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P63092 (GNAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Alternative name(s):
Adenylate cyclase-stimulating G alpha protein
Gene names
Name:GNAS
Synonyms:GNAS1, GSP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length394 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. Stimulates the Ras signaling pathway via RAPGEF2. Ref.11

Subunit structure

G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.

Subcellular location

Cell membrane; Lipid-anchor By similarity.

Involvement in disease

Albright hereditary osteodystrophy (AHO) [MIM:103580]: A disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.19 Ref.20 Ref.24 Ref.26 Ref.27 Ref.28 Ref.34 Ref.35 Ref.39 Ref.45

Pseudohypoparathyroidism 1A (PHP1A) [MIM:103580]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.36 Ref.37 Ref.40

McCune-Albright syndrome (MAS) [MIM:174800]: Characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The mutations producing MAS lead to constitutive activation of GS alpha.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.17 Ref.29

Growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]: Pituitary adenomas include somatotropinoma and prolactinoma.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Progressive osseous heteroplasia (POH) [MIM:166350]: Rare autosomal dominant disorder characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.43

ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]: A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.41

Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH.
Note: The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed. Ref.31 Ref.32 Ref.33 Ref.38 Ref.42 Ref.44 Ref.46

GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.47

Miscellaneous

This protein is produced by a bicistronic gene which also produces the ALEX protein from an overlapping reading frame.

The GNAS locus is imprinted in a complex manner, giving rise to distinct paternally, maternally and biallelically expressed proteins. The XLas isoforms are paternally derived, the Gnas isoforms are biallelically derived and the Nesp55 isoforms are maternally derived.

Sequence similarities

Belongs to the G-alpha family. G(s) subfamily.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCushing syndrome
Disease mutation
Proto-oncogene
   LigandGTP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionTransducer
   PTMADP-ribosylation
Isopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of adenylate cyclase activity

Traceable author statement Ref.27. Source: UniProtKB

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Inferred from direct assay PubMed 12719376. Source: UniProt

adenylate cyclase-activating adrenergic receptor signaling pathway

Inferred from direct assay Ref.11. Source: UniProtKB

adenylate cyclase-activating dopamine receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

blood coagulation

Traceable author statement. Source: Reactome

bone development

Inferred from direct assay PubMed 12719376. Source: UniProt

cAMP biosynthetic process

Traceable author statement. Source: GOC

cellular response to catecholamine stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cellular response to glucagon stimulus

Traceable author statement. Source: Reactome

cellular response to prostaglandin E stimulus

Inferred from sequence or structural similarity. Source: BHF-UCL

cognition

Inferred from direct assay PubMed 12719376. Source: UniProt

developmental growth

Inferred from direct assay PubMed 12719376. Source: UniProt

energy reserve metabolic process

Traceable author statement. Source: Reactome

hair follicle placode formation

Inferred from direct assay PubMed 12719376. Source: UniProt

intracellular transport

Non-traceable author statement PubMed 7997272. Source: UniProtKB

platelet aggregation

Inferred from direct assay PubMed 12719376. Source: UniProt

positive regulation of Ras GTPase activity

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of cAMP biosynthetic process

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of cAMP-mediated signaling

Inferred from direct assay Ref.11. Source: UniProtKB

regulation of insulin secretion

Traceable author statement. Source: Reactome

sensory perception of smell

Traceable author statement PubMed 3018580. Source: UniProtKB

small molecule metabolic process

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

water transport

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: LIFEdb

cytosol

Inferred from direct assay PubMed 12719376. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 20458337. Source: UniProt

heterotrimeric G-protein complex

Traceable author statement Ref.27. Source: UniProtKB

intrinsic component of membrane

Inferred from direct assay PubMed 7997272. Source: UniProtKB

membrane

Inferred from direct assay PubMed 12719376. Source: UniProt

plasma membrane

Traceable author statement Ref.28. Source: UniProtKB

trans-Golgi network membrane

Inferred from direct assay PubMed 7997272. Source: UniProtKB

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

GTPase activity

Traceable author statement Ref.27. Source: UniProtKB

adenylate cyclase activity

Traceable author statement. Source: Reactome

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

signal transducer activity

Inferred from direct assay Ref.11. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Oprm1P428662EBI-7607528,EBI-5282656From a different organism.

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]
Isoform Gnas-1 (identifier: P63092-1)

Also known as: Alpha-S2; GNASl; Alpha-S-long;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Gnas-2 (identifier: P63092-2)

Also known as: Alpha-S1; GNASs; Alpha-S-short;

The sequence of this isoform differs from the canonical sequence as follows:
     71-72: EG → DS
     73-86: Missing.
Isoform 3 (identifier: P63092-3)

The sequence of this isoform differs from the canonical sequence as follows:
     71-71: E → D
     72-86: Missing.
Note: No experimental confirmation available.
Isoform XLas-1 (identifier: Q5JWF2-1)

The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Gene prediction confirmed by EST data.
Isoform XLas-2 (identifier: Q5JWF2-2)

The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Gene prediction confirmed by EST data.
Isoform XLas-3 (identifier: Q5JWF2-3)

The sequence of this isoform can be found in the external entry Q5JWF2.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Isoform Nesp55 (identifier: O95467-1)

The sequence of this isoform can be found in the external entry O95467.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Shares no sequence similarity with other isoforms due to a novel first exon containing the entire reading frame spliced to shared exon 2 so that exons 2-13 make up the 3'-UTR.
Isoform 4 (identifier: P63092-4)

The sequence of this isoform differs from the canonical sequence as follows:
     86-86: G → GS
Note: Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 394394Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
PRO_0000203721

Regions

Nucleotide binding47 – 548GTP By similarity
Nucleotide binding198 – 2047GTP By similarity
Nucleotide binding223 – 2275GTP By similarity
Nucleotide binding292 – 2954GTP By similarity

Sites

Metal binding541Magnesium By similarity
Metal binding2041Magnesium By similarity
Binding site3661GTP; via amide nitrogen By similarity

Amino acid modifications

Modified residue2011ADP-ribosylarginine; by cholera toxin By similarity
Modified residue3521Phosphoserine Ref.12
Lipidation21N-palmitoyl glycine By similarity
Lipidation31S-palmitoyl cysteine Ref.14
Cross-link300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Alternative sequence71 – 722EG → DS in isoform Gnas-2.
VSP_001833
Alternative sequence711E → D in isoform 3.
VSP_026616
Alternative sequence72 – 8615Missing in isoform 3.
VSP_026617
Alternative sequence73 – 8614Missing in isoform Gnas-2.
VSP_001834
Alternative sequence861G → GS in isoform 4.
VSP_047325
Natural variant991L → P in AHO. Ref.15
VAR_003439
Natural variant1061I → S in AHO/PHP1A. Ref.45
VAR_031872
Natural variant1151P → L in AHO. Ref.35
VAR_017843
Natural variant1561D → N in PHP1A. Ref.36
VAR_031873
Natural variant1591V → M in PHP1A. Ref.36
VAR_031874
Natural variant1651R → C in AHO. Ref.15
VAR_003440
Natural variant2011R → C in MAS and somatotrophinoma. Ref.17 Ref.18
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_003442
Natural variant2011R → G in MAS. Ref.29
VAR_017844
Natural variant2011R → H in MAS, somatotrophinoma and AIMAH. Ref.16 Ref.17 Ref.18 Ref.41
VAR_003441
Natural variant2011R → L in non-MAS endocrine tumors. Ref.21
VAR_017845
Natural variant2011R → S in AIMAH, pituitary tumor and polyostotic fibrous dysplasia. Ref.23 Ref.25 Ref.41
VAR_017846
Natural variant2271Q → H in pituitary adenoma; ACTH-secreting adenoma; in a patient with severe Cushing syndrome complicated by psychosis. Ref.22
VAR_017847
Natural variant2271Q → R in somatotrophinoma. Ref.18
VAR_003443
Natural variant2311R → H in AHO; impairs the ability to mediate hormonal stimulation. Ref.24 Ref.27 Ref.34
VAR_017848
Natural variant2421T → I in AHO. Ref.39
VAR_031875
Natural variant2461F → S in AHO. Ref.39
VAR_031876
Natural variant2501S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. Ref.26
VAR_017849
Natural variant2581R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. Ref.28
VAR_015388
Natural variant2591E → V in AHO. Ref.39
VAR_031877
Natural variant2801R → G in PHP1A. Ref.37
VAR_031878
Natural variant2801R → K in PHP1A. Ref.36
VAR_031879
Natural variant2811W → R in POH. Ref.43
VAR_031880
Natural variant3381K → N in PHP1A. Ref.40
VAR_031881
Natural variant3661A → S in AHO; paradoxical combination of AHO and testotoxicosis; constitutively activates adenylyl cyclase in vitro; accounts for the testotoxicosis phenotype; mutant form is quite stable at testis temperature; rapidly degraded at 37 degrees explaining the AHO phenotype caused by loss of Gs activity. Ref.20
VAR_017850
Natural variant3801R → L.
Corresponds to variant rs8986 [ dbSNP | Ensembl ].
VAR_049358
Natural variant3821Missing Unable to interact with the receptor for PTH. Ref.33
VAR_034744
Natural variant3851R → H in AHO; uncouples receptors from adenylyl cyclases. Ref.19
VAR_003444
Natural variant3881L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. Ref.47
VAR_066387
Natural variant3921E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. Ref.47
VAR_066388

