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FLASH GENE
Symbol GIT2 contributors: mct - updated : 10-01-2017
HGNC name G protein-coupled receptor kinase-interactor 2
HGNC id 4273
Location 12q24.11      Physical location : 110.367.606 - 110.434.194
Synonym name
  • GRK-interacting protein 2
  • ARF GTPase-activating protein GIT2
  • cool-associated, tyrosine phosphorylated protein 2
  • Paxillin kinase linker (PKL)
  • Synonym symbol(s) CAT-2, KIAA0148, CAT2, PKL
    DNA
    TYPE functioning gene
    STRUCTURE 66.59 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    20 - 5643 - 759 - 2015 25605334
    18 - 5259 - 631 - 2015 25605334
    18 - 5403 - 679 - 2015 25605334
    15 - 2357 - 471 - 2015 25605334
    contains a truncated C terminus with 7 unique amino acids
    19 - 5409 - 681 - 2015 25605334
    19 - 5553 - 729 - 2015 25605334
    - - 2207 - 421 - 2015 25605334
    - - 5501 - 708 - 2015 25605334
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    Nervousbrain    
    Reproductivemale systemprostate   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text kidney
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a GCS type C2C2H2 zinc finger motif,
  • a triple ankyrin repeat region
  • potential SH3-binding motifs
  • one ARF-gap domain
  • HOMOLOGY
    Homologene
    FAMILY GIT protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • GTPase-activating protein for the ADP ribosylation factor family
  • has been implicated in regulating cell spreading and motility through its transient recruitment of the p21-activated kinase (PAK1) to focal adhesions
  • obligatory role for endogenous GIT2 in repression of lamellipodial extension and focal adhesion (FA) turnover by RAC1- and CDC42-dependent signaling pathways, respectively
  • inactivation of GIT2 function is a required step for induction of cell motility and GIT2 may be a target of oncogenic signaling pathways that regulate cell migration
  • is tyrosine phosphorylated in response to platelet-derived growth factor (PDGF) stimulation, in an adhesion dependent manner and is necessary for directed cell migration
  • is an integral component of growth factor and cell adhesion cross-talk signaling, controlling the development of front-rear cell polarity and directional cell migration
  • ARHGEF6 and GIT2 are required for neuronal differentiation
  • coordination between GIT2/VAV2 signaling and GIT2/ARHGEF7 signaling during cell migration
  • regulates thymocyte positive selection, neutrophil-direction sensing, and cell motility during immune responses by regulating the activity of the small GTPases ADP ribosylation factors (Arfs) and RAC1
  • is an essential terminator of TLR signaling and loss of GIT2 leads to uncontrolled inflammation and severe organ damage
  • GIT1, GIT2, ARHGEF7 and RHOJ all colocalised in focal adhesions and depended on each other for their recruitment to focal adhesions
  • plays an important role in MRE11/ATM/H2AX-mediated DNA damage responses
  • distinct roles for GIT1 and GIT2 in regulating neurotransmitter release strength, with GIT1 as a specific regulator of presynaptic release probability
  • GIT1 and GIT2, are GTPase-activating proteins (inactivators) for the ADP-ribosylation factor (Arf) small GTP-binding proteins, and function to limit the activity of Arf proteins
  • GIT2 control cell polarization and direction dependent on the regulation of Golgi through RUSC2
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with G protein-coupled receptor kinases. associates with paxillin
  • also interacts with PIX exchange factors
  • SRC and PTK2 cooperate to phosphorylate GIT2, stimulate its focal adhesion localization, and regulate cell spreading and protrusiveness
  • SH2-SH3 adaptor protein CRK is an essential target of GIT2 inhibition
  • dynamic interaction between PXN and GIT2 is regulated by SRC/PTK2-dependent phosphorylation of GIT2 and this interaction is necessary for the coordination of Rho family GTPase signaling controlling front-rear cell polarity and thus directional migration
  • GIT2 is required for VAV2 activation downstream of integrin engagement and epidermal growth factor (EGF) stimulation
  • is a previously unidentified negative regulator of Toll-like receptor (TLR)-induced NFKB1 signaling
  • RUSC2 interacts with SHD of GIT2 in various lung cancer cells, and stabilizes GIT2
  • bind to PXN to control cell polarization and directional migration
  • DOCK5 is a key regulator of epithelial invasion and metastasis, and suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of RHO and RAC1 GTPases
  • cell & other
    REGULATION
    Phosphorylated by ATM kinase and forms complexes with multiple DDR-associated factors in response to DNA damage
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • GIT2-knockout mice demonstrated a greater susceptibility to DNA damage than their wild-type littermates