HLA-E
entrez
3133
canonical
uniprot
P13747
canonical
ensembl
ENSG00000204592
resolver
ensembl
ENSG00000206493
resolver
ensembl
ENSG00000225201
resolver
ensembl
ENSG00000229252
resolver
ensembl
ENSG00000230254
resolver
ensembl
ENSG00000233904
resolver
ensembl
ENSG00000236632
resolver
ensp
ENSP00000365817
resolver
ensp
ENSP00000373091
resolver
ensp
ENSP00000390707
resolver
ensp
ENSP00000397420
resolver
ensp
ENSP00000400458
resolver
ensp
ENSP00000402694
resolver
ensp
ENSP00000409910
resolver
ensp
ENSP00000566696
resolver
ensp
ENSP00000566697
resolver
ensp
ENSP00000566699
resolver
enst
ENST00000376630
resolver
enst
ENST00000383597
resolver
enst
ENST00000415289
resolver
enst
ENST00000415649
resolver
enst
ENST00000425603
resolver
enst
ENST00000427936
resolver
enst
ENST00000444683
resolver
enst
ENST00000896637
resolver
enst
ENST00000896638
resolver
enst
ENST00000896640
resolver
genesymbol
HLA-E
resolver
genesymbol_syn
HLA-6.2
resolver
genesymbol_syn
HLAE
resolver
hgnc
HGNC:4962
resolver
uniprot
A8K8M6
resolver
uniprot
E2G051
resolver
uniprot
O19682
resolver
uniprot
Q30169
resolver
uniprot
Q6DU44
resolver
uniprot
Q9BT83
resolver
uniprot
Q9GIY7
resolver
uniprot
Q9GIY8
resolver
uniprot_entry
A8K8M6_HUMAN
resolver
uniprot_entry
HLAE_HUMAN
resolver
uniprot_entry
O19682_HUMAN
resolver
uniprot_sec
E2G051
resolver
uniprot_sec
Q30169
resolver
uniprot_sec
Q6DU44
resolver
uniprot_sec
Q9BT83
resolver
uniprot_sec
Q9GIY7
resolver
uniprot_sec
Q9GIY8
resolver
amino_acid_sequence
MVDGTLLLLLSEALALTQTWAGSHSLKYFHTSVSRPGRGEPRFISVGYVDDTQFVRFDNDAASPRMVPRAPWMEQEGSEYWDRETRSARDTAQIFRVNLRTLRGYYNQSEAGSHTLQWMHGCELGPDGRFLRGYEQFAYDGKDYLTLNEDLRSWTAVDTAAQISEQKSNDASEAEHQRAYLEDTCVEWLHKYLEKGKETLLHLEPPKTHVTHHPISDHEATLRCWALGFYPAEITLTWQQDGEGHTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPEPVTLRWKPASQPTIPIVGIIAGLVLLGSVVSGAVVAAVIWRKKSSGGKGGSYSKAEWSDSAQGSESHSL
uniprot
proteins
function
FUNCTION: Non-classical major histocompatibility class Ib molecule involved in immune self-nonself discrimination. In complex with B2M/beta-2-microglobulin binds nonamer self-peptides derived from the signal sequence of classical MHC class Ia molecules (VL9 peptides - VMAPRT[V/L][L/V/I/F]L) (PubMed:18083576, PubMed:18339401, PubMed:35705051, PubMed:37264229, PubMed:9754572). Peptide-bound HLA-E-B2M heterotrimeric complex primarily functions as a ligand for natural killer (NK) cell inhibitory receptor KLRD1-KLRC1, enabling NK cells to monitor the expression of other MHC class I molecules in healthy cells and to tolerate self (PubMed:17179229, PubMed:18083576, PubMed:37264229, PubMed:9486650, PubMed:9754572). Upon cellular stress, preferentially binds signal sequence-derived peptides from stress-induced chaperones and is no longer recognized by NK cell inhibitory receptor KLRD1-KLRC1, resulting in impaired protection from NK cells (PubMed:12461076). Binds signal sequence-derived peptides from non-classical MHC class Ib HLA-G molecules and acts as a ligand for NK cell activating receptor KLRD1-KLRC2, likely playing a role in the generation and effector functions of adaptive NK cells and in maternal-fetal tolerance during pregnancy (PubMed:30134159, PubMed:37264229, PubMed:9754572). Besides self-peptides, can also bind and present pathogen-derived peptides conformationally similar to VL9 peptides to alpha-beta T cell receptor (TCR) on unconventional CD8-positive cytotoxic T cells, ultimately triggering antimicrobial immune response (PubMed:16474394, PubMed:20195504, PubMed:30087334, PubMed:34228645). Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV17-containing TCR, triggering HLA-E-restricted T cell responses (PubMed:34228645). Presents mycobacterial peptides to HLA-E-restricted CD8-positive T cells eliciting both cytotoxic and immunoregulatory functions (PubMed:20195504, PubMed:35705051). {ECO:0000269|PubMed:12461076, ECO:0000269|PubMed:16474394, ECO:0000269|PubMed:17179229, ECO:0000269|PubMed:18083576, ECO:0000269|PubMed:18339401, ECO:0000269|PubMed:20195504, ECO:0000269|PubMed:30087334, ECO:0000269|PubMed:30134159, ECO:0000269|PubMed:34228645, ECO:0000269|PubMed:35705051, ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9486650, ECO:0000269|PubMed:9754572}.; FUNCTION: (Microbial infection) Viruses like human cytomegalovirus have evolved an escape mechanism whereby virus-induced down-regulation of