Guanine nucleotide-binding protein G(i) subunit alpha-2 (GNAI2)
The protein contains 355 amino acids for an estimated molecular weight of 40451 Da.
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division.', 'Regulates the cell surface density of dopamine receptors DRD2 by sequestrating them as an intracellular pool. (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Activation of MAPKK activity
Adenylate cyclase-activating G protein-coupled receptor signaling pathway
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Adenylate cyclase-modulating G protein-coupled receptor signaling pathway
Blood coagulation
Cell cycle
Cell division
Cell population proliferation
Chemical synaptic transmission
G protein-coupled acetylcholine receptor signaling pathway
G protein-coupled adenosine receptor signaling pathway
G protein-coupled receptor signaling pathway
Gamma-aminobutyric acid signaling pathway
Intracellular signal transduction
Metabolic process
Negative regulation of adenylate cyclase activity
Negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process
Negative regulation of apoptotic signaling pathway
Negative regulation of calcium ion-dependent exocytosis
Negative regulation of protein tyrosine phosphatase activity
Negative regulation of synaptic transmission
Platelet activation
Positive regulation of cell migration
Positive regulation of cell population proliferation
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of insulin receptor signaling pathway
Positive regulation of NAD(P)H oxidase activity
Positive regulation of neural precursor cell proliferation
Positive regulation of renal sodium excretion
Positive regulation of superoxide anion generation
Positive regulation of urine volume
Positive regulation of vascular associated smooth muscle cell proliferation
Protein folding
Regulation of calcium ion transport
Response to nutrient
Signal transduction
The reference OMIM entry for this protein is 139360
Guanine nucleotide-binding protein, alpha-inhibiting activity polypeptide 2; gnai2
G protein, alpha-inhibiting 2b; gnai2b
CLONING
Magovcevic et al. (1992) isolated a cDNA for the GNAI2 gene from a human T-cell library. Itoh et al. (1988) demonstrated 3 distinct human G-alpha inhibitory proteins. Southern blot analysis indicated that a single copy of each gene is present in the haploid human genome.GENE STRUCTURE
Itoh et al. (1988) determined that the GNAI2 and GNAI3 (139380) genes contain 8 coding exons and possess identical exon-intron organization.MAPPING
Sparkes et al. (1987, 1987) and Blatt et al. (1988) used a cDNA probe with a mouse/human somatic cell hybrid panel to assign the alpha-2 inhibitory polypeptide to chromosome 3 in man and chromosome 9 in mouse. Blatt et al. (1988) also assigned the GNAI2 gene to chromosome 3 by hybridization of cDNA clones with DNA from human-mouse somatic cell hybrids. Magovcevic et al. (1992) mapped the GNAI2 gene to 3p21 by chromosomal in situ hybridization. A related sequence, GNAI2L (139180), was mapped by the same method to 12p13-p12. The assignment to chromosome 3 was supported by PCR amplification of GNAI2-specific sequences in a human/rodent somatic cell hybrid containing only human chromosome 3. Wilkie et al. (1992) assigned the corresponding gene to mouse chromosome 9.GENE FUNCTION
Hermouet et al. (1991) demonstrated that activating and inactivating mutations of the GNAI2 gene have opposite effects on proliferation of NIH 3T3 cells. Jiang et al. (2011) found that microRNA-138 (MIR138; see 613394) was downregulated in tongue squamous cell carcinoma (TSCC) compared with normal tissue. Using microarray-based differential expression analysis on human TSCC cells transfected with an MIR138 mimic or a control mimic, followed by bioinformatic analysis, Jiang et al. (2011) identified GNAI2 and 4 other genes as high-confidence candidate targets of MIR138. They observed a reverse correlation between MIR138 and GNAI2 levels in a TSCC cell line panel and identified 2 MIR138 target sequences in the 3-prime UTR of GNAI2 mRNA. Reporter gene assays confirmed that both putative target sequences were inhibited by MIR138. Knockdown of MIR138 in TSCC cells enhanced the expression of GNAI2 at the mRNA and protein levels. In contrast, transfection of MIR138 or an MIR138 mimic reduced GNAI2 mRNA and protein expression, which was associated with reduced cell proliferation and enhanced apoptosis.MOLECULAR GENETICS
Since somatic mutations in some growth hormone-secreting pituitary tumors convert the gene for the alpha polypeptide chain of G(s) into a putative oncogene, referred to as GSP (139320), Lyons et al. (1990) considered the likelihood that similar mutations would activate other G proteins. They found mutations of the GNAI2 gene that replaced arginine-179 with either cysteine or histidine in tumors of the adrenal cortex and endocrine tumors of the ovary. They referred to this mutant GNAI2 gene as the GIP2 oncogene. Williamson et al. (1995) studied 32 adrenocorticotrophin hormone-secreting pituitary adenomas for the presence of GSP and GIP mutations. GSP mutations were demonstrated in 2 tumors at codon 227 (139320.0012) and a GIP mutation was identified in 1 tumor at codon 179 (139360.0003). Idiopathic ventricular tachycardia is a generic term that describes the various forms of ventricular arrhythmias that occur in patients without structural heart disease and in the absence of the long QT syndrome. Many of these tachycardias are focal in origin, localize to the right ven ... More on the omim web site
Jan. 22, 2020: 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 139360 was added.