Reusch B.,
RA Vitzthum H., Priem D., Demaretz S., Bergmann K., Duin L.K., Goebel H.,
RA Mache C., Thiele H., Bartram M.P., Dombret C., Altmueller J., Nuernberg P.,
RA Benzing T., Levtchenko E., Seyberth H.W., Klaus G., Yigit G., Lin S.H.,
RA Timmer A., de Koning T.J., Scherjon S.A., Schlingmann K.P., Bertrand M.J.,
RA Rinschen M.M., de Backer O., Konrad M., Koemhoff M.;
RT "Polyhydramnios, transient antenatal Bartter's syndrome, and MAGED2
RT mutations.";
RL N. Engl. J. Med. 374:1853-1863(2016).
CC -!- FUNCTION: Guanine nucleotide-binding proteins (G proteins) function as
CC transducers in numerous signaling pathways controlled by G protein-
CC coupled receptors (GPCRs). Signaling involves the activation of
CC adenylyl cyclases, resulting in increased levels of the signaling
CC molecule cAMP. GNAS functions downstream of several GPCRs, including
CC beta-adrenergic receptors. XLas isoforms interact with the same set of
CC receptors as GNAS isoforms (By similarity).
CC {ECO:0000250|UniProtKB:Q6R0H7}.
CC -!- SUBUNIT: G proteins are composed of 3 units; alpha, beta and gamma. The
CC alpha chain contains the guanine nucleotide binding site. Interacts
CC through its N-terminal region with ALEX which is produced from the same
CC locus in a different open reading frame. This interaction may inhibit
CC its adenylyl cyclase-stimulating activity (By similarity). Interacts
CC with MAGED2 (PubMed:27120771). {ECO:0000250|UniProtKB:Q63803,
CC ECO:0000250|UniProtKB:Q6R0H7, ECO:0000269|PubMed:27120771}.
CC -!- INTERACTION:
CC Q5JWF2; P49407: ARRB1; NbExp=5; IntAct=EBI-4400880, EBI-743313;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27120771};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q63803}. Apical cell
CC membrane {ECO:0000269|PubMed:27120771}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=XLas-1;
CC IsoId=Q5JWF2-1; Sequence=Displayed;
CC Name=XLas-2;
CC IsoId=Q5JWF2-2; Sequence=VSP_052174;
CC Name=XLas-3;
CC IsoId=Q5JWF2-3; Sequence=VSP_052173, VSP_052175;
CC Name=Gnas-1 {ECO:0000305}; Synonyms=Alpha-S2 {ECO:0000305}, GNASl
CC {ECO:0000305}, Alpha-S-long {ECO:0000305};
CC IsoId=P63092-1, P04895-1;
CC Sequence=External;
CC Name=3;
CC IsoId=P63092-3; Sequence=External;
CC Name=Gnas-2 {ECO:0000305}; Synonyms=Alpha-S1 {ECO:0000305}, GNASs
CC {ECO:0000305}, Alpha-S-short {ECO:0000305};
CC IsoId=P63092-2, P04895-2;
CC Sequence=External;
CC Name=Nesp55 {ECO:0000305};
CC IsoId=O95467-1; Sequence=External;
CC Name=4;
CC IsoId=P63092-4; Sequence=External;
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. {ECO:0000269|PubMed:11583302,
CC ECO:0000269|PubMed:12719376}. 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: 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:11788646}. 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 {ECO:0000250|UniProtKB:Q63803}.
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:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB83215.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GNASID40727ch20q13.html";
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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; EAW75462.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75469.1; -; Genomic_DNA.
DR EMBL; AJ251760; CAB83215.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AJ224867; CAA12164.1; -; mRNA.
DR EMBL; AJ224868; CAA12165.1; -; Genomic_DNA.
DR EMBL; AY898804; AAX51890.1; -; Genomic_DNA.
DR CCDS; CCDS46622.1; -. [Q5JWF2-1]
DR RefSeq; NP_001296812.1; NM_001309883.1.
DR RefSeq; NP_536350.2; NM_080425.3. [Q5JWF2-1]
DR RefSeq; XP_016883302.1; XM_017027813.1. [Q5JWF2-2]
DR AlphaFoldDB; Q5JWF2; -.
DR SMR; Q5JWF2; -.
DR BioGRID; 109040; 213.
DR IntAct; Q5JWF2; 28.
DR MINT; Q5JWF2; -.
DR STRING; 9606.ENSP00000360141; -.
DR BindingDB; Q5JWF2; -.
