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Details on Person UniProt:P01911 HLA-DRB1
| Class:Id | ReferenceGeneProduct:56329 |
|---|---|
| _chainChangeLog | signal peptide:1-29 added on Fri February 6 2015;chain:30-266 added on Fri February 6 2015 |
| _displayName | UniProt:P01911 HLA-DRB1 |
| _timestamp | 2026-02-20 21:39:06 |
| chain | signal peptide:1-29 chain:30-266 |
| checksum | 3B5912820A4654BE |
| comment | FUNCTION A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB1-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells (PubMed:15265931, PubMed:16148104, PubMed:22327072, PubMed:27591323, PubMed:29884618, PubMed:31495665, PubMed:8642306). Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:8145819). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (PubMed:31495665). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (PubMed:17182262, PubMed:23783831). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides (PubMed:25413013). The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (PubMed:8145819).FUNCTION Allele DRB1*01:01: Displays an immunodominant epitope derived from Bacillus anthracis pagA/protective antigen, PA (KLPLYISNPNYKVNVYAVT), to both naive and PA-specific memory CD4-positive T cells (PubMed:22327072). Presents immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (PHQFINLRSNNSATLIVPYV), contributing to viral clearance (PubMed:27591323). Displays commonly recognized peptides derived from IAV external protein HA (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK) and from internal proteins M, NP and PB1, with M-derived epitope (GLIYNRMGAVTTEV) being the most immunogenic (PubMed:25413013, PubMed:32668259, PubMed:8145819, PubMed:9075930). Presents a self-peptide derived from COL4A3 (GWISLWKGFSF) to TCR (TRAV14 biased) on CD4-positive, FOXP3-positive regulatory T cells and mediates immune tolerance to self (PubMed:28467828). May present peptides derived from oncofetal trophoblast glycoprotein TPBG 5T4, known to be recognized by both T-helper 1 and regulatory T cells (PubMed:31619516). Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP) (PubMed:9075930).FUNCTION Allele DRB1*03:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance (PubMed:27591323). Displays self-peptides derived from retinal SAG (NRERRGIALDGKIKHE) and thyroid TG (LSSVVVDPSIRHFDV) (PubMed:25413013). Presents viral epitopes derived from HHV-6B gH/U48 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). Presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and long-term protection (PubMed:19830726).FUNCTION Allele DRB1*04:01: Presents an immunodominant bacterial epitope derived from M.tuberculosis esxB/culture filtrate antigen CFP-10 (EISTNIRQAGVQYSR), eliciting CD4-positive T cell effector functions such as IFNG production and cytotoxic activity (PubMed:15265931). May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance (PubMed:27591323). Presents tumor epitopes derived from melanoma-associated TYR antigen (QNILLSNAPLGPQFP and DYSYLQDSDPDSFQD), triggering CD4-positive T cell effector functions such as GMCSF production (PubMed:8642306). Displays preferentially citrullinated self-peptides derived from VIM (GVYATR/citSSAVR and SAVRAR/citSSVPGVR) and ACAN (VVLLVATEGR/ CitVRVNSAYQDK) (PubMed:24190431). Displays self-peptides derived from COL2A1 (PubMed:9354468).FUNCTION Allele DRB1*04:02: Displays native or citrullinated self-peptides derived from VIM.FUNCTION Allele DRB1*04:04: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (HIVMQYMYVPPGAPIPTTRN) and VP2 (RGDSTITSQDVANAVVGYGV), contributing to viral clearance (PubMed:27591323). Displays preferentially citrullinated self-peptides derived from VIM (SAVRAR/citSSVPGVR) (PubMed:24190431).FUNCTION Allele DRB1*04:05: May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies.FUNCTION Allele DRB1*05:01: Presents an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load.FUNCTION Allele DRB1*07:01: Upon EBV infection, presents latent antigen EBNA2 peptide (PRSPTVFYNIPPMPLPPSQL) to CD4-positive T cells, driving oligoclonal expansion and selection of a dominant virus-specific memory T cell subset with cytotoxic potential to directly eliminate virus-infected B cells (PubMed:31308093). May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance (PubMed:27591323). In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (MTEYKLVVVGAVGVGKSALTIQLI), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:22929521). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a KRAS neoantigen (MTEYKLVVVGAVGVGKSALTIQLI) carrying G12V hotspot driver mutation and may mediate tumor regression (PubMed:30282837).FUNCTION Allele DRB1*11:01: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SDRIIQITRGDSTITSQDVA), contributing to viral clearance (PubMed:27591323). Presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and longterm protection (PubMed:19830726). In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions (PubMed:31495665).FUNCTION Allele DRB1*13:01: Presents viral epitopes derived from HHV-6B antigens to polyfunctional CD4-positive T cells implicated in control of HHV-6B infection.FUNCTION Allele DRB1*15:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SNNSATLIVPYVNAVPMDSM), contributing to viral clearance (PubMed:27591323). Displays a self-peptide derived from MBP (ENPVVHFFKNIVTPR) (PubMed:25413013, PubMed:9782128). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies.FUNCTION Allele DRB1*15:02: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:19120973).FUNCTION (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.SUBUNIT Heterotrimer that consists of an alpha chain HLA-DRA, a beta chain HLA-DRB1 and a peptide (peptide-MHCII) (PubMed:31619516, PubMed:32668259, PubMed:7477400, PubMed:9354468, PubMed:9782128). Newly synthesized alpha and beta chains forms a heterodimer (MHCII) that associates with the CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a trimer composed of three subunits and each subunit interacts with one MHCII dimer, blocking the peptide-binding cleft. As a result, MHCII molecules cannot bind peptides present in the ER (PubMed:7479981). The complex of MHCII and CD74/Ii is transported in vesicles from ER to Golgi to lysosomes, where it encounters antigenic peptides generated via proteolysis of endocytosed antigens. MHCII dimers are dissociated from CD74/Ii by the combined action of proteolysis and HLA-DM (PubMed:25413013). Lysosomal enzymes such as cathepsin, degrade CD74/Ii leaving a 24 amino acid remnant called class II-associated Ii or CLIP. Interacts (via the peptide binding cleft) with CLIP; this interaction inhibits antigen peptide binding before entry in the endosomal compartment (PubMed:7477400, PubMed:9075930). The displacement of CLIP and replacement by a high affinity peptide in lysosomes is performed by HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII, stabilizes empty MHCII and mediates the selection of high affinity peptides (PubMed:11070170, PubMed:23260142, PubMed:9075930). Interacts with HLA-DM heterodimer; this interaction is direct (PubMed:25413013). Interacts with TCR (via CDR3) (PubMed:29884618). Interacts (via beta-2 domain) with CD4 coreceptor (via Ig-like V-type domain); this interaction is of exceptionally low affinity yet necessary for optimal recognition of antigenic peptides (PubMed:21900604, PubMed:27114505).SUBUNIT (Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, enterotoxin D/entD and enterotoxin H/entH. Enterotoxins bind outside the peptide-binding cleft of MHCII: enterotoxin H/entH interacts via the beta-1 domain of MHCII and in a zinc-dependent way, whereas enterotoxin B/entB interacts primarily via the alpha-1 domain.SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus gp42 protein.INTERACTION The MHC class II complex transits through a number of intracellular compartments in the endocytic pathway until it reaches the cell membrane for antigen presentation (PubMed:18305173). Component of immunological synapses at the interface between T cell and APC (PubMed:29884618).TISSUE SPECIFICITY Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level) (PubMed:19830726, PubMed:23783831, PubMed:31495665). Expressed in thymic epithelial cells (at protein level) (PubMed:23783831).DOMAIN The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB1 alleles (PubMed:28467828, PubMed:8145819, PubMed:9354468, PubMed:9782128). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR (PubMed:19303388).DOMAIN The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor.PTM Ubiquitinated by MARCHF1 and MARCHF8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.POLYMORPHISM Highly polymorphic. Polymorphic residues encode for the beta-1 domain of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The sequence shown is that of DRB1*15:01. The sequences of common representative alleles of serologically distinct allele groups as defined in the catalog of common and well-documented HLA alleles, are described as variants of DRB1*15:01 (PubMed:23510415). In the context of hematological malignancy and T cell transplantation, alleles DRB1*03:01 and DRB1*13:01 present minor histocompatibility antigens derived respectively from host MTHFD1 and LY75 proteins, contributing to T cell-mediated graft-versus-leukemia effect and complete remission (PubMed:19706888).DISEASE In populations of European descent, allele DRB1*01:03 is associated with increased susceptibility to Crohn disease and colonic ulcerative colitis. Decreased heterozygosity in individuals with colonic ulcerative colitis suggests that it acts as a recessive risk allele.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:02, DRB1*11:01 and DRB1*12:01 are associated with sarcoidosis. Allele DRB1*04:02 is significantly associated with specific sarcodosis phenotypes such as eye, parotid and salivary gland involvement.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. In populations of European descent, allele DRB1*15:01 has the strongest association with multiple sclerosis among all HLA class II alleles. Additional risk is associated with the strongly linked alleles DRB1*03:01 and DQB1*02:01 as well as with allele DRB1*13:03 (PubMed:21833088). It is postulated that bacterial or viral infection triggers the autoimmune MS. Microbial peptides having low affinity crossreactivity to MBP autoantigen, may stimulate autoreactive T cells via molecular mimicry and initiate the autoimmune inflammation (PubMed:19303388).DISEASE Allele DRB1*15:01 is associated with increased susceptibility to Goodpasture syndrome. Can present a self-peptide derived from COL4A3 (GWISLWKGFSF) on TCR (TRAV19 biased) in pathogenic CD4-positive T-helper 1 and T-helper 17 cells, triggering autoimmune inflammation.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:01; DRB1*04:04; DRB1*04:05; DRB1*04:08; DRB1*10:01; DRB1*01:01 and DRB1*01:02 are associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis). Variations at position 40 in the peptide-binding cleft of these alleles explain most of the association to rheumatoid arthritis risk. |
