Tclin CD4 T-cell surface glycoprotein CD4

Protein Summary

Description

Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. (Microbial infection) Primary receptor for human immunodeficiency virus-1 (HIV-1) (PubMed:2214026, PubMed:16331979, PubMed:9641677, PubMed:12089508). Down-regulated by HIV-1 Vpu (PubMed:17346169). Acts as a receptor for Human Herpes virus 7/HHV-7 (PubMed:7909607). This gene encodes a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigenes and is also a receptor for the human immunodeficiency virus. This gene is expressed not only in T lymphocytes, but also in B cells, macrophages, and granulocytes. It is also expressed in specific regions of the brain. The protein functions to initiate or augment the early phase of T-cell activation, and may function as an important mediator of indirect neuronal damage in infectious and immune-mediated diseases of the central nervous system. Multiple alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Aug 2010]

Uniprot Accession IDs

• P01730
• B2R737
• D3DUS5
• Q4ZGK2
• Q5U066
• Q9UDE5

Gene Name

• CD4

Ensembl ID

• ENST00000011653
• ENSP00000011653
• ENSG00000010610

Symbol

• CD4mut

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0.98
protein domain	0.97
virus	0.89
molecular function	0.88
disease	0.83

Protein Classes

No PANTHER Classes or DTO Classes found

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: 99475.02   (req: < 5)

Gene RIFs: 284   (req: <= 3)

Antibodies: 5688   (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: 99475.02   (req: >= 5)

Gene RIFs: 284   (req: > 3)

Antibodies: 5688   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 56

Tchem

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

Active Ligands: 12

Tclin

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

Active Drug: 1

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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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 (1)

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ibalizumab

CD4Tclin

ANTIBODY BINDING :

Active Ligands (12)

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1 – 10 of 12

CHEMBL1852155,CHEMBL1819181

CD4Tclin

pIC50 : 6.68

Chloropeptin II

CD4Tclin

pIC50 : 6.89

Chloropeptin I

CD4Tclin

pIC50 : 6.89

Chloropeptin I analogue

CD4Tclin

pIC50 : 6.89

CHEMBL4747494,CHEMBL4746252

CD4Tclin

pIC50 : 6.89

CHEMBL4791666

CD4Tclin

pIC50 : 6.66

CHEMBL4750983

CD4Tclin

pIC50 : 6.27

CHEMBL4786809

CD4Tclin

pIC50 : 6.18

CHEMBL4748787

CD4Tclin

pIC50 : 6.13

CHEMBL4758659

CD4Tclin

pIC50 : 6.08

Protein-Protein Interactions (343)

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1 – 10 of 343

• See Interactions on String-DB

KIAA0319L

Tbio

Novelty:  0.02873675

p_int:  0.993327496

p_ni:  0.006655012

p_wrong:  0.000017492

Data Source:  BioPlex

POGZ

Tbio

Novelty:  0.03603188

p_int:  0.992524011

p_ni:  0.007475889

p_wrong:  9.9e-8

Score:  0.187

Data Source:  BioPlex,STRINGDB

TMEM11

Tbio

Novelty:  0.00067837

p_int:  0.963109631

p_ni:  0.02089222

p_wrong:  0.015998148

Score:  0.292

Data Source:  BioPlex,STRINGDB

ATP6V0A2

Tbio

Family:  Enzyme

Novelty:  0.00504614

p_int:  0.95437548

p_ni:  0.04562452

Data Source:  BioPlex

CCDC85C

Tbio

Novelty:  0.30053883

p_int:  0.930452032

p_ni:  0.069547968

Data Source:  BioPlex

ARV1

Tbio

Novelty:  0.03235632

p_int:  0.900144953

p_ni:  0.099765879

p_wrong:  0.000089168

Score:  0.185

Data Source:  BioPlex,STRINGDB

VAMP3

Tbio

Novelty:  0.00694332

p_int:  0.882464048

p_ni:  0.117535914

p_wrong:  3.8e-8

Score:  0.91

Data Source:  BioPlex,STRINGDB

ATP6V0A1

Tbio

Family:  Enzyme

Novelty:  0.02009317

p_int:  0.879716363

p_ni:  0.120283637

Data Source:  BioPlex

EIF2B3

Tbio

Novelty:  0.04963646

p_int:  0.818811552

p_ni:  0.181188448

Data Source:  BioPlex

SAAL1

Tdark

Novelty:  0.33089811

p_int:  0.810497501

p_ni:  0.189502499

Data Source:  BioPlex

Nearest Tclin Targets (1)

