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ENSG00000228987 Gene

protein-coding   GIFtS: 16
GCID: GC06Pk32382          (predicted)

ENSG00000228987


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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
HLA-DRA13
MHC Class II Antigen DRA3

External Ids:    Ensembl: ENSG000002289877   UniProtKB: P019033   

Export aliases for ENSG00000228987 gene to outside databases


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for ENSG00000228987 Gene:
ENSG00000228987 is a protein-coding gene.

UniProtKB/Swiss-Prot: DRA_HUMAN, P01903
Function: 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




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for ENSG00000228987
         Other transcription factors

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Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ENSG00000228987


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_DBBp21.32   

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06Pk32382:       (about GC identifiers)

Start:
32,382,335 bp from start of contig ALT_REF_LOCI_3      End:
32,387,545 bp from start of contig ALT_REF_LOCI_3
Size:
5,211 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: DRA_HUMAN, P01903 (See protein sequence)
Recommended Name: HLA class II histocompatibility antigen, DR alpha chain precursor  
Size: 254 amino acids; 28607 Da
Subunit: 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
Sequence caution: Sequence=CAA25076.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Selected PDB 3D structures from and Proteopedia for ENSG00000228987 (see all 69):
1A6A (3D)        1AQD (3D)        1BX2 (3D)        1D5M (3D)        1D5X (3D)        1D5Z (3D)    
Secondary accessions: A2BET4 Q30160 Q6IAZ1 Q861I2 Q9TP70

Explore the universe of human proteins at neXtProt for ENSG00000228987: NX_P01903

Explore proteomics data for ENSG00000228987 at MOPED

Post-translational modifications: 

  • Ubiquitinated by MARCH1 or MARCH8 at Lys-244 leading to down-regulation of MHC class II. When associated with
    ubiquitination of the beta subunit of HLA-DR: HLA-DRB4 'Lys-254', the down-regulation of MHC class II may be
    highly effective1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ENSG00000228987 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB


    ENSEMBL proteins: 
     ENSP00000410443   ENSP00000411610  
    Reactome Protein details: P01903

    ENSG00000228987 Human Recombinant Protein Products:

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    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for ENSG00000228987 

     
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    Search antibodies-online for peptides for ENSG00000228987

    ENSG00000228987 Antibody Products:

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    ENSG00000228987 Assay Products:

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    Search eBioscience for ELISAs for ENSG00000228987 
    Search antibodies-online for kits for ENSG00000228987 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR007110 Ig-like_dom
     IPR001003 MHC_II_a_N
     IPR003006 Ig/MHC_CS
     IPR011162 MHC_I/II-like_Ag-recog
     IPR013783 Ig-like_fold

    Graphical View of Domain Structure for InterPro Entry P01903

    ProtoNet protein and cluster: P01903

    2 Blocks protein domains:
    IPB001003 MHC Class II alpha chain
    IPB003597 Immunoglobulin C-type


    UniProtKB/Swiss-Prot: DRA_HUMAN, P01903
    Similarity: Belongs to the MHC class II family
    Similarity: Contains 1 Ig-like C1-type (immunoglobulin-like) domain


    Find genes that share domains with ENSG00000228987           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: DRA_HUMAN, P01903
    Function: 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

         Gene Ontology (GO): 2 molecular function terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005515protein binding ----
    GO:0032395MHC class II receptor activity ----
         
    Find genes that share ontologies with ENSG00000228987           About GenesLikeMe


    Animal Models:
       genOway: Develop your customized and physiologically relevant rodent model for ENSG00000228987

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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    DRA_HUMAN, P01903: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane;
    Single-pass type I membrane protein. Golgi apparatus, trans-Golgi network membrane; Single-pass type I membrane
    protein. Endosome membrane; Single-pass type I membrane protein. Lysosome membrane; Single-pass type I membrane
    protein. Late endosome membrane; Single-pass type I membrane protein. 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

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000139Golgi membrane ----
    GO:0005764lysosome ----
    GO:0005765lysosomal membrane ----
    GO:0005886plasma membrane ----
    GO:0005887integral component of plasma membrane ----

    Find genes that share ontologies with ENSG00000228987           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Find genes that share SuperPaths with ENSG00000228987           About GenesLikeMe