DR ChEMBL; CHEMBL4295849; -.
DR iPTMnet; Q5JWF2; -.
DR SwissPalm; Q5JWF2; -.
DR BioMuta; GNAS; -.
DR DMDM; 116248089; -.
DR EPD; Q5JWF2; -.
DR jPOST; Q5JWF2; -.
DR MassIVE; Q5JWF2; -.
DR MaxQB; Q5JWF2; -.
DR PaxDb; Q5JWF2; -.
DR PeptideAtlas; Q5JWF2; -.
DR PRIDE; Q5JWF2; -.
DR ProteomicsDB; 63384; -. [Q5JWF2-1]
DR ProteomicsDB; 63385; -. [Q5JWF2-2]
DR ProteomicsDB; 63386; -. [Q5JWF2-3]
DR Antibodypedia; 4152; 809 antibodies from 44 providers.
DR DNASU; 2778; -.
DR Ensembl; ENST00000371100.9; ENSP00000360141.3; ENSG00000087460.29. [Q5JWF2-1]
DR Ensembl; ENST00000371102.8; ENSP00000360143.4; ENSG00000087460.29. [Q5JWF2-2]
DR Ensembl; ENST00000481768.6; ENSP00000499644.2; ENSG00000087460.29. [Q5JWF2-3]
DR GeneID; 2778; -.
DR UCSC; uc002xzw.4; human. [Q5JWF2-1]
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; 139320; gene+phenotype.
DR MIM; 219080; phenotype.
DR MIM; 603233; phenotype.
DR MIM; 612462; phenotype.
DR neXtProt; NX_Q5JWF2; -.
DR OpenTargets; ENSG00000087460; -.
DR PharmGKB; PA175; -.
DR VEuPathDB; HostDB:ENSG00000087460; -.
DR eggNOG; KOG0099; Eukaryota.
DR GeneTree; ENSGT00940000156300; -.
DR HOGENOM; CLU_010619_0_0_1; -.
DR InParanoid; Q5JWF2; -.
DR OrthoDB; 754573at2759; -.
DR PhylomeDB; Q5JWF2; -.
DR TreeFam; TF300673; -.
DR PathwayCommons; Q5JWF2; -.
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; Q5JWF2; -.
DR SIGNOR; Q5JWF2; -.
DR BioGRID-ORCS; 2778; 28 hits in 1092 CRISPR screens.
DR ChiTaRS; GNAS; human.
DR GenomeRNAi; 2778; -.
DR Pharos; Q5JWF2; Tbio.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q5JWF2; protein.
DR Bgee; ENSG00000087460; Expressed in type B pancreatic cell and 213 other tissues.
DR ExpressionAtlas; Q5JWF2; baseline and differential.
DR Genevisible; Q5JWF2; HS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0010856; F:adenylate cyclase activator activity; ISS:UniProtKB.
DR GO; GO:0031698; F:beta-2 adrenergic receptor binding; IBA:GO_Central.
DR GO; GO:0051430; F:corticotropin-releasing hormone receptor 1 binding; IBA:GO_Central.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IBA:GO_Central.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0031683; F:G-protein beta/gamma-subunit complex binding; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IBA:GO_Central.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031852; F:mu-type opioid receptor binding; IBA:GO_Central.
DR GO; GO:0007191; P:adenylate cyclase-activating dopamine receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007188; P:adenylate cyclase-modulating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR GO; GO:0048589; P:developmental growth; IMP:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; IMP:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0007606; P:sensory perception of chemical stimulus; IBA:GO_Central.
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; 2.
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 ADP-ribosylation; Alternative splicing; Cell membrane; Coiled coil;
KW Cushing syndrome; Disease variant; GTP-binding; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transducer.
