InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GNAS

Summary

InnateDB Protein

IDBP-82833.7

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

ENSP00000360143

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. XLas isoforms interact with the same set of receptors as Gnas isoforms (By similarity). {ECO:0000250}.

Subcellular Localization

Cell membrane {ECO:0000250UniProtKB:Q63803}; Peripheral membrane protein {ECO:0000250UniProtKB:Q63803}.

Disease Associations

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. {ECO:0000269PubMed:11583302, ECO:0000269PubMed:12719376}. 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.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:11788646}. 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:0004871	signal transducer activity
GO:0005159	insulin-like growth factor receptor binding
GO:0005515	protein binding
GO:0005525	GTP binding
GO:0019001	guanyl nucleotide binding
GO:0031683	G-protein beta/gamma-subunit complex binding
GO:0031698	beta-2 adrenergic receptor binding
GO:0031748	D1 dopamine receptor binding
GO:0031852	mu-type opioid receptor binding
GO:0035255	ionotropic glutamate receptor binding
GO:0046872	metal ion binding
GO:0051430	corticotropin-releasing hormone receptor 1 binding

Biological Process

GO:0006184	GTP catabolic process
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007189	adenylate cyclase-activating G-protein coupled receptor signaling pathway
GO:0007191	adenylate cyclase-activating dopamine receptor signaling pathway
GO:0007606	sensory perception of chemical stimulus
GO:0048589	developmental growth
GO:0050890	cognition
GO:0060348	bone development
GO:0060789	hair follicle placode formation
GO:0070527	platelet aggregation

Cellular Component

GO:0005829	cytosol
GO:0005834	heterotrimeric G-protein complex
GO:0016020	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