General Information of Drug Off-Target (DOT) (ID: OT76CM19)

DOT Name HLA class I histocompatibility antigen, alpha chain F (HLA-F)
Synonyms CDA12; HLA F antigen; Leukocyte antigen F; MHC class I antigen F
Gene Name HLA-F
Related Disease
Advanced cancer ( )
Behcet disease ( )
Bladder cancer ( )
Colon cancer ( )
Colorectal adenocarcinoma ( )
Colorectal cancer ( )
Colorectal cancer, susceptibility to, 1 ( )
Colorectal cancer, susceptibility to, 10 ( )
Colorectal cancer, susceptibility to, 12 ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Epilepsy, idiopathic generalized ( )
Esophageal squamous cell carcinoma ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Gonorrhea ( )
Hemochromatosis ( )
Hepatitis B virus infection ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
HIV infectious disease ( )
Melanoma ( )
Multiple sclerosis ( )
Narcolepsy ( )
Neoplasm ( )
Stomach cancer ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vitiligo ( )
Autoimmune disease ( )
Juvenile myoclonic epilepsy ( )
Nasopharyngeal carcinoma ( )
Amyotrophic lateral sclerosis ( )
Coronary heart disease ( )
Granular corneal dystrophy type II ( )
Hereditary hemochromatosis ( )
Psoriatic arthritis ( )
UniProt ID
HLAF_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
5IUE; 5KNM
Pfam ID
PF07654 ; PF00129
Sequence
MAPRSLLLLLSGALALTDTWAGSHSLRYFSTAVSRPGRGEPRYIAVEYVDDTQFLRFDSD
AAIPRMEPREPWVEQEGPQYWEWTTGYAKANAQTDRVALRNLLRRYNQSEAGSHTLQGMN
GCDMGPDGRLLRGYHQHAYDGKDYISLNEDLRSWTAADTVAQITQRFYEAEEYAEEFRTY
LEGECLELLRRYLENGKETLQRADPPKAHVAHHPISDHEATLRCWALGFYPAEITLTWQR
DGEEQTQDTELVETRPAGDGTFQKWAAVVVPPGEEQRYTCHVQHEGLPQPLILRWEQSPQ
PTIPIVGIVAGLVVLGAVVTGAVVAAVMWRKKSSDRNRGSYSQAAV
Function
Non-classical major histocompatibility class Ib molecule postulated to play a role in immune surveillance, immune tolerance and inflammation. Functions in two forms, as a heterotrimeric complex with B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In complex with B2M, presents non-canonical self-peptides carrying post-translational modifications, particularly phosphorylated self-peptides. Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory receptor, a major player in maternal-fetal tolerance. Peptide-free OC acts as a ligand for KIR3DS1 and KIR3DL2 receptors. Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production. Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions. May interact with other MHC class I OCs to cross-present exogenous viral, tumor or minor histompatibility antigens to cytotoxic CD8+ T cells, triggering effector and memory responses. May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity.
Tissue Specificity
Expressed in resting B cells (at protein level). Expressed in secondary lymphoid organs rich in B and T cells such as the tonsils, spleen, and thymus (at protein level) . Expressed in the endothelial cells of the tonsils . Expressed on activated lymphoid cells including B cells, NK cells, CD4+ T cells and memory T cells (at protein level) . Expressed in motor neurons of spinal cord .
KEGG Pathway
Endocytosis (hsa04144 )
Phagosome (hsa04145 )
Cellular senescence (hsa04218 )
Cell adhesion molecules (hsa04514 )
Antigen processing and presentation (hsa04612 )
Type I diabetes mellitus (hsa04940 )
Human cytomegalovirus infection (hsa05163 )
Human papillomavirus infection (hsa05165 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Herpes simplex virus 1 infection (hsa05168 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Viral carcinogenesis (hsa05203 )
Autoimmune thyroid disease (hsa05320 )
Allograft rejection (hsa05330 )
Graft-versus-host disease (hsa05332 )
Viral myocarditis (hsa05416 )
Reactome Pathway
Endosomal/Vacuolar pathway (R-HSA-1236977 )
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933 )
Interferon gamma signaling (R-HSA-877300 )
Interferon alpha/beta signaling (R-HSA-909733 )
SARS-CoV-2 activates/modulates innate and adaptive immune responses (R-HSA-9705671 )
Antigen Presentation (R-HSA-983170 )
ER-Phagosome pathway (R-HSA-1236974 )

Molecular Interaction Atlas (MIA) of This DOT

38 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Advanced cancer DISAT1Z9 Strong Biomarker [1]
Behcet disease DISSYMBS Strong Biomarker [2]
Bladder cancer DISUHNM0 Strong Biomarker [1]
Colon cancer DISVC52G Strong Genetic Variation [3]
Colorectal adenocarcinoma DISPQOUB Strong Genetic Variation [3]
Colorectal cancer DISNH7P9 Strong Genetic Variation [3]
Colorectal cancer, susceptibility to, 1 DISZ794C Strong Genetic Variation [3]
Colorectal cancer, susceptibility to, 10 DISQXMYM Strong Genetic Variation [3]
Colorectal cancer, susceptibility to, 12 DIS4FXJX Strong Genetic Variation [3]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [4]
Colorectal neoplasm DISR1UCN Strong Genetic Variation [3]
Epilepsy, idiopathic generalized DISODZC9 Strong Genetic Variation [5]
Esophageal squamous cell carcinoma DIS5N2GV Strong Altered Expression [6]
Gastric cancer DISXGOUK Strong Biomarker [7]
Glioblastoma multiforme DISK8246 Strong Biomarker [8]
Glioma DIS5RPEH Strong Biomarker [8]
Gonorrhea DISQ5AO6 Strong Altered Expression [9]
Hemochromatosis DISAPY0H Strong Genetic Variation [10]
Hepatitis B virus infection DISLQ2XY Strong Genetic Variation [11]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [13]
HIV infectious disease DISO97HC Strong Altered Expression [14]
Melanoma DIS1RRCY Strong Biomarker [15]
Multiple sclerosis DISB2WZI Strong Genetic Variation [16]
Narcolepsy DISLCNLI Strong Genetic Variation [17]
Neoplasm DISZKGEW Strong Altered Expression [6]
Stomach cancer DISKIJSX Strong Biomarker [7]
Urinary bladder cancer DISDV4T7 Strong Biomarker [1]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [1]
Vitiligo DISR05SL Strong Genetic Variation [18]
Autoimmune disease DISORMTM moderate Altered Expression [19]
Juvenile myoclonic epilepsy DISYXV1N moderate Genetic Variation [20]
Nasopharyngeal carcinoma DISAOTQ0 moderate Genetic Variation [21]
Amyotrophic lateral sclerosis DISF7HVM Limited Biomarker [22]
Coronary heart disease DIS5OIP1 Limited Genetic Variation [23]
Granular corneal dystrophy type II DISAEE20 Limited Genetic Variation [24]
Hereditary hemochromatosis DISVG5MT Limited Biomarker [25]
Psoriatic arthritis DISLWTG2 Limited Genetic Variation [26]
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⏷ Show the Full List of 38 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
27 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [27]
Tretinoin DM49DUI Approved Tretinoin increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [28]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [29]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [30]
Estradiol DMUNTE3 Approved Estradiol increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [31]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide decreases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [32]
Vorinostat DMWMPD4 Approved Vorinostat increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [33]
Zoledronate DMIXC7G Approved Zoledronate increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [34]
Selenium DM25CGV Approved Selenium decreases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [35]
Progesterone DMUY35B Approved Progesterone increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [36]
Fluorouracil DMUM7HZ Approved Fluorouracil increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [37]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [38]
Amphotericin B DMTAJQE Approved Amphotericin B increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [39]
Simvastatin DM30SGU Approved Simvastatin affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [40]
Cyclophosphamide DM4O2Z7 Approved Cyclophosphamide increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [39]
Gefitinib DM15F0X Approved Gefitinib affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [40]
Gentamicin DMKINJO Approved Gentamicin increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [39]
Hydrochlorothiazide DMUSZHD Approved Hydrochlorothiazide affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [40]
Saquinavir DMG814N Approved Saquinavir affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [40]
Repaglinide DM5SXUV Approved Repaglinide affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [40]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [33]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [41]
APR-246 DMNFADH Phase 2 APR-246 affects the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [42]
Trichostatin A DM9C8NX Investigative Trichostatin A increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [33]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [44]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [45]
Phencyclidine DMQBEYX Investigative Phencyclidine increases the expression of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [46]
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⏷ Show the Full List of 27 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of HLA class I histocompatibility antigen, alpha chain F (HLA-F). [43]
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References

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