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Downstream (1)

1 – 1 of 1

LCK

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  6

1: T cell receptor signaling pathway

2: PD-L1 expression and PD-1 checkpoint pathway in cancer

3: Human T-cell leukemia virus 1 infection

4: Th17 cell differentiation

more:  2 more common pathways

Pathways (185)

Reactome (31)

KEGG (11)

PathwayCommons (13)

WikiPathways (130)

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	Alpha-defensins	9 targets	R-HSA-1462054
Reactome	Antimicrobial peptides	89 targets	R-HSA-6803157
Reactome	Binding and entry of HIV virion	4 targets	R-HSA-173107
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825

Name	Explore in Pharos	Explore in Source
Adaptive Immune System	894 targets	R-HSA-1280218
Alpha-defensins	9 targets	R-HSA-1462054
Antimicrobial peptides	89 targets	R-HSA-6803157
Binding and entry of HIV virion	4 targets	R-HSA-173107
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (65)

Functions (15)

Components (9)

Processes (41)

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1 – 10 of 15

GO Term	Evidence	Assigned by
interleukin-16 receptor activity	Inferred from Direct Assay (IDA)	CAFA
MHC class II protein binding	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
interleukin-16 binding	Inferred from Physical Interaction (IPI)	CAFA
protein kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
protein tyrosine kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
coreceptor activity	Traceable Author Statement (TAS)	ProtInc

Disease Associations (null)

No disease associations found

GWAS Traits (20)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	16	7	17		95.4
refractive error	MONDO_0004892	3	1	2	7.8	92.7
retinal vasculature measurement	EFO_0010554	2	1	2		87.8
sex hormone-binding globulin measurement	EFO_0004696	7	2	10	6.6	86.3
nitric oxide exhalation measurement	EFO_0005536	1	1	1		82

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood protein measurement	EFO_0007937	17		95.4
refractive error	MONDO_0004892	2	7.8	92.7
retinal vasculature measurement	EFO_0010554	2		87.8
sex hormone-binding globulin measurement	EFO_0004696	10	6.6	86.3
nitric oxide exhalation measurement	EFO_0005536	1		82

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Adaptive immunity
Cell membrane
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein
Host cell receptor for virus entry
Host-virus interaction
Immunity

GWAS Trait Find Similar Targets

No Header	No Header
age at onset
blood protein measurement
BMI-adjusted hip circumference
cholesterol:total lipids ratio
cholesteryl esters:total lipids ratio
colorectal cancer
educational attainment
ganglion cell inner plexiform layer thickness measurement
high density lipoprotein cholesterol measurement
insomnia measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
nervous system phenotype

IDG Resources

No IDG generated resources found

Orthologs (8)

1 – 5 of 8

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	CD4 molecule	VGNC:5330	450124
Macaque	CD4 molecule		713807
Mouse	CD4 antigen	MGI:88335	12504
Rat	Cd4 molecule	RGD:2306	24932
Horse	CD4 molecule	VGNC:16267	100052502

Species	Name	OMA	EggNOG	Inparanoid
Chimp	CD4 molecule
Macaque	CD4 molecule
Mouse	CD4 antigen
Rat	Cd4 molecule
Horse	CD4 molecule

Publication Statistics

PubMed Score 99475.02

PubMed score by year

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PubTator Score 38376.69

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Related Publications

Text Mined References (411)

GeneRif Annotations (284)

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PMID	Year	Title