UniProt functional annotation for Q8NHL6



	UniProt functional annotation for Q8NHL6

UniProt code: Q8NHL6.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles (PubMed:16455647, PubMed:28636952). Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of FCER1A signaling and serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions (PubMed:11907092, PubMed:9285411, PubMed:9842885). Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (PubMed:16455647). Upon interaction with peptide-bound HLA-G-B2M complex, triggers secretion of growth-promoting factors by decidual NK cells (PubMed:29262349, PubMed:19304799). Reprograms B cells toward an immune suppressive phenotype (PubMed:24453251). {ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:16455647, ECO:0000269|PubMed:19304799, ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:28636952, ECO:0000269|PubMed:29262349, ECO:0000269|PubMed:9285411, ECO:0000269|PubMed:9842885}.

Subunit: Binds PTPN6 when phosphorylated (PubMed:9285411). Binds FCER1A and FCGR1A (PubMed:9842885, PubMed:11907092). Interacts with human cytomegalovirus/HHV-5 protein UL18 (PubMed:10591185). Interacts with peptide-bound HLA-G-B2M complex (PubMed:16455647). Interacts with peptide-bound HLA-F-B2M complex but not with peptide-free HLA-F open conformer. It does not probe the peptide sequence directly (PubMed:28636952). {ECO:0000269|PubMed:10591185, ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:16455647, ECO:0000269|PubMed:28636952, ECO:0000269|PubMed:9285411, ECO:0000269|PubMed:9842885}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:29262349, ECO:0000305|PubMed:19658091}; Single-pass type I membrane protein {ECO:0000255}.

Subcellular location: [Isoform 5]: Secreted {ECO:0000269|PubMed:19658091}.

Tissue specificity: Expressed in B cells, monocytes and various dendritic cell (DC) subsets including myeloid, plasmacytoid and tolerogenic DCs (at protein level) (PubMed:20448110, PubMed:9285411, PubMed:9842885, PubMed:24453251). Expressed in decidual macrophages (at protein level) (PubMed:19304799). Expressed in decidual NK cells (at protein level) (PubMed:29262349). {ECO:0000269|PubMed:19304799, ECO:0000269|PubMed:20448110, ECO:0000269|PubMed:24453251, ECO:0000269|PubMed:29262349, ECO:0000269|PubMed:9285411, ECO:0000269|PubMed:9842885}.

Domain: Contains 4 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Ptm: Phosphorylated on tyrosine residues. Dephosphorylated by PTPN6. {ECO:0000269|PubMed:11907092, ECO:0000269|PubMed:9285411, ECO:0000269|PubMed:9842885}.

Miscellaneous: [Isoform 5]: May act as dominant negative regulator and block the interaction between membrane-associated isoforms and HLA- class I. {ECO:0000269|PubMed:19658091}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles (PubMed:16455647, PubMed:28636952). Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of FCER1A signaling and serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions (PubMed:11907092, PubMed:9285411, PubMed:9842885). Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (PubMed:16455647). Upon interaction with peptide-bound HLA-G-B2M complex, triggers secretion of growth-promoting factors by decidual NK cells (PubMed:29262349, PubMed:19304799). Reprograms B cells toward an immune suppressive phenotype (PubMed:24453251). {ECO:0000269\|PubMed:11907092, ECO:0000269\|PubMed:16455647, ECO:0000269\|PubMed:19304799, ECO:0000269\|PubMed:24453251, ECO:0000269\|PubMed:28636952, ECO:0000269\|PubMed:29262349, ECO:0000269\|PubMed:9285411, ECO:0000269\|PubMed:9842885}.


Subunit:		Binds PTPN6 when phosphorylated (PubMed:9285411). Binds FCER1A and FCGR1A (PubMed:9842885, PubMed:11907092). Interacts with human cytomegalovirus/HHV-5 protein UL18 (PubMed:10591185). Interacts with peptide-bound HLA-G-B2M complex (PubMed:16455647). Interacts with peptide-bound HLA-F-B2M complex but not with peptide-free HLA-F open conformer. It does not probe the peptide sequence directly (PubMed:28636952). {ECO:0000269\|PubMed:10591185, ECO:0000269\|PubMed:11907092, ECO:0000269\|PubMed:16455647, ECO:0000269\|PubMed:28636952, ECO:0000269\|PubMed:9285411, ECO:0000269\|PubMed:9842885}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:20448110, ECO:0000269\|PubMed:24453251, ECO:0000269\|PubMed:29262349, ECO:0000305\|PubMed:19658091}; Single-pass type I membrane protein {ECO:0000255}.
Subcellular location:		[Isoform 5]: Secreted {ECO:0000269\|PubMed:19658091}.
Tissue specificity:		Expressed in B cells, monocytes and various dendritic cell (DC) subsets including myeloid, plasmacytoid and tolerogenic DCs (at protein level) (PubMed:20448110, PubMed:9285411, PubMed:9842885, PubMed:24453251). Expressed in decidual macrophages (at protein level) (PubMed:19304799). Expressed in decidual NK cells (at protein level) (PubMed:29262349). {ECO:0000269\|PubMed:19304799, ECO:0000269\|PubMed:20448110, ECO:0000269\|PubMed:24453251, ECO:0000269\|PubMed:29262349, ECO:0000269\|PubMed:9285411, ECO:0000269\|PubMed:9842885}.
Domain:		Contains 4 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
Ptm:		Phosphorylated on tyrosine residues. Dephosphorylated by PTPN6. {ECO:0000269\|PubMed:11907092, ECO:0000269\|PubMed:9285411, ECO:0000269\|PubMed:9842885}.
Miscellaneous:		[Isoform 5]: May act as dominant negative regulator and block the interaction between membrane-associated isoforms and HLA- class I. {ECO:0000269\|PubMed:19658091}.