Tbio HLA-DRB1 HLA class II histocompatibility antigen, DRB1-12 beta chain

Protein Summary

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. HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. DRB1 is expressed at a level five times higher than its paralogs DRB3, DRB4 and DRB5. DRB1 is present in all individuals. Allelic variants of DRB1 are linked with either none or one of the genes DRB3, DRB4 and DRB5. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q95IE3
• A7LA26
• B0LUZ6
• B6VCX2
• B7UDB2
• O19585
• Q19AF2
• Q29771
• Q2L9H4
• Q2MZ92
• Q5EER6
• Q5NDB9
• Q5UT58
• Q5Y7G0
• Q768U4
• Q7YP04
• Q861H8
• Q95IT6
• Q9BD40

Gene Name

• HLA-DRB1

Ensembl ID

• ENST00000328980
• ENSP00000331343
• ENSG00000206306
• ENST00000399450
• ENSP00000382378
• ENSG00000206240
• ENST00000412634
• ENSP00000408795
• ENSG00000228080
• ENST00000415796
• ENSP00000412168
• ENST00000419393
• ENSP00000403458
• ENST00000428566
• ENSP00000392280

Symbol

• SS1
• DRB1
• HLA-DRB
• HLA-DR1B

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0
biological term	0
cell line	0
cell type or tissue	0
cellular component	0

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Target Illumination GWAS Analytics (TIGA)

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ARCHS4

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4163.15   (req: < 5)

Gene RIFs: 1105   (req: <= 3)

Antibodies: 0   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4163.15   (req: >= 5)

Gene RIFs: 1105   (req: > 3)

Antibodies: 0   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 3

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

GWAS Traits (786)

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5

1 – 5 of 786

GWAS Trait	EFO ID	ENSG ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	ENSG00000206240	5	3	0	2	99.5
rheumatoid arthritis	EFO_0000685	ENSG00000206240	5	3	0	2	99.5
rheumatoid arthritis	EFO_0000685	ENSG00000206240	5	3	0	2	99.5
rheumatoid arthritis	EFO_0000685	ENSG00000206240	5	3	0	2	99.5
rheumatoid arthritis	EFO_0000685	ENSG00000206240	5	3	0	2	99.5

Items per page:

5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	0	2	99.5
rheumatoid arthritis	EFO_0000685	0	2	99.5
rheumatoid arthritis	EFO_0000685	0	2	99.5
rheumatoid arthritis	EFO_0000685	0	2	99.5
rheumatoid arthritis	EFO_0000685	0	2	99.5

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Orthologs (2)

1 – 2 of 2

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	histocompatibility 2, class II antigen E beta	MGI:95901	14969
Rat	RT1 class II, locus Db1	RGD:1593282	294270

Species	Name	OMA	EggNOG	Inparanoid
Mouse	histocompatibility 2, class II antigen E beta
Rat	RT1 class II, locus Db1

Pathways (91)

Reactome (13)

KEGG (24)

WikiPathways (54)

Adaptive Immune System (R-HSA-1280218)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Costimulation by the CD28 family	88 targets	R-HSA-388841
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Downstream TCR signaling	117 targets	R-HSA-202424
Reactome	Generation of second messenger molecules	51 targets	R-HSA-202433

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Costimulation by the CD28 family	88 targets	R-HSA-388841
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Downstream TCR signaling	117 targets	R-HSA-202424
Generation of second messenger molecules	51 targets	R-HSA-202433

Gene Ontology Terms (14)

Components (11)

Processes (3)

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GO Term	Evidence	Assigned by
late endosome membrane	Inferred from Direct Assay (IDA)	UniProtKB
lysosomal membrane	Inferred from Direct Assay (IDA)	UniProtKB
clathrin-coated endocytic vesicle membrane	Traceable Author Statement (TAS)	Reactome
endocytic vesicle membrane	Traceable Author Statement (TAS)	Reactome
ER to Golgi transport vesicle membrane	Traceable Author Statement (TAS)	Reactome
Golgi membrane	Traceable Author Statement (TAS)	Reactome
integral component of lumenal side of endoplasmic reticulum membrane	Traceable Author Statement (TAS)	Reactome
plasma membrane	Traceable Author Statement (TAS)	Reactome
trans-Golgi network membrane	Traceable Author Statement (TAS)	Reactome
transport vesicle membrane	Traceable Author Statement (TAS)	Reactome

Protein-Protein Interactions (388)

Explore Interacting Targets

1 – 10 of 388

• See Interactions on String-DB

HLA-DRA

Tbio

Novelty: 0.0060214

Score: 0.999

Data Source: STRINGDB

CD74

Tchem

Novelty: 0.00281228

Score: 0.998

Data Source: STRINGDB

HLA-DMA

Tbio

Novelty: 0.00405566

Score: 0.997

Data Source: STRINGDB

CD4

Tclin

Novelty: 0.00001217

Score: 0.986

Data Source: STRINGDB

HLA-DRB5

Tbio

Novelty: 0.00291303

Score: 0.98

Data Source: STRINGDB

PTPN22

Tchem

Family: Enzyme

Novelty: 0.00168847

Score: 0.98

Data Source: STRINGDB

HLA-DMB

Tbio

Novelty: 0.02289537

Score: 0.979

Data Source: STRINGDB

HLA-DPA1

Tbio

Novelty: 0.01080446

Score: 0.975

Data Source: STRINGDB

HLA-DQA1

Tbio

Novelty: 0.00077488

Score: 0.964

Data Source: STRINGDB

HLA-DQA2

Tbio

Novelty: 0.00431613

Score: 0.963

Data Source: STRINGDB

Publication Statistics

PubMed Score  4163.15

PubMed score by year

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PubTator Score  4503.37

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

Cell membrane
Complete proteome
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Immunity
Lysosome
Membrane

GWAS Trait Find Similar Targets

ACPA-positive rheumatoid arthritis
allergic rhinitis
Alzheimer's disease
anti-anoctamin 2 antibody measurement
anti-drug antibody measurement
anti-Epstein Barr virus antibody measurement
anti-herpes simplex virus 6 antibody measurement
antibody measurement
appendicular lean mass
AQP4-IgG-positive neuromyelitis optica