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FLASH GENE
Symbol GNAI2 contributors: mct - updated : 13-09-2017
HGNC name guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2
HGNC id 4385
Location 3p21.31      Physical location : 50.273.646 - 50.296.786
Synonym name
  • GTP-binding regulatory protein Gi alpha-2 chain
  • adenylate cyclase-inhibiting G alpha protein
  • Synonym symbol(s) GNAI2B, GIP, H_LUCA15.1, H_LUCA16.1, Galphai2
    DNA
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem
    STRUCTURE 32.67 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site
    text structure transcriptional activation of the promoter through nuclear factor-kappaB and antioxidant response elements
    MAPPING cloned Y linked N status confirmed
    Map see SEMA3F
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 2200 - 355 - 2015 25788576
    9 - 2143 - 318 - 2015 25788576
    10 - 2591 - 339 - 2015 25788576
    9 - 2467 - 339 - 2015 25788576
    9 - 2184 - 303 - 2015 25788576
    8 - 2215 - 274 - 2015 25788576
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunetonsils   highly
    Nervousnerve   highly
    Reproductivefemale systembreastmammary gland highly
    Skin/Tegumentskin   highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • three regions named switches 1, 2 and 3 and including the sites for guanine nucleotide binding and effector interaction
  • an helical domain
  • HOMOLOGY
    Homologene
    FAMILY
  • G-alpha family
  • G(i/o/t/z) subfamily
  • CATEGORY signaling
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • regulates a number of cellular functions including cell migration, proliferation, and differentiation
  • negative modifier of Ras activation
  • required for chemokine-induced neutrophil arrest
  • having an important role in regulating thymic homing and pre-thymic and early thymocyte differentiation
  • exhibited a more prominent role than GNAI3 in guidance of CD4-CD8--double negative (DN) 1 cell migration and early thymic differentiation
  • involved specifically in the activation of TRPC4
  • variations in GNAI2 and RGS1 expression affect chemokine receptor signaling and the organization of secondary lymphoid organs
  • GNAI2 gene chromatin is a direct target of MTA1 and MTA1 might stimulate the Ras pathway, in part, by repressing the expression of GNAI2, which in turn is a negative regulator of the Raf pathway
  • is a novel CLDN5 partner required for TJ integrity in brain endothelial cells
  • GNAI2 plays an essential role in OXT and EGF signaling to induce prostate cancer cell migration
  • GNAI2, GNAI3 contribute to inflammation by redundant, overlapping, and GNAI-isoform-specific mechanism
  • GNAI2, GNAI3 are therefore critical for B cell chemoattractant receptor signaling and for normal B cell function
  • GNAI2 signaling is required for skeletal muscle growth, regeneration, and satellite cell proliferation and differentiation
  • potential role in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • guanine nucleotide binding
  • binding UNC5B (inhibitor of G protein signaling that may have broad significance for axonal guidance and chemotaxis)
  • GNAI2 and ZAP70 mediate RASGRP1 membrane localization and activation of CXCL12-induced T cell functions
  • GNAI2 interacts with CLDN5 and association is correlated with TJ (tight junctions) integrity in brain endothelial cell line
  • CEBPA plays a dual role as an activator and as a repressor of GNAI2 gene transcription
  • essential role for RGS protein/GNAI2 interactions in B lymphocyte-directed cell migration and trafficking
  • cell & other
    REGULATION
    repressed by MTA1 (MTA1 behaves as a co-repressor of GNAI2)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional germinal mutation      
    in periventricular nodular heterotopia and intellectual disability
    Susceptibility to high systolic blood pression
    Variant & Polymorphism SNP -318 C>G SNP impairs transcriptional activity through specific binding of Sp1 and is associated with high Systolic blood pression
    Candidate gene candidate genes for Noonan syndrome
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Galpha(i2) (-/-) mice have a reduced ventricular effective refractory period and a predisposition to ventricular tachycardia when challenged with programmed electrical stimulation
  • lack of Gnai2 leads to dilative cardiomyopathy and increased mortality in Adrb1 overexpressing mice