| UniProt ID | 2B13_HUMAN | |
|---|---|---|
| UniProt AC | P01912 | |
| Protein Name | HLA class II histocompatibility antigen, DRB1-3 chain | |
| Gene Name | HLA-DRB1 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 266 | |
| 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 membr |
|
| 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 | MVCLRLPGGSCMAVLTVTLMVLSSPLALAGDTRPRFLEYSTSECHFFNGTERVRYLDRYFHNQEENVRFDSDVGEFRAVTELGRPDAEYWNSQKDLLEQKRGRVDNYCRHNYGVVESFTVQRRVHPKVTVYPSKTQPLQHHNLLVCSVSGFYPGSIEVRWFRNGQEEKTGVVSTGLIHNGDWTFQTLVMLETVPRSGEVYTCQVEHPSVTSPLTVEWRARSESAQSKMLSGVGGFVLGLLFLGAGLFIYFRNQKGHSGLQPRGFLS | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
|
|
||
* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 48 | N-linked_Glycosylation | TSECHFFNGTERVRY CCCCEECCCCHHHHH | 56.38 | 19159218 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
Oops, there are no upstream regulatory protein records of 2B13_HUMAN !! | ||||||
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of 2B13_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
| 48 | N-linked Glycosylation | 54 (6) | R ⇒ Q | rs17885382 |
| 25987655 |
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| H00079 | Asthma | |||||
| H00080 | Systemic lupus erythematosus | |||||
| H00081 | Hashimoto's thyroiditis | |||||
| H00082 | Graves' disease | |||||
| H00294 | Dilated cardiomyopathy (DCM) | |||||
| H00342 | Tuberculosis | |||||
| H00408 | Type I diabetes mellitus | |||||
| OMIM Disease | ||||||
| There are no disease associations of PTM sites. | ||||||
| Kegg Drug | ||||||
| D02967 | Apolizumab (USAN/INN) | |||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
loading...
| N-linked Glycosylation | |
| Reference | PubMed |
| "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-48, AND MASS SPECTROMETRY. | |