host MHC class I molecules is coupled to the binding of viral peptides to HLA-E, restoring HLA-E expression and inducing HLA-E-dependent NK cell immune tolerance to infected cells. {ECO:0000269|PubMed:10799855, ECO:0000269|PubMed:23335510}.; FUNCTION: (Microbial infection) May bind HIV-1 gag/Capsid protein p24-derived peptide (AISPRTLNA) on infected cells and may inhibit NK cell cytotoxicity, a mechanism that allows HIV-1 to escape immune recognition. {ECO:0000269|PubMed:15751767}.; FUNCTION: (Microbial infection) Upon SARS-CoV-2 infection, may contribute to functional exhaustion of cytotoxic NK cells and CD8-positive T cells (PubMed:32859121). Binds SARS-CoV-2 S/Spike protein S1-derived peptide (LQPRTFLL) expressed on the surface of lung epithelial cells, inducing NK cell exhaustion and dampening of antiviral immune surveillance (PubMed:32859121). {ECO:0000269|PubMed:32859121}.
uniprot
proteins
mass_dalton
40058
uniprot
proteins
mutagenesis
MUTAGEN 83; /note="R->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 86; /note="R->A: Reduces the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 90; /note="D->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 93; /note="Q->A: Impairs the recognition by KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 96; /note="R->A: Abolishes the recognition by KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 97; /note="V->A: Impairs the recognition by KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 100; /note="R->A: Reduces the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 110; /note="E->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 129; /note="R->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 167; /note="K->A: Impairs folding."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 170; /note="D->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 173; /note="E->A: Impairs the recognition by KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 175; /note="E->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 176; /note="H->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 183; /note="D->A: Impairs the recognition by KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 187; /note="E->A: Reduces the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576"; MUTAGEN 235; /note="T->A: Has no impact on the affinity for KLRD1-KLRC1."; /evidence="ECO:0000269|PubMed:18083576
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:17179229}.; PTM: The soluble form (sHLA-E) can be partly produced by proteolytic cleavage at the cell surface (shedding) by a matrix metalloproteinase. Alternative splicing is also suggested as a mechanism for generation of sHLA-E, although it remains to be proved. {ECO:0000269|PubMed:17179229}.
uniprot
proteins
protein_family
MHC class I family
uniprot
proteins
pubmed
10064069
uniprot
proteins
pubmed
10799855
uniprot
proteins
pubmed
12445303
uniprot
proteins
pubmed
12461076
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15751767
uniprot
proteins
pubmed
16474394
uniprot
proteins
pubmed
16570139
uniprot
proteins
pubmed
16702430
uniprot
proteins
pubmed
17179229
uniprot
proteins
pubmed
18083576
uniprot
proteins
pubmed
18339401
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
1977695
uniprot
proteins
pubmed
20195504
uniprot
proteins
pubmed
20483783
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22665232
uniprot
proteins
pubmed
23335510
uniprot
proteins
pubmed
28127896
uniprot
proteins
pubmed
30087334
uniprot
proteins
pubmed
30134159
uniprot
proteins
pubmed
3131426
uniprot
proteins
pubmed
3260916
uniprot
proteins
pubmed
32859121
uniprot
proteins
pubmed
34228645
uniprot
proteins
pubmed
35705051
uniprot
proteins
pubmed
37264229
uniprot
proteins
pubmed
9427624
uniprot
proteins
pubmed
9486650
uniprot
proteins
pubmed
9660937
uniprot
proteins
pubmed
9754572
uniprot
proteins
sequence_length
358
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17179229, ECO:0000269|PubMed:37264229, ECO:0000269|PubMed:9427624}; Single-pass type I membrane protein. Golgi apparatus membrane {ECO:0000269|PubMed:17179229}.; SUBCELLULAR LOCATION: [Soluble HLA class I histocompatibility antigen, alpha chain E]: Secreted {ECO:0000269|PubMed:17179229}.
uniprot
proteins
transmembrane_region
TRANSMEM 306..329; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins