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Entry version 166 (17 Jun 2020)
Sequence version 2 (15 Jan 2008)
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Protein

HLA class II histocompatibility antigen, DRB1 beta chain

Gene

HLA-DRB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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:29884618, PubMed:22327072, PubMed:27591323, PubMed:8642306, PubMed:15265931, PubMed:31495665). 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). 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).8 Publications
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 IAV and H5N1 HA-derived peptides (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK) (PubMed:8145819, PubMed:9075930, PubMed:25413013). 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). Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP) (PubMed:9075930).6 Publications
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).2 Publications
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).5 Publications
Allele DRB1*04:02: Displays native or citrullinated self-peptides derived from VIM.1 Publication
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).2 Publications
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.1 Publication
Allele DRB1*07:01: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance.1 Publication
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). In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions (PubMed:31495665).3 Publications
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:9782128, PubMed:25413013).2 Publications
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.1 Publication
(Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei86Pathogen-derived peptide antigen1 Publication1
Sitei90Pathogen-derived peptide antigen1 Publication1
Sitei110Pathogen-derived peptide antigen1 Publication1
Sitei111Pathogen-derived peptide antigen; bidentate hydrogen bonds via carbonyl oxygen and amide nitrogen1 Publication1
Sitei122Pathogen-derived peptide antigen1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processAdaptive immunity, Immunity

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-202424 Downstream TCR signaling
R-HSA-202427 Phosphorylation of CD3 and TCR zeta chains
R-HSA-202430 Translocation of ZAP-70 to Immunological synapse
R-HSA-202433 Generation of second messenger molecules
R-HSA-2132295 MHC class II antigen presentation
R-HSA-389948 PD-1 signaling
R-HSA-877300 Interferon gamma signaling

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
HLA class II histocompatibility antigen, DRB1 beta chain
Alternative name(s):
Human leukocyte antigen DRB1
Short name:
HLA-DRB1
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HLA-DRB1Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Eukaryotic Pathogen Database Resources

More...
EuPathDBi
HostDB:ENSG00000196126.10

Human Gene Nomenclature Database

More...
HGNCi
HGNC:4948 HLA-DRB1

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P01911

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini30 – 227ExtracellularSequence analysisAdd BLAST198
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei228 – 248HelicalSequence analysisAdd BLAST21
Topological domaini249 – 266CytoplasmicSequence analysisAdd BLAST18

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Golgi apparatus, Lysosome, Membrane, MHC II

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

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.1 Publication
Sarcoidosis 1 (SS1)
Disease susceptibility is associated with variations 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.1 Publication
Disease descriptionAn idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved.
Related information in OMIM
Multiple sclerosis (MS)
Disease susceptibility is associated with variations 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).2 Publications
Disease descriptionA multifactorial, inflammatory, demyelinating disease of the central nervous system. Sclerotic lesions are characterized by perivascular infiltration of monocytes and lymphocytes and appear as indurated areas in pathologic specimens (sclerosis in plaques). The pathological mechanism is regarded as an autoimmune attack of the myelin sheath, mediated by both cellular and humoral immunity. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia and bladder dysfunction. Genetic and environmental factors influence susceptibility to the disease.
Related information in OMIM
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.1 Publication
Rheumatoid arthritis (RA)1 Publication
Disease susceptibility is associated with variations 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.1 Publication
Disease descriptionAn inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi181D → N: Reduces the interaction with HLA-DM complex that results in impaired dissociation of CLIP from MHCII. 2 Publications1
Mutagenesisi213L → H: Reduces the interaction with HLA-DM complex that results in impaired dissociation of CLIP from MHCII. 2 Publications1
Mutagenesisi216E → K: Reduces the interaction with HLA-DM complex that results in impaired dissociation of CLIP from MHCII. 2 Publications1
Mutagenesisi254K → A: Impairs MARCH1-dependent down-regulation through ubiquitination. 1 Publication1

Organism-specific databases

MalaCards human disease database

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MalaCardsi
HLA-DRB1

Online Mendelian Inheritance in Man (OMIM)

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MIMi
126200 phenotype
180300 phenotype
181000 phenotype

Open Targets

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OpenTargetsi
ENSG00000196126

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
703 Bullous pemphigoid
220393 Diffuse cutaneous systemic sclerosis
545 Follicular lymphoma
163908 Limbic encephalitis with LGI1 antibodies
220402 Limited cutaneous systemic sclerosis
220407 Limited systemic sclerosis
2073 Narcolepsy type 1
83465 Narcolepsy type 2
555 NON RARE IN EUROPE: Celiac disease
243377 NON RARE IN EUROPE: Diabetes mellitus type 1
802 NON RARE IN EUROPE: Multiple sclerosis
284130 NON RARE IN EUROPE: Rheumatoid arthritis
477738 Pediatric multiple sclerosis
797 Sarcoidosis
536 Systemic lupus erythematosus
85414 Systemic-onset juvenile idiopathic arthritis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA35072

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
P01911 Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1943
CHEMBL3580495
CHEMBL3831291
CHEMBL3988561

Drug and drug target database

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DrugBanki
DB05121 1D09C3
DB11294 Coccidioides immitis spherule
DB05259 Glatiramer

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 292 PublicationsAdd BLAST29
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000008074430 – 266HLA class II histocompatibility antigen, DRB1 beta chainAdd BLAST237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi44 ↔ 1083 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi48N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi146 ↔ 2023 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P01911

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P01911

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P01911

PeptideAtlas

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PeptideAtlasi
P01911

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
51511
51512
51688
52982
52983
53717
61281
61555
61557
65857
75737
80078
83918

Consortium for Top Down Proteomics

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TopDownProteomicsi
P01911

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1369
1370
1371
1372
1373
1374
1375
1376

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P01911

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P01911

SwissPalm database of S-palmitoylation events

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SwissPalmi
P01911

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed in professional APCs: macrophages, dendritic cells and B cells.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000196126 Expressed in spleen and 93 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P01911 baseline and differential

Organism-specific databases

Human Protein Atlas

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HPAi
ENSG00000196126 Tissue enhanced (blood, lung)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Heterotrimer that consists of an alpha chain HLA-DRA1, a beta chain HLA-DRB1 and a peptide (peptide-MHCII) (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 can not 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:23260142, PubMed:11070170, 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 C2-type 1 domain); this interaction is of exceptionally low affinity yet necessary for optimal recognition of antigenic peptides (PubMed:21900604).

10 Publications

(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.

4 Publications

(Microbial infection) Interacts with Epstein-Barr virus gp42 protein.

2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
109368, 39 interactors

Protein interaction database and analysis system

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IntActi
P01911, 33 interactors

Molecular INTeraction database

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MINTi
P01911

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
P01911 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1266
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P01911

Database of comparative protein structure models

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ModBasei
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Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini126 – 214Ig-like C1-typeAdd BLAST89

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni30 – 124Beta-1Add BLAST95
Regioni125 – 227Beta-2Add BLAST103

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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:8145819, PubMed:28467828, PubMed:9782128, PubMed:9354468). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of the T cell receptor (PubMed:19303388).5 Publications
The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor.1 Publication

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

Ensembl GeneTree

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GeneTreei
ENSGT00940000154993

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_047501_13_1_1

KEGG Orthology (KO)

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KOi
K06752

Database of Orthologous Groups

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OrthoDBi
1249505at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P01911

TreeFam database of animal gene trees

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TreeFami
TF336626

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
2.60.40.10, 1 hit
3.10.320.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR007110 Ig-like_dom
IPR036179 Ig-like_dom_sf
IPR013783 Ig-like_fold
IPR003006 Ig/MHC_CS
IPR003597 Ig_C1-set
IPR011162 MHC_I/II-like_Ag-recog
IPR014745 MHC_II_a/b_N
IPR000353 MHC_II_b_N

Pfam protein domain database

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Pfami
View protein in Pfam
PF07654 C1-set, 1 hit
PF00969 MHC_II_beta, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00407 IGc1, 1 hit
SM00921 MHC_II_beta, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF48726 SSF48726, 1 hit
SSF54452 SSF54452, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All

P01911-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MVCLKLPGGS CMTALTVTLM VLSSPLALSG DTRPRFLWQP KRECHFFNGT
60 70 80 90 100
ERVRFLDRYF YNQEESVRFD SDVGEFRAVT ELGRPDAEYW NSQKDILEQA
110 120 130 140 150
RAAVDTYCRH NYGVVESFTV QRRVQPKVTV YPSKTQPLQH HNLLVCSVSG
160 170 180 190 200
FYPGSIEVRW FLNGQEEKAG MVSTGLIQNG DWTFQTLVML ETVPRSGEVY
210 220 230 240 250
TCQVEHPSVT SPLTVEWRAR SESAQSKMLS GVGGFVLGLL FLGAGLFIYF
260
RNQKGHSGLQ PTGFLS
Length:266
Mass (Da):29,966
Last modified:January 15, 2008 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i3B5912820A4654BE
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5Y7D1Q5Y7D1_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1 RP1-93N13.1-001
266Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
D7RIG5D7RIG5_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A2BFX2A2BFX2_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
266Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A140T958A0A140T958_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
250Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A5S8K798A0A5S8K798_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
251Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A5S8K7D1A0A5S8K7D1_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
250Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A5S8K7D6A0A5S8K7D6_HUMAN
HLA class II histocompatibility ant...
HLA-DRB1
251Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

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*15:01.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_0827035K → R in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*10:01, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07. 18 Publications1
Natural variantiVAR_0827046L → F in allele DRB1*04:01, allele DRB1*04:02, allele DRB1*04:04, allele DRB1*04:05, allele DRB1*04:06, allele DRB1*04:07, allele DRB1*04:08, allele DRB1*04:10 and allele DRB1*04:11. 6 Publications1
Natural variantiVAR_08270513T → A in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*04:01, allele DRB1*04:02, allele DRB1*04:04, allele DRB1*04:05, allele DRB1*04:06, allele DRB1*04:07, allele DRB1*04:08, allele DRB1*04:10, allele DRB1*04:11, allele DRB1*07:01, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*09:01, allele DRB1*10:01, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07. 23 Publications1
Natural variantiVAR_08270614A → V in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*10:01, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07. 18 Publications1
Natural variantiVAR_08270729S → A in allele DRB1*01:01, allele DRB1*01:02, allele DRB1*03:01, allele DRB1*03:02, allele DRB1*04:01, allele DRB1*04:02, allele DRB1*04:04, allele DRB1*04:05, allele DRB1*04:06, allele DRB1*04:07, allele DRB1*04:08, allele DRB1*04:10, allele DRB1*04:11, allele DRB1*07:01, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*09:01, allele DRB1*10:01, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06, allele DRB1*14:07, allele DRB1*16:01 and allele DRB1*16:02. 28 Publications1
Natural variantiVAR_08270833R → Q in allele DRB1*07:01 and allele DRB1*09:01. 3 Publications1
Natural variantiVAR_08270938W → E in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*04:01, allele DRB1*04:02, allele DRB1*04:04, allele DRB1*04:05, allele DRB1*04:06, allele DRB1*04:07, allele DRB1*04:08, allele DRB1*04:10, allele DRB1*04:11, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*10:01, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07; requires 2 nucleotide substitutions. 22 Publications1
Natural variantiVAR_08271038W → K in allele DRB1*09:01; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_08271139Q → E in allele DRB1*10:01. 1 Publication1
Natural variantiVAR_08271239Q → Y in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07; requires 2 nucleotide substitutions. 18 Publications1
Natural variantiVAR_08271340P → D in allele DRB1*09:01; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_08271440P → G in allele DRB1*07:01; requires 2 nucleotide substitutions. 3 Publications1
Natural variantiVAR_08271540P → L in allele DRB1*01:01 and allele DRB1*01:02; associated with increased risk for rheumatoid arthritis. 5 Publications1
Natural variantiVAR_08271640P → S in allele DRB1*03:01, allele DRB1*03:02, allele DRB1*08:01, allele DRB1*08:02, allele DRB1*08:03, allele DRB1*08:04, allele DRB1*11:01, allele DRB1*11:04, allele DRB1*11:06, allele DRB1*11:11, allele DRB1*11:19, allele DRB1*12:01, allele DRB1*12:02, allele DRB1*13:01, allele DRB1*13:02, allele DRB1*13:03, allele DRB1*13:05, allele DRB1*13:07, allele DRB1*13:12, allele DRB1*14:01, allele DRB1*14:03, allele DRB1*14:05, allele DRB1*14:06 and allele DRB1*14:07. 18 Publications1
Natural variantiVAR_08271740P → V in allele DRB1*04:01, allele DRB1*04:02, allele DRB1*04:04, allele DRB1*04:05, allele DRB1*04:06, allele DRB1*04:07, allele DRB1*04:08, allele DRB1*04:10, allele DRB1*04:11 and allele DRB1*10:01; associated with increased risk for rheumatoid arthritis; requires 2 nucleotide substitutions. 9 Publications