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Protein

Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Gene

GNAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).5 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi54 – 541MagnesiumBy similarity
Metal bindingi204 – 2041MagnesiumBy similarity
Binding sitei366 – 3661GTP; via amide nitrogenBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi47 – 559GTPBy similarity
Nucleotide bindingi197 – 2048GTPBy similarity
Nucleotide bindingi223 – 2275GTPBy similarity
Nucleotide bindingi292 – 2954GTPBy similarity

GO - Molecular functioni

  • GTPase activity Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • signal transducer activity Source: UniProtKB

GO - Biological processi

  • activation of adenylate cyclase activity Source: UniProtKB
  • adenylate cyclase-activating adrenergic receptor signaling pathway Source: UniProtKB
  • adenylate cyclase-activating dopamine receptor signaling pathway Source: BHF-UCL
  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • bone development Source: UniProtKB
  • cellular response to catecholamine stimulus Source: BHF-UCL
  • cellular response to glucagon stimulus Source: Reactome
  • cellular response to prostaglandin E stimulus Source: BHF-UCL
  • cognition Source: UniProtKB
  • developmental growth Source: UniProtKB
  • hair follicle placode formation Source: UniProtKB
  • intracellular transport Source: UniProtKB
  • platelet aggregation Source: UniProtKB
  • positive regulation of cAMP biosynthetic process Source: UniProtKB
  • positive regulation of cAMP-mediated signaling Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • regulation of insulin secretion Source: Reactome
  • renal water homeostasis Source: Reactome
  • sensory perception of smell Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Transducer

Keywords - Ligandi

GTP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392851. Prostacyclin signalling through prostacyclin receptor.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-418597. G alpha (z) signalling events.
R-HSA-420092. Glucagon-type ligand receptors.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiP63092.

Names & Taxonomyi

Protein namesi
Recommended name:
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Alternative name(s):
Adenylate cyclase-stimulating G alpha protein
Gene namesi
Name:GNAS
Synonyms:GNAS1, GSP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:4392. GNAS.

Subcellular locationi

  • Cell membrane By similarity; Lipid-anchor By similarity

GO - Cellular componenti

  • cytoplasm Source: LIFEdb
  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • heterotrimeric G-protein complex Source: UniProtKB
  • intrinsic component of membrane Source: UniProtKB
  • membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Albright hereditary osteodystrophy (AHO)8 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.
See also OMIM:103580
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti99 – 991L → P in AHO. 1 Publication
Corresponds to variant rs137854531 [ dbSNP | Ensembl ].
VAR_003439
Natural varianti106 – 1061I → S in AHO/PHP1A. 1 Publication
VAR_031872
Natural varianti115 – 1151P → L in AHO. 1 Publication
Corresponds to variant rs137854539 [ dbSNP | Ensembl ].
VAR_017843
Natural varianti165 – 1651R → C in AHO. 1 Publication
Corresponds to variant rs137854532 [ dbSNP | Ensembl ].
VAR_003440
Natural varianti231 – 2311R → H in AHO; impairs the ability to mediate hormonal stimulation. 3 Publications
Corresponds to variant rs137854538 [ dbSNP | Ensembl ].
VAR_017848
Natural varianti242 – 2421T → I in AHO. 1 Publication
VAR_031875
Natural varianti246 – 2461F → S in AHO. 1 Publication
VAR_031876
Natural varianti250 – 2501S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. 1 Publication
Corresponds to variant rs137854534 [ dbSNP | Ensembl ].
VAR_017849
Natural varianti258 – 2581R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 Publication
Corresponds to variant rs137854535 [ dbSNP | Ensembl ].
VAR_015388
Natural varianti259 – 2591E → V in AHO. 1 Publication
VAR_031877
Natural varianti385 – 3851R → H in AHO; uncouples receptors from adenylyl cyclases. 1 Publication
VAR_003444
Pseudohypoparathyroidism 1A (PHP1A)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:103580
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti106 – 1061I → S in AHO/PHP1A. 1 Publication
VAR_031872
Natural varianti156 – 1561D → N in PHP1A. 1 Publication
VAR_031873
Natural varianti159 – 1591V → M in PHP1A. 1 Publication
VAR_031874
Natural varianti280 – 2801R → G in PHP1A. 1 Publication
VAR_031878
Natural varianti280 – 2801R → K in PHP1A. 1 Publication
VAR_031879
Natural varianti338 – 3381K → N in PHP1A. 1 Publication
VAR_031881
Natural varianti366 – 3661A → S in PHP1A; the patient also shows testotoxicosis; constitutively activates adenylyl cyclase in vitro; rapidly degraded at 37 degrees resulting in loss of Gs activity. 1 Publication
Corresponds to variant rs137854537 [ dbSNP | Ensembl ].
VAR_017850
McCune-Albright syndrome (MAS)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCharacterized 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.
See also OMIM:174800
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti201 – 2011R → C in MAS; also found in somatotrophinoma. 2 Publications
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_003442
Natural varianti201 – 2011R → G in MAS. 1 Publication
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_017844
Natural varianti201 – 2011R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 Publications
Corresponds to variant rs121913495 [ dbSNP | Ensembl ].
VAR_003441
Natural varianti201 – 2011R → L in non-MAS endocrine tumors. 1 Publication
VAR_017845
Pituitary adenoma, growth hormone-secreting, 1 (PAGH1)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA growth hormone-secreting, benign neoplasm of the anterior pituitary gland, also known as somatotropinoma. It clinically results in acromegaly, a condition characterized by coarse facial features, protruding jaw, and enlarged extremities. Excessive production of growth hormone in children or adolescents before the closure of epiphyses causes gigantism, a condition characterized by abnormally tall stature.
See also OMIM:102200
Progressive osseous heteroplasia (POH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal dominant disorder characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue.
See also OMIM:166350
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti281 – 2811W → R in POH. 1 Publication
VAR_031880
ACTH-independent macronodular adrenal hyperplasia 1 (AIMAH1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:219080
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti201 – 2011R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 Publications
Corresponds to variant rs121913495 [ dbSNP | Ensembl ].
VAR_003441
Natural varianti201 – 2011R → S in AIMAH1; also found in pituitary tumor and polyostotic fibrous dysplasia. 3 Publications
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_017846
Pseudohypoparathyroidism 1B (PHP1B)7 Publications
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.
Disease descriptionA 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.
See also OMIM:603233
GNAS hyperfunction (GNASHYP)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThis 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.
See also OMIM:139320
Pseudohypoparathyroidism 1C (PHP1C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:612462
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti388 – 3881L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
Corresponds to variant rs397514457 [ dbSNP | Ensembl ].
VAR_066387
Natural varianti392 – 3921E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
Corresponds to variant rs397514456 [ dbSNP | Ensembl ].
VAR_066388

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi170 – 1701Q → A: Increases GDP release but does not affect receptor-mediated activation. 1 Publication
Mutagenesisi258 – 2581R → A: Increases GDP release and impairs receptor-mediated activation; markedly elevated intrinsic GTPase rate which will lead to more rapid inactivation. 2 Publications

Keywords - Diseasei

Cushing syndrome, Disease mutation, Obesity, Proto-oncogene

Organism-specific databases

MalaCardsiGNAS.
MIMi102200. phenotype.
103580. phenotype.
139320. gene+phenotype.
166350. phenotype.
174800. phenotype.
219080. phenotype.
603233. phenotype.
612462. phenotype.
Orphaneti562. 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.
PharmGKBiPA175.

Chemistry

ChEMBLiCHEMBL4377.

Polymorphism and mutation databases

BioMutaiNPEPL1.
DMDMi52000961.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 394394Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortPRO_0000203721Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi2 – 21N-palmitoyl glycineBy similarity
Lipidationi3 – 31S-palmitoyl cysteine1 Publication
Modified residuei201 – 2011ADP-ribosylarginine; by cholera toxinBy similarity
Cross-linki300 – 300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei352 – 3521PhosphoserineCombined sources

Keywords - PTMi

ADP-ribosylation, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP63092.
PaxDbiP63092.
PeptideAtlasiP63092.
PRIDEiP63092.

PTM databases

iPTMnetiP63092.
PhosphoSiteiP63092.
SwissPalmiP63092.

Expressioni

Gene expression databases

BgeeiENSG00000087460.
CleanExiHS_GNAS.
ExpressionAtlasiP63092. baseline and differential.
GenevisibleiP63092. HS.

Organism-specific databases

HPAiCAB010337.

