General Information of Target

Target ID LDTP02040
Target Name HLA class I histocompatibility antigen, A alpha chain (HLA-A)
Gene Name HLA-A
Gene ID 3105
Synonyms
HLAA; HLA class I histocompatibility antigen, A alpha chain; Human leukocyte antigen A; HLA-A
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAVMAPRTLLLLLSGALALTQTWAGSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRF
DSDAASQRMEPRAPWIEQEGPEYWDQETRNVKAQSQTDRVDLGTLRGYYNQSEAGSHTIQ
IMYGCDVGSDGRFLRGYRQDAYDGKDYIALNEDLRSWTAADMAAQITKRKWEAAHEAEQL
RAYLDGTCVEWLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITLT
WQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEL
SSQPTIPIVGIIAGLVLLGAVITGAVVAAVMWRRKSSDRKGGSYTQAASSDSAQGSDVSL
TACKV
Target Type
Clinical trial
Target Bioclass
Immunoglobulin
Family
MHC class I family
Subcellular location
Cell membrane
Function
Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells. May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity. Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells. Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme. Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9.; Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus . A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent. Fails to present highly immunogenic peptides from the EBV latent antigens.; Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.; Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus. May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein.; Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections. Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK).; Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.; Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus. Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.; Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.; Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.; Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.; Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.; Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.
TTD ID
T63239
Uniprot ID
P04439
DrugMap ID
TTOMP5Y
Ensemble ID
ENST00000376809.10
HGNC ID
HGNC:4931
ChEMBL ID
CHEMBL2632

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
22RV1 SNV: p.W75Ter .
A3KAW Deletion: p.H175QfsTer27 .
BICR22 SNV: p.E43Ter .
CAL62 Substitution: p.K292E .
CALU6 SNV: p.T158I .
DEL Substitution: p.I121R .
EGI1 Substitution: p.I121R .
ETK1 Substitution: p.I121R .
HCC44 SNV: p.A348S .
HEC1 Substitution: p.I121R .
HLF Substitution: p.I121R .
HS578T Substitution: p.I119L .
HSC4 SNV: p.R135L .
IM95 Deletion: p.R45AfsTer32 .
JHH4 SNV: p.E299D; p.S301P .
JHH6 Substitution: p.L180Q .
KASUMI1 Substitution: p.I121R .
KMCH1 Substitution: p.I121R .
KMS12BM SNV: p.L134H .
KURAMOCHI Substitution: p.I121R .
KYM1 SNV: p.Y147Ter .
MFE319 Deletion: p.K210RfsTer4 .
MOLM16 SNV: p.K170E .
MOLT4 Substitution: p.I121R .
NCIH1993 Substitution: p.I121R .
OCILY3 Deletion: p.S156RfsTer18 .
OVKATE Substitution: p.I121R .
RBE Substitution: p.I121R .
RT112 Substitution: p.D357_V358delinsEM .
SH4 SNV: p.W228L
Substitution: p.I121R
DBIA    Probe Info 
SNGM SNV: p.A313T .
SNU5 Substitution: p.K168Q .
SSP25 Substitution: p.I121R .
SUPT1 SNV: p.T305N .
SW1573 Substitution: p.K292E .
SW837 SNV: p.G186D .
T98G SNV: p.P307S .
TC71 Substitution: p.K292E .
TE8 Substitution: p.I121R .
U937 Deletion: p.K210RfsTer4 DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 19 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
8RK64
 Probe Info 
N.A.  LDD0039  [2]
STPyne
 Probe Info 
K168(5.37); K210(13.44); K292(20.00)  LDD2217  [3]
ONAyne
 Probe Info 
K340(9.09)  LDD0275  [4]
OPA-S-S-alkyne
 Probe Info 
K92(3.31)  LDD3494  [5]
DBIA
 Probe Info 
C188(17.35)  LDD3327  [6]
P12
 Probe Info 
12.57  LDD0202  [7]
JZ128-DTB
 Probe Info 
N.A.  LDD0462  [8]
BTD
 Probe Info 
C363(1.83); C283(0.70)  LDD2170  [9]
YY4-yne
 Probe Info 
2.09  LDD0400  [10]
DA-P3
 Probe Info 
11.86  LDD0179  [11]
AHL-Pu-1
 Probe Info 
N.A.  LDD0172  [12]
IPM
 Probe Info 
C363(3.50)  LDD1701  [9]
4-Iodoacetamidophenylacetylene
 Probe Info 
C188(0.00); C227(0.00); C363(0.00); C283(0.00)  LDD0038  [13]
IA-alkyne
 Probe Info 
N.A.  LDD0032  [14]
Lodoacetamide azide
 Probe Info 
C188(0.00); C227(0.00); C363(0.00); C283(0.00)  LDD0037  [13]
Acrolein
 Probe Info 
N.A.  LDD0217  [15]
TER-AC
 Probe Info 
N.A.  LDD0426  [16]
TPP-AC
 Probe Info 
N.A.  LDD0427  [16]
PAL-AfBPP Probe
Click To Hide/Show 18 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C004
 Probe Info 
5.90  LDD1714  [17]
C022
 Probe Info 
7.84  LDD1728  [17]
C106
 Probe Info 
17.63  LDD1793  [17]
C158
 Probe Info 
10.78  LDD1838  [17]
C170
 Probe Info 
24.93  LDD1850  [17]
C186
 Probe Info 
11.16  LDD1864  [17]
C223
 Probe Info 
5.35  LDD1897  [17]
C302
 Probe Info 
5.70  LDD1971  [17]
C310
 Probe Info 
19.16  LDD1977  [17]
C313
 Probe Info 
12.91  LDD1980  [17]
C350
 Probe Info 
25.81  LDD2011  [17]
C354
 Probe Info 
7.94  LDD2015  [17]
C425
 Probe Info 
9.99  LDD2080  [17]
FFF probe11
 Probe Info 
20.00  LDD0471  [18]
FFF probe12
 Probe Info 
20.00  LDD0473  [18]
STS-1
 Probe Info 
N.A.  LDD0136  [19]
STS-2
 Probe Info 
N.A.  LDD0138  [19]
Photonaproxen
 Probe Info 
N.A.  LDD0157  [20]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0025  4SU-RNA HEK-293T N.A.  LDD0172  [12]
 LDCM0026  4SU-RNA+native RNA HEK-293T N.A.  LDD0173  [12]
 LDCM0545  Acetamide MDA-MB-231 C363(1.83); C283(0.70)  LDD2170  [9]
 LDCM0156  Aniline NCI-H1299 13.42  LDD0403  [1]
 LDCM0088  C45 HEK-293T 12.57  LDD0202  [7]
 LDCM0087  Capsaicin HEK-293T 5.19  LDD0185  [11]
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [15]
 LDCM0027  Dopamine HEK-293T 11.86  LDD0179  [11]
 LDCM0625  F8 Ramos C188(0.94); C363(1.17)  LDD2187  [21]
 LDCM0572  Fragment10 Ramos C363(1.04)  LDD2189  [21]
 LDCM0573  Fragment11 Ramos C188(20.00)  LDD2190  [21]
 LDCM0574  Fragment12 Ramos C363(0.86)  LDD2191  [21]
 LDCM0575  Fragment13 Ramos C363(1.06)  LDD2192  [21]
 LDCM0576  Fragment14 Ramos C188(1.54); C363(0.97)  LDD2193  [21]
 LDCM0579  Fragment20 Ramos C363(0.92)  LDD2194  [21]
 LDCM0580  Fragment21 Ramos C363(0.80)  LDD2195  [21]
 LDCM0582  Fragment23 Ramos C363(0.99)  LDD2196  [21]
 LDCM0578  Fragment27 Ramos C363(0.82)  LDD2197  [21]
 LDCM0586  Fragment28 Ramos C188(0.61); C363(0.80)  LDD2198  [21]
 LDCM0588  Fragment30 Ramos C363(1.09)  LDD2199  [21]
 LDCM0589  Fragment31 Ramos C363(0.99)  LDD2200  [21]
 LDCM0590  Fragment32 Ramos C363(1.00)  LDD2201  [21]
 LDCM0468  Fragment33 Ramos C363(0.95)  LDD2202  [21]
