HLA class I histocompatibility antigen, alpha chain F

Details

Name
HLA class I histocompatibility antigen, alpha chain F
Synonyms
  • CDA12
  • HLA F antigen
  • HLA-5.4
  • HLAF
  • Leukocyte antigen F
  • MHC class I antigen F
Gene Name
HLA-F
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052601|HLA class I histocompatibility antigen, alpha chain F
MAPRSLLLLLSGALALTDTWAGSHSLRYFSTAVSRPGRGEPRYIAVEYVDDTQFLRFDSD
AAIPRMEPREPWVEQEGPQYWEWTTGYAKANAQTDRVALRNLLRRYNQSEAGSHTLQGMN
GCDMGPDGRLLRGYHQHAYDGKDYISLNEDLRSWTAADTVAQITQRFYEAEEYAEEFRTY
LEGECLELLRRYLENGKETLQRADPPKAHVAHHPISDHEATLRCWALGFYPAEITLTWQR
DGEEQTQDTELVETRPAGDGTFQKWAAVVVPPGEEQRYTCHVQHEGLPQPLILRWEQSPQ
PTIPIVGIVAGLVVLGAVVTGAVVAAVMWRKKSSDRNRGSYSQAAV
Number of residues
346
Molecular Weight
39061.385
Theoretical pI
Not Available
GO Classification
Functions
14-3-3 protein binding / beta-2-microglobulin binding / peptide antigen binding / TAP1 binding / TAP2 binding
Processes
antigen processing and presentation of endogenous peptide antigen via MHC class Ib / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent / antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent / antigen processing and presentation of exogenous peptide antigen via MHC class Ib / antigen processing and presentation of peptide antigen via MHC class I / interferon-gamma-mediated signaling pathway / negative regulation of natural killer cell cytokine production / negative regulation of natural killer cell degranulation / negative regulation of natural killer cell mediated cytotoxicity / negative regulation of neuron death / negative regulation of T cell cytokine production / positive regulation of natural killer cell cytokine production / positive regulation of natural killer cell degranulation / positive regulation of T cell mediated cytotoxicity / regulation of immune response / type I interferon signaling pathway
Components
cell surface / early endosome membrane / endoplasmic reticulum / ER to Golgi transport vesicle membrane / external side of plasma membrane / extracellular space / Golgi membrane / integral component of lumenal side of endoplasmic reticulum membrane / lysosomal membrane / membrane / MHC class I protein complex / MHC class Ib protein complex / phagocytic vesicle membrane / plasma membrane / recycling endosome membrane
General 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 (PubMed:28636952). Upon interaction with activating KIR3DS1 receptor on NK cells, triggers NK cell degranulation and anti-viral cytokine production (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits NK and T cell effector functions (PubMed:24018270). 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 (PubMed:23851683). May play a role in inflammatory responses in the peripheral nervous system. Through interaction with KIR3DL2, may protect motor neurons from astrocyte-induced toxicity (PubMed:26928464).
Specific Function
14-3-3 protein binding
Pfam Domain Function
Transmembrane Regions
306-329
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0052602|HLA class I histocompatibility antigen, alpha chain F (HLA-F)
ATGGCGCCCCGAAGCCTCCTCCTGCTGCTCTCAGGGGCCCTGGCCCTGACCGATACTTGG
GCGGGCTCCCACTCCTTGAGGTATTTCAGCACCGCTGTGTCGCGGCCCGGCCGCGGGGAG
CCCCGCTACATCGCCGTGGAGTACGTAGACGACACGCAATTCCTGCGGTTCGACAGCGAC
GCCGCGATTCCGAGGATGGAGCCGCGGGAGCCGTGGGTGGAGCAAGAGGGGCCGCAGTAT
TGGGAGTGGACCACAGGGTACGCCAAGGCCAACGCACAGACTGACCGAGTGGCCCTGAGG
AACCTGCTCCGCCGCTACAACCAGAGCGAGGCTGGGTCTCACACCCTCCAGGGAATGAAT
GGCTGCGACATGGGGCCCGACGGACGCCTCCTCCGCGGGTATCACCAGCACGCGTACGAC
GGCAAGGATTACATCTCCCTGAACGAGGACCTGCGCTCCTGGACCGCGGCGGACACCGTG
GCTCAGATCACCCAGCGCTTCTATGAGGCAGAGGAATATGCAGAGGAGTTCAGGACCTAC
CTGGAGGGCGAGTGCCTGGAGTTGCTCCGCAGATACTTGGAGAATGGGAAGGAGACGCTA
CAGCGCGCAGATCCTCCAAAGGCACACGTTGCCCACCACCCCATCTCTGACCATGAGGCC
ACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCGGAGATCACGCTGACCTGGCAGCGG
GATGGGGAGGAACAGACCCAGGACACAGAGCTTGTGGAGACCAGGCCTGCAGGGGATGGA
ACCTTCCAGAAGTGGGCCGCTGTGGTGGTGCCTCCTGGAGAGGAACAGAGATACACATGC
CATGTGCAGCACGAGGGGCTGCCCCAGCCCCTCATCCTGAGATGGGAGCAGTCTCCCCAG
