| UniProt ID | DRA_HUMAN | |
|---|---|---|
| UniProt AC | P01903 | |
| Protein Name | HLA class II histocompatibility antigen, DR alpha chain | |
| Gene Name | HLA-DRA | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 254 | |
| Subcellular Localization |
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 pro |
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| Protein Description | 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.. | |
| Protein Sequence | MAISGVPVLGFFIIAVLMSAQESWAIKEEHVIIQAEFYLNPDQSGEFMFDFDGDEIFHVDMAKKETVWRLEEFGRFASFEAQGALANIAVDKANLEIMTKRSNYTPITNVPPEVTVLTNSPVELREPNVLICFIDKFTPPVVNVTWLRNGKPVTTGVSETVFLPREDHLFRKFHYLPFLPSTEDVYDCRVEHWGLDEPLLKHWEFDAPSPLPETTENVVCALGLTVGLVGIIIGTIFIIKGVRKSNAAERRGPL | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 78 | Phosphorylation | EEFGRFASFEAQGAL HHHCCCCCHHHHHHH | 22.40 | 27251275 | |
| 92 | Ubiquitination | LANIAVDKANLEIMT HHHHEEEHHHHEEEE | 32.35 | 21906983 | |
| 100 | Ubiquitination | ANLEIMTKRSNYTPI HHHEEEECCCCCCCC | 36.13 | 21906983 | |
| 103 | N-linked_Glycosylation | EIMTKRSNYTPITNV EEEECCCCCCCCCCC | 49.05 | 7477400 | |
| 103 | N-linked_Glycosylation | EIMTKRSNYTPITNV EEEECCCCCCCCCCC | 49.05 | 2212658 | |
| 143 | N-linked_Glycosylation | KFTPPVVNVTWLRNG CCCCCEEEEEEEECC | 26.24 | 7477400 | |
| 143 | N-linked_Glycosylation | KFTPPVVNVTWLRNG CCCCCEEEEEEEECC | 26.24 | 2212658 | |
| 151 | Ubiquitination | VTWLRNGKPVTTGVS EEEEECCEECCCCCE | 39.60 | 21906983 | |
| 172 | Ubiquitination | REDHLFRKFHYLPFL CCCCHHHCCCCCCCC | 29.20 | 21906983 | |
| 244 | Ubiquitination | FIIKGVRKSNAAERR HHHHCHHHCCHHHHC | 45.73 | 21906983 |
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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| N-linked Glycosylation | |
| Reference | PubMed |
| "The structure of an intermediate in class II MHC maturation: CLIPbound to HLA-DR3."; Ghosh P., Amaya M., Mellins E., Wiley D.C.; Nature 378:457-462(1995). Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 30-205 OF HLA-DRA/HLA-DRB1HETERODIMER IN COMPLEX WITH CD74 PEPTIDE (CLIP), SUBUNIT,GLYCOSYLATION AT ASN-103 AND ASN-143, AND DISULFIDE BOND. | |
| "Glycoproteomics analysis of human liver tissue by combination ofmultiple enzyme digestion and hydrazide chemistry."; Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; J. Proteome Res. 8:651-661(2009). Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-103 AND ASN-143, AND MASSSPECTROMETRY. | |
| Ubiquitylation | |
| Reference | PubMed |
| "The HLA-DRalpha chain is modified by polyubiquitination."; Lapaque N., Jahnke M., Trowsdale J., Kelly A.P.; J. Biol. Chem. 284:7007-7016(2009). Cited for: UBIQUITINATION AT LYS-244 BY MARCH1 AND MARCH8, MUTAGENESIS OFLYS-244, AND SUBCELLULAR LOCATION. | |
