GIT1_RAT
ID GIT1_RAT Reviewed; 770 AA.
AC Q9Z272;
DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=ARF GTPase-activating protein GIT1;
DE Short=ARF GAP GIT1;
DE AltName: Full=Cool-associated and tyrosine-phosphorylated protein 1;
DE Short=CAT-1;
DE Short=CAT1;
DE AltName: Full=G protein-coupled receptor kinase-interactor 1;
DE AltName: Full=GRK-interacting protein 1;
DE AltName: Full=GRK-interactor 1 {ECO:0000303|PubMed:9826657};
GN Name=Git1 {ECO:0000303|PubMed:9826657};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH GRK2; GRK3; GRK5 AND
RP GRK6, TISSUE SPECIFICITY, AND CHARACTERIZATION.
RX PubMed=9826657; DOI=10.1073/pnas.95.24.14082;
RA Premont R.T., Claing A., Vitale N., Freeman J.L.R., Pitcher J.A.,
RA Patton W.A., Moss J., Vaughan M., Lefkowitz R.J.;
RT "Beta2-adrenergic receptor regulation by GIT1, a G protein-coupled receptor
RT kinase-associated ADP ribosylation factor GTPase-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:14082-14087(1998).
RN [2]
RP FUNCTION, INTERACTION WITH ARHGEF7; PXN AND PTK2, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=10938112; DOI=10.1128/mcb.20.17.6354-6363.2000;
RA Zhao Z.-S., Manser E., Loo T.-H., Lim L.;
RT "Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal
RT complex disassembly.";
RL Mol. Cell. Biol. 20:6354-6363(2000).
RN [3]
RP INTERACTION WITH PXN AND TGFB1I1.
RX PubMed=12153727; DOI=10.1093/oxfordjournals.jbchem.a003222;
RA Nishiya N., Shirai T., Suzuki W., Nose K.;
RT "Hic-5 interacts with GIT1 with a different binding mode from paxillin.";
RL J. Biochem. 132:279-289(2002).
RN [4]
RP FUNCTION, INTERACTION WITH ARHGEF7; PCLO; GIT2; GRIP1; PPFIA1; PTK2 AND
RP PXN, HOMOOLIGOMERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN,
RP AND MUTAGENESIS OF PHE-285; LEU-288; ARG-298; ARG-299 AND 432-LEU--PRO-483.
RX PubMed=12473661; DOI=10.1074/jbc.m212287200;
RA Kim S., Ko J., Shin H., Lee J.R., Lim C., Han J.H., Altrock W.D.,
RA Garner C.C., Gundelfinger E.D., Premont R.T., Kaang B.K., Kim E.;
RT "The GIT family of proteins forms multimers and associates with the
RT presynaptic cytomatrix protein Piccolo.";
RL J. Biol. Chem. 278:6291-6300(2003).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12695502; DOI=10.1083/jcb.200211002;
RA Zhang H., Webb D.J., Asmussen H., Horwitz A.F.;
RT "Synapse formation is regulated by the signaling adaptor GIT1.";
RL J. Cell Biol. 161:131-142(2003).
RN [6]
RP FUNCTION, INTERACTION WITH ARHGEF7; GRIA2/3; GRIP1; PPFIA1; PPFIA2; PPFIA4;
RP PTK2; PTK2B AND PXN, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12629171; DOI=10.1523/jneurosci.23-05-01667.2003;
RA Ko J., Kim S., Valtschanoff J.G., Shin H., Lee J.R., Sheng M.,
RA Premont R.T., Weinberg R.J., Kim E.;
RT "Interaction between liprin-alpha and GIT1 is required for AMPA receptor
RT targeting.";
RL J. Neurosci. 23:1667-1677(2003).
RN [7]
RP FUNCTION, AND INTERACTION WITH MAPK1 AND MAPK3.