CCCACCATCCCCATCGTGGGCATCGTTGCTGGCCTTGTTGTCCTTGGAGCTGTGGTCACT
GGAGCTGTGGTCGCTGCTGTGATGTGGAGGAAGAAGAGCTCAGATAGAAACAGAGGGAGC
TACTCTCAGGCTGCAGTGTGA
Chromosome Location
6
Locus
6p22.1
External Identifiers
ResourceLink
UniProtKB IDP30511
UniProtKB Entry NameHLAF_HUMAN
HGNC IDHGNC:4963
General References
  1. Geraghty DE, Wei XH, Orr HT, Koller BH: Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element. J Exp Med. 1990 Jan 1;171(1):1-18. doi: 10.1084/jem.171.1.1. [Article]
  2. Lury D, Epstein H, Holmes N: The human class I MHC gene HLA-F is expressed in lymphocytes. Int Immunol. 1990;2(6):531-7. doi: 10.1093/intimm/2.6.531. [Article]
  3. Hampe A, Coriton O, Andrieux N, Carn G, Lepourcelet M, Mottier S, Dreano S, Gatius MT, Hitte C, Soriano N, Galibert F: A 356-Kb sequence of the subtelomeric part of the MHC Class I region. DNA Seq. 1999;10(4-5):263-99. doi: 10.3109/10425179909033955. [Article]
  4. He X, Xu L, Liu Y, Zeng Y: Identification of a novel HLA-F allele - HLA-F*010102. Tissue Antigens. 2004 Feb;63(2):181-3. doi: 10.1111/j.1399-0039.2004.00145.x. [Article]
  5. Pyo CW, Williams LM, Moore Y, Hyodo H, Li SS, Zhao LP, Sageshima N, Ishitani A, Geraghty DE: HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype structure and variation spanning the nonclassical class I genes. Immunogenetics. 2006 May;58(4):241-51. doi: 10.1007/s00251-005-0076-z. Epub 2006 Mar 29. [Article]
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  8. Lepin EJ, Bastin JM, Allan DS, Roncador G, Braud VM, Mason DY, van der Merwe PA, McMichael AJ, Bell JI, Powis SH, O'Callaghan CA: Functional characterization of HLA-F and binding of HLA-F tetramers to ILT2 and ILT4 receptors. Eur J Immunol. 2000 Dec;30(12):3552-61. doi: 10.1002/1521-4141(200012)30:12<3552::AID-IMMU3552>3.0.CO;2-L. [Article]
  9. Wainwright SD, Biro PA, Holmes CH: HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib protein with a restricted expression pattern. J Immunol. 2000 Jan 1;164(1):319-28. doi: 10.4049/jimmunol.164.1.319. [Article]
  10. Boyle LH, Gillingham AK, Munro S, Trowsdale J: Selective export of HLA-F by its cytoplasmic tail. J Immunol. 2006 Jun 1;176(11):6464-72. doi: 10.4049/jimmunol.176.11.6464. [Article]
  11. Lee N, Ishitani A, Geraghty DE: HLA-F is a surface marker on activated lymphocytes. Eur J Immunol. 2010 Aug;40(8):2308-18. doi: 10.1002/eji.201040348. [Article]
  12. Goodridge JP, Burian A, Lee N, Geraghty DE: HLA-F complex without peptide binds to MHC class I protein in the open conformer form. J Immunol. 2010 Jun 1;184(11):6199-208. doi: 10.4049/jimmunol.1000078. Epub 2010 May 5. [Article]
  13. Goodridge JP, Lee N, Burian A, Pyo CW, Tykodi SS, Warren EH, Yee C, Riddell SR, Geraghty DE: HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-presentation pathway. J Immunol. 2013 Aug 15;191(4):1567-77. doi: 10.4049/jimmunol.1300080. Epub 2013 Jul 12. [Article]
  14. Goodridge JP, Burian A, Lee N, Geraghty DE: HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors. J Immunol. 2013 Oct 1;191(7):3553-62. doi: 10.4049/jimmunol.1300081. Epub 2013 Sep 9. [Article]
  15. Garcia-Beltran WF, Holzemer A, Martrus G, Chung AW, Pacheco Y, Simoneau CR, Rucevic M, Lamothe-Molina PA, Pertel T, Kim TE, Dugan H, Alter G, Dechanet-Merville J, Jost S, Carrington M, Altfeld M: Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1. Nat Immunol. 2016 Sep;17(9):1067-74. doi: 10.1038/ni.3513. Epub 2016 Jul 25. [Article]
  16. Song S, Miranda CJ, Braun L, Meyer K, Frakes AE, Ferraiuolo L, Likhite S, Bevan AK, Foust KD, McConnell MJ, Walker CM, Kaspar BK: Major histocompatibility complex class I molecules protect motor neurons from astrocyte-induced toxicity in amyotrophic lateral sclerosis. Nat Med. 2016 Apr;22(4):397-403. doi: 10.1038/nm.4052. Epub 2016 Feb 29. [Article]
  17. Hackmon R, Pinnaduwage L, Zhang J, Lye SJ, Geraghty DE, Dunk CE: Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition. Am J Reprod Immunol. 2017 Jun;77(6). doi: 10.1111/aji.12643. Epub 2017 Feb 10. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails