GIT1
entrez
28964
canonical
uniprot
Q9Y2X7
canonical
ensembl
ENSG00000108262
resolver
ensp
ENSP00000225394
resolver
ensp
ENSP00000378338
resolver
ensp
ENSP00000593398
resolver
ensp
ENSP00000593401
resolver
genesymbol
GIT1
resolver
hgnc
HGNC:4272
resolver
uniprot
B4DGU9
resolver
uniprot
B4DSV3
resolver
uniprot
Q59FC3
resolver
uniprot
Q86SS0
resolver
uniprot
Q9BRJ4
resolver
uniprot_entry
GIT1_HUMAN
resolver
uniprot_entry
Q59FC3_HUMAN
resolver
uniprot_sec
B4DGU9
resolver
uniprot_sec
B4DSV3
resolver
uniprot_sec
Q86SS0
resolver
uniprot_sec
Q9BRJ4
resolver
amino_acid_sequence
MSRKGPRAEVCADCSAPDPGWASISRGVLVCDECCSVHRSLGRHISIVKHLRHSAWPPTLLQMVHTLASNGANSIWEHSLLDPAQVQSGRRKANPQDKVHPIKSEFIRAKYQMLAFVHKLPCRDDDGVTAKDLSKQLHSSVRTGNLETCLRLLSLGAQANFFHPEKGTTPLHVAAKAGQTLQAELLVVYGADPGSPDVNGRTPIDYARQAGHHELAERLVECQYELTDRLAFYLCGRKPDHKNGHYIIPQMADSLDLSELAKAAKKKLQALSNRLFEELAMDVYDEVDRRENDAVWLATQNHSTLVTERSAVPFLPVNPEYSATRNQGRQKLARFNAREFATLIIDILSEAKRRQQGKSLSSPTDNLELSLRSQSDLDDQHDYDSVASDEDTDQEPLRSTGATRSNRARSMDSSDLSDGAVTLQEYLELKKALATSEAKVQQLMKVNSSLSDELRRLQREIHKLQAENLQLRQPPGPVPTPPLPSERAEHTPMAPGGSTHRRDRQAFSMYEPGSALKPFGGPPGDELTTRLQPFHSTELEDDAIYSVHVPAGLYRIRKGVSASAVPFTPSSPLLSCSQEGSRHTSKLSRHGSGADSDYENTQSGDPLLGLEGKRFLELGKEEDFHPELESLDGDLDPGLPSTEDVILKTEQVTKNIQELLRAAQEFKHDSFVPCSEKIHLAVTEMASLFPKRPALEPVRSSLRLLNASAYRLQSECRKTVPPEPGAPVDFQLLTQQVIQCAYDIAKAAKQLVTITTREKKQ
uniprot
proteins
function
FUNCTION: GTPase-activating protein for ADP ribosylation factor family members, including ARF1. Multidomain scaffold protein that interacts with numerous proteins and therefore participates in many cellular functions, including receptor internalization, focal adhesion remodeling, and signaling by both G protein-coupled receptors and tyrosine kinase receptors (By similarity). Through PAK1 activation, positively regulates microtubule nucleation during interphase (PubMed:27012601). Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13 (PubMed:23108400). May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1 (PubMed:10938112, PubMed:11896197). May act as scaffold for MAPK1/3 signal transduction in focal adhesions. Recruits MAPK1/3/ERK1/2 to focal adhesions after EGF stimulation via a Src-dependent pathway, hence stimulating cell migration (PubMed:15923189). Plays a role in brain development and function. Involved in the regulation of spine density and synaptic plasticity that is required for processes involved in learning (By similarity). Plays an important role in dendritic spine morphogenesis and synapse formation (PubMed:12695502, PubMed:15800193). In hippocampal neurons, recruits guanine nucleotide exchange factors (GEFs), such as ARHGEF7/beta-PIX, to the synaptic membrane. These in turn locally activate RAC1, which is an essential step for spine morphogenesis and synapse formation (PubMed:12695502). May contribute to the organization of presynaptic active zones through oligomerization and formation of a Piccolo/PCLO-based protein network, which includes ARHGEF7/beta-PIX and FAK1 (By similarity). In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane (By similarity). In complex with GABA(A) receptors and ARHGEF7, plays a crucial role in regulating GABA(A) receptor synaptic stability, maintaining GPHN/gephyrin scaffolds and hence GABAergic inhibitory synaptic transmission, by locally coordinating RAC1 and PAK1 downstream effector activity, leading to F-actin stabilization (PubMed:25284783). May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input (By similarity). Required for successful bone regeneration during fracture healing (By similarity). The function in intramembranous ossification may, at least partly, exerted by macrophages in which GIT1 is a key negative regulator of redox homeostasis, IL1B production, and glycolysis, acting through the ERK1/2/NRF2/NFE2L2 axis (By similarity). May play a role in angiogenesis during fracture healing (By similarity). In this process, may regulate activation of the canonical NF-kappa-B signal in bone mesenchymal stem cells by enhancing the interaction between NEMO and 'Lys-63'-ubiquitinated RIPK1/RIP1, eventually leading to enhanced production of VEGFA and others angiogenic factors (PubMed:31502302). Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis (PubMed:19273721). {ECO:0000250|UniProtKB:Q68FF6, ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:12695502, ECO:0000269|PubMed:15800193, ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:19273721, ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:25284783, ECO:0000269|PubMed:27012601, ECO:0000269|PubMed:31502302}.
uniprot
proteins
mass_dalton
84341
uniprot
proteins
mutagenesis
MUTAGEN 39; /note="R->A: When transfected to cells, increased number of multinucleated cells."; /evidence="ECO:0000269|PubMed:23108400
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PAK1 (PubMed:27012601). Phosphorylation on tyrosine residues may be catalyzed by PTK2/FAK1 and SRC in growing fibroblasts. Phosphorylation at Tyr-383 is induced by activation of Ephrin-B1/EFNB1 and catalyzed by SRC family kinases. It is required for the interaction with NCK2 and for GIT1 recruitment to synapses in hippocampal neurons (By similarity). {ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:27012601}.
uniprot
proteins
pubmed
10896954
uniprot
proteins
pubmed
10938112
uniprot
proteins
pubmed
11896197
uniprot
proteins
pubmed
12153727
uniprot
proteins
pubmed
12695502
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15182672
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15800193
uniprot
proteins
pubmed
15923189
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18088087
uniprot
proteins
pubmed
18318008
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19041750
uniprot
proteins
pubmed
19273721
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23108400
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25284783
uniprot
proteins
pubmed
27012601
uniprot
proteins
pubmed
31502302
uniprot
proteins
sequence_length
761
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11896197}. Synapse {ECO:0000269|PubMed:12695502}. Presynapse {ECO:0000250|UniProtKB:Q9Z272}. Postsynapse {ECO:0000250|UniProtKB:Q9Z272}. Postsynaptic density {ECO:0000250|UniProtKB:Q9Z272}. Cell junction, focal adhesion {ECO:0000269|PubMed:10938112, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:15923189}. Cell projection, lamellipodium {ECO:0000269|PubMed:11896197}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:23108400, ECO:0000269|PubMed:27012601}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:27012601}. Note=Cycles between at least 3 distinct intracellular compartments, including focal adhesions, cytosolic complexes, containing at least PXN/paxillin, ARHGEF7 and PAK1, and membrane protrusions. During cell migration, moves from the disassembling adhesions into the cytosol and towards the leading edge. In adherent cells, localizes to adhesions. Recruitment to adhesions may be mediated by RAC and active tyrosine-phosphorylated PXN (PubMed:11896197). May be present in both excitatory and inhibitory synapses. In hippocampal neurons, recruitment of GIT1 to synapses is regulated by ephrinB activation and ephrinB downstream effector GRB4/NCK2. In hippocampal neurons, partially colocalizes with PCLO (By similarity). Interaction with GRIN3A limits GIT1 synaptic localization (By similarity). Localization to the centrosome does not depend upon the presence of gamma-tubulin (PubMed:27012601). {ECO:0000250|UniProtKB:Q9Z272, ECO:0000269|PubMed:11896197, ECO:0000269|PubMed:27012601}.
uniprot
proteins