Tbio HLA-DRB5 HLA class II histocompatibility antigen, DR beta 5 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-DRB5 belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DRA) and a beta (DRB) chain, 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 and its gene contains 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. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. DRB1 is expressed at a level five times higher than its paralogues DRB3, DRB4 and DRB5. The presence of DRB5 is linked with allelic variants of DRB1, otherwise it is omitted. There are 4 related pseudogenes: DRB2, DRB6, DRB7, DRB8 and DRB9. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q30154
• B2RBV6
• C7C4X3
• O00157
• O00283
• O46700
• Q29703
• Q29787
• Q29788
• Q30126
• Q30150
• Q30199
• Q6SJR2
• Q7M2H9
• Q8HWS7
• Q8WLR5
• Q9MY54
• Q9XRX6

Gene Name

• HLA-DRB5

Ensembl ID

• ENST00000374975
• ENSP00000364114
• ENSG00000198502

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
phenotype	0.96
protein domain	0.92
disease perturbation	0.87
cellular component	0.83
disease	0.79

Protein Classes

PANTHER Classes

Protein / Defense/immunity Protein / Major Histocompatibility Complex Antigen / Hla Class Ii Histocompatibility Antigen, Dr Beta 5 Chain

DTO Classes

Protein / Immune Response / Major Histocompatibility Complex Antigen / Hla Class Ii Histocompatibility Antigen, Dr Beta 5 Chain

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: 460.03   (req: < 5)

Gene RIFs: 25   (req: <= 3)

Antibodies: 121   (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: 460.03   (req: >= 5)

Gene RIFs: 25   (req: > 3)

Antibodies: 121   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 4

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

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (319)

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1 – 10 of 319

• See Interactions on String-DB

P01911

Tchem

Novelty:  0.00240724

p_int:  0.999999828

p_ni:  7.5e-8

p_wrong:  9.8e-8

Score:  0.98

Data Source:  BioPlex,STRINGDB

HLA-DRA

Tbio

Novelty:  0.0060214

p_int:  0.999899141

p_ni:  0.000004526

p_wrong:  0.000096334

Score:  0.998

Data Source:  BioPlex,STRINGDB

CHEK1

Tchem

Family:  Kinase

Novelty:  0.00066843

p_int:  0.924718385

p_ni:  0.075281081

p_wrong:  5.33e-7

Score:  0.211

Data Source:  BioPlex,STRINGDB

HSPA5

Tchem

Novelty:  0.00043424

p_int:  0.774931012

p_ni:  0.225068988

Data Source:  BioPlex

UBR3

Tbio

Family:  Enzyme

Novelty:  0.14930754

p_int:  0.76266978

p_ni:  0.23733022

Score:  0.167

Data Source:  BioPlex,STRINGDB

CD74

Tchem

Novelty:  0.00281228

Score:  0.987

Data Source:  STRINGDB

P20039

Tbio

Novelty:  0.00240724

Score:  0.98

Data Source:  STRINGDB

Q9GIY3

Tbio

Novelty:  0.00240724

Score:  0.98

Data Source:  STRINGDB

P01912

Tbio

Novelty:  0.00240724

Score:  0.98

Data Source:  STRINGDB

Q29974

Tbio

Novelty:  0.00240724

Score:  0.98

Data Source:  STRINGDB

Nearest Tclin Targets (2)

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Upstream (2)

1 – 2 of 2

JAK1

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  9

1: Human T-cell leukemia virus 1 infection

2: Tuberculosis

3: Th17 cell differentiation

4: Th1 and Th2 cell differentiation

more:  5 more common pathways

JAK2

Tclin

Family:  Kinase

KEGG Distance:  4

Common Pathways:  7

1: Tuberculosis

2: Th17 cell differentiation

3: Th1 and Th2 cell differentiation

4: Leishmaniasis

more:  3 more common pathways

Pathways (120)

Reactome (13)

KEGG (24)

WikiPathways (83)

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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (16)

Functions (1)

Components (12)

Processes (3)

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GO Term	Evidence	Assigned by
peptide antigen binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (163)

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1 – 5 of 163

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	10	10	3	2.1	99.7
multiple sclerosis	EFO_0003885	6	6	0	2.5	99.2
eosinophil count	EFO_0004842	4	4	5		98.1
neutrophil count	EFO_0004833	4	4	4		98.1
ulcerative colitis	EFO_0000729	8	5	0	1.5	98

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	3	2.1	99.7
multiple sclerosis	EFO_0003885	0	2.5	99.2
eosinophil count	EFO_0004842	5		98.1
neutrophil count	EFO_0004833	4		98.1
ulcerative colitis	EFO_0000729	0	1.5	98

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UniProt Keyword Find Similar Targets

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3D-structure
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Immunity

GWAS Trait Find Similar Targets

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ACPA-positive rheumatoid arthritis
acute-on-chronic liver failure
advanced glycosylation end product-specific receptor ligand measurement
age at diagnosis
alkaline phosphatase measurement
allergic rhinitis
allergy
Alzheimer's disease
anti-anoctamin 2 antibody measurement
anti-citrullinated protein antibody seropositivity

MGI Phenotype Find Similar Targets

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hematopoietic system phenotype
immune system phenotype
skeleton phenotype

IDG Resources

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Orthologs (1)

1 – 1 of 1

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	major histocompatibility complex, class II, DR beta 5		462592

Species	Name	OMA	EggNOG	Inparanoid
Chimp	major histocompatibility complex, class II, DR beta 5

Publication Statistics

PubMed Score 460.03

PubMed score by year

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PubTator Score 45.38

PubTator score by year

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Related Publications

Text Mined References (158)

GeneRif Annotations (25)

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PMID	Year	Title