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

The protein contains 394 amino acids for an estimated molecular weight of 45665 Da.

 

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). (updated: Aug. 13, 1987)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 91%
Model score: 0
No model available.

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VariantDescription
AHO
AHO/PHP1A
AHO
PHP1A
PHP1A
AHO
MAS
MAS
MAS and AIMAH1
non-MAS endocrine tumors
AIMAH1
pituitary adenomas
somatotrophinoma
AHO
AHO
AHO
AHO
AHO
AHO
PHP1A
PHP1A
POH
PHP1A
PHP1A
dbSNP:rs8986
AHO; uncouples receptors from adenylyl cyclases
PHP1C
PHP1C

The reference OMIM entry for this protein is 103580

Pseudohypoparathyroidism, type ia; php1a
Php ia
Albright hereditary osteodystrophy with multiple hormone resistance

A number sign (#) is used with this entry because pseudohypoparathyroidism type Ia (PHP Ia) is caused by mutation resulting in loss of function of the Gs-alpha isoform of the GNAS gene (139320) on the maternal allele. This results in expression of the Gs-alpha protein only from the paternal allele. See also pseudopseudohypoparathyroidism (PPHP; 612463), a similar disorder caused by mutations resulting in loss of function of the Gs-alpha isoform of the GNAS gene on the paternal allele and resultant expression of the Gs-alpha isoform only from the maternal allele.

DESCRIPTION

Pseudohypoparathyroidism is a term applied to a heterogeneous group of disorders whose common feature is end-organ resistance to parathyroid hormone (PTH; 168450). In addition to PTH resistance, PHP Ia is characterized by resistance to other hormones, including thyroid-stimulating hormone (TSH; see TSHB, 188540) and gonadotropins. PHP Ia is associated with a constellation of clinical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation (Mantovani and Spada, 2006). In contrast, pseudopseudohypoparathyroidism (PPHP; 612463) is characterized by the physical findings of AHO but without hormone resistance (Kinard et al., 1979; Fitch, 1982; Mantovani and Spada, 2006). PHP1A occurs only after maternal inheritance of the molecular defect, whereas PPHP occurs only after paternal inheritance of the molecular defect (Davies and Hughes, 1993; Wilson et al., 1994). This is an example of imprinting, with differential gene expression depending on the parent of origin of the allele. See

INHERITANCE

and

PATHOGENESIS

sections.

NOMENCLATURE

The classification of pseudohypoparathyroidism is based on the phenotype and cellular cyclic AMP (cAMP) response to exogenous PTH administration. Cyclic AMP is produced by an intracellular G protein hormone receptor-adenylyl cyclase (see, e.g., ADCY1, 103072) complex. The GNAS gene encodes the alpha-stimulatory subunit (Gs) of the intracellular G protein, which stimulates the production of cAMP under certain physiologic conditions (Mantovani and Spada, 2006). - Pseudohypoparathyroidism type Ia Individuals with PHP Ia have AHO features, multiple hormone resistance, decreased cellular cAMP response to PTH infusion, decreased erythrocyte Gs activity, and a GNAS1 mutation in the maternally-derived allele (Mantovani and Spada, 2006). - Pseudopseudohypoparathyroidism Individuals with PPHP (612463) have AHO without endocrine abnormalities, a normal cellular cAMP response to PTH infusion, decreased erythrocyte Gs activity, and a GNAS1 mutation in the paternally-inherited allele (Mantovani and Spada, 2006). - Pseudohypoparathyroidism type Ib Individuals with PHP Ib (PHP1B; 603233) have renal PTH resistance, decreased cAMP response to PTH infusion, normal erythrocyte Gs activity, and imprinting/methylation defects at the GNAS locus resulting in lack of expression of the maternal allele in renal tissue. Classically, patients do not have features of AHO. PHP1B is not associated with generalized hormone resistance, although resistance to thyroid-stimulating hormone (TSH; 188540) has been reported (Mantovani and Spada, 2006). Mariot et al. (2008) noted that features of AHO may rarely be observed in patients with PHP1b who have decreased expressio ... More on the omim web site

Subscribe to this protein entry history

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 103580 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).