Interactioni

Subunit structurei

Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with CRY1; the interaction may block GPCR-mediated regulation of cAMP concentrations (PubMed:20852621). Interacts with ADCY5 and stimulates its adenylyl cyclase activity (PubMed:17110384, PubMed:26206488). Interacts with ADCY6 and stimulates its adenylyl cyclase activity (PubMed:17110384). Interacts with ADCY2 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Coro1aO890532EBI-1047114,EBI-6665847From a different organism.
Oprm1P428662EBI-7607528,EBI-5282656From a different organism.

Protein-protein interaction databases

BioGridi109040. 82 interactions.
IntActiP63092. 22 interactions.
MINTiMINT-262348.
STRINGi9606.ENSP00000360141.

Structurei

3D structure databases

ProteinModelPortaliP63092.
SMRiP63092. Positions 9-394.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0099. Eukaryota.
ENOG410XPC4. LUCA.
GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038729.
HOVERGENiHBG063184.
KOiK04632.
OMAiYEHTKTL.

Family and domain databases

Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR000367. Gprotein_alpha_S.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00443. GPROTEINAS.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Gnas-1 (identifier: P63092-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE
60 70 80 90 100
SGKSTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKAT KVQDIKNNLK
110 120 130 140 150
EAIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA
160 170 180 190 200
KALWEDEGVR ACYERSNEYQ LIDCAQYFLD KIDVIKQADY VPSDQDLLRC
210 220 230 240 250
RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVAS
260 270 280 290 300
SSYNMVIRED NQTNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK
310 320 330 340 350
VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST
360 370 380 390
ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL
Length:394
Mass (Da):45,665
Last modified:August 13, 1987 - v1
Checksum:iCD541181FC4412EF
GO
Isoform Gnas-2 (identifier: P63092-2) [UniParc] [UniParc]FASTAAdd to basket
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.

Show »
Length:380
Mass (Da):44,266
Checksum:iC3D8B1E786EBC618
GO
Isoform 3 (identifier: P63092-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     71-71: E → D
     72-86: Missing.

Note: No experimental confirmation available.
Show »
Length:379
Mass (Da):44,179
Checksum:i6D095E83B1667CAA
GO
Isoform XLas-1 (identifier: Q5JWF2-1) [UniParc]FASTAAdd to basket
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.
Length:1,037
Mass (Da):111,025
GO
Isoform XLas-2 (identifier: Q5JWF2-2) [UniParc]FASTAAdd to basket
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.
Length:1,023
Mass (Da):109,626
GO
Isoform XLas-3 (identifier: Q5JWF2-3) [UniParc]FASTAAdd to basket
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.
Length:752
Mass (Da):77,643
GO
Isoform Nesp55 (identifier: O95467-1) [UniParc]FASTAAdd to basket
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.
Length:245
Mass (Da):28,029
GO
Isoform 4 (identifier: P63092-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     86-86: G → GS

Note: Gene prediction based on EST data.
Show »
Length:395
Mass (Da):45,752
Checksum:iA808ECA884A6E476
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti3 – 31C → Y in AAH66923 (PubMed:15489334).Curated
Sequence conflicti6 – 61N → T in CAA30084 (PubMed:3127824).Curated
Sequence conflicti72 – 721Missing in AAH66923 (PubMed:15489334).Curated
Sequence conflicti167 – 1671N → D in AAH22875 (PubMed:15489334).Curated
Sequence conflicti230 – 2301E → Q in AAA52583 (PubMed:3024154).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti99 – 991L → P in AHO. 1 Publication
Corresponds to variant rs137854531 [ dbSNP | Ensembl ].
VAR_003439
Natural varianti106 – 1061I → S in AHO/PHP1A. 1 Publication
VAR_031872
Natural varianti115 – 1151P → L in AHO. 1 Publication
Corresponds to variant rs137854539 [ dbSNP | Ensembl ].
VAR_017843
Natural varianti156 – 1561D → N in PHP1A. 1 Publication
VAR_031873
Natural varianti159 – 1591V → M in PHP1A. 1 Publication
VAR_031874
Natural varianti165 – 1651R → C in AHO. 1 Publication
Corresponds to variant rs137854532 [ dbSNP | Ensembl ].
VAR_003440
Natural varianti201 – 2011R → C in MAS; also found in somatotrophinoma. 2 Publications
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_003442
Natural varianti201 – 2011R → G in MAS. 1 Publication
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_017844
Natural varianti201 – 2011R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 Publications
Corresponds to variant rs121913495 [ dbSNP | Ensembl ].
VAR_003441
Natural varianti201 – 2011R → L in non-MAS endocrine tumors. 1 Publication
VAR_017845
Natural varianti201 – 2011R → S in AIMAH1; also found in pituitary tumor and polyostotic fibrous dysplasia. 3 Publications
Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
VAR_017846
Natural varianti227 – 2271Q → H in pituitary adenomas; also found in a patient with severe Cushing syndrome. 1 Publication
Corresponds to variant rs137854533 [ dbSNP | Ensembl ].
VAR_017847
Natural varianti227 – 2271Q → R in somatotrophinoma. 1 Publication
Corresponds to variant rs121913494 [ dbSNP | Ensembl ].
VAR_003443
Natural varianti231 – 2311R → H in AHO; impairs the ability to mediate hormonal stimulation. 3 Publications
Corresponds to variant rs137854538 [ dbSNP | Ensembl ].
VAR_017848
Natural varianti242 – 2421T → I in AHO. 1 Publication
VAR_031875
Natural varianti246 – 2461F → S in AHO. 1 Publication
VAR_031876
Natural varianti250 – 2501S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. 1 Publication
Corresponds to variant rs137854534 [ dbSNP | Ensembl ].
VAR_017849
Natural varianti258 – 2581R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 Publication
Corresponds to variant rs137854535 [ dbSNP | Ensembl ].
VAR_015388
Natural varianti259 – 2591E → V in AHO. 1 Publication
VAR_031877
Natural varianti280 – 2801R → G in PHP1A. 1 Publication
VAR_031878
Natural varianti280 – 2801R → K in PHP1A. 1 Publication
VAR_031879
Natural varianti281 – 2811W → R in POH. 1 Publication
VAR_031880
Natural varianti338 – 3381K → N in PHP1A. 1 Publication
VAR_031881
Natural varianti366 – 3661A → S in PHP1A; the patient also shows testotoxicosis; constitutively activates adenylyl cyclase in vitro; rapidly degraded at 37 degrees resulting in loss of Gs activity. 1 Publication
Corresponds to variant rs137854537 [ dbSNP | Ensembl ].
VAR_017850
Natural varianti380 – 3801R → L.
Corresponds to variant rs8986 [ dbSNP | Ensembl ].
VAR_049358
Natural varianti382 – 3821Missing Unable to interact with the receptor for PTH. 1 Publication
VAR_034744
Natural varianti385 – 3851R → H in AHO; uncouples receptors from adenylyl cyclases. 1 Publication
VAR_003444
Natural varianti388 – 3881L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
Corresponds to variant rs397514457 [ dbSNP | Ensembl ].
VAR_066387
Natural varianti392 – 3921E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
Corresponds to variant rs397514456 [ dbSNP | Ensembl ].
VAR_066388

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei71 – 722EG → DS in isoform Gnas-2. 2 PublicationsVSP_001833
Alternative sequencei71 – 711E → D in isoform 3. 1 PublicationVSP_026616
Alternative sequencei72 – 8615Missing in isoform 3. 1 PublicationVSP_026617Add
BLAST
Alternative sequencei73 – 8614Missing in isoform Gnas-2. 2 PublicationsVSP_001834Add
BLAST
Alternative sequencei86 – 861G → GS in isoform 4. 2 PublicationsVSP_047325

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
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.
CCDSiCCDS13472.1.
CCDS42892.1. [P63092-3]
CCDS46623.1. [P63092-4]
CCDS46624.1. [P63092-2]
PIRiB31927. RGHUA2.
C31927. RGHUA1.
RefSeqiNP_000507.1. NM_000516.5. [P63092-1]
NP_001070956.1. NM_001077488.3. [P63092-4]
NP_001070957.1. NM_001077489.3. [P63092-3]
NP_001070958.1. NM_001077490.2.
NP_001296769.1. NM_001309840.1.
NP_536350.2. NM_080425.3.
NP_536351.1. NM_080426.3. [P63092-2]
UniGeneiHs.125898.

Genome annotation databases

EnsembliENST00000265620; ENSP00000265620; ENSG00000087460. [P63092-3]
ENST00000354359; ENSP00000346328; ENSG00000087460. [P63092-4]
ENST00000371085; ENSP00000360126; ENSG00000087460. [P63092-1]
ENST00000371095; ENSP00000360136; ENSG00000087460. [P63092-2]
GeneIDi2778.
KEGGihsa:2778.
UCSCiuc002yaa.4. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

GNAS mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
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.
CCDSiCCDS13472.1.
CCDS42892.1. [P63092-3]
CCDS46623.1. [P63092-4]
CCDS46624.1. [P63092-2]
PIRiB31927. RGHUA2.
C31927. RGHUA1.
RefSeqiNP_000507.1. NM_000516.5. [P63092-1]
NP_001070956.1. NM_001077488.3. [P63092-4]
NP_001070957.1. NM_001077489.3. [P63092-3]
NP_001070958.1. NM_001077490.2.
NP_001296769.1. NM_001309840.1.
NP_536350.2. NM_080425.3.
NP_536351.1. NM_080426.3. [P63092-2]
UniGeneiHs.125898.

3D structure databases

ProteinModelPortaliP63092.
SMRiP63092. Positions 9-394.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109040. 82 interactions.
IntActiP63092. 22 interactions.
MINTiMINT-262348.
STRINGi9606.ENSP00000360141.

Chemistry

ChEMBLiCHEMBL4377.

PTM databases

iPTMnetiP63092.
PhosphoSiteiP63092.
SwissPalmiP63092.

Polymorphism and mutation databases

BioMutaiNPEPL1.
DMDMi52000961.

Proteomic databases

EPDiP63092.
PaxDbiP63092.
PeptideAtlasiP63092.
PRIDEiP63092.

Protocols and materials databases

DNASUi2778.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265620; ENSP00000265620; ENSG00000087460. [P63092-3]
ENST00000354359; ENSP00000346328; ENSG00000087460. [P63092-4]
ENST00000371085; ENSP00000360126; ENSG00000087460. [P63092-1]
ENST00000371095; ENSP00000360136; ENSG00000087460. [P63092-2]
GeneIDi2778.
KEGGihsa:2778.
UCSCiuc002yaa.4. human.

Organism-specific databases

CTDi2778.
GeneCardsiGNAS.
HGNCiHGNC:4392. GNAS.
HPAiCAB010337.
MalaCardsiGNAS.
MIMi102200. phenotype.
103580. phenotype.
139320. gene+phenotype.
166350. phenotype.
174800. phenotype.
219080. phenotype.
603233. phenotype.
612462. phenotype.
neXtProtiNX_P63092.
Orphaneti562. 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.
PharmGKBiPA175.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0099. Eukaryota.
ENOG410XPC4. LUCA.
GeneTreeiENSGT00770000120503.
HOGENOMiHOG000038729.
HOVERGENiHBG063184.
KOiK04632.
OMAiYEHTKTL.

Enzyme and pathway databases

ReactomeiR-HSA-163359. Glucagon signaling in metabolic regulation.
R-HSA-164378. PKA activation in glucagon signalling.
R-HSA-381676. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
R-HSA-392851. Prostacyclin signalling through prostacyclin receptor.
R-HSA-418555. G alpha (s) signalling events.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-418597. G alpha (z) signalling events.
R-HSA-420092. Glucagon-type ligand receptors.
R-HSA-432040. Vasopressin regulates renal water homeostasis via Aquaporins.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiP63092.

Miscellaneous databases

ChiTaRSiGNAS. human.
GenomeRNAii2778.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000087460.
CleanExiHS_GNAS.
ExpressionAtlasiP63092. baseline and differential.
GenevisibleiP63092. HS.

Family and domain databases

Gene3Di1.10.400.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR000367. Gprotein_alpha_S.
IPR001019. Gprotein_alpha_su.
IPR011025. GproteinA_insert.
IPR027417. P-loop_NTPase.
[Graphical view]
PANTHERiPTHR10218. PTHR10218. 2 hits.
PfamiPF00503. G-alpha. 1 hit.
[Graphical view]
PRINTSiPR00318. GPROTEINA.
PR00443. GPROTEINAS.
SMARTiSM00275. G_alpha. 1 hit.
[Graphical view]
SUPFAMiSSF47895. SSF47895. 1 hit.
SSF52540. SSF52540. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiGNAS2_HUMAN
AccessioniPrimary (citable) accession number: P63092
Secondary accession number(s): A6NI00
, E1P5G5, P04895, Q12927, Q14433, Q32P26, Q5JWD2, Q5JWD4, Q5JWD5, Q6NR75, Q6NXS0, Q8TBC0, Q96H70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: September 7, 2016
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.