Human Gene HLA-DRB4 (uc011hel.2) Description and Page Index
Description: Homo sapiens major histocompatibility complex, class II, DR beta 4 (HLA-DRB4), mRNA. Transcript (Including UTRs) Position: chr6_mann_hap4:3,846,266-3,860,953 Size: 14,688 Total Exon Count: 6 Strand: - Coding Region Position: chr6_mann_hap4:3,846,367-3,860,944 Size: 14,578 Coding Exon Count: 6
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Comments and Description Text from UniProtKB
ID:DRB4_HUMAN DESCRIPTION: RecName: Full=HLA class II histocompatibility antigen, DR beta 4 chain; AltName: Full=MHC class II antigen DRB4; Flags: Precursor; 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. 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. SUBCELLULAR LOCATION: 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. PTM: 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. POLYMORPHISM: 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. SIMILARITY: Belongs to the MHC class II family. SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like) domain. CAUTION: HLA-DRB3, HLA-DRB4 and HLA-DRB5 may represent a unique gene.
Genetic Association Studies of Complex Diseases and Disorders
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P13762
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
M21008 - Human MHC class II HLA-DR1 beta mRNA (DR1,DQw1,Dw), 3' end. AM056024 - Homo sapiens partial mRNA for MHC class II antigen (HLA-DRB1 gene) HLA-DRB1*15 allele, exon 2. M16942 - Human MHC class II HLA-DRw53-associated glycoprotein beta- chain mRNA, complete cds. M15178 - Human HLA-DR beta-chain mRNA, partial cds. AF048707 - Homo sapiens MHC class II antigen HLA-DR mRNA (HLA-DRB4*01 variant allele), partial cds. AF361548 - Homo sapiens MHC class II antigen (HLA-DRB4) mRNA, HLA-DRB4*0103101 allele, complete cds. AF361549 - Homo sapiens MHC class II antigen (HLA-DRB4) mRNA, HLA-DRB4*01033 allele, complete cds. DQ284431 - Homo sapiens clone ps1-17-T7 MHC class II antigen (HLA-DRB4) mRNA, HLA-DRB4*01030101 allele, complete cds. M17385 - Human MHC class II HLA-DR-beta mRNA (DR7), partial cds. GQ891550 - Homo sapiens MHC class II antigen (HLA-DRB4) mRNA, HLA-DRB4*0909 allele, complete cds. DQ284433 - Homo sapiens clone ps1-6-T7 MHC class II antigen (HLA-DRB4) mRNA, HLA-DRB4*01030101 variant allele, complete cds. U70544 - Homo sapiens HLA class II DRB4 null antigen (HLA-DRB4) pseudogene mRNA, null allele HLA-DRB4*0201N, partial cds. U70543 - Homo sapiens MHC class II antigen (HLA-DRB4) pseudogene mRNA, null allele HLA-DRB4*0201N, partial cds. M30182 - Human MHC class II HLA-DR-beta mRNA (DR2,Dw12), partial cds, clone DHO-7. M15071 - Human MHC class II HLA-DR-beta-2 chain mRNA (DR4,Dw15), partial cds. M14190 - Human MHC class II DR7-beta-1 chain mRNA (DR7), partial cds. M16732 - Human MHC class II HLA-DR4/w53 first domain coding region fo DR-beta chain mRNA (Dw4). M17388 - Human MHC class II HLA-DR-beta mRNA (DR9), partial cds.