P63092 (GNAS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	394 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
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	Defects in GNAS are the cause of Albright hereditary osteodystrophy (AHO) [MIM:103580]. AHO is an autosomal dominant disorder characterized by a short stature, brachydactyly, subcutaneous ossifications. AHO is often associated with pseudohypoparathyoidism, hypocalcemia, and elevated PTH levels. The expression or the activity of GNAS is reduced in AHO. Ref.13 Ref.17 Ref.18 Ref.22 Ref.24 Ref.25 Ref.26 Ref.32 Ref.33 Ref.37 Ref.43 Defects in GNAS are the cause of pseudohypoparathyroidism type 1A (PHP1A) [MIM:103580]. Pseudohypoparathyroidism is a term applied to a heterogeneous group of disorders whose common feature is resistance to parathyroid hormone. Ref.34 Ref.35 Ref.38 Defects in GNAS are the cause of McCune-Albright syndrome (MAS) [MIM:174800]. MAS is 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. Ref.14 Ref.15 Ref.27 Defects in GNAS are the cause of growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]. Defects in GNAS are the cause of progressive osseous heteroplasia (POH) [MIM:166350]. POH is a 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. Ref.41 Defects in GNAS are a cause of ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]; also known as adrenal Cushing syndrome due to AIMAH. 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 trunkal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes. Ref.39 Genetic variations in GNAS are the cause of pseudohypoparathyroidism type 1B (PHP1B) [MIM:603233]. PHP1B is characterized by parathyroid hormone (PTH)-resistant hypocalcemia and hyperphosphatemia. Patients affected with PHP1B have normal activity of the product of GNAS, lack developmental defects characteristic of AHO, and typically show no other endocrine abnormalities besides resistance to PTH. 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.29 Ref.30 Ref.31 Ref.36 Ref.40 Ref.42 Ref.44 Defects in GNAS are the cause of 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. Defects in GNAS are the cause of pseudohypoparathyroidism type 1C (PHP1C) [MIM:612462]. It is 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.
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 component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cushing syndrome Disease mutation Proto-oncogene
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Transducer
PTM	ADP-ribosylation Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro activation of adenylate cyclase activity Traceable author statement Ref.25. Source: UniProtKB cellular response to glucagon stimulus Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome intracellular transport Non-traceable author statement. Source: UniProtKB platelet activation Traceable author statement. Source: Reactome regulation of insulin secretion Traceable author statement. Source: Reactome sensory perception of smell Traceable author statement. Source: UniProtKB transmembrane transport Traceable author statement. Source: Reactome water transport Traceable author statement. Source: Reactome
Cellular component	heterotrimeric G-protein complex Traceable author statement Ref.25. Source: UniProtKB intrinsic to membrane Inferred from direct assay. Source: UniProtKB trans-Golgi network membrane Inferred from direct assay. Source: UniProtKB
Molecular function	GTP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement Ref.25. Source: UniProtKB adenylate cyclase activity Traceable author statement. Source: Reactome guanyl-nucleotide exchange factor activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 7 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 394	393	Guanine nucleotide-binding protein G(s) subunit alpha isoforms short		PRO_0000203721
Regions
	Nucleotide binding	47 – 54	8	GTP By similarity
	Nucleotide binding	198 – 204	7	GTP By similarity
	Nucleotide binding	223 – 227	5	GTP By similarity
	Nucleotide binding	292 – 295	4	GTP By similarity
Sites
	Metal binding	54	1	Magnesium By similarity
	Metal binding	204	1	Magnesium By similarity
	Binding site	366	1	GTP; via amide nitrogen By similarity
Amino acid modifications
	Modified residue	51	1	Phosphoserine By similarity
	Modified residue	201	1	ADP-ribosylarginine; by cholera toxin By similarity
	Lipidation	2	1	N-palmitoyl glycine By similarity
	Lipidation	3	1	S-palmitoyl cysteine Ref.12
	Cross-link	300		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.11
Natural variations
	Alternative sequence	71 – 72	2	EG → DS in isoform Gnas-2.		VSP_001833
	Alternative sequence	71	1	E → D in isoform 3.		VSP_026616
	Alternative sequence	72 – 86	15	Missing in isoform 3.		VSP_026617
	Alternative sequence	73 – 86	14	Missing in isoform Gnas-2.		VSP_001834
	Natural variant	99	1	L → P in AHO. Ref.13		VAR_003439
	Natural variant	106	1	I → S in AHO/PHP1A. Ref.43		VAR_031872
	Natural variant	115	1	P → L in AHO. Ref.33		VAR_017843
	Natural variant	156	1	D → N in PHP1A. Ref.34		VAR_031873
	Natural variant	159	1	V → M in PHP1A. Ref.34		VAR_031874
	Natural variant	165	1	R → C in AHO. Ref.13		VAR_003440
	Natural variant	201	1	R → C in MAS and somatotrophinoma. Ref.15 Ref.16 Corresponds to variant rs11554273 [ dbSNP | Ensembl ].		VAR_003442
	Natural variant	201	1	R → G in MAS. Ref.27		VAR_017844
	Natural variant	201	1	R → H in MAS, somatotrophinoma and AIMAH. Ref.14 Ref.15 Ref.16 Ref.39		VAR_003441
	Natural variant	201	1	R → L in non-MAS endocrine tumors. Ref.19		VAR_017845
	Natural variant	201	1	R → S in AIMAH, pituitary tumor and polyostotic fibrous dysplasia. Ref.21 Ref.23 Ref.39		VAR_017846
	Natural variant	227	1	Q → H in pituitary adenoma; ACTH-secreting adenoma; in a patient with severe Cushing syndrome complicated by psychosis. Ref.20		VAR_017847
	Natural variant	227	1	Q → R in somatotrophinoma. Ref.16		VAR_003443
	Natural variant	231	1	R → H in AHO; impairs the ability to mediate hormonal stimulation. Ref.22 Ref.25 Ref.32		VAR_017848
	Natural variant	242	1	T → I in AHO. Ref.37		VAR_031875
	Natural variant	246	1	F → S in AHO. Ref.37		VAR_031876
	Natural variant	250	1	S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. Ref.24		VAR_017849
	Natural variant	258	1	R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. Ref.26		VAR_015388
	Natural variant	259	1	E → V in AHO. Ref.37		VAR_031877
	Natural variant	280	1	R → G in PHP1A. Ref.35		VAR_031878
	Natural variant	280	1	R → K in PHP1A. Ref.34		VAR_031879
	Natural variant	281	1	W → R in POH. Ref.41		VAR_031880
	Natural variant	338	1	K → N in PHP1A. Ref.38		VAR_031881
	Natural variant	366	1	A → 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.18		VAR_017850
	Natural variant	380	1	R → L. Corresponds to variant rs8986 [ dbSNP | Ensembl ].		VAR_049358
	Natural variant	382	1	Missing Unable to interact with the receptor for PTH.		VAR_034744
	Natural variant	385	1	R → H in AHO; uncouples receptors from adenylyl cyclases. Ref.17		VAR_003444
	Natural variant	388	1	L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. Ref.45		VAR_066387
	Natural variant	392	1	E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. Ref.45		VAR_066388
Experimental info
	Mutagenesis	170	1	Q → A: Increases GDP release but does not affect receptor-mediated activation. Ref.28
	Mutagenesis	258	1	R → A: Increases GDP release and impairs receptor-mediated activation; markedly elevated intrinsic GTPase rate which will lead to more rapid inactivation. Ref.26 Ref.28
	Sequence conflict	3	1	C → Y in AAH66923. Ref.8
	Sequence conflict	6	1	N → T in CAA30084. Ref.3
	Sequence conflict	72	1	Missing in AAH66923. Ref.8
	Sequence conflict	86	1	G → GS in CAI42915. Ref.6
	Sequence conflict	86	1	G → GS in CAI42547. Ref.6
	Sequence conflict	86	1	G → GS in AAH08855. Ref.8
	Sequence conflict	86	1	G → GS in AAA53147. Ref.9
	Sequence conflict	167	1	N → D in AAH22875. Ref.8
	Sequence conflict	230	1	E → Q in AAA52583. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform Gnas-1 (Alpha-S2) (GNASl) (Alpha-S-long) [UniParc]. Last modified August 13, 1987. Version 1. Checksum: CD541181FC4412EF	FASTA	394	45,665
	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
	Isoform Gnas-2 (Alpha-S1) (GNASs) (Alpha-S-short) [UniParc] [UniParc]. Checksum: C3D8B1E786EBC618	FASTA	380	44,266
	10 20 30 40 50 60 MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM 70 80 90 100 110 120 RILHVNGFNG DSEKATKVQD IKNNLKEAIE TIVAAMSNLV PPVELANPEN QFRVDYILSV 130 140 150 160 170 180 MNVPDFDFPP EFYEHAKALW EDEGVRACYE RSNEYQLIDC AQYFLDKIDV IKQADYVPSD 190 200 210 220 230 240 QDLLRCRVLT SGIFETKFQV DKVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVASSSYN 250 260 270 280 290 300 MVIREDNQTN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG KSKIEDYFPE 310 320 330 340 350 360 FARYTTPEDA TPEPGEDPRV TRAKYFIRDE FLRISTASGD GRHYCYPHFT CAVDTENIRR 370 380 VFNDCRDIIQ RMHLRQYELL
	Isoform 3 [UniParc]. Checksum: 6D095E83B1667CAA	FASTA	379	44,179
	10 20 30 40 50 60 MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKSTIVKQM 70 80 90 100 110 120 RILHVNGFNG DEKATKVQDI KNNLKEAIET IVAAMSNLVP PVELANPENQ FRVDYILSVM 130 140 150 160 170 180 NVPDFDFPPE FYEHAKALWE DEGVRACYER SNEYQLIDCA QYFLDKIDVI KQADYVPSDQ 190 200 210 220 230 240 DLLRCRVLTS GIFETKFQVD KVNFHMFDVG GQRDERRKWI QCFNDVTAII FVVASSSYNM 250 260 270 280 290 300 VIREDNQTNR LQEALNLFKS IWNNRWLRTI SVILFLNKQD LLAEKVLAGK SKIEDYFPEF 310 320 330 340 350 360 ARYTTPEDAT PEPGEDPRVT RAKYFIRDEF LRISTASGDG RHYCYPHFTC AVDTENIRRV 370 FNDCRDIIQR MHLRQYELL
	Isoform XLas-1 [UniParc]. See Q5JWF2.		–	–
	Isoform XLas-2 [UniParc]. See Q5JWF2.		–	–
	Isoform XLas-3 [UniParc]. See Q5JWF2.		–	–
	Isoform Nesp55 [UniParc]. See O95467.		–	–

References

	« Hide 'large scale' referencesShow '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: 3093273] [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: 3131741] [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: 3127824] [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. , 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: 11780052] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1 AND 3). 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: 3024154] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-394 (ISOFORM GNAS-1).
[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: 15242332] [Abstract] Cited for: PROTEIN SEQUENCE OF 187-199 AND 308-317. Tissue: Adipocyte.
[11]	"Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry." Meierhofer D., Wang X., Huang L., Kaiser P. J. Proteome Res. 7:4566-4576(2008) [PubMed: 18781797] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-300, MASS SPECTROMETRY.
[12]	"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: 21044946] [Abstract] Cited for: PALMITOYLATION AT CYS-3.
[13]	"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: 8388883] [Abstract] Cited for: VARIANTS AHO PRO-99 AND CYS-165.
[14]	"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: 1594625] [Abstract] Cited for: VARIANT MAS HIS-201.
[15]	"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: 1944469] [Abstract] Cited for: VARIANTS MAS CYS-201 AND HIS-201.
[16]	"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: 2549426] [Abstract] Cited for: VARIANTS SOMATOTROPHINOMA CYS-201; HIS-201 AND ARG-227.
[17]	"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: 7523385] [Abstract] Cited for: VARIANT AHO HIS-385.
[18]	"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: 8072545] [Abstract] Cited for: CHARACTERIZATION OF VARIANT AHO SER-366.
[19]	"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: 7751320] [Abstract] Cited for: VARIANT NON-MAS ENDOCRINE TUMORS LEU-201.
[20]	"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: 7737262] [Abstract] Cited for: VARIANT PITUITARY ADENOMA HIS-227.
[21]	"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: 8766942] [Abstract] Cited for: VARIANT PITUITARY TUMOR SER-201.
[22]	"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: 8702665] [Abstract] Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
[23]	"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: 9267696] [Abstract] Cited for: VARIANT POLYOSTOTIC FIBROUS DYSPLASIA SER-201.
[24]	"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: 9328353] [Abstract] Cited for: VARIANT AHO ARG-250.
[25]	"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: 9159128] [Abstract] Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
[26]	"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: 9727013] [Abstract] Cited for: VARIANT AHO TRP-258, MUTAGENESIS OF ARG-258, CHARACTERIZATION OF VARIANT AHO TRP-258.
[27]	"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: 10571700] [Abstract] Cited for: VARIANT MAS GLY-201.
[28]	"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: 10200251] [Abstract] Cited for: MUTAGENESIS OF GLN-170 AND ARG-258.
[29]	"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: 11067869] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[30]	"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: 11294659] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[31]	"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: 11029463] [Abstract] Cited for: INVOLVEMENT IN PHP1B, VARIANT ILE-382 DEL, CHARACTERIZATION OF VARIANT ILE-382 DEL.
[32]	"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: 11450852] [Abstract] Cited for: VARIANT AHO HIS-231.
[33]	"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: 11600516] [Abstract] Cited for: VARIANT AHO LEU-115.
[34]	"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: 11788646] [Abstract] Cited for: VARIANTS PHP1A ASN-156; MET-159 AND LYS-280.
[35]	"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: 11926205] [Abstract] Cited for: VARIANT PHP1A GLY-280.
[36]	"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: 12858292] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[37]	"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: 12624854] [Abstract] Cited for: VARIANTS AHO ILE-242; SER-246 AND VAL-259.
[38]	"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: 12656668] [Abstract] Cited for: VARIANT PHP1A ASN-338.
[39]	"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: 12727968] [Abstract] Cited for: VARIANTS AIMAH HIS-201 AND SER-201.
[40]	"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: 14561710] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[41]	"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: 14723729] [Abstract] Cited for: VARIANT POH ARG-281.
[42]	"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: 15800843] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[43]	"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: 15817905] [Abstract] Cited for: VARIANT AHO/PHP1A SER-106.
[44]	"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: 15592469] [Abstract] Cited for: INVOLVEMENT IN PHP1B.
[45]	"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: 21488135] [Abstract] Cited for: VARIANTS PHP1C ARG-388 AND LYS-392, CHARACTERIZATION OF VARIANTS PHP1C ARG-388 AND LYS-392.
+	Additional computationally mapped references.

Web resources

GNAS mutation db

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	X04408 mRNA. Translation: CAA27996.1. X04409 mRNA. Translation: CAA27997.1. M21142 , M21139, M21740, M21140, M21741, M21141 Genomic DNA. Translation: AAA53147.1. M21142 , M21139, M21740, M21140, M21741, M21141 Genomic DNA. Translation: AAA53146.1. M21142 , M21139, M21141, M21740, M21741 Genomic DNA. Translation: AAA53148.1. M21142 , 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. 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.
IPI	IPI00219835. IPI00514055. IPI00644936.
PIR	RGHUA2. B31927. RGHUA1. C31927.
RefSeq	NP_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.
UniGene	Hs.125898. Hs.694849.
3D structure databases
ProteinModelPortal	P63092.
SMR	P63092. Positions 9-394.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63092. 3 interactions.
STRING	P63092.
PTM databases
PhosphoSite	P63092.
Polymorphism databases
DMDM	52000961.
Proteomic databases
PRIDE	P63092.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371082; ENSP00000360123; ENSG00000087460. ENST00000371085; ENSP00000360126; ENSG00000087460.
GeneID	2778.
KEGG	hsa:2778.
Organism-specific databases
CTD	2778.
GeneCards	GC20P057414.
HGNC	HGNC:4392. GNAS.
HPA	CAB010337.
MIM	102200. phenotype. 103580. phenotype. 139320. gene+phenotype. 166350. phenotype. 174800. phenotype. 219080. phenotype. 603233. phenotype. 612462. phenotype.
neXtProt	NX_P63092.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00560000077005.
HOVERGEN	HBG063184.
PhylomeDB	P63092.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_calcium_pathway. Noncanonical Wnt signaling pathway.
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_15518. Transmembrane transport of small molecules. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	P63092.
Bgee	P63092.
CleanEx	HS_GNAS.
Genevestigator	P63092.
GermOnline	ENSG00000087460. Homo sapiens.
Family and domain databases
InterPro	IPR000367. Gprotein_alpha_S. IPR001019. Gprotein_alpha_su. IPR011025. GproteinA_insert. [Graphical view]
Gene3D	G3DSA:1.10.400.10. GproteinA_insert. 1 hit.
KO	K04632.
PANTHER	PTHR10218. Gprotein_alph_bd. 1 hit.
Pfam	PF00503. G-alpha. 1 hit. [Graphical view]
PRINTS	PR00318. GPROTEINA. PR00443. GPROTEINAS.
SMART	SM00275. G_alpha. 1 hit. [Graphical view]
SUPFAM	SSF47895. Transducn_insert. 1 hit.
ProtoNet	Search...
Other
NextBio	10928.
SOURCE	Search...

Entry information

Entry name

GNAS2_HUMAN

Accession

Primary (citable) accession number: P63092
Secondary accession number(s): 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:	January 25, 2012
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.