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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)DescriptionActionsGraphical viewLength
Metal bindingi54MagnesiumBy similarity1
Metal bindingi204MagnesiumBy similarity1
Binding sitei366GTP; via amide nitrogenBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi47 – 55GTPBy similarity9
Nucleotide bindingi197 – 204GTPBy similarity8
Nucleotide bindingi223 – 227GTPBy similarity5
Nucleotide bindingi292 – 295GTPBy similarity4

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_00343999L → P in AHO. 1 PublicationCorresponds to variant rs137854531dbSNPEnsembl.1
Natural variantiVAR_031872106I → S in AHO/PHP1A. 1 Publication1
Natural variantiVAR_017843115P → L in AHO. 1 PublicationCorresponds to variant rs137854539dbSNPEnsembl.1
Natural variantiVAR_003440165R → C in AHO. 1 PublicationCorresponds to variant rs137854532dbSNPEnsembl.1
Natural variantiVAR_017848231R → H in AHO; impairs the ability to mediate hormonal stimulation. 3 PublicationsCorresponds to variant rs137854538dbSNPEnsembl.1
Natural variantiVAR_031875242T → I in AHO. 1 Publication1
Natural variantiVAR_031876246F → S in AHO. 1 Publication1
Natural variantiVAR_017849250S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. 1 PublicationCorresponds to variant rs137854534dbSNPEnsembl.1
Natural variantiVAR_015388258R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 PublicationCorresponds to variant rs137854535dbSNPEnsembl.1
Natural variantiVAR_031877259E → V in AHO. 1 Publication1
Natural variantiVAR_003444385R → H in AHO; uncouples receptors from adenylyl cyclases. 1 Publication1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_031872106I → S in AHO/PHP1A. 1 Publication1
Natural variantiVAR_031873156D → N in PHP1A. 1 Publication1
Natural variantiVAR_031874159V → M in PHP1A. 1 Publication1
Natural variantiVAR_031878280R → G in PHP1A. 1 Publication1
Natural variantiVAR_031879280R → K in PHP1A. 1 Publication1
Natural variantiVAR_031881338K → N in PHP1A. 1 Publication1
Natural variantiVAR_017850366A → 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 PublicationCorresponds to variant rs137854537dbSNPEnsembl.1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_003442201R → C in MAS; also found in somatotrophinoma. 2 PublicationsCorresponds to variant rs11554273dbSNPEnsembl.1
Natural variantiVAR_017844201R → G in MAS. 1 PublicationCorresponds to variant rs11554273dbSNPEnsembl.1
Natural variantiVAR_003441201R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 PublicationsCorresponds to variant rs121913495dbSNPEnsembl.1
Natural variantiVAR_017845201R → L in non-MAS endocrine tumors. 1 Publication1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_031880281W → R in POH. 1 Publication1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_003441201R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 PublicationsCorresponds to variant rs121913495dbSNPEnsembl.1
Natural variantiVAR_017846201R → S in AIMAH1; also found in pituitary tumor and polyostotic fibrous dysplasia. 3 PublicationsCorresponds to variant rs11554273dbSNPEnsembl.1
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_066387388L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 PublicationCorresponds to variant rs397514457dbSNPEnsembl.1
Natural variantiVAR_066388392E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 PublicationCorresponds to variant rs397514456dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi170Q → A: Increases GDP release but does not affect receptor-mediated activation. 1 Publication1
Mutagenesisi258R → A: Increases GDP release and impairs receptor-mediated activation; markedly elevated intrinsic GTPase rate which will lead to more rapid inactivation. 2 Publications1

Keywords - Diseasei

Cushing syndrome, Disease mutation, Obesity, Proto-oncogene

Organism-specific databases

DisGeNETi2778.
MalaCardsiGNAS.
MIMi102200. phenotype.
103580. phenotype.
139320. gene+phenotype.
166350. phenotype.
174800. phenotype.
219080. phenotype.
603233. phenotype.
612462. phenotype.
OpenTargetsiENSG00000087460.
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 databases

ChEMBLiCHEMBL4377.

Polymorphism and mutation databases

BioMutaiNPEPL1.
DMDMi52000961.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002037211 – 394Guanine nucleotide-binding protein G(s) subunit alpha isoforms shortAdd BLAST394

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-palmitoyl glycineBy similarity1
Lipidationi3S-palmitoyl cysteine1 Publication1
Modified residuei201ADP-ribosylarginine; by cholera toxinBy similarity1
Cross-linki300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residuei352PhosphoserineCombined sources1

Keywords - PTMi

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

Proteomic databases

EPDiP63092.
MaxQBiP63092.
PaxDbiP63092.
PeptideAtlasiP63092.
PRIDEiP63092.

PTM databases

iPTMnetiP63092.
PhosphoSitePlusiP63092.
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. 84 interactors.
IntActiP63092. 22 interactors.
MINTiMINT-262348.
STRINGi9606.ENSP00000360141.

Structurei

Secondary structure

1394
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi41 – 47Combined sources7
Helixi53 – 60Combined sources8
Beta strandi209 – 214Combined sources6
Beta strandi217 – 223Combined sources7
Beta strandi226 – 230Combined sources5
Helixi231 – 235Combined sources5
Beta strandi242 – 251Combined sources10
Helixi265 – 278Combined sources14
Turni281 – 284Combined sources4
Beta strandi286 – 292Combined sources7
Helixi294 – 303Combined sources10
Helixi308 – 311Combined sources4
Helixi313 – 317Combined sources5
Helixi332 – 351Combined sources20
Beta strandi359 – 363Combined sources5
Helixi371 – 390Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5G53X-ray3.40C/D26-60[»]
C/D204-394[»]
ProteinModelPortaliP63092.
SMRiP63092.
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

CDDicd00066. G-alpha. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti3C → Y in AAH66923 (PubMed:15489334).Curated1
Sequence conflicti6N → T in CAA30084 (PubMed:3127824).Curated1
Sequence conflicti72Missing in AAH66923 (PubMed:15489334).Curated1
Sequence conflicti167N → D in AAH22875 (PubMed:15489334).Curated1
Sequence conflicti230E → Q in AAA52583 (PubMed:3024154).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00343999L → P in AHO. 1 PublicationCorresponds to variant rs137854531dbSNPEnsembl.1
Natural variantiVAR_031872106I → S in AHO/PHP1A. 1 Publication1
Natural variantiVAR_017843115P → L in AHO. 1 PublicationCorresponds to variant rs137854539dbSNPEnsembl.1
Natural variantiVAR_031873156D → N in PHP1A. 1 Publication1
Natural variantiVAR_031874159V → M in PHP1A. 1 Publication1
Natural variantiVAR_003440165R → C in AHO. 1 PublicationCorresponds to variant rs137854532dbSNPEnsembl.1
Natural variantiVAR_003442201R → C in MAS; also found in somatotrophinoma. 2 PublicationsCorresponds to variant rs11554273dbSNPEnsembl.1
Natural variantiVAR_017844201R → G in MAS. 1 PublicationCorresponds to variant rs11554273dbSNPEnsembl.1
Natural variantiVAR_003441201R → H in MAS and AIMAH1; also found in somatotrophinoma. 4 PublicationsCorresponds to variant rs121913495dbSNPEnsembl.1
Natural variantiVAR_017845201R → L in non-MAS endocrine tumors. 1 Publication1
Natural variantiVAR_017846201R → S in AIMAH1; also found in pituitary tumor and polyostotic fibrous dysplasia. 3 PublicationsCorresponds to variant rs11554273dbSNPEnsembl.1
Natural variantiVAR_017847227Q → H in pituitary adenomas; also found in a patient with severe Cushing syndrome. 1 PublicationCorresponds to variant rs137854533dbSNPEnsembl.1
Natural variantiVAR_003443227Q → R in somatotrophinoma. 1 PublicationCorresponds to variant rs121913494dbSNPEnsembl.1
Natural variantiVAR_017848231R → H in AHO; impairs the ability to mediate hormonal stimulation. 3 PublicationsCorresponds to variant rs137854538dbSNPEnsembl.1
Natural variantiVAR_031875242T → I in AHO. 1 Publication1
Natural variantiVAR_031876246F → S in AHO. 1 Publication1
Natural variantiVAR_017849250S → R in AHO; may alter guanine nucleotide binding which could lead to thermolability and impaired function. 1 PublicationCorresponds to variant rs137854534dbSNPEnsembl.1
Natural variantiVAR_015388258R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 PublicationCorresponds to variant rs137854535dbSNPEnsembl.1
Natural variantiVAR_031877259E → V in AHO. 1 Publication1
Natural variantiVAR_031878280R → G in PHP1A. 1 Publication1
Natural variantiVAR_031879280R → K in PHP1A. 1 Publication1
Natural variantiVAR_031880281W → R in POH. 1 Publication1
Natural variantiVAR_031881338K → N in PHP1A. 1 Publication1
Natural variantiVAR_017850366A → 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 PublicationCorresponds to variant rs137854537dbSNPEnsembl.1
Natural variantiVAR_049358380R → L.Corresponds to variant rs8986dbSNPEnsembl.1
Natural variantiVAR_034744382Missing Unable to interact with the receptor for PTH. 1 Publication1
Natural variantiVAR_003444385R → H in AHO; uncouples receptors from adenylyl cyclases. 1 Publication1
Natural variantiVAR_066387388L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 PublicationCorresponds to variant rs397514457dbSNPEnsembl.1
Natural variantiVAR_066388392E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 PublicationCorresponds to variant rs397514456dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00183371 – 72EG → DS in isoform Gnas-2. 2 Publications2
Alternative sequenceiVSP_02661671E → D in isoform 3. 1 Publication1
Alternative sequenceiVSP_02661772 – 86Missing in isoform 3. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_00183473 – 86Missing in isoform Gnas-2. 2 PublicationsAdd BLAST14
Alternative sequenceiVSP_04732586G → GS in isoform 4. 2 Publications1

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

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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5G53X-ray3.40C/D26-60[»]
C/D204-394[»]
ProteinModelPortaliP63092.
SMRiP63092.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109040. 84 interactors.
IntActiP63092. 22 interactors.
MINTiMINT-262348.
STRINGi9606.ENSP00000360141.

Chemistry databases

ChEMBLiCHEMBL4377.

PTM databases

iPTMnetiP63092.
PhosphoSitePlusiP63092.
SwissPalmiP63092.

Polymorphism and mutation databases

BioMutaiNPEPL1.
DMDMi52000961.

Proteomic databases

EPDiP63092.
MaxQBiP63092.
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.
DisGeNETi2778.
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.
OpenTargetsiENSG00000087460.
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

CDDicd00066. G-alpha. 1 hit.
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: November 30, 2016
This is version 145 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.