HLAF_HUMAN
ID HLAF_HUMAN Reviewed; 346 AA.
AC P30511; Q5JQI8; Q5JQJ1; Q5SPT5; Q860R0; Q8MGQ1; Q8WLP5; Q95HC0; Q9TP68;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=HLA class I histocompatibility antigen, alpha chain F;
DE AltName: Full=CDA12;
DE AltName: Full=HLA F antigen;
DE AltName: Full=Leukocyte antigen F {ECO:0000303|PubMed:1688605};
DE AltName: Full=MHC class I antigen F;
DE Flags: Precursor;
GN Name=HLA-F {ECO:0000303|PubMed:1688605, ECO:0000303|PubMed:1707659,
GN ECO:0000312|HGNC:HGNC:4963};
GN Synonyms=HLA-5.4 {ECO:0000303|PubMed:1688605, ECO:0000303|PubMed:1707659},
GN HLAF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP VARIANT SER-272.
RX PubMed=1688605; DOI=10.1084/jem.171.1.1;
RA Geraghty D.E., Wei X., Orr H.T., Koller B.H.;
RT "Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a
RT class I coding sequence linked to a novel transcribed repetitive element.";
RL J. Exp. Med. 171:1-18(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP VARIANT SER-272.
RX PubMed=1707659; DOI=10.1093/intimm/2.6.531;
RA Lury D., Epstein H., Holmes N.;
RT "The human class I MHC gene HLA-F is expressed in lymphocytes.";
RL Int. Immunol. 2:531-537(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP VARIANT SER-272.
RX PubMed=10727083; DOI=10.3109/10425179909033955;
RA Hampe A., Coriton O., Andrieux N., Carn G., Lepourcelet M., Mottier S.,
RA Dreano S., Gatius M.T., Hitte C., Soriano N., Galibert F.;
RT "A 356-Kb sequence of the subtelomeric part of the MHC class I region.";
RL DNA Seq. 10:263-299(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT SER-272.
RX PubMed=14705989; DOI=10.1111/j.1399-0039.2004.00145.x;
RA He X., Xu L., Liu Y., Zeng Y.;
RT "Identification of a novel HLA-F allele - HLA-F*010102.";
RL Tissue Antigens 63:181-183(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 1), AND
RP VARIANT SER-272.
RX PubMed=16570139; DOI=10.1007/s00251-005-0076-z;
RA Pyo C.W., Williams L.M., Moore Y., Hyodo H., Li S.S., Zhao L.P.,
RA Sageshima N., Ishitani A., Geraghty D.E.;
RT "HLA-E, HLA-F, and HLA-G polymorphism: genomic sequence defines haplotype
RT structure and variation spanning the nonclassical class I genes.";
RL Immunogenetics 58:241-251(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-272.
RA Gharwan H., Sageshima N., Ishitani A., Geraghty D.E.;
RT "A comparative study of the MHC-F expression patterns between humans and
RT nonhuman primates.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-272.
RA Shiina S., Tamiya G., Oka A., Inoko H.;
RT "Homo sapiens 2,229,817bp genomic DNA of 6p21.3 HLA class I region.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-272.
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP SER-272.
RC TISSUE=Lung, and Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP SUBUNIT, INTERACTION WITH LILRB1 AND LILRB2, AND TISSUE SPECIFICITY.
RX PubMed=11169396;
RX DOI=10.1002/1521-4141(200012)30:12<3552::aid-immu3552>3.0.co;2-l;
RA Lepin E.J., Bastin J.M., Allan D.S., Roncador G., Braud V.M., Mason D.Y.,
RA van der Merwe P.A., McMichael A.J., Bell J.I., Powis S.H.,
RA O'Callaghan C.A.;
RT "Functional characterization of HLA-F and binding of HLA-F tetramers to
RT ILT2 and ILT4 receptors.";
RL Eur. J. Immunol. 30:3552-3561(2000).
RN [12]
RP SUBUNIT, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, GLYCOSYLATION,
RP INTERACTION WITH TAP1, INTERACTION WITH TAP2, INTERACTION WITH CALR, AND
RP INTERACTION WITH B2M.
