Guanine nucleotide-binding protein G(i) subunit alpha-1 (GNAI1)
The protein contains 354 amino acids for an estimated molecular weight of 40361 Da.
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). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Adenylate cyclase-modulating G protein-coupled receptor signaling pathway
Cell cycle
Cell division
Cellular response to forskolin
G protein-coupled receptor signaling pathway
Negative regulation of synaptic transmission
Platelet activation
Positive regulation of protein localization to cell cortex
Protein folding
Regulation of cAMP-mediated signaling
Regulation of mitotic spindle organization
Response to peptide hormone
The reference OMIM entry for this protein is 139310
Guanine nucleotide-binding protein, alpha-inhibiting activity polypeptide 1; gnai1
G protein, alpha-inhibiting 1; gi
Inhibitory g protein
Adenylate cyclase inhibitory protein
DESCRIPTION
Guanine nucleotide-binding proteins (G proteins) form a large family of signal-transducing molecules. They are found as heterotrimers made up of alpha, beta, and gamma subunits. Members of the G protein family have been characterized most extensively on the basis of the alpha subunit, which binds guanine nucleotide, is capable of hydrolyzing GTP, and interacts with specific receptor and effector molecules. The G protein family includes Gs (139320) and Gi, the stimulatory and inhibitory GTP-binding regulators of adenylate cyclase; Go, a protein abundant in brain (GNAO1; 139311); and transducin-1 (GNAT1; 139330) and transducin-2 (GNAT2; 139340), proteins involved in phototransduction in retinal rods and cones, respectively (Sullivan et al., 1986; Bray et al., 1987). Suki et al. (1987) concluded that the human genome contains at least 3 nonallelic genes for alpha-i-type subunits of G protein; see, e.g., GNAI2 (139360), GNAI3 (139370), and GNAIH (139180).CLONING
Sullivan et al. (1986) used a cDNA encoding bovine alpha chain of transducin-1 to isolate and sequence murine cDNAs for alpha(s) and alpha(i). Homologies and differences among the deduced amino acid sequences of the G protein and transducin alpha chains pointed to specific regions that may interact with guanine nucleotides, receptors, effector enzymes, and the G protein beta-gamma complex. Bray et al. (1987) isolated cDNA clones corresponding to the alpha(i) subunit from a human brain cDNA library. The deduced 349-residue protein is identical to the bovine protein. Northern blot analysis identified a 3.8-kb mRNA transcript. Neer et al. (1987) cloned and characterized cDNA encoding the predominant alpha(i) of brain, together with a very similar cDNA that encodes another putative G protein, alpha(h). By screening human genomic libraries with rat cDNAs for Gi-alpha as probes, Itoh et al. (1988) isolated 3 genes for the alpha subunit. Southern blot analysis indicated that a single copy of each of the 3 genes is present in the haploid human genome.MAPPING
Blatt et al. (1988) mapped GNAI1 to chromosome 7 by hybridization of cDNA clones with DNA from human-mouse somatic cell hybrids. Bloch et al. (1988) mapped the GNAI1 gene to chromosome 7q21 by in situ hybridization. They confirmed the regional location by studying human/mouse somatic cell hybrid lines containing portions of human chromosome 7. By the study of restriction fragment length variation (RFLV) in an interspecific backcross between C57BL/6J and Mus spretus mice, Wilkie et al. (1992) demonstrated that the corresponding murine gene is located on chromosome 5.GENE FUNCTION
In a bacterial expression system, Lan et al. (1998) found that point mutations in the Gnai1 and Gnao1 genes, G183S and G184S, respectively, resulted in resistance to regulators of G protein signaling proteins (RGS). The mutant G-alpha proteins showed significantly decreased affinity for RGS4 (602516) and RGS7 (602517). Ogden et al. (2008) presented in vitro and in vivo evidence in Drosophila that Smoothened (601500) activates G-alpha-i to modulate intracellular cAMP levels in response to hedgehog (see 600725). Ogden et al. (2008) concluded that Smoothened functions as a canonical G protein-coupled receptor, which signals through Gnai1 to regulate hedgehog pathway activation. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 139310 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).