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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
    Physical map
    HYPE 12q24.1 cut-like 2 (Drosophila) SART3 12q24.1 squamous cell carcinoma antigen recognised by T cells 3 NIFU 12-q24.1 squamous cell carcinoma antigen recognised by T cells 3 LOC338773 12q24.12 hypothetical protein LOC338773 SELPLG 12q24 selectin P ligand CORO1C 12q24.1 coronin, actin binding protein, 1C SSH1 12q24.12 slingshot 1 DAO 12q24.12 D-amino-acid oxidase DKFZp761H039 12q24.12 hypothetical protein DKFZp761H039 USP30 12q23.3 ubiquitin specific protease 30 LOC121642 12q24.12 similar to hypothetical protein 9530023G02 UNG 12q23-q24.1 uracil-DNA glycosylase LOC387883 12 LOC387883 ACACB 12q24.1 acetyl-Coenzyme A carboxylase beta FOXN4 12q24.12 forkhead box N4 LOC387884 12 LOC387884 FLJ37587 12q24.12 hypothetical protein FLJ37587 KCTD10 12q24.12 potassium channel tetramerisation domain containing 10 UBE3B 12q24.12 potassium channel tetramerisation domain containing 10 MMAB MVK 12q24 mevalonate kinase (mevalonic aciduria) MGC14436 12q24.12 hypothetical protein MGC14436 FLJ14721 12q24.12 hypothetical protein FLJ14721 TRPV4 12q24.1 transient receptor potential cation channel, subfamily V, member 4 GLTP 12q24.12 glycolipid transfer protein MGC10854 12q24.12 hypothetical protein MGC10854 GIT2 12q24.1 G protein-coupled receptor kinase-interactor 2 ANKRD13 12q24.12 ankyrin repeat domain 13 LOC144705 12q24.12 hypothetical gene supported by AF086409 CDV-1 12q24.13 carnitine deficiency-associated gene expressed in ventricle 1 ATP2A2 12q24.1 ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 HMGA1L3 12q24.13 high mobility group AT-hook 1-like 3 ARPC3 12q24 actin related protein 2/3 complex, subunit 3, 21kDa MGC14560 12q24.13 protein x 0004 HSU79274 12q24.13 protein predicted by clone 23733 VPS29 12q24 vacuolar protein sorting 29 (yeast) RAD9B 12q24.13 RAD9 homolog B (S. cerevisiae) TA-PP2C 12q24.13 T-cell activation protein phosphatase 2C FLJ21127 12q24.13 hypothetical protein FLJ21127 MGC15619 12q24.13 hypothetical protein MGC15619 PPP1CC 12q24.1 protein phosphatase 1, catalytic subunit, gamma isoform FLJ35843 12q24.13 hypothetical protein FLJ35843 MYL2 12q23-q24.3 myosin, light polypeptide 2, regulatory, cardiac, slow CUTL2 12q24.12 cut-like 2 (Drosophila)
    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