ID:DRB5_HUMAN DESCRIPTION: RecName: Full=HLA class II histocompatibility antigen, DR beta 5 chain; AltName: Full=DR beta-5; AltName: Full=DR2-beta-2; AltName: Full=Dw2; AltName: Full=MHC class II antigen DRB5; 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 miroenvironment 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 down-regulation of MHC class II (Probable). POLYMORPHISM: The following alleles of DRB5 are known: DRB5*01:01, DRB5*01:02, DRB5*01:03, DRB5*01:04, DRB5*01:05, DRB5*01:06, DRB5*01:07, DRB5*01:09, DRB5*01:11, DRB5*01:12 DRB5*01:13, DRB5*01:14, DRB5*02:02, DRB5*02:03, DRB5*02:04, DRB5*02:05. The sequence shown is that of DRB5*01:01. 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.
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 Q30154
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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.
Biological Process: GO:0002376 immune system process GO:0002504 antigen processing and presentation of peptide or polysaccharide antigen via MHC class II GO:0006955 immune response GO:0019882 antigen processing and presentation GO:0019886 antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0050852 T cell receptor signaling pathway GO:0060333 interferon-gamma-mediated signaling pathway
DQ284432 - Homo sapiens clone ps1-23-T7 MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*040501 allele, complete cds. M16954 - Human MHC class II HLA-DR2 (Dw2) a-associated glycoprotein beta-chain mRNA, 3' end. M16956 - Human MHC class II HLA-DR2 (non-Dw2/non-Dw12) a-associated glycoprotein beta-chain mRNA, 3' end. M17377 - Homo sapiens MHC HLA-DR-beta cell surface glycoprotein (HLA-DRB2) mRNA, partial cds. AF291675 - Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*04 allele, complete cds. AJ297586 - Homo sapiens mRNA for MHC class II antigen (HLA-DRB1 gene), DRB1*0402 allele. AY961068 - Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*0408 allele, complete cds. AY961075 - Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*040701 allele, complete cds. HG974573 - Homo sapiens mRNA for MHC class II antigen (HLA-DRB1 gene), isolate 18072, allele DRB1*04:25ext. HG974575 - Homo sapiens mRNA for MHC class II antigen (HLA-DRB1 gene), isolate 19671, allele DRB1*04:15ext. HG974603 - Homo sapiens mRNA for MHC class II antigen (HLA-DRB1 gene), isolate 38210, allele DRB1*04:14ext. HM067845 - Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*04:01:01 allele, complete cds. HM067846 - Homo sapiens MHC class II antigen (HLA-DRB1) mRNA, HLA-DRB1*04:05:01 allele, complete cds. M30179 - Human MHC class II HLA-DR-beta chain mRNA (DR2,MN2), 5' end. M16955 - Human MHC class II HLA-DR2 (Dw12) a-associated glycoprotein beta-chain mRNA, 3' end. M20429 - Human MHC class II HLA-DR-beta mRNA (DR2-DQw1/DR4 DQw3), complete cds, clone ROF-beta-2a. M32578 - Human MHC class II HLA-DR beta-1 mRNA (DR2.3), 5'end. M57648 - Human MHC HLA-Dw12 mRNA, complete cds. BC009234 - Homo sapiens major histocompatibility complex, class II, DR beta 5, mRNA (cDNA clone MGC:16550 IMAGE:4054398), complete cds. M15992 - Human (clone FJ0-6) MHC class II DR subtype Dw2 mRNA, 3' end, haplotype HLA-DR2. JD185222 - Sequence 166246 from Patent EP1572962. M16086 - Human (clone DHO-7) MHC class II DR subtype Dw12 mRNA, 3' end, haplotype HLA-DR2. JD086917 - Sequence 67941 from Patent EP1572962. M20503 - Human MHC class II HLA-DR-beta-1 mRNA, complete cds. AK314834 - Homo sapiens cDNA, FLJ95720, Homo sapiens major histocompatibility complex, class II, DR beta 5(HLA-DRB5), mRNA. HQ447115 - Synthetic construct Homo sapiens clone IMAGE:100070402; CCSB006668_02 major histocompatibility complex, class II, DR beta 5 (HLA-DRB5) gene, encodes complete protein. KJ891352 - Synthetic construct Homo sapiens clone ccsbBroadEn_00746 HLA-DRB5 gene, encodes complete protein. AB463852 - Synthetic construct DNA, clone: pF1KB6353, Homo sapiens HLA-DRB5 gene for major histocompatibility complex class II DR beta 5, without stop codon, in Flexi system. KU556414 - Homo sapiens clone RR32-7 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556425 - Homo sapiens clone RB4-2 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556426 - Homo sapiens clone RB9-10 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556413 - Homo sapiens clone RR6-15 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556415 - UNVERIFIED: Homo sapiens clone RR13-8 MHC class II antigen-like (HLA-DRB) mRNA, partial sequence. KU556416 - Homo sapiens clone RR23-5 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556417 - Homo sapiens clone RR28-4 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556418 - Homo sapiens clone RR38-5 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556419 - Homo sapiens clone RR28-12 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556420 - Homo sapiens clone RR6-1 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556421 - Homo sapiens clone RR4-6 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556422 - Homo sapiens clone RR11-10 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556423 - Homo sapiens clone RR38-12 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556424 - Homo sapiens clone RR4-9 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556427 - Homo sapiens clone RB13-6 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556428 - Homo sapiens clone RB5-10 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556429 - Homo sapiens clone RB1-1 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556430 - Homo sapiens clone RB3-7 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556431 - Homo sapiens clone RB5-8 MHC class II antigen (HLA-DRB) mRNA, partial cds. KU556432 - Homo sapiens clone RB6-7 MHC class II antigen (HLA-DRB) mRNA, partial cds. U17380 - Human MHC class I HLA-DRB1 gene (HLA-DR1101V allele) mRNA, partial cds. U31770 - Homo sapiens HLA-drb5 (DRB5*0104) mRNA, partial cds. M30182 - Human MHC class II HLA-DR-beta mRNA (DR2,Dw12), partial cds, clone DHO-7. AF097680 - Homo sapiens MHC class II antigen (HLA-DRB5) pseudogene, partial sequence. M30181 - Human MHC class II HLA-DR-beta chain mRNA (DR2,MN2), 5' end, clone MN2-2. MK342638 - Homo sapiens isolate Patient 8 MHC class II antigen (HLA-DRB1) mRNA, partial cds.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q30154 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