RX PubMed=10605026; DOI=10.4049/jimmunol.164.1.319;
RA Wainwright S.D., Biro P.A., Holmes C.H.;
RT "HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ib
RT protein with a restricted expression pattern.";
RL J. Immunol. 164:319-328(2000).
RN [13]
RP SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-346, MUTAGENESIS OF
RP 336-ARG--ARG-338, SUBUNIT, AND MOTIF.
RX PubMed=16709803; DOI=10.4049/jimmunol.176.11.6464;
RA Boyle L.H., Gillingham A.K., Munro S., Trowsdale J.;
RT "Selective export of HLA-F by its cytoplasmic tail.";
RL J. Immunol. 176:6464-6472(2006).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=20865824; DOI=10.1002/eji.201040348;
RA Lee N., Ishitani A., Geraghty D.E.;
RT "HLA-F is a surface marker on activated lymphocytes.";
RL Eur. J. Immunol. 40:2308-2318(2010).
RN [15]
RP SUBUNIT, AND INTERACTION WITH HLA-E.
RX PubMed=20483783; DOI=10.4049/jimmunol.1000078;
RA Goodridge J.P., Burian A., Lee N., Geraghty D.E.;
RT "HLA-F complex without peptide binds to MHC class I protein in the open
RT conformer form.";
RL J. Immunol. 184:6199-6208(2010).
RN [16]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=23851683; DOI=10.4049/jimmunol.1300080;
RA Goodridge J.P., Lee N., Burian A., Pyo C.W., Tykodi S.S., Warren E.H.,
RA Yee C., Riddell S.R., Geraghty D.E.;
RT "HLA-F and MHC-I open conformers cooperate in a MHC-I antigen cross-
RT presentation pathway.";
RL J. Immunol. 191:1567-1577(2013).
RN [17]
RP FUNCTION, SUBUNIT, INTERACTION WITH KIR3DL2, AND INTERACTION WITH KIR2DS4.
RX PubMed=24018270; DOI=10.4049/jimmunol.1300081;
RA Goodridge J.P., Burian A., Lee N., Geraghty D.E.;
RT "HLA-F and MHC class I open conformers are ligands for NK cell Ig-like
RT receptors.";
RL J. Immunol. 191:3553-3562(2013).
RN [18]
RP FUNCTION, SUBUNIT, INTERACTION WITH KIR3DS1, TISSUE SPECIFICITY, INDUCTION
RP BY HIV-1 INFECTION, GLYCOSYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=27455421; DOI=10.1038/ni.3513;
RA Garcia-Beltran W.F., Hoelzemer A., Martrus G., Chung A.W., Pacheco Y.,
RA Simoneau C.R., Rucevic M., Lamothe-Molina P.A., Pertel T., Kim T.E.,
RA Dugan H., Alter G., Dechanet-Merville J., Jost S., Carrington M.,
RA Altfeld M.;
RT "Open conformers of HLA-F are high-affinity ligands of the activating NK-
RT cell receptor KIR3DS1.";
RL Nat. Immunol. 17:1067-1074(2016).
RN [19]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=26928464; DOI=10.1038/nm.4052;
RA Song S., Miranda C.J., Braun L., Meyer K., Frakes A.E., Ferraiuolo L.,
RA Likhite S., Bevan A.K., Foust K.D., McConnell M.J., Walker C.M.,
RA Kaspar B.K.;
RT "Major histocompatibility complex class I molecules protect motor neurons
RT from astrocyte-induced toxicity in amyotrophic lateral sclerosis.";
RL Nat. Med. 22:397-403(2016).
RN [20]
RP DEVELOPMENTAL STAGE.
RX PubMed=28185362; DOI=10.1111/aji.12643;
RA Hackmon R., Pinnaduwage L., Zhang J., Lye S.J., Geraghty D.E., Dunk C.E.;
RT "Definitive class I human leukocyte antigen expression in gestational
RT placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast
RT invasion on placentation, pregnancy, and parturition.";
RL Am. J. Reprod. Immunol. 77:0-0(2017).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.62 ANGSTROMS) OF 22-305 IN COMPLEX WITH
RP SELF-PEPTIDE, DISULFIDE BOND, FUNCTION, SUBUNIT, INTERACTION WITH LILRB1,
RP INTERACTION WITH KIR3DS1 AND KIR3DL2, AND MUTAGENESIS OF TRP-83.
