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P63092

- GNAS2_HUMAN

UniProt

P63092 - GNAS2_HUMAN

Protein

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

Gene

GNAS

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (13 Aug 1987)
      Previous versions | rss
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    Functioni

    Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. Stimulates the Ras signaling pathway via RAPGEF2.1 Publication

    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 – 548GTPBy similarity
    Nucleotide bindingi198 – 2047GTPBy similarity
    Nucleotide bindingi223 – 2275GTPBy similarity
    Nucleotide bindingi292 – 2954GTPBy similarity

    GO - Molecular functioni

    1. adenylate cyclase activity Source: Reactome
    2. GTPase activity Source: UniProtKB
    3. GTP binding Source: UniProtKB-KW
    4. metal ion binding Source: UniProtKB-KW
    5. protein binding Source: IntAct
    6. signal transducer activity Source: UniProtKB

    GO - Biological processi

    1. activation of adenylate cyclase activity Source: UniProtKB
    2. adenylate cyclase-activating adrenergic receptor signaling pathway Source: UniProtKB
    3. adenylate cyclase-activating dopamine receptor signaling pathway Source: BHF-UCL
    4. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProt
    5. blood coagulation Source: Reactome
    6. bone development Source: UniProt
    7. cAMP biosynthetic process Source: GOC
    8. cellular response to catecholamine stimulus Source: BHF-UCL
    9. cellular response to glucagon stimulus Source: Reactome
    10. cellular response to prostaglandin E stimulus Source: BHF-UCL
    11. cognition Source: UniProt
    12. developmental growth Source: UniProt
    13. energy reserve metabolic process Source: Reactome
    14. hair follicle placode formation Source: UniProt
    15. intracellular transport Source: UniProtKB
    16. platelet aggregation Source: UniProt
    17. positive regulation of cAMP biosynthetic process Source: UniProtKB
    18. positive regulation of cAMP-mediated signaling Source: UniProtKB
    19. positive regulation of Ras GTPase activity Source: UniProtKB
    20. regulation of insulin secretion Source: Reactome
    21. sensory perception of smell Source: UniProtKB
    22. small molecule metabolic process Source: Reactome
    23. transmembrane transport Source: Reactome
    24. water transport Source: Reactome

    Keywords - Molecular functioni

    Transducer

    Keywords - Ligandi

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

    Enzyme and pathway databases

    ReactomeiREACT_1665. Glucagon signaling in metabolic regulation.
    REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
    REACT_18377. Glucagon-type ligand receptors.
    REACT_19231. G alpha (i) signalling events.
    REACT_19327. G alpha (s) signalling events.
    REACT_19333. G alpha (z) signalling events.
    REACT_1946. PKA activation in glucagon signalling.
    REACT_23946. Prostacyclin signalling through prostacyclin receptor.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    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
    ProteomesiUP000005640: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:4392. GNAS.

