Tbio HLA-DQB1 HLA class II histocompatibility antigen, DQ beta 1 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-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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 it contains six exons. Exon 1 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 DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• P01920
• A1KR27
• A2RPH3
• A4Q9R4
• A4USG2
• A4USG5
• A6N8I7
• A9YQA0
• B0S7Y7
• B1A0K6
• B1GXI3
• B3VLT3
• B5BLN7
• B7VU69
• C0MQ34
• C0MQ35
• C8ZL52
• C8ZLJ8
• C8ZLJ9
• C9DRQ3
• O19708
• O19713
• O19724
• O62861
• O78046
• O78221
• O78223
• O98034
• O98201
• P01917
• P01918
• P01919
• P03992
• P05537
• P79482
• P79526
• P79544
• P79551
• Q08GC8
• Q09035
• Q0E4V9
• Q1M312
• Q29731
• Q29877
• Q29884
• Q29915
• Q29966
• Q2P9N3
• Q2QK85
• Q30061
• Q30075
• Q30076
• Q30080
• Q30081
• Q30082
• Q30083
• Q30084
• Q30089
• Q30095
• Q31633
• Q38I47
• Q45UE3
• Q4QZB5
• Q53I44
• Q564J6
• Q5G841
• Q5ISH1
• Q5ISH3
• Q5W1E1
• Q5Y7G8
• Q643R4
• Q6B9X1
• Q70VH8
• Q7YP69
• Q8HWH0
• Q8MH58
• Q8SNB4
• Q8SND1
• Q8SP70
• Q8WMA3
• Q9BD17
• Q9MYH2
• Q9TPA9
• Q9XRY6
• Q9XRY7
• Q9XRZ2

Gene Name

• HLA-DQB1

Ensembl ID

• ENST00000399088
• ENSP00000382038
• ENSG00000231286
• ENST00000413089
• ENSP00000396539
• ENST00000416192
• ENSP00000410107
• ENSG00000233209
• ENST00000419914
• ENSP00000402865
• ENSG00000225824
• ENST00000422950
• ENSP00000414079
• ENST00000424806
• ENSP00000410330

Symbol

• HLA-DQB
• IDDM1
• CELIAC1
• HLA-DQB

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
disease	0.94
protein domain	0.92
gene perturbation	0.91
PubMedID	0.89

Protein Classes

PANTHER Classes

Protein / Defense/immunity Protein / Major Histocompatibility Complex Antigen / Hla Class Ii Histocompatibility Antigen, Dq Beta 1 Chain

DTO Classes

Protein / Immune Response / Major Histocompatibility Complex Antigen / Hla Class Ii Histocompatibility Antigen, Dq Beta 1 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: 1067.56   (req: < 5)

Gene RIFs: 475   (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: 1067.56   (req: >= 5)

Gene RIFs: 475   (req: > 3)

Antibodies: 0   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 8

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

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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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 (324)

Explore Interacting Targets

1 – 10 of 324

• See Interactions on String-DB

TAPBP

Tbio

Novelty:  0.00328098

p_int:  0.999993769

p_ni:  0.000006177

p_wrong:  5.4e-8

Score:  0.24

Data Source:  BioPlex,STRINGDB

NDUFB8

Tclin

Family:  Enzyme

Novelty:  0.019021

p_int:  0.967514466

p_ni:  0.032485084

p_wrong:  4.5e-7

Score:  0.196

Data Source:  BioPlex,STRINGDB

DNAJB9

Tbio

Novelty:  0.00536296

p_int:  0.959783514

p_ni:  0.037577627

p_wrong:  0.002638859

Data Source:  BioPlex

NDUFA12

Tclin

Family:  Enzyme

Novelty:  0.04679316

p_int:  0.944159244

p_ni:  0.055836333

p_wrong:  0.000004423

Data Source:  BioPlex

KCNJ8

Tbio

Family:  IC

Novelty:  0.00369886

p_int:  0.920219093

p_ni:  0.079780907

Data Source:  BioPlex

NDUFB9

Tclin

Family:  Enzyme

Novelty:  0.00715628

p_int:  0.916087393

p_ni:  0.08391175

p_wrong:  8.57e-7

Data Source:  BioPlex

CPT1A

Tchem

Family:  Enzyme

Novelty:  0.00281783

p_int:  0.853049534

p_ni:  0.146950466

Data Source:  BioPlex

SEMA4F

Tbio

Novelty:  0.00574057

p_int:  0.804201707

p_ni:  0.195798071

p_wrong:  2.22e-7

Data Source:  BioPlex

NPC2

Tbio

Novelty:  0.00342898

p_int:  0.768786134

p_ni:  0.230953938

p_wrong:  0.000259928

Data Source:  BioPlex

MOGS

Tbio

Family:  Enzyme

Novelty:  0.00527993

p_int:  0.765207067

p_ni:  0.234792933

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 (60)

Reactome (13)

KEGG (24)

PathwayCommons (4)

WikiPathways (19)

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 (20)

Functions (2)

Components (12)

Processes (6)

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1 – 2 of 2

GO Term	Evidence	Assigned by
peptide antigen binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
MHC class II receptor activity	Non-traceable Author Statement (NAS)	UniProtKB

Disease Associations ()

No disease associations found

GWAS Traits (660)

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5

1 – 5 of 660

GWAS Trait	EFO ID	ENSG ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
asthma	EFO_0000270	ENSG00000225824	15	27	0	1.2	99.8
asthma	EFO_0000270	ENSG00000231286	15	27	0	1.2	99.8
asthma	EFO_0000270	ENSG00000233209	15	27	0	1.2	99.8
rheumatoid arthritis	EFO_0000685	ENSG00000225824	11	10	0	2.4	99.7
rheumatoid arthritis	EFO_0000685	ENSG00000231286	11	10	0	2.4	99.7

Items per page:

5

1 – 5 of 660

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
asthma	EFO_0000270	0	1.2	99.8
asthma	EFO_0000270	0	1.2	99.8
asthma	EFO_0000270	0	1.2	99.8
rheumatoid arthritis	EFO_0000685	0	2.4	99.7
rheumatoid arthritis	EFO_0000685	0	2.4	99.7

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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
Addison disease
adult onset asthma
age at diagnosis
age at first birth measurement
age at onset
alkaline phosphatase measurement
allergic rhinitis
allergic sensitization measurement
allergy

MGI Phenotype Find Similar Targets

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cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
nervous system phenotype
renal/urinary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (2)

1 – 2 of 2

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	histocompatibility 2, class II antigen A, beta 1	MGI:103070	14961
Cow	major histocompatibility complex, class II, DQ beta		282495

Species	Name	OMA	EggNOG	Inparanoid
Mouse	histocompatibility 2, class II antigen A, beta 1
Cow	major histocompatibility complex, class II, DQ beta

Publication Statistics

PubMed Score 1067.56

PubMed score by year

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PubTator Score 2206.57

PubTator score by year

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Related Publications

Text Mined References (1414)

GeneRif Annotations (475)

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PMID	Year	Title