    Pathways by sourceSee SuperPaths
    Show all pathways


    Selected Reactome Pathways for ENSG00000228987 (see all 7)
        Translocation of ZAP-70 to Immunological synapse
    Interferon gamma signaling
    Downstream TCR signaling
    PD-1 signaling
    MHC class II antigen presentation


        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ENSG00000228987
    Interactions:

        Search GeneGlobe Interaction Network for ENSG00000228987

    STRING Interaction Network Preview (showing 5 interactants - click image to see 16)

    Selected Interacting proteins for ENSG00000228987 (P019032, 3 ENSP000004104434) via UniProtKB, MINT, STRING, and/or I2D (see all 49)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    HLA-DRB1P019122, 3, ENSP000003530994I2D: score=1 I2D: score=1 MINT-24881 I2D: score=2 MINT-24910 I2D: score=1 I2D: score=1 STRING: ENSP00000353099
    ENSG00000206240P019122, 3MINT-24910 I2D: score=1 
    ENSG00000206306P019122, 3MINT-24910 I2D: score=1 
    CD74P042332, 3MINT-72789 I2D: score=2 
    ENSG00000234154P280683, ENSP000004148174I2D: score=2 STRING: ENSP00000414817
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0006955immune response ----
    GO:0019221cytokine-mediated signaling pathway ----
    GO:0019882antigen processing and presentation ----
    GO:0019886antigen processing and presentation of exogenous peptide antigen via MHC class II ----
    GO:0031295T cell costimulation ----

    Find genes that share ontologies with ENSG00000228987           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ENSG00000228987 (DRA)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000416883(uc011gju.2 uc011gjv.2) ENST00000481943 ENST00000411505

    miRNA
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    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --

    ENSG00000228987 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ENSG00000228987 Protein Expression
        Custom PCR Arrays for ENSG00000228987
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    In Situ
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    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for ENSG00000228987

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    ENSEMBL Gene Tree for ENSG00000228987 (if available)
    TreeFam Gene Tree for ENSG00000228987 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    DRA_HUMAN, P01903: The following alleles of DRA are known: DRA*01:01 and DRA*01:02. The sequence shown is that of
    DRA*01:01
    DRA_HUMAN, P01903: Genetic variations in HLA-DRA influence susceptibility to hepatitis B virus (HBV) infection
    [MIM:610424]

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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      --

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ENSG00000228987 gene, integrated from 10 sources (see all 35):
    (articles sorted by number of sources associating them with ENSG00000228987)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Initial characterization of the human central proteome. (PubMed id 21269460)2 Burkard T.R.... Colinge J. (BMC Syst. Biol. 2011)
    2. Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. (PubMed id 19159218)2 Chen R.... Zou H. (J. Proteome Res. 2009)
    3. MHC class II transport at a glance. (PubMed id 19092054)2 Berger A.C. and Roche P.A. (J. Cell Sci. 2009)
    4. CD74 in antigen presentation, inflammation, and cancers of the gastrointestinal tract. (PubMed id 19533806)2 Beswick E.J. and Reyes V.E. (World J. Gastroenterol. 2009)
    5. The HLA-DRalpha chain is modified by polyubiquitination. (PubMed id 19117940)2 Lapaque N.... Kelly A.P. (J. Biol. Chem. 2009)
    6. The structure of HLA-DR52c: comparison to other HLA-DRB3 alleles. (PubMed id 18697946)2 Dai S.... Kappler J.W. (Proc. Natl. Acad. Sci. U.S.A. 2008)
    7. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. (PubMed id 18305173)2 De Gassart A.... Gatti E. (Proc. Natl. Acad. Sci. U.S.A. 2008)
    8. MHC class II molecules on the move for successful antigen presentation. (PubMed id 18046453)2 Rocha N. and Neefjes J. (EMBO J. 2008)
    9. Autophagy in MHC class II presentation: sampling from within. (PubMed id 17241953)2 Menendez-Benito V. and Neefjes J. (Immunity 2007)
    10. Crystallographic structure of the human leukocyte antigen DRA, DRB3*0101: models of a directional alloimmune response and autoimmunity. (PubMed id 17583734)2 Parry C.S.... Stern L.J. (J. Mol. Biol. 2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Ensembl:ENSG00000228987

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ENSG00000228987 gene:
    Search GeneIP for patents involving ENSG00000228987

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