| description | recommendedName: HLA class II histocompatibility antigen, DRB1 beta chain alternativeName: Human leukocyte antigen DRB1 shortName: HLA-DRB1 |
| geneName | HLA-DRB1 |
| identifier | P01911 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Cell membrane Cytoplasmic vesicle Direct protein sequencing Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Immunity Isopeptide bond Lysosome Membrane MHC II Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | HLA-DRB1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8988244] ENSEMBL:ENSG00000196126 HLA-DRB1 [Homo sapiens] |
| secondaryIdentifier | DRB1_HUMAN A0MWF2 A0N0W1 A2ICT1 A2TGX3 A4F5N0 A4ZXA5 A4ZXA6 A4ZY86 A5H000 A5HKN8 A7DZP9 A7LA26 A7UHG2 A7X5B1 A7X5B7 A7X5E0 A7X5E6 A7X5H8 A7X5J4 A7X5K7 A8K098 A8YQE9 A9JPG0 B0BK85 B0LUZ6 B0UYW1 B1GWE7 B2CR03 B2LVF9 B2NJ29 B2ZCY1 B3VTP8 B3VTQ3 B5A8Y2 B5A8Y3 B5B8U0 B5B9V5 B5B9V6 B5LZ25 B5QSK8 B6VCX2 B6VEL9 B7UDB2 B9VRA4 B9X248 C0LAB5 O02876 O02930 O19585 O19717 O19718 O19739 O19788 O46699 O46793 O46872 O62869 O62889 O77969 O78047 O78210 O98212 P01912 P01914 P04229 P13758 P13759 P13760 P13761 P20039 P79545 Q06662 Q0PGR5 Q0PQ39 Q14280 Q14QT2 Q155F7 Q19AF2 Q19K86 Q1AP33 Q1G0Z9 Q1JRP3 Q1KLJ6 Q27PR6 Q27PR7 Q29673 Q29720 Q29722 Q29734 Q29770 Q29771 Q29772 Q29790 Q29792 Q29800 Q29806 Q29833 Q29874 Q29875 Q29886 Q29968 Q29974 Q29975 Q2A120 Q2HZE5 Q2L9H4 Q2LE76 Q2MF40 Q2MJA6 Q2MZ92 Q2VQU1 Q2YHQ2 Q30006 Q30108 Q30112 Q30115 Q30116 Q30117 Q30120 Q30134 Q30142 Q30145 Q30149 Q30159 Q30166 Q30167 Q30200 Q307W5 Q31636 Q32MY7 Q3HUP9 Q3KTM1 Q3LA84 Q3LA87 Q3LA88 Q3LA89 Q3LA90 Q3LA91 Q3LA92 Q3LA93 Q3LA94 Q3LA95 Q3LA96 Q3LA97 Q3LA98 Q3LA99 Q3LAA0 Q3LAA1 Q3LAA2 Q3MQ60 Q3T919 Q4PRC3 Q4PRC5 Q4VZY7 Q53IG1 Q56FN9 Q56FP1 Q56FP2 Q56FP3 Q58F52 Q5BM92 Q5EER6 Q5K3W2 Q5NDB9 Q5U9W6 Q5UBA2 Q5UT58 Q5W3L4 Q5Y7A7 Q5Y7B0 Q5Y7B9 Q5Y7E9 Q5Y7G0 Q683P7 Q6REE2 Q6T865 Q6U387 Q701T1 Q70GL2 Q70Q85 Q768U2 Q768U4 Q7M2H4 Q7YNY9 Q7YP03 Q7YP04 Q7YQ26 Q7YQA3 Q7YQA5 Q860D8 Q860D9 Q860E5 Q860H8 Q860S0 Q860Z3 Q861G6 Q861H0 Q861H4 Q861H5 Q861H7 Q861H8 Q8HWQ6 Q8MH59 Q8MH60 Q8WLU3 Q8WMA0 Q95348 Q95383 Q95389 Q95461 Q95HK1 Q95HL0 Q95HL1 Q95IE3 Q95IG2 Q95IT6 Q96HZ9 Q9BCL7 Q9BCP0 Q9BCP1 Q9BCP2 Q9BCP5 Q9BD21 Q9BD33 Q9BD40 Q9GIK5 Q9GIL5 Q9GIL6 Q9GIP3 Q9GIX8 Q9GIX9 Q9GIY0 Q9GIY1 Q9GIY2 Q9GIY3 Q9GIY4 Q9GJ25 Q9GJ56 Q9GJ57 Q9GJ58 Q9GJ60 Q9GJF8 Q9GJF9 Q9GJG0 Q9MXZ0 Q9MXZ5 Q9MY13 Q9MY45 Q9MY56 Q9MYF5 Q9TPB6 Q9TPW1 Q9TPW3 Q9TPW9 Q9TPX4 Q9TQ37 Q9TQ91 Q9TQE0 Q9UBY1 Q9UIM9 Q9UIN0 Q9XRX1 Q9XRY4 Q9XRY5 Q9Y453 Q9Y4H7 |
| sequenceLength | 266 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:197644] HLA class II histocompatibility antigen, DRB1-15 beta chain [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130328] HLA class II histocompatibility antigen, DRB1-15 beta chain [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130344] HLA class II histocompatibility antigen, DRB1-15 beta chain [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130363] HLA class II histocompatibility antigen, DRB1-15 beta chain [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130448] HLA class II histocompatibility antigen, DRB1-15 beta chain [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130587] HLA class II histocompatibility antigen, DRB1-15 beta chain [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130626] HLA class II histocompatibility antigen, DRB1-15 beta chain [transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130737] HLA class II histocompatibility antigen, DRB1-15 beta chain [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:2214371] HLA class II histocompatibility antigen, DRB1-15 beta chain [Golgi membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P01911 HLA-DRB1 (56329)