    Subcellular locationi

    Cell membrane By similarity; Lipid-anchor By similarity

    GO - Cellular componenti

    1. cytoplasm Source: LIFEdb
    2. cytosol Source: UniProt
    3. extracellular vesicular exosome Source: UniProt
    4. heterotrimeric G-protein complex Source: UniProtKB
    5. intrinsic component of membrane Source: UniProtKB
    6. membrane Source: UniProt
    7. plasma membrane Source: UniProtKB
    8. trans-Golgi network membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Albright hereditary osteodystrophy (AHO) [MIM:103580]: A disorder characterized by short stature, obesity, round facies, brachydactyly and subcutaneous calcification. It is often associated with pseudohypoparathyoidism, hypocalcemia and elevated PTH levels.8 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti99 – 991L → P in AHO. 1 Publication
    VAR_003439
    Natural varianti106 – 1061I → S in AHO/PHP1A. 1 Publication
    VAR_031872
    Natural varianti115 – 1151P → L in AHO. 1 Publication
    VAR_017843
    Natural varianti165 – 1651R → C in AHO. 1 Publication
    VAR_003440
    Natural varianti231 – 2311R → H in AHO; impairs the ability to mediate hormonal stimulation. 1 Publication
    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
    VAR_017849
    Natural varianti258 – 2581R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 Publication
    VAR_015388
    Natural varianti259 – 2591E → V in AHO. 1 Publication
    VAR_031877
    Natural varianti366 – 3661A → 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.
    VAR_017850
    Natural varianti385 – 3851R → H in AHO; uncouples receptors from adenylyl cyclases. 1 Publication
    VAR_003444
    Pseudohypoparathyroidism 1A (PHP1A) [MIM:103580]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    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
    McCune-Albright syndrome (MAS) [MIM:174800]: Characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The mutations producing MAS lead to constitutive activation of GS alpha.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti201 – 2011R → C in MAS and somatotrophinoma. 2 Publications
    Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
    VAR_003442
    Natural varianti201 – 2011R → G in MAS. 1 Publication
    VAR_017844
    Natural varianti201 – 2011R → H in MAS, somatotrophinoma and AIMAH. 4 Publications
    VAR_003441
    Natural varianti201 – 2011R → L in non-MAS endocrine tumors. 1 Publication
    VAR_017845
    Growth hormone-secreting pituitary adenoma (GHSPA) [MIM:102200]: Pituitary adenomas include somatotropinoma and prolactinoma.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Progressive osseous heteroplasia (POH) [MIM:166350]: Rare autosomal dominant disorder characterized by extensive dermal ossification during childhood, followed by disabling and widespread heterotopic ossification of skeletal muscle and deep connective tissue.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti281 – 2811W → R in POH. 1 Publication
    VAR_031880
    ACTH-independent macronodular adrenal hyperplasia (AIMAH) [MIM:219080]: A rare adrenal defect characterized by multiple, bilateral, non-pigmented, benign, adrenocortical nodules. It results in excessive production of cortisol leading to ACTH-independent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti201 – 2011R → H in MAS, somatotrophinoma and AIMAH. 4 Publications
    VAR_003441
    Natural varianti201 – 2011R → S in AIMAH, pituitary tumor and polyostotic fibrous dysplasia. 3 Publications
    VAR_017846
    Pseudohypoparathyroidism 1B (PHP1B) [MIM:603233]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. Patients affected with PHP1B lack developmental defects characteristic of Albright hereditary osteodystrophy, and typically show no other endocrine abnormalities besides resistance to PTH.7 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed.
    GNAS hyperfunction (GNASHYP) [MIM:139320]: This condition is characterized by increased trauma-related bleeding tendency, prolonged bleeding time, brachydactyly and mental retardation. Both the XLas isoforms and the ALEX protein are mutated which strongly reduces the interaction between them and this may allow unimpeded activation of the XLas isoforms.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Pseudohypoparathyroidism 1C (PHP1C) [MIM:612462]: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti388 – 3881L → R in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
    VAR_066387
    Natural varianti392 – 3921E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
    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, Proto-oncogene

    Organism-specific databases

    MIMi102200. phenotype.
    103580. phenotype.
    139320. gene+phenotype.
    166350. phenotype.
    174800. phenotype.
    219080. phenotype.
    603233. phenotype.
    612462. phenotype.
    Orphaneti57782. Mazabraud syndrome.
    562. McCune-Albright syndrome.
    93277. Monostotic fibrous dysplasia.
    93276. Polyostotic fibrous dysplasia.
    2762. Progressive osseous heteroplasia.
    79443. Pseudohypoparathyroidism type 1A.
    94089. Pseudohypoparathyroidism type 1B.
    79444. Pseudohypoparathyroidism type 1C.
    79445. Pseudopseudohypoparathyroidism.
    PharmGKBiPA175.

    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 – 3521Phosphoserine1 Publication

    Keywords - PTMi

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

    Proteomic databases

    PRIDEiP63092.

    PTM databases

    PhosphoSiteiP63092.

    Expressioni

    Gene expression databases

    ArrayExpressiP63092.
    BgeeiP63092.
    CleanExiHS_GNAS.
    GenevestigatoriP63092.

    Organism-specific databases

    HPAiCAB010337.