RX PubMed=28636952; DOI=10.1016/j.immuni.2017.06.002;
RA Dulberger C.L., McMurtrey C.P., Holzemer A., Neu K.E., Liu V.,
RA Steinbach A.M., Garcia-Beltran W.F., Sulak M., Jabri B., Lynch V.J.,
RA Altfeld M., Hildebrand W.H., Adams E.J.;
RT "Human Leukocyte Antigen F Presents Peptides and Regulates Immunity through
RT Interactions with NK Cell Receptors.";
RL Immunity 46:1018-1029(2017).
CC -!- FUNCTION: Non-classical major histocompatibility class Ib molecule
CC postulated to play a role in immune surveillance, immune tolerance and
CC inflammation. Functions in two forms, as a heterotrimeric complex with
CC B2M/beta-2 microglobulin and a peptide (peptide-bound HLA-F-B2M) and as
CC an open conformer (OC) devoid of peptide and B2M (peptide-free OC). In
CC complex with B2M, presents non-canonical self-peptides carrying post-
CC translational modifications, particularly phosphorylated self-peptides.
CC Peptide-bound HLA-F-B2M acts as a ligand for LILRB1 inhibitory
CC receptor, a major player in maternal-fetal tolerance. Peptide-free OC
CC acts as a ligand for KIR3DS1 and KIR3DL2 receptors (PubMed:28636952).
CC Upon interaction with activating KIR3DS1 receptor on NK cells, triggers
CC NK cell degranulation and anti-viral cytokine production
CC (PubMed:27455421). Through interaction with KIR3DL2 receptor, inhibits
CC NK and T cell effector functions (PubMed:24018270). May interact with
CC other MHC class I OCs to cross-present exogenous viral, tumor or minor
CC histompatibility antigens to cytotoxic CD8+ T cells, triggering
CC effector and memory responses (PubMed:23851683). May play a role in
CC inflammatory responses in the peripheral nervous system. Through
CC interaction with KIR3DL2, may protect motor neurons from astrocyte-
CC induced toxicity (PubMed:26928464). {ECO:0000269|PubMed:23851683,
CC ECO:0000269|PubMed:24018270, ECO:0000269|PubMed:26928464,
CC ECO:0000269|PubMed:27455421, ECO:0000269|PubMed:28636952}.
CC -!- SUBUNIT: Forms a heterotrimer with B2M and a self-peptide
CC (PubMed:28636952). Binds a diverse number of peptides ranging from 7 to
CC more than 30 amino acids (PubMed:28636952). Peptide-bound HLA-F-B2M
CC interacts with LILRB1 and LILRB2 but not with KIR3DS1 or KIR3DL2; this
CC interaction is direct (PubMed:28636952, PubMed:11169396). The OC form
CC interacts with KIR3DS1, KIR2DS4 and KIR3DL2; this interaction is direct
CC (PubMed:28636952, PubMed:27455421, PubMed:24018270). Interacts with
CC TAP1-TAP2 complex and CALR; this interaction is required for
CC appropriate folding and peptide loading (PubMed:10605026,
CC PubMed:11169396). Interacts with the coat protein complex II and 14-3-3
CC proteins; these interactions likely control the anterograde ER-to-Golgi
CC transport of HLA-F (PubMed:16709803). HLA-F-B2M complex interacts with
CC the heavy chain of other MHC class I molecules including HLA-A and HLA-
CC E; this interaction may regulate the intracellular trafficking and the
CC stability of peptide-free MHC class I OCs (PubMed:20483783).
CC {ECO:0000269|PubMed:10605026, ECO:0000269|PubMed:11169396,
CC ECO:0000269|PubMed:16709803, ECO:0000269|PubMed:20483783,
CC ECO:0000269|PubMed:24018270, ECO:0000269|PubMed:27455421,
CC ECO:0000269|PubMed:28636952}.