RX PubMed=15923189; DOI=10.1074/jbc.m502271200;
RA Yin G., Zheng Q., Yan C., Berk B.C.;
RT "GIT1 is a scaffold for ERK1/2 activation in focal adhesions.";
RL J. Biol. Chem. 280:27705-27712(2005).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15800193; DOI=10.1523/jneurosci.3553-04.2005;
RA Zhang H., Webb D.J., Asmussen H., Niu S., Horwitz A.F.;
RT "A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and
RT synapse formation through MLC.";
RL J. Neurosci. 25:3379-3388(2005).
RN [9]
RP FUNCTION, INTERACTION WITH ARHGEF7; EFNB1 AND NCK2, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-392, AND MUTAGENESIS OF TYR-392.
RX PubMed=17310244; DOI=10.1038/nn1858;
RA Segura I., Essmann C.L., Weinges S., Acker-Palmer A.;
RT "Grb4 and GIT1 transduce ephrinB reverse signals modulating spine
RT morphogenesis and synapse formation.";
RL Nat. Neurosci. 10:301-310(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371; SER-384; SER-397;
RP THR-401; SER-419; SER-570; SER-580; SER-601 AND SER-639, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [11]
RP FUNCTION, INTERACTION WITH ARHGEF7 AND GRIN3A, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=24297929; DOI=10.1073/pnas.1312211110;
RA Fiuza M., Gonzalez-Gonzalez I., Perez-Otano I.;
RT "GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1
RT signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:20807-20812(2013).
RN [12]
RP FUNCTION, INTERACTION WITH GABRB3 AND GABRG2, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=25284783; DOI=10.1016/j.celrep.2014.08.061;
RA Smith K.R., Davenport E.C., Wei J., Li X., Pathania M., Vaccaro V., Yan Z.,
RA Kittler J.T.;
RT "GIT1 and betaPIX are essential for GABA(A) receptor synaptic stability and
RT inhibitory neurotransmission.";
RL Cell Rep. 9:298-310(2014).
RN [13]
RP FUNCTION.
RX PubMed=25009255; DOI=10.1523/jneurosci.5183-13.2014;
RA Kehoe L.A., Bellone C., De Roo M., Zandueta A., Dey P.N., Perez-Otano I.,
RA Muller D.;
RT "GluN3A promotes dendritic spine pruning and destabilization during
RT postnatal development.";
RL J. Neurosci. 34:9213-9221(2014).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 426-483, DIMERIZATION,
RP INTERACTION WITH ARHGEF7, AND DOMAIN.
RX PubMed=19136011; DOI=10.1016/j.jmb.2008.12.050;
RA Schlenker O., Rittinger K.;
RT "Structures of dimeric GIT1 and trimeric beta-PIX and implications for GIT-
RT PIX complex assembly.";
RL J. Mol. Biol. 386:280-289(2009).
CC -!- FUNCTION: GTPase-activating protein for ADP ribosylation factor family
CC members, including ARF1 (PubMed:9826657). Multidomain scaffold protein
CC that interacts with numerous proteins and therefore participates in
CC many cellular functions, including receptor internalization, focal
CC adhesion remodeling, and signaling by both G protein-coupled receptors
CC and tyrosine kinase receptors (PubMed:9826657). Through PAK1
CC activation, positively regulates microtubule nucleation during
CC interphase. Plays a role in the regulation of cytokinesis; for this
CC function, may act in a pathway also involving ENTR1 and PTPN13 (By
CC similarity). May promote cell motility both by regulating focal complex
CC dynamics and by the activation of RAC1 (PubMed:10938112). May act as
CC scaffold for MAPK1/3 signal transduction, recruiting MAPK1/3 to focal
CC adhesions after EGF stimulation via a Src-dependent pathway, hence
CC stimulating cell migration (PubMed:15923189). Plays a role in brain
CC development and function. Involved in the regulation of spine density
CC and synaptic plasticity that is required for processes involved in
CC learning (By similarity). Plays an important role in dendritic spine
CC morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193,
CC PubMed:17310244, PubMed:24297929, PubMed:25009255). In hippocampal
CC neurons, recruits guanine nucleotide exchange factors (GEFs), such as
CC ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally
CC activate RAC1, which is an essential step for spine morphogenesis and
CC synapse formation (PubMed:12473661). May contribute to the organization
CC of presynaptic active zones through oligomerization and formation of a
CC Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and
CC FAK1 (PubMed:12473661). In neurons, through its interaction with
CC liprin-alpha family members, may be required for AMPA receptor
CC (GRIA2/3) proper targeting to the cell membrane (PubMed:12629171). In
CC complex with GABA(A) receptors and ARHGEF7, plays a crucial role in
CC regulating GABA(A) receptor synaptic stability, maintaining
CC GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic
CC transmission, by locally coordinating RAC1 and PAK1 downstream effector
CC activity, leading to F-actin stabilization (PubMed:25284783). May also
CC be important for RAC1 downstream signaling pathway through PAK3 and
CC regulation of neuronal inhibitory transmission at presynaptic input (By
CC similarity). Required for successful bone regeneration during fracture
CC healing. The function in intramembranous ossification may, at least
CC partly, exerted by macrophages in which GIT1 is a key negative
CC regulator of redox homeostasis, IL1B production, and glycolysis, acting
CC through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May also play a
CC role in angiogenesis during fracture healing (By similarity). In this
CC process, may regulate activation of the canonical NF-kappa-B signal in
CC bone mesenchymal stem cells by enhancing the interaction between NEMO
CC and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced
CC production of VEGFA and others angiogenic factors (By similarity).
CC Essential for VEGF signaling through the activation of phospholipase C-
CC gamma and ERK1/2, hence may control endothelial cell proliferation and
CC angiogenesis (By similarity). {ECO:0000250|UniProtKB:Q68FF6,
CC ECO:0000250|UniProtKB:Q9Y2X7, ECO:0000269|PubMed:10938112,
CC ECO:0000269|PubMed:12473661, ECO:0000269|PubMed:12629171,
CC ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193,
CC ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:17310244,
CC ECO:0000269|PubMed:24297929, ECO:0000269|PubMed:25009255,
CC ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:9826657}.
CC -!- SUBUNIT: Forms homodimers and possibly oligomers (PubMed:12473661,
CC PubMed:19136011). May form heterooligomers with GIT2 (Probable).
CC Interacts with G protein-coupled receptor kinases, including GRK2,
CC GRK3, GRK5 and GRK6 (PubMed:9826657). Interacts with PPFIA1, PPFIA2 and
CC PPFIA4 (PubMed:12473661, PubMed:12629171). Interacts with GRIP1 and
CC forms a ternary complex with PPFIA1 and GRIP1 (PubMed:12473661,
CC PubMed:12629171). Directly interacts with ARHGEF7/beta-PIX, forming in
CC vitro a heptameric complex made of a GIT1 dimer and an ARHGEF7 trimer
CC (PubMed:10938112, PubMed:12473661, PubMed:12629171, PubMed:17310244,
CC PubMed:19136011). Directly interacts with PXN/paxillin; this
CC interaction is enhanced in the presence of ARHGEF7 (PubMed:10938112,
CC PubMed:12153727, PubMed:12473661, PubMed:12629171). Directly interacts
CC (via C-terminus) with TGFB1I1/Hic-5 (via LD motif 3) (PubMed:12153727).