Experimental info

Mutagenesis1701Q → A: Increases GDP release but does not affect receptor-mediated activation. Ref.30
Mutagenesis2581R → A: Increases GDP release and impairs receptor-mediated activation; markedly elevated intrinsic GTPase rate which will lead to more rapid inactivation. Ref.28 Ref.30
Sequence conflict31C → Y in AAH66923. Ref.8
Sequence conflict61N → T in CAA30084. Ref.3
Sequence conflict721Missing in AAH66923. Ref.8
Sequence conflict1671N → D in AAH22875. Ref.8
Sequence conflict2301E → Q in AAA52583. Ref.9

Sequences

Sequence LengthMass (Da)Tools
Isoform Gnas-1 (Alpha-S2) (GNASl) (Alpha-S-long) [UniParc].

Last modified August 13, 1987. Version 1.
Checksum: CD541181FC4412EF

FASTA39445,665
        10         20         30         40         50         60 
MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM 

        70         80         90        100        110        120 
RILHVNGFNG EGGEEDPQAA RSNSDGEKAT KVQDIKNNLK EAIETIVAAM SNLVPPVELA 

       130        140        150        160        170        180 
NPENQFRVDY ILSVMNVPDF DFPPEFYEHA KALWEDEGVR ACYERSNEYQ LIDCAQYFLD 

       190        200        210        220        230        240 
KIDVIKQADY VPSDQDLLRC RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND 

       250        260        270        280        290        300 
VTAIIFVVAS SSYNMVIRED NQTNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK 

       310        320        330        340        350        360 
VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST ASGDGRHYCY 

       370        380        390 
PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL 

« Hide

Isoform Gnas-2 (Alpha-S1) (GNASs) (Alpha-S-short) [UniParc] [UniParc].

Checksum: C3D8B1E786EBC618
Show »

FASTA38044,266
Isoform 3 [UniParc].

Checksum: 6D095E83B1667CAA
Show »

FASTA37944,179
Isoform XLas-1 [UniParc].

See Q5JWF2.

Isoform XLas-2 [UniParc].

See Q5JWF2.

Isoform XLas-3 [UniParc].

See Q5JWF2.

Isoform Nesp55 [UniParc].

See O95467.

Isoform 4 [UniParc].

Checksum: A808ECA884A6E476
Show »

FASTA39545,752

References

« Hide 'large scale' references
[1]"Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase."
Mattera R., Codina J., Crozat A., Kidd V., Woo S.L.C., Birnbaumer L.
FEBS Lett. 206:36-42(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
Tissue: Liver.
[2]"Complete cDNA sequence of a human stimulatory GTP-binding protein alpha subunit."
Harris B.A.
Nucleic Acids Res. 16:3585-3585(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GNAS-1).
[3]"Isolation and characterization of the human Gs alpha gene."
Kozasa T., Itoh H., Tsukamoto T., Kaziro Y.
Proc. Natl. Acad. Sci. U.S.A. 85:2081-2085(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS GNAS-1 AND GNAS-2).
[4]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Puhl H.L. III, Ikeda S.R., Aronstam R.S.
Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GNAS-1).
[6]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1; 3 AND 4).
Tissue: Bone marrow, Brain, Muscle and Pancreas.
[9]"Human cDNA clones for four species of G alpha s signal transduction protein."
Bray P., Carter A., Simons C., Guo V., Puckett C., Kamholz J., Spiegel A., Nirenberg M.
Proc. Natl. Acad. Sci. U.S.A. 83:8893-8897(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-394 (ISOFORMS GNAS-1 AND 4).
[10]"Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes."
Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.
Biochem. J. 383:237-248(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 187-199 AND 308-317.
Tissue: Adipocyte.
[11]"Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation."
Pak Y., Pham N., Rotin D.
Mol. Cell. Biol. 22:7942-7952(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"Site-specific analysis of protein S-acylation by resin-assisted capture."
Forrester M.T., Hess D.T., Thompson J.W., Hultman R., Moseley M.A., Stamler J.S., Casey P.J.
J. Lipid Res. 52:393-398(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-3.
[15]"Heterogeneous mutations in the gene encoding the alpha-subunit of the stimulatory G protein of adenylyl cyclase in Albright hereditary osteodystrophy."
Miric A., Vechio J.D., Levine M.A.
J. Clin. Endocrinol. Metab. 76:1560-1568(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AHO PRO-99 AND CYS-165.
[16]"Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome."
Schwindinger W.F., Francomano C.A., Levine M.A.
Proc. Natl. Acad. Sci. U.S.A. 89:5152-5156(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MAS HIS-201.
[17]"Activating mutations of the stimulatory G protein in the McCune-Albright syndrome."
Weinstein L.S., Shenker A., Gejman P.V., Merino M.J., Friedman E., Spiegel A.M.
N. Engl. J. Med. 325:1688-1695(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MAS CYS-201 AND HIS-201.
[18]"GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours."
Landis C.A., Masters S.B., Spada A., Pace A.M., Bourne H.R., Vallar L.
Nature 340:692-696(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SOMATOTROPHINOMA CYS-201; HIS-201 AND ARG-227.
[19]"A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase."
Schwindinger W.F., Miric A., Zimmerman D., Levine M.A.
J. Biol. Chem. 269:25387-25391(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO HIS-385.
[20]"Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function."
Iiri T., Herzmark P., Nakamoto J.M., van Dop C., Bourne H.R.
Nature 371:164-168(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AHO SER-366.
[21]"Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs alpha gene."
Gorelov V.N., Dumon K., Barteneva N.S., Palm D., Roher H.-D., Goretzki P.E.
J. Cancer Res. Clin. Oncol. 121:219-224(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NON-MAS ENDOCRINE TUMORS LEU-201.
[22]"G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas."
Williamson E.A., Ince P.G., Harrison D., Kendall-Taylor P., Harris P.E.
Eur. J. Clin. Invest. 25:128-131(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PITUITARY ADENOMA HIS-227.
[23]"Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients."
Yang I., Park S., Ryu M., Woo J., Kim S., Kim J., Kim Y., Choi Y.
Eur. J. Endocrinol. 134:720-726(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PITUITARY TUMOR SER-201.
[24]"Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation."
Farfel Z., Iiri T., Shapira H., Roitman A., Mouallem M., Bourne H.R.
J. Biol. Chem. 271:19653-19655(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
[25]"Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G alpha s from patients with fibrous dysplasia of bone."
Candeliere G.A., Roughley P.J., Glorieux F.H.
Bone 21:201-206(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT POLYOSTOTIC FIBROUS DYSPLASIA SER-201.
[26]"A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism."
Warner D.R., Gejman P.V., Collins R.M., Weinstein L.S.
Mol. Endocrinol. 11:1718-1727(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO ARG-250.
[27]"Conditional activation defect of a human Gsalpha mutant."
Iiri T., Farfel Z., Bourne H.R.
Proc. Natl. Acad. Sci. U.S.A. 94:5656-5661(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
[28]"A novel mutation in the switch 3 region of Gs-alpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation."
Warner D.R., Weng G., Yu S., Matalon R., Weinstein L.S.
J. Biol. Chem. 273:23976-23983(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO TRP-258, MUTAGENESIS OF ARG-258, CHARACTERIZATION OF VARIANT AHO TRP-258.
[29]"A novel GNAS1 mutation, R201G, in McCune-albright syndrome."
Riminucci M., Fisher L.W., Majolagbe A., Corsi A., Lala R., De Sanctis C., Robey P.G., Bianco P.
J. Bone Miner. Res. 14:1987-1989(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MAS GLY-201.
[30]"A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein alpha-subunit with impaired receptor-mediated activation because of elevated GTPase activity."
Warner D.R., Weinstein L.S.
Proc. Natl. Acad. Sci. U.S.A. 96:4268-4272(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLN-170 AND ARG-258.
[31]"A GNAS1 imprinting defect in pseudohypoparathyroidism type IB."
Liu J., Litman D., Rosenberg M.J., Yu S., Biesecker L.G., Weinstein L.S.
J. Clin. Invest. 106:1167-1174(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[32]"Paternal uniparental isodisomy of chromosome 20q -- and the resulting changes in GNAS1 methylation -- as a plausible cause of pseudohypoparathyroidism."
Bastepe M., Lane A.H., Jueppner H.
Am. J. Hum. Genet. 68:1283-1289(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[33]"Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib."
Wu W.-I., Schwindinger W.F., Aparicio L.F., Levine M.A.
J. Biol. Chem. 276:165-171(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B, VARIANT ILE-382 DEL, CHARACTERIZATION OF VARIANT ILE-382 DEL.
[34]"Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia."
Ishikawa Y., Tajima T., Nakae J., Nagashima T., Satoh K., Okuhara K., Fujieda K.
J. Hum. Genet. 46:426-430(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO HIS-231.
[35]"Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy."
Ahrens W., Hiort O., Staedt P., Kirschner T., Marschke C., Kruse K.
J. Clin. Endocrinol. Metab. 86:4630-4634(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO LEU-115.
[36]"GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance."
Linglart A., Carel J.-C., Garabedian M., Le T., Mallet E., Kottler M.-L.
J. Clin. Endocrinol. Metab. 87:189-197(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHP1A ASN-156; MET-159 AND LYS-280.
[37]"Mutational analysis of the GNAS1 exons encoding the stimulatory G protein in five patients with pseudohypoparathyroidism type 1a."
Lim S.H., Poh L.K., Cowell C.T., Tey B.H., Loke K.Y.
J. Pediatr. Endocrinol. Metab. 15:259-268(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHP1A GLY-280.
[38]"Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1."
Jan de Beur S., Ding C., Germain-Lee E., Cho J., Maret A., Levine M.A.
Am. J. Hum. Genet. 73:314-322(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[39]"Analysis of GNAS1 and overlapping transcripts identifies the parental origin of mutations in patients with sporadic Albright hereditary osteodystrophy and reveals a model system in which to observe the effects of splicing mutations on translated and untranslated messenger RNA."
Rickard S.J., Wilson L.C.
Am. J. Hum. Genet. 72:961-974(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AHO ILE-242; SER-246 AND VAL-259.
[40]"A new heterozygous mutation (L338N) in the human Gsalpha (GNAS1) gene as a cause for congenital hypothyroidism in Albright's hereditary osteodystrophy."
Pohlenz J., Ahrens W., Hiort O.
Eur. J. Endocrinol. 148:463-468(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHP1A ASN-338.
[41]"Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene."
Fragoso M.C.B.V., Domenice S., Latronico A.C., Martin R.M., Pereira M.A.A., Zerbini M.C.N., Lucon A.M., Mendonca B.B.
J. Clin. Endocrinol. Metab. 88:2147-2151(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AIMAH HIS-201 AND SER-201.
[42]"Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS."
Bastepe M., Froehlich L.F., Hendy G.N., Indridason O.S., Josse R.G., Koshiyama H., Koerkkoe J., Nakamoto J.M., Rosenbloom A.L., Slyper A.H., Sugimoto T., Tsatsoulis A., Crawford J.D., Jueppner H.
J. Clin. Invest. 112:1255-1263(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[43]"Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene."
Chan I., Hamada T., Hardman C., McGrath J.A., Child F.J.
Clin. Exp. Dermatol. 29:77-80(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT POH ARG-281.
[44]"A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS."
Linglart A., Gensure R.C., Olney R.C., Jueppner H., Bastepe M.
Am. J. Hum. Genet. 76:804-814(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[45]"Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene."
Riepe F.G., Ahrens W., Krone N., Foelster-Holst R., Brasch J., Sippell W.G., Hiort O., Partsch C.-J.
Eur. J. Endocrinol. 152:515-519(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT AHO/PHP1A SER-106.
[46]"Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib."
Bastepe M., Froehlich L.F., Linglart A., Abu-Zahra H.S., Tojo K., Ward L.M., Jueppner H.
Nat. Genet. 37:25-27(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PHP1B.
[47]"Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction."
Thiele S., de Sanctis L., Werner R., Grotzinger J., Aydin C., Juppner H., Bastepe M., Hiort O.
Hum. Mutat. 32:653-660(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHP1C ARG-388 AND LYS-392, CHARACTERIZATION OF VARIANTS PHP1C ARG-388 AND LYS-392.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04408 mRNA. Translation: CAA27996.1.
X04409 mRNA. Translation: CAA27997.1.
M21142 expand/collapse EMBL AC list , M21139, M21740, M21140, M21741, M21141 Genomic DNA. Translation: AAA53147.1.
M21142 expand/collapse EMBL AC list , M21139, M21740, M21140, M21741, M21141 Genomic DNA. Translation: AAA53146.1.
M21142 expand/collapse EMBL AC list , M21139, M21141, M21740, M21741 Genomic DNA. Translation: AAA53148.1.
M21142 expand/collapse EMBL AC list , M21139, M21740, M21741, M21141 Genomic DNA. Translation: AAA53149.1.
U12466 Genomic DNA. Translation: AAB60334.2.
X07036 mRNA. Translation: CAA30084.1.
AF493897 mRNA. Translation: AAM12611.1.
AF493898 mRNA. Translation: AAM12612.1.
BT009905 mRNA. Translation: AAP88907.1.
AL109840, AL121917 Genomic DNA. Translation: CAI42914.1.
AL109840, AL121917 Genomic DNA. Translation: CAI42915.1.
AL109840, AL121917 Genomic DNA. Translation: CAI42916.1.
AL109840, AL121917 Genomic DNA. Translation: CAI42917.1.
AL121917, AL109840 Genomic DNA. Translation: CAI42546.1.
AL121917, AL109840 Genomic DNA. Translation: CAI42547.1.
AL121917, AL109840 Genomic DNA. Translation: CAI42548.1.
AL121917, AL109840 Genomic DNA. Translation: CAI42549.1.
AL132655 Genomic DNA. No translation available.
CH471077 Genomic DNA. Translation: EAW75468.1.
CH471077 Genomic DNA. Translation: EAW75460.1.
CH471077 Genomic DNA. Translation: EAW75463.1.
BC002722 mRNA. Translation: AAH02722.1.
BC008855 mRNA. Translation: AAH08855.1.
BC066923 mRNA. Translation: AAH66923.1.
BC022875 mRNA. Translation: AAH22875.1.
BC104928 mRNA. Translation: AAI04929.1.
BC108315 mRNA. Translation: AAI08316.2.
M14631 mRNA. Translation: AAA52583.1.
PIRRGHUA2. B31927.
RGHUA1. C31927.
RefSeqNP_000507.1. NM_000516.4.
NP_001070956.1. NM_001077488.2.
NP_001070957.1. NM_001077489.2.
NP_001070958.1. NM_001077490.1.
NP_536350.2. NM_080425.2.
NP_536351.1. NM_080426.2.
UniGeneHs.125898.

3D structure databases

ProteinModelPortalP63092.
SMRP63092. Positions 9-394.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109040. 36 interactions.
IntActP63092. 5 interactions.
MINTMINT-262348.

Chemistry

ChEMBLCHEMBL4377.

PTM databases

PhosphoSiteP63092.

Polymorphism databases

DMDM52000961.

Proteomic databases

PRIDEP63092.

Protocols and materials databases

DNASU2778.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265620; ENSP00000265620; ENSG00000087460. [P63092-3]
ENST00000306090; ENSP00000304472; ENSG00000087460. [P63092-2]
ENST00000354359; ENSP00000346328; ENSG00000087460. [P63092-4]
ENST00000371085; ENSP00000360126; ENSG00000087460. [P63092-1]
ENST00000371095; ENSP00000360136; ENSG00000087460. [P63092-2]
GeneID2778.
KEGGhsa:2778.
UCSCuc002xzt.3. human.
uc002yaa.3. human. [P63092-3]
uc002yae.3. human. [P63092-2]

Organism-specific databases

CTD2778.
GeneCardsGC20P057414.
HGNCHGNC:4392. GNAS.
HPACAB010337.
MIM102200. phenotype.
103580. phenotype.
139320. gene+phenotype.
166350. phenotype.
174800. phenotype.
219080. phenotype.
603233. phenotype.
612462. phenotype.
neXtProtNX_P63092.
Orphanet57782. Mazabraud syndrome.
562. McCune-Albright syndrome.
93277. Monostotic fibrous dysplasia.
93276. Polyostotic fibrous dysplasia.
2762. Progressive osseous heteroplasia.
79443. Pseudohypoparathyroidism type 1A.
94089. Pseudohypoparathyroidism type 1B.
79444. Pseudohypoparathyroidism type 1C.
79445. Pseudopseudohypoparathyroidism.
PharmGKBPA175.
GenAtlasSearch...

Phylogenomic databases

HOVERGENHBG063184.
KOK04632.
OMAYEHTKTL.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP63092.
BgeeP63092.
CleanExHS_GNAS.
GenevestigatorP63092.

Family and domain databases

Gene3D1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProIPR000367. Gprotein_alpha_S.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERPTHR10218. PTHR10218. 1 hit.
PfamPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSPR00318. GPROTEINA.
PR00443. GPROTEINAS.
SMARTSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetSearch...

Other

ChiTaRSGNAS. human.
GenomeRNAi2778.
NextBio10928.
PROP63092.
SOURCESearch...

Entry information

Entry nameGNAS2_HUMAN
AccessionPrimary (citable) accession number: P63092
Secondary accession number(s): A6NI00 expand/collapse secondary AC list , E1P5G5, P04895, Q12927, Q14433, Q32P26, Q5JWD2, Q5JWD4, Q5JWD5, Q6NR75, Q6NXS0, Q8TBC0, Q96H70
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: April 16, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM