Homo sapiens Protein: HLA-DRB1 | |||||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-80865.6 | ||||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||
Gene Symbol | HLA-DRB1 | ||||||||||||||||||||||||||||||||||||||
Protein Name | major histocompatibility complex, class II, DR beta 1 | ||||||||||||||||||||||||||||||||||||||
Synonyms | DRB1; DRw10; HLA-DR1B; HLA-DRB; SS1; | ||||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000353099 | ||||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-80863 (HLA-DRB1) | ||||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||||
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. | ||||||||||||||||||||||||||||||||||||||
Subcellular Localization | Cell membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. Endoplasmic reticulum membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. Golgi apparatus, trans-Golgi network membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. Endosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. Lysosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. Late endosome membrane {ECO:0000269PubMed:18305173}; Single-pass type I membrane protein {ECO:0000269PubMed:18305173}. 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. | ||||||||||||||||||||||||||||||||||||||
Disease Associations | Sarcoidosis 1 (SS1) [MIM:181000]: An idiopathic, systemic, inflammatory disease characterized by the formation of immune granulomas in involved organs. Granulomas predominantly invade the lungs and the lymphatic system, but also skin, liver, spleen, eyes and other organs may be involved. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. | ||||||||||||||||||||||||||||||||||||||
Tissue Specificity | |||||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 23 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||||
InterPro |
IPR000353
MHC class II, beta chain, N-terminal IPR003597 Immunoglobulin C1-set IPR007110 Immunoglobulin-like domain IPR011162 MHC classes I/II-like antigen recognition protein |
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PFAM |
PF00969
PF07654 |
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PRINTS | |||||||||||||||||||||||||||||||||||||||
PIRSF | |||||||||||||||||||||||||||||||||||||||
SMART |
SM00921
SM00407 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||||
SwissProt | Q9GIY3 | ||||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-P04229 | ||||||||||||||||||||||||||||||||||||||
TrEMBL | X5DNQ0 | ||||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||
Entrez Gene | 3123 | ||||||||||||||||||||||||||||||||||||||
UniGene | |||||||||||||||||||||||||||||||||||||||
RefSeq | NP_002115 | ||||||||||||||||||||||||||||||||||||||
HUGO | HGNC:4948 | ||||||||||||||||||||||||||||||||||||||
OMIM | 142857 | ||||||||||||||||||||||||||||||||||||||
CCDS | CCDS47409 | ||||||||||||||||||||||||||||||||||||||
HPRD | 08349 | ||||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||||
EMBL | AB015184 AB049830 AB049831 AB049832 AB062112 AB087875 AB087876 AB106127 AB436778 AB485773 AF028010 AF029288 AF029293 AF089723 AF112879 AF142467 AF172071 AF177215 AF239244 AF363727 AF400066 AF439712 AJ010982 AJ242985 AJ251985 AJ276206 AJ289123 AJ297582 AJ297583 AJ297584 AJ297585 AJ303118 AJ431718 AJ507782 AJ508388 AJ543433 AJ581744 AJ812566 AJ969417 AK289463 AK291987 AL713966 AM084908 AM109998 AM109999 AM110000 AM110001 AM110002 AM110003 AM110006 AM233907 AM259285 AM419948 AM774161 AM922324 AM933133 AY050186 AY054375 AY174092 AY174181 