Tbio HLA-DRA HLA class II histocompatibility antigen, DR alpha 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-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta 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 alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P01903
• A2BET4
• Q30160
• Q6IAZ1
• Q861I2
• Q9TP70

Gene Name

• HLA-DRA

Ensembl ID

• ENST00000383127
• ENSP00000372608
• ENSG00000227993
• ENST00000383259
• ENSP00000372746
• ENSG00000206308
• ENST00000395388
• ENSP00000378786
• ENSG00000204287
• ENST00000411524
• ENSP00000405295
• ENSG00000234794
• ENST00000414698
• ENSP00000402951
• ENSG00000230726
• ENST00000416883
• ENSP00000410443
• ENSG00000228987
• ENST00000442960
• ENSP00000404533
• ENSG00000226260

Symbol

• HLA-DRA1
• HLA-DRA1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
trait	1
virus perturbation	0.94
protein domain	0.92
phenotype	0.79
disease	0.76

Protein Classes

PANTHER Classes

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

DTO Classes

Protein / Immune Response / Major Histocompatibility Complex Antigen / Hla Class Ii Histocompatibility Antigen, Dr Alpha 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: 164.4   (req: < 5)

Gene RIFs: 62   (req: <= 3)

Antibodies: 1684   (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: 164.4   (req: >= 5)

Gene RIFs: 62   (req: > 3)

Antibodies: 1684   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

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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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 (423)

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1 – 10 of 423

• See Interactions on String-DB

DDX19B

Tbio

Family:  Enzyme

Novelty:  0.0504568

p_int:  0.999991565

p_ni:  0.000008428

p_wrong:  8e-9

Data Source:  BioPlex

HLA-DRB5

Tbio

Novelty:  0.00291303

p_int:  0.999899141

p_ni:  0.000004526

p_wrong:  0.000096334

Score:  0.998

Data Source:  BioPlex,STRINGDB

AP1G2

Tbio

Novelty:  0.17203425

p_int:  0.999625724

p_ni:  0.000374273

p_wrong:  2e-9

Data Source:  BioPlex

SDR39U1

Tdark

Family:  Enzyme

Novelty:  0.38626113

p_int:  0.999575412

p_ni:  0.000004245

p_wrong:  0.000420343

Data Source:  BioPlex

KLK4

Tchem

Family:  Enzyme

Novelty:  0.00019849

p_int:  0.999486575

p_ni:  0.000016976

p_wrong:  0.000496449

Score:  0.806

Data Source:  BioPlex,STRINGDB

NXPE3

Tdark

Novelty:  1.5063521

p_int:  0.998688983

p_ni:  0.001311009

p_wrong:  8e-9

Data Source:  BioPlex

HLA-DMB

Tbio

Novelty:  0.02289537

p_int:  0.998524208

p_ni:  0.001148806

p_wrong:  0.000326987

Score:  0.996

Data Source:  BioPlex,Reactome,STRINGDB

SLC25A42

Tbio

Family:  Transporter

Novelty:  0.15737382

p_int:  0.998150434

p_ni:  0.000010192

p_wrong:  0.001839374

Data Source:  BioPlex

TMEM214

Tdark

Novelty:  0.32604613

p_int:  0.998036503

p_ni:  0.001963497

Data Source:  BioPlex

DSE

Tbio

Family:  Enzyme

Novelty:  0.02945465

p_int:  0.99705408

p_ni:  0.002911553

p_wrong:  0.000034367

Data Source:  BioPlex

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 (49)

Reactome (13)

KEGG (24)

PathwayCommons (8)

WikiPathways (4)

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 (27)

Functions (3)

Components (15)

Processes (9)

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Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
peptide antigen binding	Inferred from Direct Assay (IDA)	UniProtKB
MHC class II protein complex binding	Inferred from High Throughput Direct Assay (HDA)	UniProtKB
MHC class II receptor activity	Non-traceable Author Statement (NAS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (847)

Items per page:

5

1 – 5 of 847

GWAS Trait	EFO ID	ENSG ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	ENSG00000226260	7	7	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	ENSG00000206308	7	7	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	ENSG00000204287	7	7	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	ENSG00000228987	7	7	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	ENSG00000227993	7	7	3	2.3	99.4

Items per page:

5

1 – 5 of 847

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
rheumatoid arthritis	EFO_0000685	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	3	2.3	99.4
rheumatoid arthritis	EFO_0000685	3	2.3	99.4

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Endoplasmic reticulum
Endosome
Glycoprotein
Golgi apparatus
Host-virus interaction

GWAS Trait Find Similar Targets

No Header	No Header
ACPA-positive rheumatoid arthritis
acute-on-chronic liver failure
advanced glycosylation end product-specific receptor ligand measurement
age at diagnosis
alkaline phosphatase measurement
Alzheimer's disease
anti-anoctamin 2 antibody measurement
anti-citrullinated protein antibody seropositivity
anti-Epstein Barr virus antibody measurement
anti-polyomavirus 2 antibody measurement

IDG Resources

No IDG generated resources found

Orthologs (4)

1 – 4 of 4

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	major histocompatibility complex, class II, DR alpha		462591
Rat	RT1 class II, locus Da	RGD:1593283	294269
Cow	major histocompatibility complex, class II, DR alpha		506214
Platypus	MHC class II DR alpha		100079322

Species	Name	OMA	EggNOG	Inparanoid
Chimp	major histocompatibility complex, class II, DR alpha
Rat	RT1 class II, locus Da
Cow	major histocompatibility complex, class II, DR alpha
Platypus	MHC class II DR alpha

Publication Statistics

PubMed Score 164.40

PubMed score by year

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PubTator Score 133.23

PubTator score by year

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Related Publications

Text Mined References (199)

GeneRif Annotations (62)

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PMID	Year	Title