 LDCM0596  Fragment38 Ramos C363(1.34)  LDD2203  [21]
 LDCM0566  Fragment4 Ramos C363(0.93)  LDD2184  [21]
 LDCM0610  Fragment52 Ramos C363(1.17)  LDD2204  [21]
 LDCM0614  Fragment56 Ramos C363(1.23)  LDD2205  [21]
 LDCM0569  Fragment7 Ramos C363(0.89)  LDD2186  [21]
 LDCM0571  Fragment9 Ramos C363(1.08)  LDD2188  [21]
 LDCM0179  JZ128 PC-3 N.A.  LDD0462  [8]
 LDCM0022  KB02 Ramos C363(1.09)  LDD2182  [21]
 LDCM0023  KB03 MDA-MB-231 C363(3.50)  LDD1701  [9]
 LDCM0024  KB05 WM115 C188(17.35)  LDD3327  [6]
 LDCM0154  YY4 T cell 2.09  LDD0400  [10]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Coccidioides Immitis Spherule . DB11294
Investigative
Click To Hide/Show 2 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
3-indolebutyric Acid . DB02740
Nelipepimut-s . DB06226

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 Small-Molecule Activity-Based Probe for Monitoring Ubiquitin C-Terminal Hydrolase L1 (UCHL1) Activity in Live Cells and Zebrafish Embryos. J Am Chem Soc. 2020 Sep 30;142(39):16825-16841. doi: 10.1021/jacs.0c07726. Epub 2020 Sep 18.
Mass spectrometry data entry: PXD021557 , PXD015828
3 Global profiling of lysine reactivity and ligandability in the human proteome. Nat Chem. 2017 Dec;9(12):1181-1190. doi: 10.1038/nchem.2826. Epub 2017 Jul 31.
4 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
5 A chemical proteomics approach for global mapping of functional lysines on cell surface of living cell. Nat Commun. 2024 Apr 8;15(1):2997. doi: 10.1038/s41467-024-47033-w.
Mass spectrometry data entry: PXD042888
6 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
7 Discovery of Potent and Selective Inhibitors against Protein-Derived Electrophilic Cofactors. J Am Chem Soc. 2022 Mar 30;144(12):5377-5388. doi: 10.1021/jacs.1c12748. Epub 2022 Mar 2.
8 A Chemoproteomic Strategy for Direct and Proteome-Wide Covalent Inhibitor Target-Site Identification. J Am Chem Soc. 2019 Jan 9;141(1):191-203. doi: 10.1021/jacs.8b07911. Epub 2018 Dec 20.
9 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
10 A Chemical Proteomic Probe for the Mitochondrial Pyruvate Carrier Complex. Angew Chem Int Ed Engl. 2020 Mar 2;59(10):3896-3899. doi: 10.1002/anie.201914391. Epub 2020 Feb 11.
11 A chemical probe unravels the reactive proteome of health-associated catechols. Chem Sci. 2023 Jul 22;14(32):8635-8643. doi: 10.1039/d3sc00888f. eCollection 2023 Aug 16.
Mass spectrometry data entry: PXD043348
12 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
13 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
14 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
15 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.
16 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
17 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
18 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
19 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.
20 Small Molecule Interactome Mapping by Photoaffinity Labeling Reveals Binding Site Hotspots for the NSAIDs. J Am Chem Soc. 2018 Mar 28;140(12):4259-4268. doi: 10.1021/jacs.7b11639. Epub 2018 Mar 15.
Mass spectrometry data entry: PXD007094
21 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