CC Directly interacts with PTK2/FAK1 (PubMed:10938112, PubMed:12473661,
CC PubMed:12629171). May interact with PTK2B/PYK2; this interaction may be
CC indirect (PubMed:12629171). Interacts with AMPA receptors GRIA2/3
CC (PubMed:12629171). Directly interacts with protein Piccolo/PCLO
CC (PubMed:12473661). Forms a complex with Ephrin-B1/EFNB1 and NCK2/GRB4
CC (via SH2); this interaction is important for spine morphogenesis and
CC synapse formation. Interaction with NCK2 is transient and depends upon
CC GIT1 phosphorylation at Tyr-392 (PubMed:17310244). Interacts with
CC GRIN3A/GluN3A (via C-terminus); this interaction competes with GIT1
CC interaction with ARHGEF7 and limits synaptic localization of GIT1
CC (PubMed:24297929). Interacts with IKBKG/NEMO in resting bone
CC mesenchymal stem cells, as well as in TNF-stimulated cells; this
CC interaction may increase IKBKG affinity for 'Lys-63'-linked
CC polyubiquitin chains (By similarity). Interacts with GABA(A) receptors,
CC including GABRB3 and GABRG2 (PubMed:25284783). Interacts with SCRIB (By
CC similarity). Interacts (via N- and C-terminus) with ENTR1/SDCCAG3 (via
CC N-terminus); this interaction is direct. May form a tripartite complex
CC with ENTR1 and PTPN13 (By similarity). Interacts with YWHAZ (By
CC similarity). Interacts with PAK1 and PAK3 (By similarity). Directly
CC interacts (via N-terminus) with gamma-tubulin (By similarity).
CC Interacts with MAPK1 and MAPK3; this interaction is required for
CC MAPK1/3 recruitment to focal adhesions (PubMed:15923189).
CC {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Y2X7,
CC ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:12153727,
CC ECO:0000269|PubMed:12473661, ECO:0000269|PubMed:12629171,
CC ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:17310244,
CC ECO:0000269|PubMed:19136011, ECO:0000269|PubMed:24297929,
CC ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:9826657,
CC ECO:0000305|PubMed:12473661}.
CC -!- INTERACTION:
CC Q9Z272; Q9ES28: Arhgef7; Xeno; NbExp=2; IntAct=EBI-3842379, EBI-642580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y2X7}. Synapse
CC {ECO:0000269|PubMed:17310244, ECO:0000269|PubMed:25284783}. Presynapse
CC {ECO:0000269|PubMed:12473661, ECO:0000269|PubMed:12629171,
CC ECO:0000269|PubMed:12695502}. Postsynapse {ECO:0000269|PubMed:12629171,
CC ECO:0000269|PubMed:12695502}. Postsynaptic density
CC {ECO:0000269|PubMed:12629171}. Cell junction, focal adhesion
CC {ECO:0000305|PubMed:10938112}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:Q9Y2X7}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q9Y2X7}.
CC Cytoplasm, cytoskeleton, spindle pole {ECO:0000250|UniProtKB:Q9Y2X7}.
CC Note=Cycles between at least 3 distinct intracellular compartments,
CC including focal adhesions, cytosolic complexes, containing at least
CC PXN/paxillin, ARHGEF7 and PAK1, and membrane protrusions. During cell
CC migration, moves from the disassembling adhesions into the cytosol and
CC towards the leading edge. In adherent cells, localizes to adhesions.
CC Recruitment to adhesions may be mediated by RAC1 and active tyrosine-
CC phosphorylated PXN (By similarity). May be present in both excitatory,
CC as well as inhibitory synapses (PubMed:12695502, PubMed:25284783). In
CC hippocampal neurons, recruitment of GIT1 to synapses is regulated by
CC ephrinB activation and ephrinB downstream effector GRB4/NCK2
CC (PubMed:17310244). In hippocampal neurons, partially colocalizes with
CC PCLO (PubMed:12473661). Interaction with GRIN3A limits GIT1 synaptic
CC localization (PubMed:24297929). Localization to the centrosome does not
CC depend upon the presence of gamma-tubulin (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y2X7, ECO:0000269|PubMed:12473661,
CC ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:17310244,
CC ECO:0000269|PubMed:24297929, ECO:0000269|PubMed:25284783}.
