HLA-F

Protein identityUniProt · HPA

UniProt accession

P30511

Gene

HLA-F

Ensembl

ENSG00000204642

Chromosome

6

Canonical length

346 aa

Protein class

Plasma proteins, Predicted membrane proteins

OverviewNCBI Gene

This gene belongs to the HLA class I heavy chain paralogues. It encodes a non-classical heavy chain that forms a heterodimer with a beta-2 microglobulin light chain, with the heavy chain anchored in the membrane. Unlike most other HLA heavy chains, this molecule is localized in the endoplasmic reticulum and Golgi apparatus, with a small amount present at the cell surface in some cell types. It contains a divergent peptide-binding groove, and is thought to bind a restricted subset of peptides for immune presentation. This gene exhibits few polymorphisms. Multiple transcript variants encoding different isoforms have been found for this gene. These variants lack a coding exon found in transcripts from other HLA paralogues due to an altered splice acceptor site, resulting in a shorter cytoplasmic domain. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

346 residues, UniProt reviewed canonical sequence.

>P30511|HLA-F
     1  MAPRSLLLLL SGALALTDTW AGSHSLRYFS TAVSRPGRGE PRYIAVEYVD DTQFLRFDSD
    61  AAIPRMEPRE PWVEQEGPQY WEWTTGYAKA NAQTDRVALR NLLRRYNQSE AGSHTLQGMN
   121  GCDMGPDGRL LRGYHQHAYD GKDYISLNED LRSWTAADTV AQITQRFYEA EEYAEEFRTY
   181  LEGECLELLR RYLENGKETL QRADPPKAHV AHHPISDHEA TLRCWALGFY PAEITLTWQR
   241  DGEEQTQDTE LVETRPAGDG TFQKWAAVVV PPGEEQRYTC HVQHEGLPQP LILRWEQSPQ
   301  PTIPIVGIVA GLVVLGAVVT GAVVAAVMWR KKSSDRNRGS YSQAAV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HLA-F can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

173 nTPM

Expression across tissuesHPA

ReferencesPubMed · IEDB

Publications for HLA-F from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.93

gnomAD pLI

0

gnomAD missense Z

1.1

DepMap mean gene effect

-0.07

DepMap dependency class

none

OntologyGO

Biological processes

• antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independent
• antigen processing and presentation of endogenous peptide antigen via MHC class Ib
• antigen processing and presentation of exogenous peptide antigen via MHC class Ib
• immune response
• negative regulation of natural killer cell cytokine production
• negative regulation of natural killer cell mediated cytotoxicity
• 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
• negative regulation of natural killer cell degranulation

Molecular functions

• 14-3-3 protein binding
• beta-2-microglobulin binding
• peptide antigen binding
• signaling receptor binding
• TAP1 binding
• TAP2 binding

Cellular components

• cell surface
• early endosome membrane
• endoplasmic reticulum
• ER to Golgi transport vesicle membrane
• external side of plasma membrane
• extracellular space
• Golgi membrane
• 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

Protein domainsUniProt · Pfam · InterPro

• MHC class I alpha chain, alpha1 alpha2 domains
• Immunoglobulin/major histocompatibility complex, conserved site
• Immunoglobulin C1-set
• Immunoglobulin-like domain
• MHC class I-like antigen recognition-like
• MHC classes I/II-like antigen recognition protein
• Immunoglobulin-like fold
• Immunoglobulin-like domain superfamily
• MHC class I-like antigen recognition-like superfamily
• Antigen-presenting and immune regulatory MHC class I-related
• Class I Histocompatibility antigen, domains alpha 1 and 2
• Immunoglobulin C1-set domain

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Endosome
• Glycoprotein
• Immunity
• Lysosome
• Membrane
• MHC I
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of HLA-F in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CALR
• HLA-E
• KIR2DS4
• KIR3DL2
• KIR3DS1
• LILRB1