AY267905 AY267906 AY277390 AY428805 AY663395 AY663400 AY663406 AY663408 AY663409 AY663411 AY663414 AY770520 AY912074 AY912075 AY935719 AY961071 AY961072 AY961073 BC033827 BC108922 D86502 D86504 D88310 DQ021915 DQ060439 DQ060441 DQ179036 DQ192647 DQ235685 DQ327711 DQ333353 DQ358688 DQ390459 DQ390460 DQ494324 DQ514601 DQ514603 DQ643390 DQ782331 DQ837166 EF078985 EF078986 EF156366 EF199810 EF495154 EF536016 EU029787 EU029788 EU029792 EU029793 EU029798 EU029801 EU545181 EU588391 EU643616 EU812536 EU924810 FJ358153 FJ358154 FJ358155 FJ358157 FJ358161 FJ358162 FJ358163 FJ358164 FJ358169 FJ358171 FJ358172 FJ358173 FJ358174 FJ358177 FJ379259 FJ594768 FJ766013 FJ875603 FJ875604 FJ888507 FJ917720 FM179681 FM196525 FM955270 FR822200 FR839024 GQ132056 GQ149338 GQ254401 GQ410114 GQ900585 GU128056 GU128057 GU128058 GU354139 GU551914 GU551915 GU551928 HE654767 HG797652 HM004236 HM004237 HM067861 HM125891 HM141085 HM187710 HM187718 HM187719 HM187720 HM187721 HM187722 HM562349 HM562350 HQ230524 HQ230537 HQ230540 HQ230552 HQ337765 HQ840743 HQ850053 JF261241 JF292485 JF309443 JF309444 JF796681 JN119502 JN119504 JN157603 JN159878 JN406383 JN418843 JN561762 JQ824712 JQ824715 JQ824717 JQ824724 JQ824725 JQ824726 JQ824736 JQ911928 JQ935228 KJ534866 L02545 M11161 M16957 M16959 M17378 M20430 M20504 M21008 M28583 M28584 M33600 M77673 U26659 U41489 U59686 U95115 X03069 X64546 X64547 X86974 X99839 X99896 Z38072 Z50730 Z50871 Z72424 | ||||||||||||||||||||||||||||||||||||||
GenPept | AAA36279 AAA36281 AAA59680 AAA59681 AAA59777 AAA59780 AAA59781 AAA59782 AAA59801 AAA59827 AAA59831 AAA73131 AAA86242 AAB52230 AAB58397 AAB94612 AAD09441 AAD29584 AAD31311 AAD51131 AAD51970 AAD53910 AAF59946 AAF65497 AAF65502 AAH33827 AAI08923 AAK51524 AAK85431 AAL15169 AAL23547 AAL35224 AAO17053 AAO20089 AAP32696 AAP32697 AAP34694 AAR07616 AAU87979 AAU87993 AAU88008 AAU88014 AAU88018 AAU88023 AAU88033 AAV37191 AAX33315 AAX63459 AAX63460 AAX63461 AAY17287 AAY17288 AAY59541 AAY59543 AAY85747 ABA06594 ABA39176 ABB52004 ABC59115 ABC59293 ABC84557 ABD60300 ABD60301 ABF50050 ABF60564 ABF60566 ABG25965 ABG91054 ABH05946 ABK56695 ABK56696 ABL98033 ABM90423 ABP38039 ABQ08747 ABU86846 ABU86847 ABU86851 ABU86852 ABU86857 ABU86860 ACB30275 ACB97664 ACD01094 ACE88696 ACH57405 ACJ06537 ACM47962 ACN81310 ACO87689 ACO87690 ACO87691 ACO87693 ACO87697 ACO87698 ACO87699 ACO87700 ACO87705 ACO87707 ACO87708 ACO87709 ACO87710 ACO87713 ACP27930 ACP27931 ACP40977 ACV31954 ADB55623 ADC32271 ADC45489 ADE58763 ADE58764 ADE58777 ADE73190 ADE73258 ADE73426 ADE73427 ADE73428 ADE73589 ADE73724 ADE73725 ADI59573 ADJ67221 ADZ05575 ADZ05588 ADZ05591 ADZ05603 ADZ73165 AEA49853 AEB21071 AEB21079 AEB21080 AEB21081 AEB21082 AEB21083 AEF13156 AEF13157 AEJ22089 AEJ87208 AEK27140 AEK94850 AEK94964 AEK95000 AEK95097 AEK95098 AEK95233 AEK95235 AEV76920 AEW23004 AEW90708 AFA42775 AFZ94253 AFZ94256 AFZ94258 AFZ94265 AFZ94266 AFZ94267 AFZ94277 AFZ94449 AFZ94477 AHW56506 BAA13097 BAA13099 BAA13587 BAA28761 BAB16682 BAB16683 BAB16684 BAB84521 BAC02938 BAC02939 BAC66086 BAF82152 BAF84676 BAG32234 BAH23562 CAA09450 CAA26873 CAA45844 CAA45845 CAA68150 CAA68171 CAA86217 CAB45249 CAC08822 CAC08823 CAC08824 CAC08825 CAC19015 CAC19086 CAC19693 CAC27123 CAD24479 CAD47818 CAD48196 CAD65908 CAE46451 CAH23708 CAI18081 CAI94542 CAJ29895 CAJ33605 CAJ33606 CAJ33607 CAJ33608 CAJ33609 CAJ33610 CAJ33613 CAJ80873 CAJ90660 CAL99240 CAO81738 CAP58300 CAP69806 CAQ77159 CAQ86516 CAV31551 CBZ41221 CCA30655 CCF77340 CDL67654 | ||||||||||||||||||||||||||||||||||||||