CC -!- INTERACTION:
CC P30511; P13747: HLA-E; NbExp=2; IntAct=EBI-2811134, EBI-726583;
CC P30511; P43632: KIR2DS4; NbExp=4; IntAct=EBI-2811134, EBI-13916812;
CC P30511; P43629: KIR3DL1; NbExp=4; IntAct=EBI-2811134, EBI-3910993;
CC P30511; P43630: KIR3DL2; NbExp=6; IntAct=EBI-2811134, EBI-6165894;
CC P30511; Q14943: KIR3DS1; NbExp=6; IntAct=EBI-2811134, EBI-15316524;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16709803,
CC ECO:0000269|PubMed:23851683, ECO:0000305|PubMed:27455421}; Single-pass
CC type I membrane protein. Early endosome membrane
CC {ECO:0000269|PubMed:23851683}. Lysosome membrane
CC {ECO:0000269|PubMed:23851683}. Note=For cross-presentation transits
CC from the cell surface through endosomal pathway to lysosomes, where the
CC peptide is generated from internalized exogenous antigen.
CC {ECO:0000269|PubMed:23851683}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P30511-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30511-2; Sequence=VSP_038846;
CC Name=3;
CC IsoId=P30511-3; Sequence=VSP_040349;
CC -!- TISSUE SPECIFICITY: Expressed in resting B cells (at protein level).
CC Expressed in secondary lymphoid organs rich in B and T cells such as
CC the tonsils, spleen, and thymus (at protein level) (PubMed:10605026,
CC PubMed:11169396). Expressed in the endothelial cells of the tonsils
CC (PubMed:11169396). Expressed on activated lymphoid cells including B
CC cells, NK cells, CD4+ T cells and memory T cells (at protein level)
CC (PubMed:27455421, PubMed:20865824). Expressed in motor neurons of
CC spinal cord (PubMed:26928464). {ECO:0000269|PubMed:10605026,
CC ECO:0000269|PubMed:11169396, ECO:0000269|PubMed:20865824,
CC ECO:0000269|PubMed:26928464, ECO:0000269|PubMed:27455421}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver (at protein level)
CC (PubMed:10605026). Expressed in placenta villous mesenchyme,
CC cytotrophoblast, syncytiotrophoblast and invasive extravillous
CC trophoblast (at protein level) (PubMed:28185362).
CC {ECO:0000269|PubMed:10605026, ECO:0000269|PubMed:28185362}.
CC -!- INDUCTION: Up-regulated in CD4+ T cells upon stimulation via TCR and
CC upon HIV-1 infection. {ECO:0000269|PubMed:27455421}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10605026,
CC ECO:0000269|PubMed:27455421}.
CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC24827.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=AAH09260.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAB63337.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAA34947.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=CAB46623.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; X17093; CAA34947.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF055066; AAC24827.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AY253269; AAO86773.1; -; mRNA.
DR EMBL; AY253270; AAO86774.1; -; mRNA.
DR EMBL; AY253271; AAO86775.1; -; mRNA.
DR EMBL; AF523284; AAM74979.1; -; Genomic_DNA.
DR EMBL; AF523285; AAM74980.1; -; Genomic_DNA.
DR EMBL; AF523286; AAM74981.1; -; Genomic_DNA.
DR EMBL; AF523287; AAM74982.1; -; Genomic_DNA.
DR EMBL; AF523288; AAM74983.1; -; Genomic_DNA.
DR EMBL; AF523289; AAM74984.1; -; Genomic_DNA.
DR EMBL; AF523290; AAM74985.1; -; Genomic_DNA.
DR EMBL; AF523291; AAM74986.1; -; Genomic_DNA.
DR EMBL; AF523292; AAM74987.1; -; Genomic_DNA.
DR EMBL; AF523293; AAM74988.1; -; Genomic_DNA.
DR EMBL; AF523294; AAM74989.1; -; Genomic_DNA.
DR EMBL; AF523295; AAM74990.1; -; Genomic_DNA.
DR EMBL; AF523296; AAM74991.1; -; Genomic_DNA.
DR EMBL; AF523297; AAM74992.1; -; Genomic_DNA.
DR EMBL; AY645742; AAT73225.1; -; Genomic_DNA.
