Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P01889 HLA-B
| Class:Id | ReferenceGeneProduct:48971 |
|---|---|
| _chainChangeLog | signal peptide:1-24 added on Fri February 6 2015;chain:25-362 added on Fri February 6 2015 |
| _displayName | UniProt:P01889 HLA-B |
| _timestamp | 2026-02-20 22:33:03 |
| chain | signal peptide:1-24 chain:25-362 |
| checksum | 5E5A7BDE031403D6 |
| comment | FUNCTION Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-B-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:23209413, PubMed:25808313, PubMed:29531227, PubMed:9620674). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:18991276, PubMed:7743181). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:24600035, PubMed:29531227, PubMed:9620674). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via constitutive proteasome and IFNG-induced immunoproteasome (PubMed:23209413). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:25808313, PubMed:29531227).FUNCTION Allele B*07:02: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and mainly a Leu anchor residue at the C-terminus (PubMed:7743181). Presents a long peptide (APRGPHGGAASGL) derived from the cancer-testis antigen CTAG1A/NY-ESO-1, eliciting a polyclonal CD8-positive T cell response against tumor cells (PubMed:29531227). Presents viral epitopes derived from HIV-1 gag-pol (TPQDLNTML) and Nef (RPQVPLRPM) (PubMed:25808313). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (SPRWYFYYL) (PubMed:32887977). Displays self-peptides including a peptide derived from the signal sequence of HLA-DPB1 (APRTVALTA) (PubMed:7743181).FUNCTION Allele B*08:01: Presents to CD8-positive T cells viral epitopes derived from EBV/HHV-4 EBNA3 (QAKWRLQTL), eliciting cytotoxic T cell response.FUNCTION Allele B*13:02: Presents multiple HIV-1 epitopes derived from gag (RQANFLGKI, GQMREPRGSDI), nef (RQDILDLWI), gag-pol (RQYDQILIE, GQGQWTYQI) and rev (LQLPPLERL), all having in common a Gln residue at position 2 and mainly hydrophobic amino acids Leu, Ile or Val at the C-terminus. Associated with successful control of HIV-1 infection.FUNCTION Allele B*18:01: Preferentially presents octameric and nonameric peptides sharing a common motif, namely a Glu at position 2 and Phe or Tyr anchor residues at the C-terminus (PubMed:14978097, PubMed:18991276, PubMed:23749632). Presents an EBV/HHV-4 epitope derived from BZLF1 (SELEIKRY) (PubMed:23749632). May present to CD8-positive T cells an antigenic peptide derived from MAGEA3 (MEVDPIGHLY), triggering an anti-tumor immune response (PubMed:12366779). May display a broad repertoire of self-peptides with a preference for peptides derived from RNA-binding proteins (PubMed:14978097).FUNCTION Allele B*27:05: Presents to CD8-positive T cells immunodominant viral epitopes derived from HCV POLG (ARMILMTHF), HIV-1 gag (KRWIILGLNK), IAV NP (SRYWAIRTR), SARS-CoV-2 N/nucleoprotein (QRNAPRITF), EBV/HHV-4 EBNA4 (HRCQAIRKK) and EBV/HHV-4 EBNA6 (RRIYDLIEL), conferring longterm protection against viral infection (PubMed:15113903, PubMed:18385228, PubMed:19139562, PubMed:32887977, PubMed:9620674). Can present self-peptides derived from cytosolic and nuclear proteins. All peptides carry an Arg at position 2 (PubMed:1922338). The peptide-bound form interacts with NK cell inhibitory receptor KIR3DL1 and inhibits NK cell activation in a peptide-specific way, being particularly sensitive to the nature of the amino acid side chain at position 8 of the antigenic peptide (PubMed:15657948, PubMed:8879234). KIR3DL1 fails to recognize HLA-B*27:05 in complex with B2M and EBV/HHV-4 EBNA6 (RRIYDLIEL) peptide, which can lead to increased activation of NK cells during infection (PubMed:15657948). May present an altered repertoire of peptides in the absence of TAP1-TAP2 and TAPBPL (PubMed:9620674).FUNCTION Allele B*40:01: Presents immunodominant viral epitopes derived from EBV/HHV-4 LMP2 (IEDPPFNSL) and SARS-CoV-2 N/nucleoprotein (MEVTPSGTWL), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:32887977). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and a Leu anchor residue at the C-terminus (PubMed:18991276).FUNCTION Allele B*41:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.FUNCTION Allele B*44:02: Presents immunodominant viral epitopes derived from EBV/HHV-4 EBNA4 (VEITPYKPTW) and EBNA6 (AEGGVGWRHW, EENLLDFVRF), triggering memory CD8-positive T cell response (PubMed:18991276, PubMed:9620674). Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Phe, Tyr or Trp anchor residues at the C-terminus (PubMed:18991276).FUNCTION Allele B*45:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.FUNCTION Allele B*46:01: Preferentially presents nonameric peptides sharing a signature motif, namely Ala and Leu at position 2 and Tyr, Phe, Leu, or Met anchor residues at the C-terminus. The peptide-bound form interacts with KIR2DL3 and inhibits NK cell cytotoxic response in a peptide-specific way.FUNCTION Allele B*47:01: Displays self-peptides sharing a signature motif, namely an Asp at position 2 and Leu or Met anchor residues at the C-terminus.FUNCTION Allele B*49:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ile or Val anchor residues at the C-terminus.FUNCTION Allele B*50:01: Displays self-peptides sharing a signature motif, namely a Glu at position 2 and Ala or Pro anchor residues at the C-terminus.FUNCTION Allele B*51:01: Presents an octameric HIV-1 epitope derived from gag-pol (TAFTIPSI) to the public TRAV17/TRBV7-3 TCR clonotype, strongly suppressing HIV-1 replication.FUNCTION Allele B*54:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.FUNCTION Allele B*55:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.FUNCTION Allele B*56:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Ala anchor residue at the C-terminus.FUNCTION Allele B*57:01: The peptide-bound form recognizes KIR3DL1 and inhibits NK cell cytotoxic response. Presents HIV gag peptides (immunodominant KAFSPEVIPMF and subdominant KALGPAATL epitopes) predominantly to CD8-positive T cell clones expressing a TRAV41-containing TCR, triggering HLA-B-restricted T cell responses.FUNCTION Allele B*67:01: Displays peptides sharing a common signature motif, namely a Pro residue at position 2 and Leu anchor residue at the C-terminus.SUBUNIT Heterotrimer that consists of an alpha chain HLA-B, a beta chain B2M and a peptide (peptide-HLA-B-B2M) (PubMed:15657948, PubMed:17057332, PubMed:22020283, PubMed:24600035, PubMed:25808313, PubMed:29531227). Early in biogenesis, HLA-B-B2M dimer interacts with the components of the peptide-loading complex composed of TAPBP, TAP1-TAP2, TAPBPL, PDIA3/ERP57 and CALR (PubMed:26416272, PubMed:26439010, PubMed:9036970, PubMed:9620674). Interacts with TAP1-TAP2 transporter via TAPBP; this interaction is obligatory for the loading of peptide epitopes delivered to the ER by TAP1-TAP2 transporter (PubMed:9036970, PubMed:9620674). Interacts with TAPBPL; TAPBPL binds peptide-free HLA-B-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange for higher affinity peptides (PubMed:26439010). Only optimally assembled peptide-HLA-B-B2M trimer translocates to the surface of antigen-presenting cells, where it interacts with TCR and CD8 coreceptor on the surface of T cells. HLA-B (via polymorphic alpha-1 and alpha-2 domains) interacts with antigen-specific TCR (via CDR1, CDR2 and CDR3 domains) (PubMed:24600035, PubMed:29531227). One HLA-B molecule (mainly via nonpolymorphic alpha-3 domain) interacts with one CD8A homodimer (via CDR-like loop); this interaction ensures peptide-HLA-B-B2M recognition by CD8-positive T cells only (PubMed:29531227). Allele B*57:01 interacts (via Bw4 motif) with KIR3DL1 (via Ig-like C2-type domain); this interaction may interfere with peptide binding (PubMed:22020283, PubMed:25480565). Allele B*46:01 interacts with KIR2DL3 (PubMed:28514659).SUBUNIT (Microbial infection) Interacts with HTLV-1 accessory protein p12I.INTERACTION The alpha-1 domain is a structural part of the peptide-binding cleft (PubMed:25808313). Residues 101-107 determine Bw4/Bw6 motifs, which serologically distinguish HLA-B alleles. Each HLA-B allele possesses either the Bw4 or Bw6 motif. Only HLA-B alleles bearing the Bw4 epitope are recognized by NK cell inhibitory receptor KIR3DL1 (PubMed:22020283, PubMed:25480565).DOMAIN The alpha-2 domain is a structural part of the peptide-binding cleft (PubMed:25808313). Mediates the interaction with TAP1-TAP2 complex (By similarity).DOMAIN The alpha-3 Ig-like domain mediates the interaction with CD8 coreceptor.DOMAIN The VL9 peptide/epitope (VMAPRT[V/L][L/V/I/F]L) derived from the signal sequence is loaded onto HLA-E and enables HLA-E expression at the plasma membrane. Distinct VL9 peptides presented by HLA-E variably affect its recognition by KLRD1-KLRC1 or KLRD1-KLRC2 receptors on NK cells. Most HLA-B allotypes contain VL9 peptides with low affinity for HLA-E. The VL9 peptide derived from HLA-B*07, B*08, B*14, B*38, B*39, B*42 and B*48 allotypes, displays high affinity for HLA-E yet fails to drive NK cell activation. It outcompetes other VL9 peptides derived from HLA-A and HLA-C for binding to HLA-E, lowering the threshold of NK cell activation.POLYMORPHISM The most polymorphic of the mammalian genome. Polymorphic residues encode for alpha-1 and alpha-2 domains of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The human population is estimated to have millions of HLA-B alleles. But only 17 common HLA-A alleles are considered core alleles, representing all functionally significant variation (polymorphism) in alpha-1 and alpha-2 domains. These are: B*07:02; B*08:01; B*13:02; B*15:01; B*18:01; B*27:05; B*35:01; B*37:01; B*38:01; B*40:01; B*44:02; B*45:01; B*51:01; B*54:01; B*57:01 and B*73:01. Among these, B*07:02; B*15:01; B*18:01; B*37:01; B*51:01; B*54:01; B*57:01 and B*73:01, were likely passed by introgression from archaic to modern humans. Functional alleles of more recent origin (non-core) were derived by recombination (PubMed:28650991). The sequence shown is that of B*07:02. The sequences of core alleles and common representative alleles of serologically distinct allele groups are described as variants of B*07:02. Allelic variations of HLA-B signal peptide regulate HLA-E recognition by KLRD1-KLRC1 and KLRD1-KLRC2 receptors in viral infection and tumorigenesis by affecting its processing and by changing the affinity of HLA-E-VL9 complex for KLRD1-KLRC1 and KLRD1-KLRC2 receptors.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Increased susceptibility to Stevens-Johnson syndrome is conferred by allele B*15:02.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. A restricted number of HLA-B*27 subtypes can be associated with ankylosing spondylitis and other B*27-related diseases, and an elevated frequency of the B*27:02 allele in ankylosing spondylitis patients is identified. The allele B*27:07 seems to have a protective role in some populations because it was found only in the healthy controls.DISEASE There is evidence that HLA-B*51 is associated with susceptibility to Behcet disease (BD). However, it is not certain whether HLA-B*51 itself or a closely linked gene is responsible for susceptibility. The world distribution of HLA-B*51 in healthy people corresponds to the global distribution of BD; in Southern hemisphere countries (Africa, South Pacific, etc.) and in some parts of Europe, the prevalence of HLA-B*51 in healthy people is low or null, corresponding to a low prevalence of BD. The wide variation that exists in the relative risk of HLA-B*51 would support other nongenetic risk factors.DISEASE The presence of allele B*57:01 is associated with increased susceptibility to abacavir hypersensitivity [MIM:142830] in HIV-1 patients.DISEASE Allele group B*08 is associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis). |
