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

    Gene ID: 2771, updated on 28-Oct-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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    See GNAI2 in Genome Data Viewer
    Location:
    3p21.31
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (50227068..50263358)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (50256406..50288697)
    RS_2024_09 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 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. Abnormal regulation of G protein alpha(i2) subunit in skin fibroblasts from insulin-resistant hypertensive individuals. Baritono E, et al. J Hypertens, 2004 Apr. PMID 15126921
    2. GNAi2/gip2-Regulated Transcriptome and Its Therapeutic Significance in Ovarian Cancer. Ha JH, et al. Biomolecules, 2021 Aug 14. PMID 34439877, Free PMC Article
    3. Role of a Galphai2 protein splice variant in the formation of an intracellular dopamine D2 receptor pool. LĂłpez-Aranda MF, et al. J Cell Sci, 2007 Jul 1. PMID 17550964
    4. Identification and subcellular distribution of the Gi-proteins in the enterocytic-differentiated adenocarcinoma cell-line, Caco-2. Lacombe C, et al. Biol Cell, 1996. PMID 9237368
    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 (245) 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 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 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 hippocampal mossy fiber to CA3 synapse IEA
    Inferred from Electronic Annotation
    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
    		  

    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_2024_08

    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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