DR EMBL; AY645743; AAT73226.1; -; Genomic_DNA.
DR EMBL; AY645744; AAT73227.1; -; Genomic_DNA.
DR EMBL; AY645745; AAT73228.1; -; Genomic_DNA.
DR EMBL; AY645746; AAT73229.1; -; Genomic_DNA.
DR EMBL; AY645748; AAT73231.1; -; Genomic_DNA.
DR EMBL; AY645749; AAT73232.1; -; Genomic_DNA.
DR EMBL; AY645750; AAT73233.1; -; Genomic_DNA.
DR EMBL; AY645751; AAT73234.1; -; Genomic_DNA.
DR EMBL; AY645752; AAT73235.1; -; Genomic_DNA.
DR EMBL; AY645753; AAT73236.1; -; Genomic_DNA.
DR EMBL; AY645754; AAT73237.1; -; Genomic_DNA.
DR EMBL; AY645756; AAT73239.1; -; Genomic_DNA.
DR EMBL; AY645757; AAT73240.1; -; Genomic_DNA.
DR EMBL; AY645758; AAT73241.1; -; Genomic_DNA.
DR EMBL; AY645759; AAT73242.1; -; Genomic_DNA.
DR EMBL; DQ367723; ABD38924.1; -; mRNA.
DR EMBL; BA000025; BAB63337.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL022723; CAB46623.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL645939; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL669813; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL844851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX005428; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR753818; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX927250; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03223.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03226.1; -; Genomic_DNA.
DR EMBL; BC009260; AAH09260.2; ALT_INIT; mRNA.
DR EMBL; BC062991; AAH62991.1; -; mRNA.
DR CCDS; CCDS43437.1; -. [P30511-3]
DR CCDS; CCDS43438.1; -. [P30511-1]
DR CCDS; CCDS43439.1; -. [P30511-2]
DR PIR; A60384; A60384.
DR RefSeq; NP_001091948.1; NM_001098478.1. [P30511-2]
DR RefSeq; NP_001091949.1; NM_001098479.1. [P30511-3]
DR RefSeq; NP_061823.2; NM_018950.2. [P30511-1]
DR PDB; 5IUE; X-ray; 2.62 A; A/E/G/I=22-305.
DR PDB; 5KNM; X-ray; 3.30 A; A=22-305.
DR PDBsum; 5IUE; -.
DR PDBsum; 5KNM; -.
DR AlphaFoldDB; P30511; -.
DR SMR; P30511; -.
DR BioGRID; 109379; 131.
DR IntAct; P30511; 19.
DR MINT; P30511; -.
DR STRING; 9606.ENSP00000259951; -.
DR GlyGen; P30511; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P30511; -.
DR PhosphoSitePlus; P30511; -.
DR BioMuta; HLA-F; -.
DR DMDM; 317373438; -.
DR EPD; P30511; -.
DR jPOST; P30511; -.
DR MassIVE; P30511; -.
DR MaxQB; P30511; -.
DR PaxDb; P30511; -.
DR PeptideAtlas; P30511; -.
DR PRIDE; P30511; -.
DR ProteomicsDB; 54704; -. [P30511-1]
DR ProteomicsDB; 54705; -. [P30511-2]
DR ProteomicsDB; 54706; -. [P30511-3]
DR Antibodypedia; 26089; 201 antibodies from 27 providers.
DR DNASU; 3134; -.
DR Ensembl; ENST00000259951.12; ENSP00000259951.6; ENSG00000204642.14. [P30511-3]
DR Ensembl; ENST00000334668.8; ENSP00000334263.4; ENSG00000204642.14. [P30511-1]
DR Ensembl; ENST00000359076.7; ENSP00000351977.3; ENSG00000206509.13. [P30511-2]
DR Ensembl; ENST00000376848.8; ENSP00000366044.4; ENSG00000229698.11. [P30511-2]
DR Ensembl; ENST00000376861.5; ENSP00000366057.1; ENSG00000204642.14. [P30511-1]
DR Ensembl; ENST00000383515.6; ENSP00000373007.2; ENSG00000137403.19. [P30511-2]
DR Ensembl; ENST00000420067.5; ENSP00000393535.1; ENSG00000235220.10. [P30511-2]
DR Ensembl; ENST00000434407.6; ENSP00000397376.2; ENSG00000204642.14. [P30511-2]
DR Ensembl; ENST00000440590.5; ENSP00000399835.1; ENSG00000237508.10. [P30511-2]
DR GeneID; 3134; -.
DR KEGG; hsa:3134; -.
DR MANE-Select; ENST00000259951.12; ENSP00000259951.6; NM_001098479.2; NP_001091949.1. [P30511-3]
DR UCSC; uc003nnm.5; human. [P30511-1]
DR CTD; 3134; -.
DR DisGeNET; 3134; -.
DR GeneCards; HLA-F; -.
DR HGNC; HGNC:4963; HLA-F.
DR HPA; ENSG00000204642; Tissue enhanced (lymphoid).
DR MIM; 143110; gene.
DR neXtProt; NX_P30511; -.
DR OpenTargets; ENSG00000204642; -.
DR PharmGKB; PA35082; -.
DR VEuPathDB; HostDB:ENSG00000204642; -.
DR eggNOG; ENOG502RQEK; Eukaryota.
DR GeneTree; ENSGT00980000198488; -.
DR HOGENOM; CLU_047501_1_1_1; -.
DR InParanoid; P30511; -.
DR OMA; FVRYNSE; -.
DR PhylomeDB; P30511; -.
DR TreeFam; TF336617; -.
DR PathwayCommons; P30511; -.
DR Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; P30511; -.
DR SIGNOR; P30511; -.
DR BioGRID-ORCS; 3134; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; HLA-F; human.
DR GeneWiki; HLA-F; -.
DR GenomeRNAi; 3134; -.
DR Pharos; P30511; Tbio.
DR PRO; PR:P30511; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P30511; protein.
DR Bgee; ENSG00000204642; Expressed in granulocyte and 96 other tissues.
DR ExpressionAtlas; P30511; baseline and differential.
DR Genevisible; P30511; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0032398; C:MHC class Ib protein complex; IDA:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; TAS:Reactome.
DR GO; GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
DR GO; GO:0030881; F:beta-2-microglobulin binding; IDA:UniProtKB.
DR GO; GO:0042605; F:peptide antigen binding; IDA:UniProtKB.
DR GO; GO:0046978; F:TAP1 binding; IPI:UniProtKB.
DR GO; GO:0046979; F:TAP2 binding; IPI:UniProtKB.
DR GO; GO:0002476; P:antigen processing and presentation of endogenous peptide antigen via MHC class Ib; IDA:UniProtKB.
DR GO; GO:0002477; P:antigen processing and presentation of exogenous peptide antigen via MHC class Ib; IDA:UniProtKB.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR GO; GO:0002728; P:negative regulation of natural killer cell cytokine production; IDA:UniProtKB.
DR GO; GO:0043322; P:negative regulation of natural killer cell degranulation; IDA:UniProtKB.
DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; IDA:UniProtKB.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:UniProtKB.
DR GO; GO:0002725; P:negative regulation of T cell cytokine production; IDA:UniProtKB.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IDA:UniProtKB.
DR GO; GO:0043323; P:positive regulation of natural killer cell degranulation; IDA:UniProtKB.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IMP:UniProtKB.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR001039; MHC_I_a_a1/a2.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00129; MHC_I; 1.
