InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GNAS

Summary

InnateDB Protein

IDBP-82851.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

GNAS

Protein Name

GNAS complex locus

Synonyms

AHO; C20orf45; GNAS1; GPSA; GSA; GSP; NESP; PHP1A; PHP1B; PHP1C; POH;

Species

Homo sapiens

Ensembl Protein

ENSP00000265620

InnateDB Gene

IDBG-82827 (GNAS)

Protein Structure

UniProt Annotation

Function

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(s) protein is involved in hormonal regulation of adenylate cyclase: it activates the cyclase in response to beta-adrenergic stimuli. Stimulates the Ras signaling pathway via RAPGEF2. {ECO:0000269PubMed:12391161}.

Subcellular Localization

Cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}.

Disease Associations

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. {ECO:0000269PubMed:11450852, ECO:0000269PubMed:11600516, ECO:0000269PubMed:12624854, ECO:0000269PubMed:15817905, ECO:0000269PubMed:7523385, ECO:0000269PubMed:8388883, ECO:0000269PubMed:9328353, ECO:0000269PubMed:9727013}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:11788646, ECO:0000269PubMed:11926205, ECO:0000269PubMed:12656668}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:10571700, ECO:0000269PubMed:1594625, ECO:0000269PubMed:1944469, ECO:0000269PubMed:7751320}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:14723729}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:12727968}. Note=The disease is caused by mutations affecting the gene represented in this entry.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. {ECO:0000269PubMed:11029463, ECO:0000269PubMed:11067869, ECO:0000269PubMed:11294659, ECO:0000269PubMed:12858292, ECO:0000269PubMed:14561710, ECO:0000269PubMed:15592469, ECO:0000269PubMed:15800843}. 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. {ECO:0000269PubMed:21488135}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 52 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	52 [view]
Protein-Protein	51 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003924	GTPase activity
GO:0004016	adenylate cyclase activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0005525	GTP binding
GO:0019001	guanyl nucleotide binding
GO:0031683	G-protein beta/gamma-subunit complex binding
GO:0046872	metal ion binding

Biological Process

GO:0006112	energy reserve metabolic process
GO:0006171	cAMP biosynthetic process
GO:0006184	GTP catabolic process
GO:0006833	water transport
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007190	activation of adenylate cyclase activity
GO:0007191	adenylate cyclase-activating dopamine receptor signaling pathway
GO:0007596	blood coagulation
GO:0007608	sensory perception of smell
GO:0030819	positive regulation of cAMP biosynthetic process
GO:0032320	positive regulation of Ras GTPase activity
GO:0043950	positive regulation of cAMP-mediated signaling
GO:0044281	small molecule metabolic process
GO:0046907	intracellular transport
GO:0048589	developmental growth
GO:0050796	regulation of insulin secretion
GO:0050890	cognition
GO:0055085	transmembrane transport
GO:0060348	bone development
GO:0060789	hair follicle placode formation
GO:0070527	platelet aggregation
GO:0071377	cellular response to glucagon stimulus
GO:0071380	cellular response to prostaglandin E stimulus
GO:0071870	cellular response to catecholamine stimulus
GO:0071880	adenylate cyclase-activating adrenergic receptor signaling pathway

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005834	heterotrimeric G-protein complex
GO:0005886	plasma membrane
GO:0016020	membrane
GO:0031224	intrinsic component of membrane
GO:0032588	trans-Golgi network membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000367 G-protein alpha subunit, group S
IPR001019 Guanine nucleotide binding protein (G-protein), alpha subunit
IPR006689 Small GTPase superfamily, ARF/SAR type
IPR011025 G protein alpha subunit, helical insertion
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00503
PF00025

PRINTS

PR00443
PR00318
PR00328

PIRSF

SMART

SM00275

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt