GNAI2 G protein subunit alpha i2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GNAI2provided by HGNC
Official Full Name: G protein subunit alpha i2provided by HGNC
Primary source: HGNC:HGNC:4385
See related: Ensembl:ENSG00000114353 MIM:139360; AllianceGenome:HGNC:4385
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GIP; HG1C; GNAI2B; H_LUCA15.1; H_LUCA16.1
Summary: The protein encoded by this gene is an alpha subunit of guanine nucleotide binding proteins (G proteins). The encoded protein contains the guanine nucleotide binding site and is involved in the hormonal regulation of adenylate cyclase. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
Expression: Ubiquitous expression in spleen (RPKM 106.7), bone marrow (RPKM 93.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p21.31

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (50227068..50263358)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (50256406..50288697)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (50264500..50296794)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Galphai2-induced conductin/axin2 condensates inhibit Wnt/beta-catenin signaling and suppress cancer growth.
Title: Gαi2-induced conductin/axin2 condensates inhibit Wnt/β-catenin signaling and suppress cancer growth.
Guanine Nucleotide-Binding Protein G(i) Subunit Alpha 2 Exacerbates NASH Progression by Regulating Peroxiredoxin 1-Related Inflammation and Lipophagy.
Title: Guanine Nucleotide-Binding Protein G(i) Subunit Alpha 2 Exacerbates NASH Progression by Regulating Peroxiredoxin 1-Related Inflammation and Lipophagy.
GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer.
Title: GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer.
Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals.
Title: Increased functional coupling of the mu opioid receptor in the anterior insula of depressed individuals.
The Galphai protein subclass selectivity to the dopamine D2 receptor is also decided by their location at the cell membrane.
Title: The Gαi protein subclass selectivity to the dopamine D(2) receptor is also decided by their location at the cell membrane.
S-nitrosylation-mediated coupling of G-protein alpha-2 with CXCR5 induces Hippo/YAP-dependent diabetes-accelerated atherosclerosis.
Title: S-nitrosylation-mediated coupling of G-protein alpha-2 with CXCR5 induces Hippo/YAP-dependent diabetes-accelerated atherosclerosis.
Preferential Coupling of Dopamine D2S and D2L Receptor Isoforms with Gi1 and Gi2 Proteins-In Silico Study.
Title: Preferential Coupling of Dopamine D(2S) and D(2L) Receptor Isoforms with G(i1) and G(i2) Proteins-In Silico Study.
CXCL2-CXCR2 axis mediates through Galphai-2 and Galphaq/11 to promote tumorigenesis and contributes to cancer stem cell properties of CPT-11-resistant LoVo cells.
Title: CXCL2/CXCR2 axis induces cancer stem cell characteristics in CPT-11-resistant LoVo colon cancer cells via Gαi-2 and Gαq/11.
We conclude that Gia2 protein acts at two different levels which are both dependent and independent of GPCR signaling to induce cell migration and invasion in prostate cancer cells and its action is downstream of PI3-kinase-AKT-Rac1 axis.
Title: Novel role of Giα2 in cell migration: Downstream of PI3-kinase-AKT and Rac1 in prostate cancer cells.
genotyping at GNAI2 may be a useful biomarker in identifying individuals at risk for developing salt-sensitive blood pressure.
Title: GNAI2 polymorphic variance associates with salt sensitivity of blood pressure in the Genetic Epidemiology Network of Salt Sensitivity study.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial ventricular tachycardia MedGen: C0340485 OMIM: 192605 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-mediated phosphorylation of WAVE2 requires both G(alpha)i-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages	PubMed
	env	HIV-1 gp120 induces IL-1beta release from macrophages in a time- and concentration-dependent manner through binding to the chemokine receptor CCR5 and coupling to G(i)alpha protein	PubMed
	env	CXCR4-tropic and CXCR4/CCR5 dual-tropic HIV-1 gp120 induce the cleavage of CD62 ligand by a mechanism dependent on matrix metalloproteinases 1 and 3, CD4, CXCR4, Galpha(i), and p38 MAPK, whereas CCR5-tropic gp120 does not	PubMed
Nef	nef	HIV-1 Nef induced degradation of GNAI2 involves E3 ubiquitin ligases AIP4 and NEDD4 through recruitment of AIP4 and NEDD4 by Nef	PubMed
	nef	HIV-1 Nef interacts with GNAI2 and induces lysosomal degradation of GNAI2 by ubiquitinylating GNAI2 at position Lys-296. The N-terminal myristoyl group, 62EEEE65 motif, and 72PXXP75 motif of Nef are critical for this effect to occur	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G07074 (e-PCR)
- UniSTS:30223

GDB:181210 (e-PCR)
- UniSTS:155178

PMC156606P1 (e-PCR)
- UniSTS:271408

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

Gnai2 (e-PCR), detects polymorphism
- UniSTS:506940

L18426 (e-PCR)
- UniSTS:34648

RH17625 (e-PCR)
- UniSTS:52613

GDB:251998 (e-PCR)
- UniSTS:156322

M13963 (e-PCR)
- UniSTS:124916

SGC31568 (e-PCR)
- UniSTS:34294

BI273769 (e-PCR)
- UniSTS:248822

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables G protein-coupled receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables G-protein beta/gamma-subunit complex binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables GTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled acetylcholine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in G protein-coupled adenosine receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell division	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in gamma-aminobutyric acid signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of adenylate cyclase activity	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of calcium ion-dependent exocytosis	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of synaptic transmission	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neural precursor cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of superoxide anion generation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of urine volume	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular associated smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in cell body	IEA Inferred from Electronic Annotation more info
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in dendrite	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular vesicle	HDA more info	PubMed
part_of heterotrimeric G-protein complex	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	HDA more info	PubMed
located_in midbody	IDA Inferred from Direct Assay more info	PubMed
located_in neuronal dense core vesicle	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: guanine nucleotide-binding protein G(i) subunit alpha-2

Names: GTP-binding regulatory protein Gi alpha-2 chain; adenylate cyclase-inhibiting G alpha protein; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2; guanine nucleotide-binding protein G(i), alpha-2 subunit; heterotrimeric guanine nucleotide-binding protein 1C

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016002.3 RefSeqGene

Range

14138..37296

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166425.2 → NP_001159897.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 2

See identical proteins and their annotated locations for NP_001159897.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK055574, AK126708, AK302330, DB044421, U73166

Consensus CDS

CCDS54587.1

UniProtKB/TrEMBL

B3KX51

Related

ENSP00000406369.1, ENST00000451956.1

Conserved Domains (1) summary

cd00066
Location:3 → 312

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
NM_001282617.2 → NP_001269546.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 3

See identical proteins and their annotated locations for NP_001269546.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (3) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AK055574, AK096595, AK126708, U73166, U73169

Consensus CDS

CCDS63644.1

UniProtKB/TrEMBL

B3KX51

Related

ENSP00000266027.6, ENST00000266027.9

Conserved Domains (1) summary

cd00066
Location:1 → 297

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
NM_001282618.2 → NP_001269547.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 4

See identical proteins and their annotated locations for NP_001269547.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (4) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AK055574, AK096595, U73166

UniProtKB/TrEMBL

B3KP24

Conserved Domains (1) summary

cd00066
Location:2 → 268

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
NM_001282619.2 → NP_001269548.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 5

See identical proteins and their annotated locations for NP_001269548.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (5) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK055574, BC016995, U73166

UniProtKB/TrEMBL

B3KX51

Conserved Domains (2) summary

cd00066
Location:24 → 333

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)

smart00275
Location:24 → 337

G_alpha; G protein alpha subunit
NM_001282620.2 → NP_001269549.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 6

See identical proteins and their annotated locations for NP_001269549.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (6) has a shorter and distinct N-terminus compared to isoform 1.

Source sequence(s)

AK055574, AK096595, U73166

Consensus CDS

CCDS63642.1

UniProtKB/TrEMBL

B3KX51

Related

ENSP00000406871.1, ENST00000422163.5

Conserved Domains (1) summary

cd00066
Location:24 → 333

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)
NM_002070.4 → NP_002061.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform 1

See identical proteins and their annotated locations for NP_002061.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AK055574, BC012138, U73166

Consensus CDS

CCDS2813.1

UniProtKB/Swiss-Prot

B3KTZ0, B4DYA0, B4E2X5, P04899, Q6B6N3, Q8IZ71

UniProtKB/TrEMBL

Q96C71

Related

ENSP00000312999.6, ENST00000313601.11

Conserved Domains (1) summary

cd00066
Location:34 → 349

G-alpha; Alpha subunit of G proteins (guanine nucleotide binding)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

50227068..50263358

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047447979.1 → XP_047303935.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

B3KTZ0, B4DYA0, B4E2X5, P04899, Q6B6N3, Q8IZ71

RNA

XR_007095663.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

50256406..50288697

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346201.1 → XP_054202176.1 guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1

UniProtKB/Swiss-Prot

B3KTZ0, B4DYA0, B4E2X5, P04899, Q6B6N3, Q8IZ71