FT CHAIN 1..1037
FT /note="Guanine nucleotide-binding protein G(s) subunit
FT alpha isoforms XLas"
FT /id="PRO_0000253984"
FT DOMAIN 682..1037
FT /note="G-alpha"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 1..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 283..588
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 640..666
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..698
FT /note="G1 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 711..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 839..847
FT /note="G2 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 862..871
FT /note="G3 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 931..938
FT /note="G4 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT REGION 1007..1012
FT /note="G5 motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01230"
FT COILED 641..667
FT /evidence="ECO:0000255"
FT COILED 730..756
FT /evidence="ECO:0000255"
FT COMPBIAS 287..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..358
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 554..569
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 690..698
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 697
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 840..847
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 847
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT BINDING 866..870
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63096"
FT BINDING 935..938
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P63096"
FT BINDING 1009
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P04896"
FT MOD_RES 844
FT /note="ADP-ribosylarginine; by cholera toxin"
FT /evidence="ECO:0000250"
FT MOD_RES 995
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT VAR_SEQ 691..752
FT /note="AGESGKSTIVKQMRILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNL
FT KEAIETIVAA -> RKVVPSDTEGRFRLDRPAPATVSWTGRGFSVSSLLIRSPNPPAFT
FT VEKPDTQVLENLVKAPL (in isoform XLas-3)"
FT /evidence="ECO:0000303|PubMed:9707596"
FT /id="VSP_052173"
FT VAR_SEQ 714..729
FT /note="EGGEEDPQAARSNSDG -> DS (in isoform XLas-2)"
FT /evidence="ECO:0000305"
FT /id="VSP_052174"
FT VAR_SEQ 753..1037
FT /note="Missing (in isoform XLas-3)"
FT /evidence="ECO:0000303|PubMed:9707596"
FT /id="VSP_052175"
FT VARIANT 436
FT /note="A -> D (in GNASHYP; dbSNP:rs61749698)"
FT /evidence="ECO:0000269|PubMed:11583302,
FT ECO:0000269|PubMed:12719376"
FT /id="VAR_028777"
FT VARIANT 437
FT /note="A -> APADPDSGAAPDA (in GNAS hyperfunction)"
FT /evidence="ECO:0000269|PubMed:11583302,
FT ECO:0000269|PubMed:12719376"
FT /id="VAR_028778"
FT VARIANT 459
FT /note="P -> R (in GNASHYP; dbSNP:rs148033592)"
FT /evidence="ECO:0000269|PubMed:11583302,
FT ECO:0000269|PubMed:12719376"
FT /id="VAR_028779"
FT VARIANT 1023
FT /note="R -> L (in dbSNP:rs8986)"
FT /id="VAR_059656"
FT CONFLICT 15
FT /note="Q -> E (in Ref. 3; CAB83215)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="A -> S (in Ref. 3; CAB83215)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="E -> A (in Ref. 3; CAB83215)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1037 AA; 111025 MW; 02CB52383015E75D CRC64;
MGVRNCLYGN NMSGQRDIPP EIGEQPEQPP LEAPGAAAPG AGPSPAEEME TEPPHNEPIP
VENDGEACGP PEVSRPNFQV LNPAFREAGA HGSYSPPPEE AMPFEAEQPS LGGFWPTLEQ
PGFPSGVHAG LEAFGPALME PGAFSGARPG LGGYSPPPEE AMPFEFDQPA QRGCSQLLLQ
VPDLAPGGPG AAGVPGAPPE EPQALRPAKA GSRGGYSPPP EETMPFELDG EGFGDDSPPP
GLSRVIAQVD GSSQFAAVAA SSAVRLTPAA NAPPLWVPGA IGSPSQEAVR PPSNFTGSSP
WMEISGPPFE IGSAPAGVDD TPVNMDSPPI ALDGPPIKVS GAPDKRERAE RPPVEEEAAE
MEGAADAAEG GKVPSPGYGS PAAGAASADT AARAAPAAPA DPDSGATPED PDSGTAPADP
DSGAFAADPD SGAAPAAPAD PDSGAAPDAP ADPDSGAAPD APADPDAGAA PEAPAAPAAA
ETRAAHVAPA APDAGAPTAP AASATRAAQV RRAASAAPAS GARRKIHLRP PSPEIQAADP
PTPRPTRASA WRGKSESSRG RRVYYDEGVA SSDDDSSGDE SDDGTSGCLR WFQHRRNRRR
RKPQRNLLRN FLVQAFGGCF GRSESPQPKA SRSLKVKKVP LAEKRRQMRK EALEKRAQKR
AEKKRSKLID KQLQDEKMGY MCTHRLLLLG AGESGKSTIV KQMRILHVNG FNGEGGEEDP
QAARSNSDGE KATKVQDIKN NLKEAIETIV AAMSNLVPPV ELANPENQFR VDYILSVMNV
PDFDFPPEFY EHAKALWEDE GVRACYERSN EYQLIDCAQY FLDKIDVIKQ ADYVPSDQDL
LRCRVLTSGI FETKFQVDKV NFHMFDVGGQ RDERRKWIQC FNDVTAIIFV VASSSYNMVI
REDNQTNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR
YTTPEDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCAV DTENIRRVFN
DCRDIIQRMH LRQYELL
