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Aliases for HLA-DRB4 Gene

Aliases for HLA-DRB4 Gene

  • Major Histocompatibility Complex, Class II, DR Beta 4 2 3
  • MHC Class II Antigen DRB4 3 4
  • HLA Class II Histocompatibility Antigen, DR Beta 4 Chain 3
  • MHC Class II Antigen HLA-DR-Beta 3
  • DRB1 Transplantation Antigen 3
  • Human Leucocyte Antigen DRB4 3
  • MHC HLA DR-Beta Chain 3
  • MHC Class2 Antigen 3
  • Leukocyte Antigen 3
  • HLA-DR4B 3
  • DR-4 3
  • DRB4 3
  • DR4 3

External Ids for HLA-DRB4 Gene

Previous HGNC Symbols for HLA-DRB4 Gene

  • HLA-DR4B

Previous GeneCards Identifiers for HLA-DRB4 Gene

  • GC06U990051
  • GC06P9R0072
  • GC06M032556
  • GC06M032076
  • GC06M032507
  • GC06Me32508
  • GC06M032657
  • GC06Pe32515
  • GC06Mf32600
  • GC06Mf32601
  • GC06Mm32579
  • GC06Mo32509
  • GC06Ml32465
  • GC06M8U3850
  • GC06M8R3846

Summaries for HLA-DRB4 Gene

Entrez Gene Summary for HLA-DRB4 Gene

  • HLA-DRB4 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. The presence of DRB4 is linked with allelic variants of DRB1, otherwise it is omitted. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [provided by RefSeq, Jul 2008]

GeneCards Summary for HLA-DRB4 Gene

HLA-DRB4 (Major Histocompatibility Complex, Class II, DR Beta 4) is a Protein Coding gene. Diseases associated with HLA-DRB4 include pityriasis rosea and hemorrhagic fever with renal syndrome. Among its related pathways are Class I MHC mediated antigen processing and presentation and GPCR Pathway. GO annotations related to this gene include peptide antigen binding and MHC class II receptor activity.

UniProtKB/Swiss-Prot for HLA-DRB4 Gene

  • 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 Wiki entry for HLA-DRB4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HLA-DRB4 Gene

Genomics for HLA-DRB4 Gene

Genomic Location for HLA-DRB4 Gene

Start:
3,840,424 bp from pter
End:
3,855,395 bp from pter
Size:
14,972 bases
Orientation:
Minus strand

Genomic View for HLA-DRB4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:

RefSeq DNA sequence for HLA-DRB4 Gene

No data available for Regulatory Elements for HLA-DRB4 Gene

Proteins for HLA-DRB4 Gene

  • Protein details for HLA-DRB4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P13762-DRB4_HUMAN
    Recommended name:
    HLA class II histocompatibility antigen, DR beta 4 chain
    Protein Accession:
    P13762
    Secondary Accessions:
    • B0S863
    • O78042
    • P79664
    • Q29889
    • Q30163
    • Q6TLK6
    • Q860N4
    • Q861F3
    • Q8WLT9
    • Q9BS54

    Protein attributes for HLA-DRB4 Gene

    Size:
    266 amino acids
    Molecular mass:
    29941 Da
    Quaternary structure:
    • 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

neXtProt entry for HLA-DRB4 Gene

Proteomics data for HLA-DRB4 Gene at MOPED

Post-translational modifications for HLA-DRB4 Gene

  • Ubiquitinated by MARCH1 and MARCH8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHC class II. When associated with ubiquitination of the alpha subunit of HLA-DR: HLA-DRA Lys-244, the down-regulation of MHC class II may be highly effective.
  • Ubiquitination at Lys254
  • Glycosylation at Asn48

Other Protein References for HLA-DRB4 Gene

Reactome Protein details:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for HLA-DRB4 Gene

Domains for HLA-DRB4 Gene

Gene Families for HLA-DRB4 Gene

HGNC:
  • C1SET :Immunoglobulin superfamily / C1-set domain containing
  • HLA :Histocompatibility complex

Graphical View of Domain Structure for InterPro Entry

P13762

UniProtKB/Swiss-Prot:

DRB4_HUMAN :
  • P13762
Domain:
  • Contains 1 Ig-like C1-type (immunoglobulin-like) domain.
Family:
  • Belongs to the MHC class II family.
genes like me logo Genes that share domains with HLA-DRB4: view

Function for HLA-DRB4 Gene

Molecular function for HLA-DRB4 Gene

GENATLAS Biochemistry:
HLA-DR,beta 4 chain,determining DRW53
UniProtKB/Swiss-Prot 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) - Molecular Function for HLA-DRB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 15795121
GO:0032395 MHC class II receptor activity TAS 10425186
GO:0042605 peptide antigen binding ISS --
genes like me logo Genes that share ontologies with HLA-DRB4: view

No data available for Enzyme Numbers (IUBMB) , Phenotypes , Animal Models , miRNA , Transcription Factor Targeting and HOMER Transcription for HLA-DRB4 Gene

Localization for HLA-DRB4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HLA-DRB4 Gene

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.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for HLA-DRB4 Gene COMPARTMENTS Subcellular localization image for HLA-DRB4 gene
Compartment Confidence
endoplasmic reticulum 5
endosome 5
lysosome 5
plasma membrane 5
vacuole 5
golgi apparatus 4
extracellular 3
nucleus 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for HLA-DRB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane TAS --
GO:0005765 lysosomal membrane TAS --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 10425186
GO:0009897 external side of plasma membrane ISS --
genes like me logo Genes that share ontologies with HLA-DRB4: view

Pathways for HLA-DRB4 Gene

genes like me logo Genes that share pathways with HLA-DRB4: view

Interacting Proteins for HLA-DRB4 Gene

Selected Interacting proteins: P13762-DRB4_HUMAN for HLA-DRB4 Gene via I2D

Gene Ontology (GO) - Biological Process for HLA-DRB4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response ISS --
GO:0002437 inflammatory response to antigenic stimulus IDA 15795121
GO:0002455 humoral immune response mediated by circulating immunoglobulin ISS --
GO:0002503 peptide antigen assembly with MHC class II protein complex IDA 22733780
GO:0002862 negative regulation of inflammatory response to antigenic stimulus IDA 18039812
genes like me logo Genes that share ontologies with HLA-DRB4: view

Transcripts for HLA-DRB4 Gene

mRNA/cDNA for HLA-DRB4 Gene

Unigene Clusters for HLA-DRB4 Gene

Major histocompatibility complex, class II, DR beta 4:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for HLA-DRB4

Primer Products

  • QuantiTect SYBR Green Assays in human,mouse,rat
  • Pre-validated RT² qPCR Primer Assay in human,mouse,rat
  • QuantiFast Probe-based Assays in human,mouse,rat

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HLA-DRB4 Gene

No ASD Table

Relevant External Links for HLA-DRB4 Gene

GeneLoc Exon Structure for
HLA-DRB4
ECgene alternative splicing isoforms for
HLA-DRB4

Expression for HLA-DRB4 Gene

mRNA expression in normal human tissues for HLA-DRB4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for HLA-DRB4 Gene

This gene is overexpressed in Oral epithelium (17.6) and Lymph node (15.7).

Integrated Proteomics: protein expression from ProteomicsDB and MOPED for HLA-DRB4 Gene

SOURCE GeneReport for Unigene cluster for HLA-DRB4 Gene Hs.716081

genes like me logo Genes that share expressions with HLA-DRB4: view

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Expression partners for HLA-DRB4 Gene

Orthologs for HLA-DRB4 Gene

No data available for Orthologs and Evolution for HLA-DRB4 Gene

Paralogs for HLA-DRB4 Gene

genes like me logo Genes that share paralogs with HLA-DRB4: view

No data available for Paralogs for HLA-DRB4 Gene

Variants for HLA-DRB4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for HLA-DRB4 Gene

P13762-DRB4_HUMAN
The following alleles of DRB4 are known: DRB4*01:01, DRB4*01:02, DRB4*01:03, DRB4*01:04, DRB4*01:05, DRB4*01:06 and DRB4*01:07. The sequence shown is that of DRB4*01:03

Sequence variations from dbSNP and Humsavar for HLA-DRB4 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type MAF
VAR_060778 -
VAR_060779 -
VAR_060780 -
VAR_060781 -
VAR_060782 -

Relevant External Links for HLA-DRB4 Gene

HapMap Linkage Disequilibrium report
HLA-DRB4
Human Gene Mutation Database (HGMD)
HLA-DRB4
Locus Specific Mutation Databases (LSDB)
HLA-DRB4

No data available for Structural Variations from Database of Genomic Variants (DGV) for HLA-DRB4 Gene

Disorders for HLA-DRB4 Gene

(2) University of Copenhagen DISEASES for HLA-DRB4 Gene

(3) Novoseek inferred disease relationships for HLA-DRB4 Gene

Disease -log(P) Hits PubMed IDs
hashimotos thyroiditis 39.9 2
mimicry 37.2 2
autoimmune diseases 3.01 1

Relevant External Links for HLA-DRB4

Genetic Association Database (GAD)
HLA-DRB4
Human Genome Epidemiology (HuGE) Navigator
HLA-DRB4
genes like me logo Genes that share disorders with HLA-DRB4: view

No data available for OMIM , UniProtKB/Swiss-Prot and Genatlas for HLA-DRB4 Gene

Publications for HLA-DRB4 Gene

  1. HLA-DRB4 as a genetic risk factor for Churg-Strauss syndrome. (PMID: 17763415) Vaglio A. … Neri T.M. (Arthritis Rheum. 2007) 3 23 48
  2. Specific amplification of the HLA-DRB4 gene from c-DNA. Complete coding sequence of the HLA alleles DRB4*0103101 and DRB4*01033. (PMID: 11972878) De Pablo R. … Vilches C. (Tissue Antigens 2002) 3 4 23
  3. HLA-DR and DQB1 gene polymorphism in the North-western Colombian population. (PMID: 12144632) Correa P.A. … Anaya J.M. (Tissue Antigens 2002) 3 23 48
  4. Interactions of HLA-DRB4 and CTLA-4 genes influence thyroid function in Hashimoto's thyroiditis in Japanese population. (PMID: 15055474) Terauchi M. … Saruta T. (J. Endocrinol. Invest. 2003) 3 23 48
  5. HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. (PMID: 15902698) Dorak M.T. … Kaslow R.A. (J. Med. Virol. 2005) 3 23 48

Products for HLA-DRB4 Gene

Sources for HLA-DRB4 Gene

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