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9826657). Expressed at
CC high levels in testis (at protein level) (PubMed:10938112). Expressed
CC in the brain, including in CA1 hippocampal neurons, in the amygdala,
CC and thalamic nuclei (at protein level) (PubMed:10938112,
CC PubMed:12473661, PubMed:12695502, PubMed:12629171, PubMed:15800193,
CC PubMed:17310244, PubMed:24297929, PubMed:25284783).
CC {ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:12473661,
CC ECO:0000269|PubMed:12629171, ECO:0000269|PubMed:12695502,
CC ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:17310244,
CC ECO:0000269|PubMed:24297929, ECO:0000269|PubMed:25284783,
CC ECO:0000269|PubMed:9826657}.
CC -!- DEVELOPMENTAL STAGE: In the brain cortex and in the hippocampus,
CC continuously expressed from P0 to adult age (at protein level).
CC {ECO:0000269|PubMed:24297929}.
CC -!- DOMAIN: The coiled coil region mediates dimerization.
CC {ECO:0000269|PubMed:12473661, ECO:0000269|PubMed:19136011}.
CC -!- PTM: Phosphorylated on tyrosine residues by PTK2/FAK1 and SRC in
CC growing fibroblasts (PubMed:10938112). Phosphorylation at Tyr-392 is
CC induced by activation of Ephrin-B1/EFNB1 and catalyzed by SRC family
CC kinases. It is required for the interaction with NCK2 and for GIT1
CC recruitment to synapses in hippocampal neurons (PubMed:17310244).
CC {ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:17310244}.
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DR EMBL; AF085693; AAC83348.1; -; mRNA.
DR RefSeq; NP_114002.1; NM_031814.1.
DR PDB; 2JX0; NMR; -; A=640-770.
DR PDB; 2W6A; X-ray; 1.40 A; A/B=426-483.
DR PDB; 6IUH; X-ray; 1.80 A; A/B=645-770.
DR PDB; 6IUI; X-ray; 2.60 A; A/B=645-770.
DR PDBsum; 2JX0; -.
DR PDBsum; 2W6A; -.
DR PDBsum; 6IUH; -.
DR PDBsum; 6IUI; -.
DR AlphaFoldDB; Q9Z272; -.
DR SMR; Q9Z272; -.
DR BioGRID; 249809; 9.
DR CORUM; Q9Z272; -.
DR IntAct; Q9Z272; 6.
DR MINT; Q9Z272; -.
DR STRING; 10116.ENSRNOP00000052961; -.
DR iPTMnet; Q9Z272; -.
DR PhosphoSitePlus; Q9Z272; -.
DR SwissPalm; Q9Z272; -.
DR jPOST; Q9Z272; -.
DR PaxDb; Q9Z272; -.
DR PRIDE; Q9Z272; -.
DR ABCD; Q9Z272; 1 sequenced antibody.
DR GeneID; 83709; -.
DR KEGG; rno:83709; -.
DR CTD; 28964; -.
DR RGD; 69331; Git1.
DR eggNOG; KOG0818; Eukaryota.
DR InParanoid; Q9Z272; -.
DR OrthoDB; 349344at2759; -.
DR PhylomeDB; Q9Z272; -.
DR Reactome; R-RNO-3928664; Ephrin signaling.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013404; RAC2 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013409; RHOJ GTPase cycle.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9013424; RHOV GTPase cycle.
DR EvolutionaryTrace; Q9Z272; -.
DR PRO; PR:Q9Z272; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044305; C:calyx of Held; ISO:RGD.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0005925; C:focal adhesion; TAS:RGD.
DR GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0097431; C:mitotic spindle pole; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0098794; C:postsynapse; IDA:SynGO.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:RGD.
DR GO; GO:0031267; F:small GTPase binding; IDA:RGD.
DR GO; GO:0098879; F:structural constituent of postsynaptic specialization; IDA:SynGO.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; IDA:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; IGI:MGI.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISO:RGD.
