General Information of Target

Target ID LDTP13926
Target Name ARF GTPase-activating protein GIT1 (GIT1)
Gene Name GIT1
Gene ID 28964
Synonyms
ARF GTPase-activating protein GIT1; ARF GAP GIT1; Cool-associated and tyrosine-phosphorylated protein 1; CAT-1; CAT1; G protein-coupled receptor kinase-interactor 1; GRK-interacting protein 1; p95-APP1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MLVLFETSVGYAIFKVLNEKKLQEVDSLWKEFETPEKANKIVKLKHFEKFQDTAEALAAF
TALMEGKINKQLKKVLKKIVKEAHEPLAVADAKLGGVIKEKLNLSCIHSPVVNELMRGIR
SQMDGLIPGVEPREMAAMCLGLAHSLSRYRLKFSADKVDTMIVQAISLLDDLDKELNNYI
MRCREWYGWHFPELGKIISDNLTYCKCLQKVGDRKNYASAKLSELLPEEVEAEVKAAAEI
SMGTEVSEEDICNILHLCTQVIEISEYRTQLYEYLQNRMMAIAPNVTVMVGELVGARLIA
HAGSLLNLAKHAASTVQILGAEKALFRALKSRRDTPKYGLIYHASLVGQTSPKHKGKISR
MLAAKTVLAIRYDAFGEDSSSAMGVENRAKLEARLRTLEDRGIRKISGTGKALAKTEKYE
HKSEVKTYDPSGDSTLPTCSKKRKIEQVDKEDEITEKKAKKAKIKVKVEEEEEEKVAEEE
ETSVKKKKKRGKKKHIKEEPLSEEEPCTSTAIASPEKKKKKKKKRENED
Target Bioclass
Other
Subcellular location
Cytoplasm
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. Through PAK1 activation, positively regulates microtubule nucleation during interphase. Plays a role in the regulation of cytokinesis; for this function, may act in a pathway also involving ENTR1 and PTPN13. May promote cell motility both by regulating focal complex dynamics and by local activation of RAC1. 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. 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. Plays an important role in dendritic spine morphogenesis and synapse formation. 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. 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. In neurons, through its interaction with liprin-alpha family members, may be required for AMPA receptor (GRIA2/3) proper targeting to the cell membrane. 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. May also be important for RAC1 downstream signaling pathway through PAK3 and regulation of neuronal inhibitory transmission at presynaptic input. Required for successful bone regeneration during fracture healing. 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. May play a role in angiogenesis during fracture healing. 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. Essential for VEGF signaling through the activation of phospholipase C-gamma and ERK1/2, hence may control endothelial cell proliferation and angiogenesis.
Uniprot ID
Q9Y2X7
Ensemble ID
ENST00000225394.8
HGNC ID
HGNC:4272