DR PRINTS; PR01638; MHCCLASSI.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Disulfide bond;
KW Endosome; Glycoprotein; Immunity; Lysosome; Membrane; MHC I;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..346
FT /note="HLA class I histocompatibility antigen, alpha chain
FT F"
FT /id="PRO_0000018884"
FT TOPO_DOM 22..305
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 306..329
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 330..346
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 206..296
FT /note="Ig-like C1-type"
FT /evidence="ECO:0000255"
FT REGION 22..111
FT /note="Alpha-1"
FT REGION 112..203
FT /note="Alpha-2"
FT REGION 204..295
FT /note="Alpha-3"
FT REGION 296..305
FT /note="Connecting peptide"
FT MOTIF 336..338
FT /note="Sorting signal sequence; Golgi-retention signal; ER-
FT retention signal"
FT /evidence="ECO:0000269|PubMed:16709803"
FT BINDING 91
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:28636952"
FT BINDING 105
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:28636952"
FT BINDING 164
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:28636952"
FT BINDING 168
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:28636952"
FT BINDING 176
FT /ligand="a peptide antigen"
FT /ligand_id="ChEBI:CHEBI:166823"
FT /ligand_note="self-peptide antigen"
FT /evidence="ECO:0000269|PubMed:28636952"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT DISULFID 122..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:28636952"
FT DISULFID 224..280
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:28636952"
FT VAR_SEQ 204..295
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14705989"
FT /id="VSP_038846"
FT VAR_SEQ 346
FT /note="V -> AYSVVSGNLMITWWSSLFLLGVLFQGYLGCLRSHSVLGRRKVGDMWI
FT LFFLWLWTSFNTAFLALQSLRFGFGFRRGRSFLLRSWHHLMKRVQIKIFD (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040349"
FT VARIANT 13
FT /note="A -> V (in dbSNP:rs17875379)"
FT /id="VAR_056525"
FT VARIANT 71
FT /note="P -> Q (in dbSNP:rs17875380)"
FT /id="VAR_056526"
FT VARIANT 272
FT /note="P -> S (in dbSNP:rs1736924)"
FT /evidence="ECO:0000269|PubMed:10727083,
FT ECO:0000269|PubMed:14574404, ECO:0000269|PubMed:14705989,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:16570139,
FT ECO:0000269|PubMed:1688605, ECO:0000269|PubMed:1707659,
FT ECO:0000269|Ref.6, ECO:0000269|Ref.7"
FT /id="VAR_018327"
FT MUTAGEN 83
FT /note="W->R: Impairs peptide binding."
FT /evidence="ECO:0000269|PubMed:28636952"
FT MUTAGEN 336..338
FT /note="RNR->AAA: Impairs the interaction with 14-3-3
FT proteins."
FT /evidence="ECO:0000269|PubMed:16709803"
FT MUTAGEN 336..338
FT /note="RNR->GKG: Impairs the anterograde ER-to-Golgi
FT transport."
FT /evidence="ECO:0000269|PubMed:16709803"
FT MUTAGEN 346
FT /note="V->S: Impairs the anterograde ER-to-Golgi
FT transport."
FT /evidence="ECO:0000269|PubMed:16709803"
FT MUTAGEN 346
FT /note="Missing: Impairs the interaction with coat protein
FT complex II; impairs the anterograde ER-to-Golgi transport."
FT /evidence="ECO:0000269|PubMed:16709803"
FT STRAND 24..35
FT /evidence="ECO:0007829|PDB:5IUE"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 39..49
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 52..58
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 78..105
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 115..124
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 128..139
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 142..147
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 161..170
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 173..182
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 184..195
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 207..214
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 216..232
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:5IUE"
FT TURN 246..248
FT /evidence="ECO:0007829|PDB:5KNM"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 262..271
FT /evidence="ECO:0007829|PDB:5IUE"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:5IUE"
FT STRAND 291..293
FT /evidence="ECO:0007829|PDB:5IUE"
FT CONFLICT P30511-3:353
FT /note="N -> L (in Ref. 10; AAH09260)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 39062 MW; D4782968A67E9B7D CRC64;
MAPRSLLLLL SGALALTDTW AGSHSLRYFS TAVSRPGRGE PRYIAVEYVD DTQFLRFDSD
AAIPRMEPRE PWVEQEGPQY WEWTTGYAKA NAQTDRVALR NLLRRYNQSE AGSHTLQGMN
GCDMGPDGRL LRGYHQHAYD GKDYISLNED LRSWTAADTV AQITQRFYEA EEYAEEFRTY
LEGECLELLR RYLENGKETL QRADPPKAHV AHHPISDHEA TLRCWALGFY PAEITLTWQR
DGEEQTQDTE LVETRPAGDG TFQKWAAVVV PPGEEQRYTC HVQHEGLPQP LILRWEQSPQ
PTIPIVGIVA GLVVLGAVVT GAVVAAVMWR KKSSDRNRGS YSQAAV