| description | recommendedName: HLA class I histocompatibility antigen, B alpha chain alternativeName: Human leukocyte antigen B shortName: HLA-B |
| geneName | HLA-B HLAB |
| identifier | P01889 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Cell membrane Direct protein sequencing Disulfide bond Endoplasmic reticulum Glycoprotein Host-virus interaction Immunity Innate immunity Membrane MHC I Phosphoprotein Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | HLA-B |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8962423] ENSEMBL:ENSG00000234745 HLA-B [Homo sapiens] |
| secondaryIdentifier | HLAB_HUMAN A0A2I6Q7B5 B0V0B8 G3GN01 O02862 O02956 O02957 O02960 O19555 O19556 O19595 O19615 O19624 O19625 O19627 O19641 O19651 O19675 O19692 O19758 O19779 O19783 O46702 O62897 O62901 O62915 O62917 O62919 O77933 O77959 O78053 O78138 O78160 O78163 O78172 O78173 O78180 O78217 O95730 O98140 P01890 P03989 P10317 P10318 P10319 P10320 P18463 P18464 P18465 P19373 P30460 P30461 P30462 P30463 P30464 P30465 P30466 P30467 P30468 P30469 P30470 P30471 P30472 P30473 P30474 P30475 P30476 P30477 P30478 P30479 P30480 P30481 P30482 P30483 P30484 P30485 P30486 P30487 P30488 P30489 P30490 P30491 P30492 P30493 P30494 P30495 P30496 P30497 P30498 P30513 P30685 P79489 P79490 P79496 P79504 P79523 P79524 P79542 P79555 Q04826 Q08136 Q29633 Q29636 Q29638 Q29661 Q29665 Q29678 Q29679 Q29681 Q29693 Q29695 Q29697 Q29718 Q29742 Q29749 Q29762 Q29764 Q29829 Q29836 Q29842 Q29845 Q29846 Q29847 Q29848 Q29850 Q29851 Q29852 Q29854 Q29855 Q29857 Q29858 Q29861 Q29924 Q29925 Q29933 Q29935 Q29936 Q29940 Q29953 Q29961 Q29982 Q30173 Q30198 Q31603 Q31610 Q31612 Q31613 Q546L8 Q546M4 Q5JP37 Q5QT24 Q5RIP1 Q5SRJ2 Q5TK76 Q5TK77 Q860I4 Q861B5 Q8HWF0 Q8MGQ3 Q8MHN4 Q8SNC5 Q95343 Q95344 Q95365 Q95369 Q95392 Q95HA3 Q95HA8 Q95HM9 Q95IA6 Q95IB8 Q95IH5 Q95J00 Q96IT9 Q9BCM6 Q9BCM7 Q9BCM8 Q9BD06 Q9BD38 Q9BD43 Q9GIL3 Q9GIM3 Q9GIX1 Q9GIY5 Q9GIZ0 Q9GIZ9 Q9GJ00 Q9GJ17 Q9GJ20 Q9GJ23 Q9GJ31 Q9GJF0 Q9GJM7 Q9MX21 Q9MY37 Q9MY42 Q9MY43 Q9MY61 Q9MY75 Q9MY78 Q9MY79 Q9MY84 Q9MY92 Q9MY93 Q9MY94 Q9MYB8 Q9MYC3 Q9MYC7 Q9MYF4 Q9MYG1 Q9TP35 Q9TP36 Q9TP37 Q9TP95 Q9TPQ7 Q9TPQ9 Q9TPR2 Q9TPR4 Q9TPS6 Q9TPT2 Q9TPT4 Q9TPT6 Q9TPV2 Q9TQG1 Q9TQH3 Q9TQH6 Q9TQH7 Q9TQH8 Q9TQH9 Q9TQM2 Q9TQN4 Q9TQN6 Q9UQS8 Q9UQT0 |
| sequenceLength | 362 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:167756] class I MHC B7 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:983073] class I MHC B7 [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:983362] class I MHC B7 [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:983379] class I MHC B7 [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:1236753] class I MHC B7 [phagocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:1236872] class I MHC B7 [early endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:6804794] class I MHC B7 [secretory granule membrane] [Homo sapiens] [EntityWithAccessionedSequence:8863942] class I MHC B7 [recycling endosome membrane] [Homo sapiens] |
| (referenceSequence) | [GroupModifiedResidue:9985195] N4-(N-acetylamino)glucosyl-L-asparagine (N-(α-Glc-(1→3)-α-Man-(1→2)-α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→3)-(α-Man-(1→2)-α-Man-(1→6))-α-Man-(1→6))-β-Man-(1→4)-β-GlcNAc-(1→4)-β-GlcNAc)-L-Asn residue) at 110 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P01889 HLA-B (48971)