    Interactioni

    Subunit structurei

    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.1 Publication

    Binary interactionsi

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

    Protein-protein interaction databases

    BioGridi109040. 36 interactions.
    IntActiP63092. 6 interactions.
    MINTiMINT-262348.

    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

    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. 1 hit.
    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. Align

    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

    MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE    50
    SGKSTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKAT KVQDIKNNLK 100
    EAIETIVAAM SNLVPPVELA NPENQFRVDY ILSVMNVPDF DFPPEFYEHA 150
    KALWEDEGVR ACYERSNEYQ LIDCAQYFLD KIDVIKQADY VPSDQDLLRC 200
    RVLTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVAS 250
    SSYNMVIRED NQTNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAEK 300
    VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRDEFLRIST 350
    ASGDGRHYCY PHFTCAVDTE NIRRVFNDCR DIIQRMHLRQ YELL 394
    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
    VAR_003439
    Natural varianti106 – 1061I → S in AHO/PHP1A. 1 Publication
    VAR_031872
    Natural varianti115 – 1151P → L in AHO. 1 Publication
    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
    VAR_003440
    Natural varianti201 – 2011R → C in MAS and somatotrophinoma. 2 Publications
    Corresponds to variant rs11554273 [ dbSNP | Ensembl ].
    VAR_003442
    Natural varianti201 – 2011R → G in MAS. 1 Publication
    VAR_017844
    Natural varianti201 – 2011R → H in MAS, somatotrophinoma and AIMAH. 4 Publications
    VAR_003441
    Natural varianti201 – 2011R → L in non-MAS endocrine tumors. 1 Publication
    VAR_017845
    Natural varianti201 – 2011R → S in AIMAH, pituitary tumor and polyostotic fibrous dysplasia. 3 Publications
    VAR_017846
    Natural varianti227 – 2271Q → H in pituitary adenoma; ACTH-secreting adenoma; in a patient with severe Cushing syndrome complicated by psychosis. 1 Publication
    VAR_017847
    Natural varianti227 – 2271Q → R in somatotrophinoma. 1 Publication
    VAR_003443
    Natural varianti231 – 2311R → H in AHO; impairs the ability to mediate hormonal stimulation. 1 Publication
    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
    VAR_017849
    Natural varianti258 – 2581R → W in AHO; defective GDP binding resulting in increased thermolability and decreased activation. 1 Publication
    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 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.
    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
    VAR_066387
    Natural varianti392 – 3921E → K in PHP1C; significantly reduces receptor-mediated activation; displays normal receptor-independent activation. 1 Publication
    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:
    EMBL
    GenBank
    DDBJ
    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_000516.4. [P63092-1]
    NP_001070956.1. NM_001077488.2. [P63092-4]
    NP_001070957.1. NM_001077489.2. [P63092-3]
    NP_001070958.1. NM_001077490.1.
    NP_536350.2. NM_080425.2.
    NP_536351.1. NM_080426.2. [P63092-2]
    UniGeneiHs.125898.

    Genome annotation databases

    EnsembliENST00000265620; ENSP00000265620; ENSG00000087460. [P63092-3]
    ENST00000306090; ENSP00000304472; ENSG00000087460. [P63092-2]
    ENST00000354359; ENSP00000346328; ENSG00000087460. [P63092-4]
    ENST00000371085; ENSP00000360126; ENSG00000087460. [P63092-1]
    ENST00000371095; ENSP00000360136; ENSG00000087460. [P63092-2]
    GeneIDi2778.
    KEGGihsa:2778.
    UCSCiuc002xzt.3. human.
    uc002yaa.3. human. [P63092-3]
    uc002yae.3. human. [P63092-2]

    Polymorphism databases

    DMDMi52000961.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    GNAS mutation db

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS13472.1.
    CCDS42892.1. [P63092-3 ]
    CCDS46623.1. [P63092-4 ]
    CCDS46624.1. [P63092-2 ]
    PIRi B31927. RGHUA2.
    C31927. RGHUA1.
    RefSeqi NP_000507.1. NM_000516.4. [P63092-1 ]
    NP_001070956.1. NM_001077488.2. [P63092-4 ]
    NP_001070957.1. NM_001077489.2. [P63092-3 ]
    NP_001070958.1. NM_001077490.1.
    NP_536350.2. NM_080425.2.
    NP_536351.1. NM_080426.2. [P63092-2 ]
    UniGenei Hs.125898.

    3D structure databases

    ProteinModelPortali P63092.
    SMRi P63092. Positions 9-394.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109040. 36 interactions.
    IntActi P63092. 6 interactions.
    MINTi MINT-262348.

    Chemistry

    ChEMBLi CHEMBL4377.

    PTM databases

    PhosphoSitei P63092.

    Polymorphism databases

    DMDMi 52000961.

    Proteomic databases

    PRIDEi P63092.

    Protocols and materials databases

    DNASUi 2778.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000265620 ; ENSP00000265620 ; ENSG00000087460 . [P63092-3 ]
    ENST00000306090 ; ENSP00000304472 ; ENSG00000087460 . [P63092-2 ]
    ENST00000354359 ; ENSP00000346328 ; ENSG00000087460 . [P63092-4 ]
    ENST00000371085 ; ENSP00000360126 ; ENSG00000087460 . [P63092-1 ]
    ENST00000371095 ; ENSP00000360136 ; ENSG00000087460 . [P63092-2 ]
    GeneIDi 2778.
    KEGGi hsa:2778.
    UCSCi uc002xzt.3. human.
    uc002yaa.3. human. [P63092-3 ]
    uc002yae.3. human. [P63092-2 ]

    Organism-specific databases

    CTDi 2778.
    GeneCardsi GC20P057414.
    HGNCi HGNC:4392. GNAS.
    HPAi CAB010337.
    MIMi 102200. phenotype.
    103580. phenotype.
    139320. gene+phenotype.
    166350. phenotype.
    174800. phenotype.
    219080. phenotype.
    603233. phenotype.
    612462. phenotype.
    neXtProti NX_P63092.
    Orphaneti 57782. Mazabraud syndrome.
    562. McCune-Albright syndrome.
    93277. Monostotic fibrous dysplasia.
    93276. Polyostotic fibrous dysplasia.
    2762. Progressive osseous heteroplasia.
    79443. Pseudohypoparathyroidism type 1A.
    94089. Pseudohypoparathyroidism type 1B.
    79444. Pseudohypoparathyroidism type 1C.
    79445. Pseudopseudohypoparathyroidism.
    PharmGKBi PA175.
    GenAtlasi Search...

    Phylogenomic databases

    HOVERGENi HBG063184.
    KOi K04632.
    OMAi YEHTKTL.

    Enzyme and pathway databases

    Reactomei REACT_1665. Glucagon signaling in metabolic regulation.
    REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
    REACT_18377. Glucagon-type ligand receptors.
    REACT_19231. G alpha (i) signalling events.
    REACT_19327. G alpha (s) signalling events.
    REACT_19333. G alpha (z) signalling events.
    REACT_1946. PKA activation in glucagon signalling.
    REACT_23946. Prostacyclin signalling through prostacyclin receptor.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    Miscellaneous databases

    ChiTaRSi GNAS. human.
    GenomeRNAii 2778.
    NextBioi 10928.
    PROi P63092.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P63092.
    Bgeei P63092.
    CleanExi HS_GNAS.
    Genevestigatori P63092.

    Family and domain databases

    Gene3Di 1.10.400.10. 1 hit.
    3.40.50.300. 2 hits.
    InterProi IPR000367. Gprotein_alpha_S.
    IPR001019. Gprotein_alpha_su.
    IPR011025. GproteinA_insert.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    PANTHERi PTHR10218. PTHR10218. 1 hit.
    Pfami PF00503. G-alpha. 1 hit.
    [Graphical view ]
    PRINTSi PR00318. GPROTEINA.
    PR00443. GPROTEINAS.
    SMARTi SM00275. G_alpha. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47895. SSF47895. 1 hit.
    SSF52540. SSF52540. 2 hits.
    ProtoNeti Search...