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HEC1 SNV: p.R123W DBIA    Probe Info 
LNCaP clone FGC SNV: p.G156S DBIA    Probe Info 
SUPT1 SNV: p.R43H DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 20 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
STPyne
 Probe Info 
K267(0.79)  LDD0277  [2]
Probe 1
 Probe Info 
Y224(18.99); Y710(16.11)  LDD3495  [3]
DBIA
 Probe Info 
C222(1.64)  LDD3312  [4]
BTD
 Probe Info 
C716(1.46)  LDD2099  [5]
AHL-Pu-1
 Probe Info 
C576(3.22)  LDD0168  [6]
HHS-475
 Probe Info 
Y545(0.52); Y554(1.22)  LDD0264  [7]
5E-2FA
 Probe Info 
N.A.  LDD2235  [8]
4-Iodoacetamidophenylacetylene
 Probe Info 
C222(0.00); C674(0.00); C576(0.00); C740(0.00)  LDD0038  [9]
IA-alkyne
 Probe Info 
C674(0.00); C576(0.00); C740(0.00); C222(0.00)  LDD0036  [9]
Lodoacetamide azide
 Probe Info 
C674(0.00); C235(0.00); C222(0.00); C149(0.00)  LDD0037  [9]
IPM
 Probe Info 
N.A.  LDD0025  [10]
NAIA_4
 Probe Info 
N.A.  LDD2226  [11]
TFBX
 Probe Info 
C576(0.00); C149(0.00)  LDD0027  [10]
VSF
 Probe Info 
N.A.  LDD0007  [12]
Acrolein
 Probe Info 
N.A.  LDD0217  [13]
Methacrolein
 Probe Info 
N.A.  LDD0218  [13]
W1
 Probe Info 
D205(0.00); Y206(0.00)  LDD0236  [14]
AOyne
 Probe Info 
9.90  LDD0443  [15]
NAIA_5
 Probe Info 
C674(0.00); C222(0.00); C740(0.00)  LDD2223  [11]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
STS-1
 Probe Info 
N.A.  LDD0137  [16]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0558  2-Cyano-N-phenylacetamide MDA-MB-231 C149(1.36)  LDD2152  [5]
 LDCM0025  4SU-RNA HEK-293T C576(3.22)  LDD0168  [6]
 LDCM0026  4SU-RNA+native RNA HEK-293T C576(5.05)  LDD0169  [6]
 LDCM0156  Aniline NCI-H1299 N.A.  LDD0404  [1]
 LDCM0625  F8 Ramos C576(1.35)  LDD2187  [17]
 LDCM0572  Fragment10 Ramos C576(1.16)  LDD2189  [17]
 LDCM0573  Fragment11 Ramos C576(14.52)  LDD2190  [17]
 LDCM0574  Fragment12 Ramos C576(0.82)  LDD2191  [17]
 LDCM0575  Fragment13 Ramos C576(0.81)  LDD2192  [17]
 LDCM0576  Fragment14 Ramos C576(0.95)  LDD2193  [17]
 LDCM0579  Fragment20 Ramos C576(0.82)  LDD2194  [17]
 LDCM0580  Fragment21 Ramos C576(0.79)  LDD2195  [17]
 LDCM0582  Fragment23 Ramos C576(0.81)  LDD2196  [17]
 LDCM0578  Fragment27 Ramos C576(0.84)  LDD2197  [17]
 LDCM0586  Fragment28 Ramos C576(1.23)  LDD2198  [17]
 LDCM0588  Fragment30 Ramos C576(0.92)  LDD2199  [17]
 LDCM0589  Fragment31 Ramos C576(0.81)  LDD2200  [17]
 LDCM0590  Fragment32 Ramos C576(1.31)  LDD2201  [17]
 LDCM0468  Fragment33 Ramos C576(0.91)  LDD2202  [17]
 LDCM0596  Fragment38 Ramos C576(0.71)  LDD2203  [17]
 LDCM0566  Fragment4 Ramos C576(1.02)  LDD2184  [17]
 LDCM0610  Fragment52 Ramos C576(1.22)  LDD2204  [17]
 LDCM0614  Fragment56 Ramos C576(0.98)  LDD2205  [17]
 LDCM0569  Fragment7 Ramos C576(1.12)  LDD2186  [17]
 LDCM0571  Fragment9 Ramos C576(0.88)  LDD2188  [17]
 LDCM0116  HHS-0101 DM93 Y545(0.52); Y554(1.22)  LDD0264  [7]
 LDCM0117  HHS-0201 DM93 Y545(0.54); Y554(0.67)  LDD0265  [7]
 LDCM0118  HHS-0301 DM93 Y545(0.49); Y554(0.79)  LDD0266  [7]
 LDCM0119  HHS-0401 DM93 Y545(0.48); Y554(0.99)  LDD0267  [7]
 LDCM0120  HHS-0701 DM93 Y545(0.66); Y554(1.65)  LDD0268  [7]
 LDCM0022  KB02 HEK-293T C149(0.91); C235(0.93); C576(0.94)  LDD1492  [18]
 LDCM0023  KB03 HEK-293T C149(0.95); C235(0.98); C576(1.01)  LDD1497  [18]
 LDCM0024  KB05 HMCB C222(1.64)  LDD3312  [4]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C716(1.46)  LDD2099  [5]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C716(1.08)  LDD2107  [5]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C716(0.95)  LDD2109  [5]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C716(1.11)  LDD2125  [5]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C716(1.67)  LDD2136  [5]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C716(1.22)  LDD2137  [5]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C716(1.22)  LDD2140  [5]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C149(0.92)  LDD2146  [5]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 4 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Beta-adrenergic receptor kinase 1 (GRK2) AGC Ser/Thr protein kinase family P25098
Serine/threonine-protein kinase PAK 1 (PAK1) STE Ser/Thr protein kinase family Q13153
Chromodomain-helicase-DNA-binding protein 3 (CHD3) SNF2/RAD54 helicase family Q12873
BRCA1-associated RING domain protein 1 (BARD1) . Q99728
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Huntingtin (HTT) Huntingtin family P42858
Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Ligand-dependent nuclear receptor-interacting factor 1 (LRIF1) LRIF1 family Q5T3J3
Paxillin (PXN) Paxillin family P49023
Centrosomal protein of 126 kDa (CEP126) . Q9P2H0
Rho guanine nucleotide exchange factor 7 (ARHGEF7) . Q14155

References

1 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 An Azo Coupling-Based Chemoproteomic Approach to Systematically Profile the Tyrosine Reactivity in the Human Proteome. Anal Chem. 2021 Jul 27;93(29):10334-10342. doi: 10.1021/acs.analchem.1c01935. Epub 2021 Jul 12.
4 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
5 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
6 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
7 Discovery of a Cell-Active SuTEx Ligand of Prostaglandin Reductase 2. Chembiochem. 2021 Jun 15;22(12):2134-2139. doi: 10.1002/cbic.202000879. Epub 2021 Apr 29.
8 Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling. Nat Chem. 2024 Jun 4. doi: 10.1038/s41557-024-01545-6. Online ahead of print.
Mass spectrometry data entry: PXD042377
9 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
10 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
11 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
12 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
13 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
14 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
15 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
16 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
17 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
18 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402