DR GO; GO:0001771; P:immunological synapse formation; IGI:MGI.
DR GO; GO:0001957; P:intramembranous ossification; ISS:UniProtKB.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0061743; P:motor learning; ISO:RGD.
DR GO; GO:0032013; P:negative regulation of ARF protein signal transduction; IDA:RGD.
DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS:UniProtKB.
DR GO; GO:0106015; P:negative regulation of inflammatory response to wounding; ISS:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0099645; P:neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0090063; P:positive regulation of microtubule nucleation; ISS:UniProtKB.
DR GO; GO:2000646; P:positive regulation of receptor catabolic process; IMP:RGD.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:RGD.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IBA:GO_Central.
DR GO; GO:0032465; P:regulation of cytokinesis; ISO:RGD.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0036465; P:synaptic vesicle recycling; IBA:GO_Central.
DR Gene3D; 1.10.220.150; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR037278; ARFGAP/RecO.
DR InterPro; IPR001164; ArfGAP_dom.
DR InterPro; IPR038508; ArfGAP_dom_sf.
DR InterPro; IPR032352; GIT1/2_CC.
DR InterPro; IPR022018; GIT1_C.
DR InterPro; IPR013724; GIT_SHD.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF01412; ArfGap; 1.
DR Pfam; PF12205; GIT1_C; 1.
DR Pfam; PF16559; GIT_CC; 1.
DR Pfam; PF08518; GIT_SHD; 2.
DR PRINTS; PR00405; REVINTRACTNG.
DR SMART; SM00248; ANK; 3.
DR SMART; SM00105; ArfGap; 1.
DR SMART; SM00555; GIT; 2.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF57863; SSF57863; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS50115; ARFGAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ANK repeat; Cell junction; Cell projection; Coiled coil;
KW Cytoplasm; Cytoskeleton; GTPase activation; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Synapse; Zinc; Zinc-finger.
FT CHAIN 1..770
FT /note="ARF GTPase-activating protein GIT1"
FT /id="PRO_0000074202"
FT DOMAIN 1..124
FT /note="Arf-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REPEAT 132..161
FT /note="ANK 1"
FT REPEAT 166..195
FT /note="ANK 2"
FT REPEAT 199..228
FT /note="ANK 3"
FT ZN_FING 11..34
FT /note="C4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00288"
FT REGION 1..124
FT /note="Interaction with gamma-tubulin and localization to
FT the centrosome"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT REGION 245..374
FT /note="Interaction with PCLO"
FT /evidence="ECO:0000269|PubMed:12473661"
FT REGION 253..424
FT /note="Interaction with PTK2/FAK1"
FT /evidence="ECO:0000269|PubMed:10938112"
FT REGION 254..376
FT /note="Interaction with ARHGEF7"
FT /evidence="ECO:0000269|PubMed:10938112"
FT REGION 363..425
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 375..596
FT /note="Interaction with NCK2 and GRIN3A"
FT /evidence="ECO:0000269|PubMed:17310244,
FT ECO:0000269|PubMed:24297929"
FT REGION 375..596
FT /note="Required for localization at synapses"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT REGION 420..475
FT /note="Interaction with MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT REGION 429..629
FT /note="Interaction with IKBKG"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT REGION 574..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 646..770
FT /note="Interaction with PXN and TGFB1I1"
FT /evidence="ECO:0000269|PubMed:10938112,
FT ECO:0000269|PubMed:12153727"
FT COILED 449..483
FT /evidence="ECO:0000255, ECO:0000269|PubMed:19136011"
FT COMPBIAS 363..380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 574..591
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 224
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 373
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 379
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 392
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 401
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 507
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 546
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q68FF6"
FT MOD_RES 554
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 563
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 580
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 605
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 610
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2X7"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 285
FT /note="F->A: Loss of interaction with FAK1, decreased
FT interaction with PCLO, no effect on interaction with
FT ARHGEF7."
FT /evidence="ECO:0000269|PubMed:12473661"
FT MUTAGEN 288
FT /note="L->A: Loss of interaction with PCLO and FAK1, no
FT effect on interaction with ARHGEF7."
FT /evidence="ECO:0000269|PubMed:12473661"
FT MUTAGEN 298
FT /note="R->A: Loss of interaction with FAK1, decreased
FT interaction with PCLO, no effect on interaction with
FT ARHGEF7."
FT /evidence="ECO:0000269|PubMed:12473661"
FT MUTAGEN 299
FT /note="R->A: Loss of interaction with FAK1, decreased
FT interaction with PCLO, no effect on interaction with
FT ARHGEF7."
FT /evidence="ECO:0000269|PubMed:12473661"
FT MUTAGEN 392
FT /note="Y->F: Loss of interaction with NCK2."
FT /evidence="ECO:0000269|PubMed:17310244"
FT MUTAGEN 432..483
FT /note="Missing: Decreased homooligomerization and loss of
FT formation of a ternary complex between GIT1, ARHGEF7 and
FT PCLO. Does not affect ARHGEF7- and PCLO-binding to GIT1
FT monomer."
FT /evidence="ECO:0000269|PubMed:12473661"
FT HELIX 432..481
FT /evidence="ECO:0007829|PDB:2W6A"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:2JX0"
FT HELIX 651..673
FT /evidence="ECO:0007829|PDB:6IUH"
FT HELIX 677..679
FT /evidence="ECO:0007829|PDB:6IUH"
FT HELIX 680..695
FT /evidence="ECO:0007829|PDB:6IUH"
FT STRAND 700..702
FT /evidence="ECO:0007829|PDB:2JX0"
FT HELIX 705..725
FT /evidence="ECO:0007829|PDB:6IUH"
FT HELIX 726..728
FT /evidence="ECO:0007829|PDB:6IUH"
FT HELIX 739..766
FT /evidence="ECO:0007829|PDB:6IUH"
SQ SEQUENCE 770 AA; 85231 MW; 797C8EB7FCB3F481 CRC64;
MSRKGPRAEV CADCSAPDPG WASISRGVLV CDECCSVHRS LGRHISIVKH LRHSAWPPTL
LQMVHTLASN GANSIWEHSL LDPAQVQSGR RKANPQDKVH PIKSEFIRAK YQMLAFVHKL
PCRDDDGVTA KDLSKQLHSS VRTGNLETCL RLLSLGAQAN FFHPEKGTTP LHVAAKAGQT
LQAELLVVYG ADPGSPDVNG RTPIDYARQA GHHELAERLV ECQYELTDRL AFYLCGRKPD
HKNGHYIIPQ MADRSRQKCM SQSLDLSELA KAAKKKLQAL SNRLFEELAM DVYDEVDRRE
NDAVWLATQN HSTLVTERSA VPFLPVNPEY SATRNQGRQK LARFNAREFA TLIIDILSEA
KRRQQGKSLS SPTDNLELSA RNQSDLDDQH DYDSVASDED TDQEPLPSAG ATRNNRARSM
DSSDLSDGAV TLQEYLELKK ALATSEAKVQ QLMKVNSSLS DELRKLQREI HKLQAENLQL
RQPPGPVPVP SLPSERAEHT LMGPGGSTHR RDRQAFSMYE PGSALKPFGG APGDELATRL
QPFHSTELED DAIYSVHVPA GLYRIRKGVS ASSVTFTPSS PLLSSSQEGS RHASKLSRHG
SGAESDYENT QSGEPLLGLE GKRFLELSKE DELHAELESL DGDPDPGLPS TEDVILKTEQ
VTKNIQELLR AAQEFKHDSF VPCSEKIHLA VTEMASLFPK RPALEPVRSS LRLLNASAYR
LQSECRKTVP PEPGAPVDFQ LLTQQVIQCA YDIAKAAKQL VTITTREKKQ
