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Details on Person UniProt:P79483 HLA-DRB3
| Class:Id | ReferenceGeneProduct:84125 |
|---|---|
| _chainChangeLog | signal peptide:1-29 added on Sat February 7 2015;chain:30-266 added on Sat February 7 2015 |
| _displayName | UniProt:P79483 HLA-DRB3 |
| _timestamp | 2025-05-21 21:36:18 |
| chain | signal peptide:1-29 chain:30-266 |
| checksum | 2FC3AE68D3B10EAD |
| 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-DRB3-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. Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:16148104, PubMed:19531622, PubMed:19830726, PubMed:20368442, PubMed:22929521, PubMed:23569328, PubMed:2463305, PubMed:2788702, PubMed:30282837, PubMed:31020640, PubMed:31308093, PubMed:31333679). 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 (By similarity). 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 (By similarity). 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. 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 (By similarity).FUNCTION ALLELE DRB3*01:01: Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2463305, PubMed:2788702). Presents viral epitopes derived from HHV-6B U11, TRX2/U56 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640).FUNCTION ALLELE DRB3*02:02 Exclusively presents several immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a significant role in immune recognition and long-term protection (PubMed:19830726, PubMed:2788702). Upon EBV infection, presents to CD4-positive T cells latent antigen EBNA2 (PRSPTVFYNIPPMPLPPSQL) and lytic antigen BZLF1 (LTAYHVSTAPTGSWF) peptides, driving oligoclonal expansion and selection of virus-specific memory T cell subsets with cytotoxic potential to directly eliminate virus-infected B cells (PubMed:23569328, PubMed:31308093). Presents viral epitopes derived from HHV-6B U11, gB/U39 and gH/U48 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). Plays a minor role in CD4-positive T cell immune response against Dengue virus by presenting conserved peptides from capsid and non-structural NS3 proteins (PubMed:31333679). Displays peptides derived from IAV matrix protein M, implying a role in protection against IAV infection (PubMed:19830726). In the context of tumor immunesurveillance, 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:22929521). Presents to Vbeta2-positive T-helper 1 cells specifically an immunodominant peptide derived from tumor antigen CTAG1A/NY-ESO-1(PGVLLKEFTVSGNILTIRLTAADHR) and confers protective memory response (PubMed:19531622, PubMed:20368442). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a TP53 neoantigen (HYNYMCNSSCMGSMNRRPILTIITL) carrying G245S hotspot driver mutation and may mediate tumor regression (PubMed:30282837).FUNCTION ALLELE DRB3*03:01: Presents a series of conserved peptides derived from the M.tuberculosis PPE family of proteins, in particular PPE29 and PPE33, known to be highly immunogenic (PubMed:32341563). Presents immunogenic epitopes derived from C.tetani neurotoxin tetX, playing a role in immune recognition and long-term protection (PubMed:2788702). Displays immunodominant viral peptides from HCV non-structural protein NS2, as part of a broad range T-helper response to resolve infection (PubMed:16148104).SUBUNIT Heterotrimer that consists of an alpha chain HLA-DRA, a beta chain HLA-DRB1 and a peptide (peptide-MHCII) (PubMed:17583734, PubMed:18697946). 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 (By similarity). 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 (By similarity). 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. 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 (By similarity). Interacts with HLA-DM heterodimer; this interaction is direct (By similarity). Interacts with TCR (via CDR3) (By similarity). 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 (By similarity).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.TISSUE SPECIFICITY Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level).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-DRB3 alleles (PubMed:17583734, PubMed:18697946). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR (By similarity).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 MHC class II.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 DRB3*01:01. 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 DRB3*01:01. The most frequent alleles in human population are DRB3*01:01 (DR52a), DRB3*02:02 (DR52b) and DRB3*03:01 (DR52c) (PubMed:23510415). Allele DRB3*01:01 belongs to an ancestral haplotype and is associated with autoimmune diseases that are linked to antigen presentation. It is found in more than 95% of the homozygous HPA-1B mothers that produce anti-HPA-1A antibodies, leading to neonatal alloimmune thrombocytopenia (NAIT) (PubMed:19494351, PubMed:19535639). In the context of hematological malignancy and T cell transplantation, alleles DRB3*01:01 and DRB3*02:02 present minor histocompatibility antigens derived respectively from host PTK2B and MR1 proteins, contributing to T cell-mediated graft-versus-leukemia effect and complete remission (PubMed:19706888). Allele DRB3*03:01 plays an important role in the outcome of HLA-identical sex-mismatched organ transplantation. Presents to T-helper cells a minor histocompatibility antigen encoded by the Y chromosome RPS4Y1 (VIKVNDTVQI), leading to the maturation of dendritic cells and expansion of antigen-specific cytotoxic T cells, ultimately triggering transplant rejection (PubMed:12944060).SIMILARITY Belongs to the MHC class II family.CAUTION HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene. |
| description | recommendedName: HLA class II histocompatibility antigen, DR beta 3 chain alternativeName: MHC class II antigen DRB3 |
| geneName | HLA-DRB3 |
| identifier | P79483 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Adaptive immunity Cell membrane Cytoplasmic vesicle Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Immunity Lysosome Membrane MHC II Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5083144] Weiser, JD [InstanceEdit:5263031] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:8934940] Weiser, JD [InstanceEdit:9027688] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9715482] Weiser, JD [InstanceEdit:9773244] Weiser, Joel [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 |
| name | HLA-DRB3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9034247] ENSEMBL:ENSG00000196101 HLA-DRB3 [Homo sapiens] |
| secondaryIdentifier | DRB3_HUMAN A0ZXY9 A7MA46 B5AU12 B5AU13 B5AU14 B8YAC6 C6H115 C6H116 O02875 O19590 O46701 O46794 O78049 O78162 P01913 P79663 Q29721 Q29809 Q2PPD0 Q30144 Q507L8 Q5SP44 Q5STE0 Q6YJU6 Q70M87 Q7YQ62 Q860I9 Q8SP69 Q8WLT7 Q8WLT8 Q95359 Q95HM8 Q95IE5 Q96H16 Q9BCP3 Q9BD18 Q9MYA4 Q9MYH3 Q9MYH4 Q9TP01 Q9TP02 Q9TPB5 Q9TQ21 Q9UIN3 Q9UIN5 |
| sequenceLength | 266 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:197577] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130377] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130432] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [ER to Golgi transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130452] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [trans-Golgi network membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130513] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [lumenal side of endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130515] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [clathrin-coated endocytic vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130559] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [transport vesicle membrane] [Homo sapiens] [EntityWithAccessionedSequence:2130676] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [lysosomal membrane] [Homo sapiens] [EntityWithAccessionedSequence:2214381] HLA class II histocompatibility antigen, DRB3-1 beta chain precursor [Golgi membrane] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:P79483 HLA-DRB3 (84125)
