Guanine nucleotide-binding protein G(i) subunit alpha-3 (GNAI3)

The protein contains 354 amino acids for an estimated molecular weight of 40532 Da.

 

Heterotrimeric guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541, PubMed:19478087). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (PubMed:19478087). Stimulates the activity of receptor-regulated K(+) channels (PubMed:2535845). The active GTP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division (PubMed:17635935). (updated: Feb. 10, 2021)

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. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. 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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

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


Interpro domains
Total structural coverage: 100%
Model score: 0
No model available.

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VariantDescription
ARCND1

The reference OMIM entry for this protein is 139370

Guanine nucleotide-binding protein, alpha-inhibiting activity polypeptide 3; gnai3
G protein, alpha-inhibiting 3

CLONING

The GNAI3 gene encodes a 340-amino acid protein with a relative molecular mass of approximately 40 kD. The protein sequence is closely related to but distinct from that of GNAI2 (139360) (Itoh et al., 1988).

GENE STRUCTURE

Itoh et al. (1988) determined that the GNAI2 and GNAI3 genes contain 8 coding exons and possess identical exon-intron organization.

MAPPING

Using a cDNA probe against a mouse/human somatic cell hybrid panel, Sparkes et al. (1987) mapped the alpha-inhibiting polypeptide-3 of G protein to chromosome 1. See also Blatt et al. (1988). By in situ hybridization, Wilkie et al. (1992) assigned the GNAI3 gene to chromosome 1p13. They assigned the corresponding gene to mouse chromosome 3 by study of restriction fragment length variation in an interspecific backcross. Baron et al. (1994) demonstrated that the Gnai3 gene in the hamster is less than 60 kb from the Ampd2 gene (102771) with which it is coamplified in coformycin-resistant cells. The hamster Gnai3 gene did not contain sequences corresponding to the combined U6 snRNA and E protein pseudogene, previously identified within intron 7 of the human gene.

MOLECULAR GENETICS

In 2 unrelated probands with auriculocondylar syndrome (ARCND1; 602483), Rieder et al. (2012) identified heterozygosity for a missense mutation at a highly conserved residue in the GNAI3 gene (G40R; 139370.0001). Functional analysis demonstrated significant reduction of downstream targets of the G protein-coupled endothelin receptor pathway in mutant cultured mandibular osteoblasts compared to controls. Gordon et al. (2013) analyzed the GNAI3 and PLCB4 (600810) genes in 27 patients, including 8 with clinical ARCND, 5 with 'atypical' ARCND who were previously described by McGowan et al. (2011), 3 with isolated question mark ears (612798), 6 diagnosed with either oculoauriculovertebral syndrome (OAVS) or Goldenhar syndrome (see 164210), and 4 with nonsyndromic auricular dysplasia with or without mandibular dysplasia. In 1 ARCND proband and her affected father, they identified a missense mutation in the GNAI3 gene (139370.0002). In addition, 7 mutations were found in the PLCB4 gene in patients with ARCND (ARCND2; 614669). Gordon et al. (2013) noted that of 15 reported mutation-positive ARCND patients, 12 (80%) had a mutation in PLCB4 and 3 (20%) had a mutation in GNAI3. ... More on the omim web site

Subscribe to this protein entry history

Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 139370 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed