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- 2B17_HUMAN


P13761 - 2B17_HUMAN


HLA class II histocompatibility antigen, DRB1-7 beta chain



Homo sapiens (Human)
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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      Entry version 132 (01 Oct 2014)
      Sequence version 1 (01 Jan 1990)
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    Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells. The peptide binding cleft accommodates peptides of 10-30 residues. The peptides presented by MHC class II molecules are generated mostly by degradation of proteins that access the endocytic route; where they are processed by lysosomal proteases and other hydrolases. Exogenous antigens that have been endocytosed by the APC are thus readily available for presentation via MHC II molecules; and for this reason this antigen presentation pathway is usually referred to as exogenous. As membrane proteins on their way to degradation in lysosomes as part of their normal turn-over are also contained in the endosomal/lysosomal compartments; exogenous antigens must compete with those derived from endogenous components. Autophagy is also a source of endogenous peptides; autophagosomes constitutively fuse with MHC class II loading compartments. In addition to APCs; other cells of the gastrointestinal tract; such as epithelial cells; express MHC class II molecules and CD74 and act as APCs; which is an unusual trait of the GI tract. To produce a MHC class II molecule that presents an antigen; three MHC class II molecules (heterodimers of an alpha and a beta chain) associate with a CD74 trimer in the ER to form a heterononamer. Soon after the entry of this complex into the endosomal/lysosomal system where antigen processing occurs; CD74 undergoes a sequential degradation by various proteases; including CTSS and CTSL; leaving a small fragment termed CLIP (class-II-associated invariant chain peptide). The removal of CLIP is facilitated by HLA-DM via direct binding to the alpha-beta-CLIP complex so that CLIP is released. HLA-DM stabilizes MHC class II molecules until primary high affinity antigenic peptides are bound. The MHC II molecule bound to a peptide is then transported to the cell membrane surface. In B-cells; the interaction between HLA-DM and MHC class II molecules is regulated by HLA-DO. Primary dendritic cells (DCs) also to express HLA-DO. Lysosomal microenvironment has been implicated in the regulation of antigen loading into MHC II molecules; increased acidification produces increased proteolysis and efficient peptide loading.

    GO - Molecular functioni

    1. MHC class II receptor activity Source: UniProtKB
    2. peptide antigen binding Source: UniProtKB
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
    2. cytokine-mediated signaling pathway Source: Reactome
    3. detection of bacterium Source: UniProtKB
    4. humoral immune response mediated by circulating immunoglobulin Source: UniProtKB
    5. immune response Source: UniProtKB
    6. immunoglobulin production involved in immunoglobulin mediated immune response Source: UniProtKB
    7. inflammatory response to antigenic stimulus Source: UniProtKB
    8. interferon-gamma-mediated signaling pathway Source: Reactome
    9. negative regulation of interferon-gamma production Source: UniProtKB
    10. negative regulation of T cell proliferation Source: UniProtKB
    11. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
    12. protein tetramerization Source: UniProtKB
    13. regulation of interleukin-10 secretion Source: UniProtKB
    14. regulation of interleukin-4 production Source: UniProtKB
    15. T cell costimulation Source: Reactome
    16. T cell receptor signaling pathway Source: Reactome
    17. T-helper 1 type immune response Source: UniProtKB

    Keywords - Biological processi


    Enzyme and pathway databases

    ReactomeiREACT_121399. MHC class II antigen presentation.
    REACT_12555. Downstream TCR signaling.
    REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
    REACT_12596. Translocation of ZAP-70 to Immunological synapse.
    REACT_12623. Generation of second messenger molecules.
    REACT_19324. PD-1 signaling.
    REACT_25078. Interferon gamma signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    HLA class II histocompatibility antigen, DRB1-7 beta chain
    Alternative name(s):
    MHC class II antigen DRB1*7
    Short name:
    Short name:
    Gene namesi
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Unplaced

    Organism-specific databases

    HGNCiHGNC:4948. HLA-DRB1.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Endoplasmic reticulum membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Golgi apparatustrans-Golgi network membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Endosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Lysosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication. Late endosome membrane 1 Publication; Single-pass type I membrane protein 1 Publication
    Note: 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.

    GO - Cellular componenti

    1. clathrin-coated endocytic vesicle membrane Source: Reactome
    2. endocytic vesicle membrane Source: Reactome
    3. ER to Golgi transport vesicle membrane Source: Reactome
    4. external side of plasma membrane Source: UniProtKB
    5. Golgi membrane Source: Reactome
    6. integral component of lumenal side of endoplasmic reticulum membrane Source: Reactome
    7. late endosome membrane Source: UniProtKB
    8. lysosomal membrane Source: UniProtKB
    9. membrane Source: UniProtKB
    10. MHC class II protein complex Source: UniProtKB-KW
    11. plasma membrane Source: Reactome
    12. trans-Golgi network membrane Source: Reactome
    13. transport vesicle membrane Source: Reactome

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Organism-specific databases

    MIMi609532. phenotype.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2929Add
    Chaini30 – 266237HLA class II histocompatibility antigen, DRB1-7 beta chainPRO_0000018951Add

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi44 ↔ 108PROSITE-ProRule annotation
    Glycosylationi48 – 481N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi146 ↔ 202PROSITE-ProRule annotation
    Cross-linki254 – 254Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

    Proteomic databases



    Gene expression databases



    Subunit structurei

    Heterodimer of an alpha and a beta subunit; also referred as MHC class II molecule. In the endoplasmic reticulum (ER) it forms a heterononamer; 3 MHC class II molecules bind to a CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system; CD74 undergoes sequential degradation by various proteases; leaving a small fragment termed CLIP on each MHC class II molecule. MHC class II molecule interacts with HLA_DM, and HLA_DO in B-cells, in order to release CLIP and facilitate the binding of antigenic peptides.


    3D structure databases

    SMRiP13761. Positions 32-219.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini30 – 227198ExtracellularSequence AnalysisAdd
    Topological domaini251 – 26616CytoplasmicSequence AnalysisAdd


    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei228 – 25023HelicalSequence AnalysisAdd

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini126 – 21691Ig-like C1-typeAdd


    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni30 – 12495Beta-1Add
    Regioni125 – 227103Beta-2Add

    Sequence similaritiesi

    Belongs to the MHC class II family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases


    Family and domain databases

    Gene3Di2.60.40.10. 1 hit.
    3.10.320.10. 1 hit.
    InterProiIPR007110. Ig-like_dom.
    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.
    [Graphical view]
    PfamiPF07654. C1-set. 1 hit.
    PF00969. MHC_II_beta. 1 hit.
    [Graphical view]
    ProDomiPD000328. MHC_II_b_N. 1 hit.
    [Graphical view] [Entries sharing at least one domain]
    SMARTiSM00407. IGc1. 1 hit.
    SM00921. MHC_II_beta. 1 hit.
    [Graphical view]
    SUPFAMiSSF54452. SSF54452. 1 hit.
    PROSITEiPS50835. IG_LIKE. 1 hit.
    PS00290. IG_MHC. 1 hit.
    [Graphical view]


    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P13761-1 [UniParc]FASTAAdd to Basket

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    Mass (Da):29,822
    Last modified:January 1, 1990 - v1


    The following alleles of DRB1-7 are known: DRB1*07:01, DRB1*07:03, DRB1*07:04, DRB1*07:05, DRB1*07:06, DRB1*07:07, DRB1*07:08, DRB1*07:09, DRB1*07:11, DRB1*07:12, DRB1*07:13, DRB1*07:14, DRB1*07:15, DRB1*07:16 and DRB1*07:17. The sequence shown is that of DRB1*07:01.
    Allele DRB1*07:01 is associated with persistent hepatitis C virus (HCV) infections [MIMi:609532].

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti5 – 51K → R.
    Corresponds to variant rs9270305 [ dbSNP | Ensembl ].
    Natural varianti58 – 581R → S in allele DRB1*07:03.
    Natural varianti106 – 1061T → N in allele DRB1*07:04.
    Natural varianti107 – 1071V → Y in allele DRB1*07:04; requires 2 nucleotide substitutions.
    Natural varianti236 – 2361V → M.
    Corresponds to variant rs2230816 [ dbSNP | Ensembl ].
    Natural varianti262 – 2621T → R.
    Corresponds to variant rs9269744 [ dbSNP | Ensembl ].

    Sequence databases

    Select the link destinations:
    Links Updated
    M16941 mRNA. Translation: AAA36282.1.
    CR753309 Genomic DNA. Translation: CAQ07518.1.
    CR753835 Genomic DNA. Translation: CAQ08239.1.
    BC001023 mRNA. Translation: AAH01023.1.
    Y13785 Genomic DNA. Translation: CAA74112.1.
    Y16224 Genomic DNA. Translation: CAA76123.1.

    Genome annotation databases

    EnsembliENST00000437784; ENSP00000405960; ENSG00000229074.
    ENST00000444645; ENSP00000409322; ENSG00000236884.
    UCSCiuc011gjy.2. human.

    Polymorphism databases


    Keywords - Coding sequence diversityi



    Sequence databases

    Select the link destinations:
    Links Updated
    M16941 mRNA. Translation: AAA36282.1 .
    CR753309 Genomic DNA. Translation: CAQ07518.1 .
    CR753835 Genomic DNA. Translation: CAQ08239.1 .
    BC001023 mRNA. Translation: AAH01023.1 .
    Y13785 Genomic DNA. Translation: CAA74112.1 .
    Y16224 Genomic DNA. Translation: CAA76123.1 .
    PIRi A28031.
    UniGenei Hs.696211.

    3D structure databases

    ProteinModelPortali P13761.
    SMRi P13761. Positions 32-219.
    ModBasei Search...
    MobiDBi Search...

    Polymorphism databases

    DMDMi 122256.

    Proteomic databases

    PaxDbi P13761.
    PeptideAtlasi P13761.
    PRIDEi P13761.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000437784 ; ENSP00000405960 ; ENSG00000229074 .
    ENST00000444645 ; ENSP00000409322 ; ENSG00000236884 .
    UCSCi uc011gjy.2. human.

    Organism-specific databases

    GeneCardsi GC06M032546.
    HGNCi HGNC:4948. HLA-DRB1.
    MIMi 142857. gene.
    609532. phenotype.
    neXtProti NX_P13761.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG68200.
    HOVERGENi HBG012730.
    InParanoidi P13761.
    PhylomeDBi P13761.

    Enzyme and pathway databases

    Reactomei REACT_121399. MHC class II antigen presentation.
    REACT_12555. Downstream TCR signaling.
    REACT_12582. Phosphorylation of CD3 and TCR zeta chains.
    REACT_12596. Translocation of ZAP-70 to Immunological synapse.
    REACT_12623. Generation of second messenger molecules.
    REACT_19324. PD-1 signaling.
    REACT_25078. Interferon gamma signaling.

    Miscellaneous databases

    ChiTaRSi HLA-DRB1. human.
    NextBioi 34054816.
    PROi P13761.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_HLA-DRB1.
    Genevestigatori P13761.

    Family and domain databases

    Gene3Di 1 hit.
    3.10.320.10. 1 hit.
    InterProi IPR007110. Ig-like_dom.
    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.
    [Graphical view ]
    Pfami PF07654. C1-set. 1 hit.
    PF00969. MHC_II_beta. 1 hit.
    [Graphical view ]
    ProDomi PD000328. MHC_II_b_N. 1 hit.
    [Graphical view ] [Entries sharing at least one domain ]
    SMARTi SM00407. IGc1. 1 hit.
    SM00921. MHC_II_beta. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54452. SSF54452. 1 hit.
    PROSITEi PS50835. IG_LIKE. 1 hit.
    PS00290. IG_MHC. 1 hit.
    [Graphical view ]
    ProtoNeti Search...


    1. "Sequence and evolution of HLA-DR7- and -DRw53-associated beta-chain genes."
      Young J.A.T., Wilkinson D., Bodmer W.F., Trowsdale J.
      Proc. Natl. Acad. Sci. U.S.A. 84:4929-4933(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE DRB1*07:01).
    2. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Tissue: Lymph.
    4. "Identification of novel DR7, DRB5 and DQB1*03 alleles using the CANTYPE assay."
      Buyse I.M., Couture C., Ouellet S., Hashemi-tavoularis S.
      Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-115 (ALLELE DRB1*07:03).
      Tissue: Blood.
    5. "Molecular, serological and genetic studies on two new HLA-DRB1 alleles -- HLA-DRB1*0704 and HLA-DRB1*1507."
      Darke C., Guttridge M.G., Street J., Thompson J., Thomas M.
      Tissue Antigens 56:467-469(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 36-117 (ALLELE DRB1*07:04).
      Tissue: Blood.
    6. "Influence of MHC class II genotype on outcome of infection with hepatitis C virus."
      Hepatitis C European Network for Cooperative Research
      Thursz M., Yallop R., Goldin R., Trepo C., Thomas H.C.
      Lancet 354:2119-2124(1999) [PubMed] [Europe PMC] [Abstract]
    7. "Invariant chain structure and MHC class II function."
      Cresswell P.
      Cell 84:505-507(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    8. "Presentation of antigens by MHC class II molecules: getting the most out of them."
      Villadangos J.A.
      Mol. Immunol. 38:329-346(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    9. "Autophagy in MHC class II presentation: sampling from within."
      Menendez-Benito V., Neefjes J.
      Immunity 26:1-3(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    10. "MHC class II molecules on the move for successful antigen presentation."
      Rocha N., Neefjes J.
      EMBO J. 27:1-5(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    11. "MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation."
      De Gassart A., Camosseto V., Thibodeau J., Ceppi M., Catalan N., Pierre P., Gatti E.
      Proc. Natl. Acad. Sci. U.S.A. 105:3491-3496(2008) [PubMed] [Europe PMC] [Abstract]
    12. "MHC class II transport at a glance."
      Berger A.C., Roche P.A.
      J. Cell Sci. 122:1-4(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    13. "CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract."
      Beswick E.J., Reyes V.E.
      World J. Gastroenterol. 15:2855-2861(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry namei2B17_HUMAN
    AccessioniPrimary (citable) accession number: P13761
    Secondary accession number(s): B0UYW1, O46699, O46872
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: January 1, 1990
    Last modified: October 1, 2014
    This is version 132 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.


    Keywords - Technical termi

    Complete proteome, Reference proteome


    1. Human chromosome 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3