    Publicationsi

    1. "Identification by molecular cloning of two forms of the alpha-subunit of the human liver stimulatory (GS) regulatory component of adenylyl cyclase."
      Mattera R., Codina J., Crozat A., Kidd V., Woo S.L.C., Birnbaumer L.
      FEBS Lett. 206:36-42(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
      Tissue: Liver.
    2. "Complete cDNA sequence of a human stimulatory GTP-binding protein alpha subunit."
      Harris B.A.
      Nucleic Acids Res. 16:3585-3585(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GNAS-1).
    3. "Isolation and characterization of the human Gs alpha gene."
      Kozasa T., Itoh H., Tsukamoto T., Kaziro Y.
      Proc. Natl. Acad. Sci. U.S.A. 85:2081-2085(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS GNAS-1 AND GNAS-2).
    4. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Puhl H.L. III, Ikeda S.R., Aronstam R.S.
      Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1 AND GNAS-2).
    5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GNAS-1).
    6. "The DNA sequence and comparative analysis of human chromosome 20."
      Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
      , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
      Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS GNAS-1; 3 AND 4).
      Tissue: Bone marrow, Brain, Muscle and Pancreas.
    9. "Human cDNA clones for four species of G alpha s signal transduction protein."
      Bray P., Carter A., Simons C., Guo V., Puckett C., Kamholz J., Spiegel A., Nirenberg M.
      Proc. Natl. Acad. Sci. U.S.A. 83:8893-8897(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-394 (ISOFORMS GNAS-1 AND 4).
    10. "Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes."
      Aboulaich N., Vainonen J.P., Stralfors P., Vener A.V.
      Biochem. J. 383:237-248(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 187-199 AND 308-317.
      Tissue: Adipocyte.
    11. "Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation."
      Pak Y., Pham N., Rotin D.
      Mol. Cell. Biol. 22:7942-7952(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis."
      Zhang E.E., Liu Y., Dentin R., Pongsawakul P.Y., Liu A.C., Hirota T., Nusinow D.A., Sun X., Landais S., Kodama Y., Brenner D.A., Montminy M., Kay S.A.
      Nat. Med. 16:1152-1156(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CRY1.
    13. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-352, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    14. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    15. "Site-specific analysis of protein S-acylation by resin-assisted capture."
      Forrester M.T., Hess D.T., Thompson J.W., Hultman R., Moseley M.A., Stamler J.S., Casey P.J.
      J. Lipid Res. 52:393-398(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-3.
    16. "Heterogeneous mutations in the gene encoding the alpha-subunit of the stimulatory G protein of adenylyl cyclase in Albright hereditary osteodystrophy."
      Miric A., Vechio J.D., Levine M.A.
      J. Clin. Endocrinol. Metab. 76:1560-1568(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHO PRO-99 AND CYS-165.
    17. "Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome."
      Schwindinger W.F., Francomano C.A., Levine M.A.
      Proc. Natl. Acad. Sci. U.S.A. 89:5152-5156(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT MAS HIS-201.
    18. "Activating mutations of the stimulatory G protein in the McCune-Albright syndrome."
      Weinstein L.S., Shenker A., Gejman P.V., Merino M.J., Friedman E., Spiegel A.M.
      N. Engl. J. Med. 325:1688-1695(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS MAS CYS-201 AND HIS-201.
    19. "GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours."
      Landis C.A., Masters S.B., Spada A., Pace A.M., Bourne H.R., Vallar L.
      Nature 340:692-696(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS SOMATOTROPHINOMA CYS-201; HIS-201 AND ARG-227.
    20. "A novel Gs alpha mutant in a patient with Albright hereditary osteodystrophy uncouples cell surface receptors from adenylyl cyclase."
      Schwindinger W.F., Miric A., Zimmerman D., Levine M.A.
      J. Biol. Chem. 269:25387-25391(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO HIS-385.
    21. "Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function."
      Iiri T., Herzmark P., Nakamoto J.M., van Dop C., Bourne H.R.
      Nature 371:164-168(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT AHO SER-366.
    22. "Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs alpha gene."
      Gorelov V.N., Dumon K., Barteneva N.S., Palm D., Roher H.-D., Goretzki P.E.
      J. Cancer Res. Clin. Oncol. 121:219-224(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT NON-MAS ENDOCRINE TUMORS LEU-201.
    23. "G-protein mutations in human pituitary adrenocorticotrophic hormone-secreting adenomas."
      Williamson E.A., Ince P.G., Harrison D., Kendall-Taylor P., Harris P.E.
      Eur. J. Clin. Invest. 25:128-131(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PITUITARY ADENOMA HIS-227.
    24. "Characteristics of gsp-positive growth hormone-secreting pituitary tumors in Korean acromegalic patients."
      Yang I., Park S., Ryu M., Woo J., Kim S., Kim J., Kim Y., Choi Y.
      Eur. J. Endocrinol. 134:720-726(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PITUITARY TUMOR SER-201.
    25. "Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation."
      Farfel Z., Iiri T., Shapira H., Roitman A., Mouallem M., Bourne H.R.
      J. Biol. Chem. 271:19653-19655(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
    26. "Polymerase chain reaction-based technique for the selective enrichment and analysis of mosaic arg201 mutations in G alpha s from patients with fibrous dysplasia of bone."
      Candeliere G.A., Roughley P.J., Glorieux F.H.
      Bone 21:201-206(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT POLYOSTOTIC FIBROUS DYSPLASIA SER-201.
    27. "A novel mutation adjacent to the switch III domain of G(S alpha) in a patient with pseudohypoparathyroidism."
      Warner D.R., Gejman P.V., Collins R.M., Weinstein L.S.
      Mol. Endocrinol. 11:1718-1727(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO ARG-250.
    28. "Conditional activation defect of a human Gsalpha mutant."
      Iiri T., Farfel Z., Bourne H.R.
      Proc. Natl. Acad. Sci. U.S.A. 94:5656-5661(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT AHO HIS-231.
    29. "A novel mutation in the switch 3 region of Gs-alpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation."
      Warner D.R., Weng G., Yu S., Matalon R., Weinstein L.S.
      J. Biol. Chem. 273:23976-23983(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO TRP-258, MUTAGENESIS OF ARG-258, CHARACTERIZATION OF VARIANT AHO TRP-258.
    30. Cited for: VARIANT MAS GLY-201.
    31. "A mutation in the heterotrimeric stimulatory guanine nucleotide binding protein alpha-subunit with impaired receptor-mediated activation because of elevated GTPase activity."
      Warner D.R., Weinstein L.S.
      Proc. Natl. Acad. Sci. U.S.A. 96:4268-4272(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF GLN-170 AND ARG-258.
    32. "A GNAS1 imprinting defect in pseudohypoparathyroidism type IB."
      Liu J., Litman D., Rosenberg M.J., Yu S., Biesecker L.G., Weinstein L.S.
      J. Clin. Invest. 106:1167-1174(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    33. "Paternal uniparental isodisomy of chromosome 20q -- and the resulting changes in GNAS1 methylation -- as a plausible cause of pseudohypoparathyroidism."
      Bastepe M., Lane A.H., Jueppner H.
      Am. J. Hum. Genet. 68:1283-1289(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    34. "Selective resistance to parathyroid hormone caused by a novel uncoupling mutation in the carboxyl terminus of G alpha(s). A cause of pseudohypoparathyroidism type Ib."
      Wu W.-I., Schwindinger W.F., Aparicio L.F., Levine M.A.
      J. Biol. Chem. 276:165-171(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B, VARIANT ILE-382 DEL, CHARACTERIZATION OF VARIANT ILE-382 DEL.
    35. "Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia."
      Ishikawa Y., Tajima T., Nakae J., Nagashima T., Satoh K., Okuhara K., Fujieda K.
      J. Hum. Genet. 46:426-430(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO HIS-231.
    36. "Analysis of the GNAS1 gene in Albright's hereditary osteodystrophy."
      Ahrens W., Hiort O., Staedt P., Kirschner T., Marschke C., Kruse K.
      J. Clin. Endocrinol. Metab. 86:4630-4634(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO LEU-115.
    37. "GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance."
      Linglart A., Carel J.-C., Garabedian M., Le T., Mallet E., Kottler M.-L.
      J. Clin. Endocrinol. Metab. 87:189-197(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PHP1A ASN-156; MET-159 AND LYS-280.
    38. "Mutational analysis of the GNAS1 exons encoding the stimulatory G protein in five patients with pseudohypoparathyroidism type 1a."
      Lim S.H., Poh L.K., Cowell C.T., Tey B.H., Loke K.Y.
      J. Pediatr. Endocrinol. Metab. 15:259-268(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PHP1A GLY-280.
    39. "Discordance between genetic and epigenetic defects in pseudohypoparathyroidism type 1b revealed by inconsistent loss of maternal imprinting at GNAS1."
      Jan de Beur S., Ding C., Germain-Lee E., Cho J., Maret A., Levine M.A.
      Am. J. Hum. Genet. 73:314-322(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    40. "Analysis of GNAS1 and overlapping transcripts identifies the parental origin of mutations in patients with sporadic Albright hereditary osteodystrophy and reveals a model system in which to observe the effects of splicing mutations on translated and untranslated messenger RNA."
      Rickard S.J., Wilson L.C.
      Am. J. Hum. Genet. 72:961-974(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AHO ILE-242; SER-246 AND VAL-259.
    41. "A new heterozygous mutation (L338N) in the human Gsalpha (GNAS1) gene as a cause for congenital hypothyroidism in Albright's hereditary osteodystrophy."
      Pohlenz J., Ahrens W., Hiort O.
      Eur. J. Endocrinol. 148:463-468(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PHP1A ASN-338.
    42. "Cushing's syndrome secondary to adrenocorticotropin-independent macronodular adrenocortical hyperplasia due to activating mutations of GNAS1 gene."
      Fragoso M.C.B.V., Domenice S., Latronico A.C., Martin R.M., Pereira M.A.A., Zerbini M.C.N., Lucon A.M., Mendonca B.B.
      J. Clin. Endocrinol. Metab. 88:2147-2151(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AIMAH HIS-201 AND SER-201.
    43. "Autosomal dominant pseudohypoparathyroidism type Ib is associated with a heterozygous microdeletion that likely disrupts a putative imprinting control element of GNAS."
      Bastepe M., Froehlich L.F., Hendy G.N., Indridason O.S., Josse R.G., Koshiyama H., Koerkkoe J., Nakamoto J.M., Rosenbloom A.L., Slyper A.H., Sugimoto T., Tsatsoulis A., Crawford J.D., Jueppner H.
      J. Clin. Invest. 112:1255-1263(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    44. "Progressive osseous heteroplasia resulting from a new mutation in the GNAS1 gene."
      Chan I., Hamada T., Hardman C., McGrath J.A., Child F.J.
      Clin. Exp. Dermatol. 29:77-80(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT POH ARG-281.
    45. "A novel STX16 deletion in autosomal dominant pseudohypoparathyroidism type Ib redefines the boundaries of a cis-acting imprinting control element of GNAS."
      Linglart A., Gensure R.C., Olney R.C., Jueppner H., Bastepe M.
      Am. J. Hum. Genet. 76:804-814(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    46. "Early manifestation of calcinosis cutis in pseudohypoparathyroidism type Ia associated with a novel mutation in the GNAS gene."
      Riepe F.G., Ahrens W., Krone N., Foelster-Holst R., Brasch J., Sippell W.G., Hiort O., Partsch C.-J.
      Eur. J. Endocrinol. 152:515-519(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AHO/PHP1A SER-106.
    47. "Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib."
      Bastepe M., Froehlich L.F., Linglart A., Abu-Zahra H.S., Tojo K., Ward L.M., Jueppner H.
      Nat. Genet. 37:25-27(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN PHP1B.
    48. "Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction."
      Thiele S., de Sanctis L., Werner R., Grotzinger J., Aydin C., Juppner H., Bastepe M., Hiort O.
      Hum. Mutat. 32:653-660(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS PHP1C ARG-388 AND LYS-392, CHARACTERIZATION OF VARIANTS PHP1C ARG-388 AND LYS-392.

    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: October 1, 2014
    This is version 120 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

    External Data

    Dasty 3