HLA-DRB3 Gene (Protein Coding)

• HLA-DRB3 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. 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. There are multiple pseudogenes of this gene. [provided by RefSeq, Feb 2020]

HLA-DRB3 (Major Histocompatibility Complex, Class II, DR Beta 3) is a Protein Coding gene. Diseases associated with HLA-DRB3 include Pityriasis Rosea and Fetal And Neonatal Alloimmune Thrombocytopenia. Among its related pathways are TCR Signaling (Qiagen) and Tuberculosis. Gene Ontology (GO) annotations related to this gene include peptide antigen binding and MHC class II receptor activity.

• 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.

  • DRB3_HUMAN,P79483

• HGNC(4951)
• Entrez Gene(3125)
• OMIM(612735)
• UniProtKB(P79483)
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• Search for HLA-DRB3 at DataMed
• Search for HLA-DRB3 at HumanCyc

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for HLA-DRB3 Gene

No data available for GeneHancer (GH) Regulatory Elements for HLA-DRB3 Gene

No data available for DME Specific Peptides for HLA-DRB3 Gene

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for HLA-DRB3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HLA-DRB3 Gene

No data available for Subcellular locations from COMPARTMENTS and Subcellular locations from the Human Protein Atlas (HPA) for HLA-DRB3 Gene

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for HLA-DRB3 Gene

No data available for Orthologs and Evolution for HLA-DRB3 Gene

No data available for Paralogs for HLA-DRB3 Gene

No data available for Structural Variations from Database of Genomic Variants (DGV) and Variation tolerance for HLA-DRB3 Gene

No data available for UniProtKB/Swiss-Prot and Genatlas for HLA-DRB3 Gene

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