General Information of Target

Target ID LDTP09823
Target Name Rho GTPase-activating protein 45 (ARHGAP45)
Gene Name ARHGAP45
Gene ID 23526
Synonyms
HMHA1; KIAA0223; Rho GTPase-activating protein 45 [Cleaved into: Minor histocompatibility antigen HA-1; mHag HA-1)]
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MDRNREAEMELRRGPSPTRAGRGHEVDGDKATCHTCCICGKSFPFQSSLSQHMRKHTGEK
PYKCPYCDHRASQKGNLKIHIRSHRTGTLIQGHEPEAGEAPLGEMRASEGLDACASPTKS
ASACNRLLNGASQADGARVLNGASQADSGRVLLRSSKKGAEGSACAPGEAKAAVQCSFCK
SQFERKKDLELHVHQAHKPFKCRLCSYATLREESLLSHIERDHITAQGPGSGEACVENGK
PELSPGEFPCEVCGQAFSQTWFLKAHMKKHRGSFDHGCHICGRRFKEPWFLKNHMKAHGP
KTGSKNRPKSELDPIATINNVVQEEVIVAGLSLYEVCAKCGNLFTNLDSLNAHNAIHRRV
EASRTRAPAEEGAEGPSDTKQFFLQCLNLRPSAAGDSCPGTQAGRRVAELDPVNSYQAWQ
LATRGKVAEPAEYLKYGAWDEALAGDVAFDKDRREYVLVSQEKRKREQDAPAAQGPPRKR
ASGPGDPAPAGHLDPRSAARPNRRAAATTGQGKSSECFECGKIFRTYHQMVLHSRVHRRA
RRERDSDGDRAARARCGSLSEGDSASQPSSPGSACAAADSPGSGLADEAAEDSGEEGAPE
PAPGGQPRRCCFSEEVTSTELSSGDQSHKMGDNASERDTGESKAGIAASVSILENSSRET
SRRQEQHRFSMDLKMPAFHPKQEVPVPGDGVEFPSSTGAEGQTGHPAEKLSDLHNKEHSG
GGKRALAPDLMPLDLSARSTRDDPSNKETASSLQAALVVHPCPYCSHKTYYPEVLWMHKR
IWHRVSCNSVAPPWIQPNGYKSIRSNLVFLSRSGRTGPPPALGGKECQPLLLARFTRTQV
PGGMPGSKSGSSPLGVVTKAASMPKNKESHSGGPCALWAPGPDGYRQTKPCHGQEPHGAA
TQGPLAKPRQEASSKPVPAPGGGGFSRSATPTPTVIARAGAQPSANSKPVEKFGVPPAGA
GFAPTNKHSAPDSLKAKFSAQPQGPPPAKGEGGAPPLPPREPPSKAAQELRTLATCAAGS
RGDAALQAQPGVAGAPPVLHSIKQEPVAEGHEKRLDILNIFKTYIPKDFATLYQGWGVSG
PGLEHRGTLRTQARPGEFVCIECGKSFHQPGHLRAHMRAHSVVFESDGPRGSEVHTTSAD
APKQGRDHSNTGTVQTVPLRKGT
Target Bioclass
Other
Subcellular location
Cytoplasm
Function
Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity.; Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL.
Uniprot ID
Q92619
Ensemble ID
ENST00000313093.7
HGNC ID
HGNC:17102

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 SNV: p.R706W .
HCT116 SNV: p.A585V .
HCT15 SNV: p.S531N; p.D554N DBIA    Probe Info 
JURKAT SNV: p.A459V; p.E461K .
MOLT4 SNV: p.A637T IA-alkyne    Probe Info 
NCIH1155 SNV: p.A424S DBIA    Probe Info 
NCIH1944 SNV: p.D347N .
NCIH1993 SNV: p.C714G .
RD SNV: p.A473V .
RKO SNV: p.R403H .
SNGM Deletion: p.G281AfsTer16 .
SNU1 SNV: p.S648P .
SUPT1 SNV: p.V282M DBIA    Probe Info 
TE4 SNV: p.R496W .
TOV21G SNV: p.E204Ter .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 11 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 
K319(0.16); K406(10.00); K780(10.00)  LDD0277  [2]
ONAyne
 Probe Info 
K406(10.00)  LDD0275  [2]
BTD
 Probe Info 
C324(3.74)  LDD2109  [3]
DBIA
 Probe Info 
C324(136.80); C739(44.22)  LDD0209  [4]
IPM
 Probe Info 
C1128(1.88)  LDD1701  [3]
4-Iodoacetamidophenylacetylene
 Probe Info 
C153(0.00); C278(0.00); C469(0.00); C809(0.00)  LDD0038  [5]
IA-alkyne
 Probe Info 
C153(0.00); C278(0.00); C136(0.00); C739(0.00)  LDD0036  [5]
Lodoacetamide azide
 Probe Info 
C278(0.00); C809(0.00); C136(0.00); C153(0.00)  LDD0037  [5]
JW-RF-010
 Probe Info 
N.A.  LDD0026  [6]
NAIA_4
 Probe Info 
C809(0.00); C1020(0.00)  LDD2226  [7]

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 C153(2.01)  LDD2152  [3]
 LDCM0226  AC11 HEK-293T C1128(1.01)  LDD1509  [8]
 LDCM0237  AC12 HEK-293T C1128(1.64)  LDD1510  [8]
 LDCM0278  AC19 HEK-293T C1128(1.07)  LDD1517  [8]
 LDCM0280  AC20 HEK-293T C1128(1.23)  LDD1519  [8]
 LDCM0287  AC27 HEK-293T C1128(0.95)  LDD1526  [8]
 LDCM0288  AC28 HEK-293T C1128(1.05)  LDD1527  [8]
 LDCM0290  AC3 HEK-293T C1128(1.07)  LDD1529  [8]
 LDCM0296  AC35 HEK-293T C1128(0.97)  LDD1535  [8]
 LDCM0297  AC36 HEK-293T C1128(1.58)  LDD1536  [8]
 LDCM0301  AC4 HEK-293T C1128(1.38)  LDD1540  [8]
 LDCM0305  AC43 HEK-293T C1128(0.99)  LDD1544  [8]
 LDCM0306  AC44 HEK-293T C1128(1.11)  LDD1545  [8]
 LDCM0314  AC51 HEK-293T C1128(1.38)  LDD1553  [8]
 LDCM0315  AC52 HEK-293T C1128(1.37)  LDD1554  [8]
 LDCM0322  AC59 HEK-293T C1128(1.68)  LDD1561  [8]
 LDCM0324  AC60 HEK-293T C1128(1.22)  LDD1563  [8]
 LDCM0156  Aniline NCI-H1299 11.80  LDD0403  [1]
 LDCM0406  CL19 HEK-293T C1128(1.42)  LDD1610  [8]
 LDCM0408  CL20 HEK-293T C1128(1.34)  LDD1612  [8]
 LDCM0420  CL31 HEK-293T C1128(0.83)  LDD1624  [8]
 LDCM0421  CL32 HEK-293T C1128(1.73)  LDD1625  [8]
 LDCM0433  CL43 HEK-293T C1128(0.92)  LDD1637  [8]
 LDCM0434  CL44 HEK-293T C1128(2.01)  LDD1638  [8]
 LDCM0446  CL55 HEK-293T C1128(1.20)  LDD1649  [8]
 LDCM0447  CL56 HEK-293T C1128(1.43)  LDD1650  [8]
 LDCM0459  CL67 HEK-293T C1128(0.99)  LDD1662  [8]
 LDCM0460  CL68 HEK-293T C1128(1.25)  LDD1663  [8]
 LDCM0462  CL7 HEK-293T C1128(0.90)  LDD1665  [8]
 LDCM0472  CL79 HEK-293T C1128(1.45)  LDD1675  [8]
 LDCM0473  CL8 HEK-293T C1128(1.56)  LDD1676  [8]
 LDCM0474  CL80 HEK-293T C1128(1.68)  LDD1677  [8]
 LDCM0486  CL91 HEK-293T C1128(1.20)  LDD1689  [8]
 LDCM0487  CL92 HEK-293T C1128(1.52)  LDD1690  [8]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C324(1.49); C1128(1.43)  LDD1702  [3]
 LDCM0625  F8 Ramos C153(1.13); C278(1.05); C809(0.99)  LDD2187  [9]
 LDCM0572  Fragment10 Ramos C153(0.94); C278(1.14); C599(0.89)  LDD2189  [9]
 LDCM0573  Fragment11 Ramos C153(0.98); C278(2.46); C809(1.82)  LDD2190  [9]
 LDCM0574  Fragment12 Ramos C153(1.45); C278(1.26)  LDD2191  [9]
 LDCM0575  Fragment13 Ramos C278(0.99)  LDD2192  [9]
 LDCM0576  Fragment14 Ramos C278(0.70); C809(3.24); C599(0.80)  LDD2193  [9]
 LDCM0579  Fragment20 Ramos C153(1.36); C278(1.08); C599(0.61)  LDD2194  [9]
 LDCM0580  Fragment21 Ramos C153(1.31); C278(1.25); C599(0.70)  LDD2195  [9]
 LDCM0582  Fragment23 Ramos C153(0.89); C278(1.20); C599(1.24)  LDD2196  [9]
 LDCM0578  Fragment27 Ramos C153(1.13); C278(0.84)  LDD2197  [9]
 LDCM0586  Fragment28 Ramos C153(0.78); C278(0.73); C599(0.61)  LDD2198  [9]
 LDCM0588  Fragment30 Ramos C153(1.23); C278(1.12); C599(0.56)  LDD2199  [9]
 LDCM0589  Fragment31 Ramos C278(0.92); C599(1.03)  LDD2200  [9]
 LDCM0590  Fragment32 Ramos C153(1.31); C278(0.92)  LDD2201  [9]
 LDCM0468  Fragment33 Ramos C153(1.04); C278(1.09); C599(0.91)  LDD2202  [9]
 LDCM0596  Fragment38 Ramos C278(0.77); C599(1.97)  LDD2203  [9]
 LDCM0566  Fragment4 Ramos C153(1.06); C278(0.74); C809(0.85); C599(1.09)  LDD2184  [9]
 LDCM0610  Fragment52 Ramos C153(1.26); C278(0.99)  LDD2204  [9]
 LDCM0614  Fragment56 Ramos C153(1.36); C278(0.82)  LDD2205  [9]
 LDCM0569  Fragment7 Ramos C153(0.76); C278(1.25); C809(1.20); C599(0.66)  LDD2186  [9]
 LDCM0571  Fragment9 Ramos C153(1.06); C278(1.03); C599(1.19)  LDD2188  [9]
 LDCM0022  KB02 T cell C278(8.01)  LDD1703  [10]
 LDCM0023  KB03 Jurkat C324(136.80); C739(44.22)  LDD0209  [4]
 LDCM0024  KB05 COLO792 C340(4.92)  LDD3310  [11]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C324(3.74)  LDD2109  [3]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C324(1.45)  LDD2119  [3]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C153(1.44)  LDD2123  [3]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C153(1.38)  LDD2125  [3]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C153(2.10)  LDD2127  [3]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C153(1.21)  LDD2140  [3]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C153(2.59)  LDD2144  [3]
 LDCM0131  RA190 MM1.R C278(1.42)  LDD0304  [12]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Zinc finger-containing ubiquitin peptidase 1 (ZUP1) Peptidase C78 family Q96AP4
Ras-related C3 botulinum toxin substrate 1 (RAC1) Rho family P63000
E3 ubiquitin-protein ligase TRIM50 (TRIM50) TRIM/RBCC family Q86XT4
Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Apoptosis-stimulating of p53 protein 1 (PPP1R13B) ASPP family Q96KQ4
Golgin subfamily A member 2 (GOLGA2) GOLGA2 family Q08379
RAD50-interacting protein 1 (RINT1) RINT1 family Q6NUQ1
GEM-interacting protein (GMIP) . Q9P107
Heat shock factor 2-binding protein (HSF2BP) . O75031

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 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
4 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
5 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
6 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
7 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
8 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
9 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
10 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
11 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
12 Physical and Functional Analysis of the Putative Rpn13 Inhibitor RA190. Cell Chem Biol. 2020 Nov 19;27(11):1371-1382.e6. doi: 10.1016/j.chembiol.2020.08.007. Epub 2020 Aug 27.