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FLASH GENE
Symbol GIT1 contributors: mct/pgu - updated : 11-02-2016
HGNC name G protein-coupled receptor kinase-interactor 1
HGNC id 4272
Location 17p11.2      Physical location : 27.900.486 - 27.916.610
Synonym name
  • GRK-interacting protein 1
  • GPCR kinase-interacting protein 1
  • cool-associated and tyrosine-phosphorylated protein 1
  • Synonym symbol(s) CAT1, CAT-1, ARF GAP GIT1
    DNA
    TYPE functioning gene
    STRUCTURE 16.12 kb     20 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    SDF2 17q11.2 stromal cell-derived factor 2 SUPT6H 17q11.2 suppressor of Ty 6 homolog (S. cerevisiae) MGC39650 17q11.2 hypothetical protein MGC39650 RAB34 17q11.1 RAB34, member RAS oncogene family RPL23A 17q11 ribosomal protein L23a LOC116238 17q11.2 hypothetical protein BC014072 NEK8 17q11.1 NIMA (never in mitosis gene a)- related kinase 8 TRAF4 17q11-q12 TNF receptor-associated factor 4 FLJ10700 17q11.2 hypothetical protein FLJ10700 ERAL1 17q11.2 Era G-protein-like 1 (E. coli) FLOT2 17q11.2-q12 flotillin 2 MGC23280 17q11.2 hypothetical protein MGC23280 PHF12 17q11.2 PHD finger protein 12 SEZ6 17q11.2 seizure related 6 homolog (mouse) LOC342659 17q11.2 similar to NADH-ubiquinone oxidoreductase 15 kDa subunit (Complex I-15 kDa) (CI-15 kDa) PIPOX 17q11.2 pipecolic acid oxidase TIAF1 17q11.1-q11.2 TGFB1-induced anti-apoptotic factor 1 LOC390783 17 hypothetical gene supported by U02680; NM_002822 CRYBA1 17q11.2-q12 crystallin, beta A1 182-FIP 17q11.2 82-kD FMRP Interacting Protein KIAA1361 17q11.2 serine/threonine protein kinase TAO1 homolog LOC116236 17q11.2 hypothetical protein LOC116236 LOC90313 17q11.2 hypothetical protein BC004507 GIT1 17p11.2 G protein-coupled receptor kinase-interactor 1 FLJ25555 17q11.2 hypothetical protein FLJ25555 FLJ14871 17q11.2 hypothetical protein FLJ14871 SSH2 17q11.2 slingshot 2 FLJ46247 17q11.2 FLJ46247 protein DKFZP434K1421 17q11.2 hypothetical protein DKFZp434K1421 SLC6A4 17q11.2 solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 BLMH 17q11.2 bleomycin hydrolase LOC388364 17 similar to AWKS9372 CPD 17q11.2 carboxypeptidase D
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3778 85 770 - 2010 20568227
    20 - 3751 84 761 - 2010 20568227
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Lymphoid/Immunethymus   highly
    Nervousbrain   moderately
     nervecranial nerve  highly Homo sapiens
    Reproductivefemale systemovary  highly
     male systemprostate  lowly
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  moderately
    Muscularsmoothvessel   Homo sapiens
    Muscularstriatumcardiac highly
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticplatelet
    Cardiovascularendothelial cell Homo sapiens
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal, pregnancy
    Text umbilical cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal ARF GTPase-activating protein (ARF-GAP) domain (AAs 1–124)
  • three ankyrin (ANK) repeats (AAs 130–254)
  • a Spa2-homology domain (SHD) (AAs 264–374), that mediates binding to the RAC1/CDC42-specific exchange factor PIX
  • a coiled-coil domain
  • a C terminus that includes paxillin-binding domain (AAs 624–770)
  • mono polymer heteromer , complex
    HOMOLOGY
    interspecies homolog to rattus Git1 (96.85 pc)
    homolog to murine Git1 (97.77 pc)
    Homologene
    FAMILY GIT protein family
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • observed at different subcellular locations, including focal adhesions (FAs), membrane protrusions, adherens junctions, and the centrosome
  • basic FUNCTION
  • GTPase-activating protein for the ADP ribosylation factor family
  • involved in controlling vesicle trafficking, adhesion
  • and cytoskeletal organization
  • may be acting as a scaffold protein to facilitate c-Src-dependent activation of MAP2K1-MAPK1/MAPK2 in response to both GPCRs and TKRs
  • playing a critical role in spine and synapse formation
  • regulating protrusive activity in cells by phosphorylation of serine 709 in GIT1
  • may play a role for cytoskeletal reorganization during platelet aggregation
  • play an important role in initiating the disassembly of focal adhesions
  • multidomain protein that plays an important role in cell adhesion, motility, cytoskeletal remodeling, and membrane trafficking
  • essential mediator for VEGFA-induced endothelial cells podosome formation and cell migration via PLCgamma
  • critical role for GIT1 in pulmonary vascular development by regulating VEGF-induced PLCG and ERK1/2 activation
  • with ARHGEF7 regulate HGF-induced lamellipodia formation and WASF2 transport
  • key regulator of bone mass by regulating osteoclast function
  • multi-function scaffold protein, regulator of mitochondrial biogenesis and function, which is necessary for postnatal cardiac maturation
  • plays an important role in NOS3 function, in both normal and abnormal pathophysiologic states
  • could be important in vascular signaling and disease
  • multifunctional protein that acts as a GTPase-activating protein (GAP) for Arf GTPases, as well as serves as a scaffold for a number of different signaling proteins
  • multidomain protein GIT1 is involved in cytoskeletal rearrangements and cell motility
  • is known to be important for cell spreading and migration, processes which rely on paxillin trafficking and focal adhesion turnover
  • MAT2B and GIT1 form a scaffold, which recruits and activates MEK and ERK to promote growth and tumorigenesis
  • is a novel mediator of vascular remodeling by regulating vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis through phospholipase C gamma and extracellular signal-regulated kinase 1/2 signaling pathways
  • GIT1, GIT2, ARHGEF7 and RHOJ all colocalised in focal adhesions and depended on each other for their recruitment to focal adhesions
  • GIT1 and ARHGEF7 are involved in Ag-induced chemotaxis, a possible mecanism of concerted action of tyrosine kinases, GIT1/ARHGEF7 proteins, and Ca(2+) in the propagation of signals leading to the regulation of microtubule nucleation in activated mast cells
  • distinct roles for GIT1 and GIT2 in regulating neurotransmitter release strength, with GIT1 as a specific regulator of presynaptic release probability
  • GIT1/ARHGEF7 signaling proteins with PAK1 kinase represent a novel regulatory mechanism of microtubule nucleation in interphase cells
  • 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
  • CELLULAR PROCESS cell organization/biogenesis
    cell communication
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • signaling complex, consisting of GIT1, ARHGEF6, AKT1, and PAKs, that plays an essential role in the regulation of dendritic spine and synapse formation
  • forming a complex Scrib-ARHGEF7-GIT1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with G protein-coupled receptor kinases : ADRBK1, PPFIA1 and PPFIA4
  • interacting with ARHGEF6
  • RAC1 and RAC3 interact with GIT1, a multifunctional Arf-GAP protein, which regulates cell-matrix adhesion, cell spreading and endocytosis
  • GIT1 and ARHGEF7 form a constitutively associated complex that acts as a scaffold to allow the formation of large multiprotein assemblies that regulate synaptogenesis, cell polarity and cell migration
  • interacts with paxillin through the LD2 and LD4 motif
  • PTK2
  • binding of GIT1 and ERK1/2 was functionally important (CC domain of ERK1/2 is necessary for binding to GIT1, for ERK1/2 activation in focal adhesions, and for cell spreading and migration)
  • substrate of PTPRZ1, with MAGI1, and GTPase-activating protein for Rho GTPase (ARHGAP35)
  • interacted with NOS3 in the endothelial cell cytoplasm, and this robust association was associated with stimulatory NOS3 phosphorylation (Ser1177), enzyme activation
  • roles for GIT1 and its interactions with the Arf GTPases and paxillin in oncogenic transformation
  • cellular activity of GIT1 via serine 46 phosphorylation is exclusively regulated by PRKD3, thus identifying GIT1 as the first specific substrate ofPRKD3
  • GRIN3A binds GIT1, a postsynaptic scaffold that assembles actin regulatory complexes, including the RAC1 guanine nucleotide exchange factor ARHGEF7, to promote RAC1 activation in spines
  • PDGFA regulates chondrocyte proliferation through activation of ERK1/2 pathway by upregulation of GIT1 expression and RAC1 phosphorylation
  • ARHGEF7 and GIT1 are required for synaptic GABA(A)R surface stability through the activity of the GTPase RAC1 and downstream effector PAK1
  • ARHGEF6 is constitutively linked to GIT1, a GAP of Arf family small G proteins, and ARHGEF6 phosphorylation enables binding of the 14-3-3 adaptor protein to the ARHGEF6/GIT1 complex
  • cell & other
    REGULATION
    Phosphorylated by regulated by protein kinase D3 (PRKD3) through direct phosphorylation on serine 46 (this phosphorylation represents a molecular switch by which GIT1 localization, paxillin trafficking, and cellular protrusive activity are regulated)
    Other regulated in a vascular endothelial liver injury model
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility to Attention deficit hyperactivity disorder (ADHD)
    Variant & Polymorphism SNP
  • intronic SNP, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility
  • Candidate gene
    Marker
  • ITGA2B, ITGA8, GIT1, and SHC1 were identified as independent prognostic factors of overall survival of clear cell renal cell carcinoma
  • Therapy target
    SystemTypeDisorderPubmed
    osteoarticularboneostéoporosis
    potential target for osteoporosis therapy
    ANIMAL & CELL MODELS
  • Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory