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

Gene ID: 2771, updated on 7-Apr-2024

Summary

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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

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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_000003.12Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50230799-50231315 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50231316-50231832 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50231833-50232348 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50232401-50232932 Neighboring gene G protein subunit alpha transducin 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14384 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50246621-50247149 Neighboring gene solute carrier family 38 member 3 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50250030-50250839 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_70487 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50257474-50257974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50257975-50258475 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50263389-50264198 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14385 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19890 Neighboring gene microRNA 5787 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50272293-50272903 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50272904-50273514 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19891 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50275957-50276566 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14387 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19892 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50280231-50280841 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50280842-50281451 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50283071-50283786 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50283787-50284502 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14388 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50297648-50298153 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:50298661-50299165 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:50301209-50301784 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr3:50301785-50302358 and GRCh37_chr3:50302359-50302934 Neighboring gene SEMA3B antisense RNA 1 (head to head) Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19897 Neighboring gene semaphorin 3B Neighboring gene microRNA 6872

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer. Ha JH, et al. Biomolecules, 2021 Aug 14. PMID 34439877, Free PMC Article
  2. GNAI2 polymorphic variance associates with salt sensitivity of blood pressure in the Genetic Epidemiology Network of Salt Sensitivity study. Zhang X, et al. Physiol Genomics, 2018 Sep 1. PMID 29906209, Free PMC Article
  3. Suppression of GNAI2 message in ovarian cancer. Raymond JR Jr, et al. J Ovarian Res, 2014 Jan 14. PMID 24423449, Free PMC Article
  4. Increased Gsα within blood cell membrane lipid microdomains in some depressive disorders: an exploratory study. Mooney JJ, et al. J Psychiatr Res, 2013 Jun. PMID 23490066, Free PMC Article
  5. GNAI2 and regulators of G protein signaling as a potential Noonan syndrome mechanism. Huang X, et al. Med Hypotheses, 2009 Jul. PMID 19282110, Free PMC Article

See all (229) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer.
    Title: GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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)

Genotypes

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

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 cycle IEA
Inferred from Electronic Annotation
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 PubMed 
located_in extracellular vesicle HDA PubMed 
part_of heterotrimeric G-protein complex IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in membrane HDA 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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NEW Try the new Transcript table

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

  1. NG_016002.3 RefSeqGene

    Range
    14138..37296
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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)

  2. 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)

  3. 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)

  4. 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

  5. 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)

  6. 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

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    50227068..50263358
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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

  1. XR_007095663.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    50256406..50288697
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P04899.3 GenPept UniProtKB/Swiss-Prot:P04899

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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