GNAS complex locus

GNAS complex locus
PDB rendering based on 1azs.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1azs​, 1azt​, 1cjk​, 1cjt​, 1cju​, 1cjv​, 1cs4​, 1cul​, 1tl7​, 1u0h​, 2gvd​, 2gvz​
Identifiers
Symbols	GNAS ; AHO; C20orf45; GNAS1; GPSA; GSA; GSP; NESP; POH; SCG6; SgVI
External IDs	OMIM: 139320 MGI: 95777 HomoloGene: 55534 ChEMBL: 4377 GeneCards: GNAS Gene
Gene ontology Molecular function • molecular_function • GTPase activity • adenylate cyclase activity • signal transducer activity • insulin-like growth factor receptor binding • protein binding • GTP binding • G-protein beta/gamma-subunit complex binding • beta-2 adrenergic receptor binding • D1 dopamine receptor binding • mu-type opioid receptor binding • ionotropic glutamate receptor binding • metal ion binding • corticotropin-releasing hormone receptor 1 binding Cellular component • ruffle • extracellular region • nucleus • cytoplasm • cytosol • heterotrimeric G-protein complex • plasma membrane • membrane • transport vesicle • dendrite • intrinsic component of membrane • trans-Golgi network membrane • perinuclear region of cytoplasm • extracellular exosome Biological process • tissue homeostasis • endochondral ossification • renal water homeostasis • energy reserve metabolic process • cAMP biosynthetic process • DNA methylation • water transport • adenylate cyclase-activating G-protein coupled receptor signaling pathway • activation of adenylate cyclase activity • adenylate cyclase-activating dopamine receptor signaling pathway • female pregnancy • blood coagulation • sensory perception of chemical stimulus • sensory perception of smell • protein secretion • regulation of signal transduction • positive regulation of cAMP biosynthetic process • embryonic hindlimb morphogenesis • multicellular organism growth • negative regulation of multicellular organism growth • post-embryonic body morphogenesis • response to drug • positive regulation of GTPase activity • positive regulation of cAMP-mediated signaling • small molecule metabolic process • positive regulation of osteoblast differentiation • positive regulation of osteoclast differentiation • intracellular transport • developmental growth • embryonic cranial skeleton morphogenesis • regulation of insulin secretion • cognition • cartilage development • transmembrane transport • bone development • hair follicle placode formation • platelet aggregation • response to parathyroid hormone • cellular response to glucagon stimulus • cellular response to prostaglandin E stimulus • genetic imprinting • cellular response to catecholamine stimulus • adenylate cyclase-activating adrenergic receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2778	14683
Ensembl	ENSG00000087460	ENSMUSG00000027523
UniProt	O95467	P63094
RefSeq (mRNA)	NM_000516	NM_001077507
RefSeq (protein)	NP_000507	NP_001070975
Location (UCSC)	Chr 20: 58.84 – 58.91 Mb	Chr 2: 174.28 – 174.35 Mb
PubMed search

GNAS complex locus, also known as GNAS, is a protein which in humans is encoded by the GNAS gene. The protein encoded by this gene is the stimulatory G-protein alpha subunit (G_s-α), a key component of many signal transduction pathways.

Gene

This gene locus has a highly complex imprinted expression pattern. It gives rise to maternally, paternally, and biallelically expressed transcripts that are derived from four alternative promoters and 5' exons. Some transcripts contains a differentially methylated region (DMR) at their 5' exons, and this DMR is commonly found in imprinted genes and correlates with transcript expression. An antisense transcript exists, and this antisense transcript and one of the transcripts are paternally expressed, produce noncoding RNAs, and may regulate imprinting in this region. In addition, one of the transcripts contains a second overlapping ORF, which encodes a structurally unrelated protein.

The GNAS locus is imprinted and encodes 5 main transcripts:

• G_s-α
• XLAS
• NESP55
• A/B transcript
• antisense GNAS transcript

Protein

Alternative splicing of downstream exons is also observed, which results in different forms of the stimulatory G-protein alpha subunit (G_s-α), a key element of the classical signal transduction pathway linking receptor-ligand interactions with the activation of adenylyl cyclase and a variety of cellular responses. Multiple transcript variants have been found for this gene, but the full-length nature and/or biological validity of some variants have not been determined.

Clinical significance

Deficiencies are associated with:

• Albright hereditary osteodystrophy
• pseudohypoparathyroidism type Ia
• pseudohypoparathyroidism type Ib
• pseudopseudohypoparathyroidism
• McCune-Albright syndrome

Mutations in this gene also result in progressive osseus heteroplasia, polyostotic fibrous dysplasia of bone, and some pituitary tumors.^[1]

Interactions

GNAS complex locus has been shown to interact with RIC8A.^[2]

References

1. "Entrez Gene: GNAS GNAS complex locus".
2. Klattenhoff, Carla; Montecino Martín; Soto Ximena; Guzmán Leonardo; Romo Ximena; García María Angeles; Mellstrom Britt; Naranjo José Ramón; Hinrichs María Victoria; Olate Juan (May 2003). "Human brain synembryn interacts with Gsalpha and Gqalpha and is translocated to the plasma membrane in response to isoproterenol and carbachol". J. Cell. Physiol. (United States) 195 (2): 151–7. doi:10.1002/jcp.10300. ISSN 0021-9541. PMID 12652642.

Further reading

• Tinschert S, Gerl H, Gewies A; et al. (1999). "McCune-Albright syndrome: clinical and molecular evidence of mosaicism in an unusual giant patient.". Am. J. Med. Genet. 83 (2): 100–8. doi:10.1002/(SICI)1096-8628(19990312)83:2<100::AID-AJMG5>3.0.CO;2-K. PMID 10190480.
• Faivre L, Nivelon-Chevallier A, Kottler ML; et al. (2001). "Mazabraud syndrome in two patients: clinical overlap with McCune-Albright syndrome.". Am. J. Med. Genet. 99 (2): 132–6. doi:10.1002/1096-8628(2000)9999:999<00::AID-AJMG1135>3.0.CO;2-A. PMID 11241472.
• Raymond JR, Mukhin YV, Gelasco A; et al. (2002). "Multiplicity of mechanisms of serotonin receptor signal transduction.". Pharmacol. Ther. 92 (2-3): 179–212. doi:10.1016/S0163-7258(01)00169-3. PMID 11916537.
• Weinstein LS, Chen M, Liu J (2002). "Gs(alpha) mutations and imprinting defects in human disease.". Ann. N. Y. Acad. Sci. 968: 173–97. doi:10.1111/j.1749-6632.2002.tb04335.x. PMID 12119276.
• Bastepe M, Jüppner H (2005). "GNAS locus and pseudohypoparathyroidism.". Horm. Res. 63 (2): 65–74. doi:10.1159/000083895. PMID 15711092.
• de Sanctis L, Delmastro L, Russo MC; et al. (2006). "Genetics of McCune-Albright syndrome.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 577–82. PMID 16789620.
• Aldred MA (2006). "Genetics of pseudohypoparathyroidism types Ia and Ic.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 635–40. PMID 16789628.
• Jüppner H, Bastepe M (2006). "Different mutations within or upstream of the GNAS locus cause distinct forms of pseudohypoparathyroidism.". J. Pediatr. Endocrinol. Metab. 19 Suppl 2: 641–6. PMID 16789629.
• Mantovani G, Spada A (2007). "Mutations in the Gs alpha gene causing hormone resistance.". Best Pract. Res. Clin. Endocrinol. Metab. 20 (4): 501–13. doi:10.1016/j.beem.2006.09.001. PMID 17161328.

External links

• GNAS protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)