Tbio C4A Complement C4-A

Protein Summary

Description

Non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway. Covalently binds to immunoglobulins and immune complexes and enhances the solubilization of immune aggregates and the clearance of IC through CR1 on erythrocytes. C4A isotype is responsible for effective binding to form amide bonds with immune aggregates or protein antigens, while C4B isotype catalyzes the transacylation of the thioester carbonyl group to form ester bonds with carbohydrate antigens. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes. This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

Uniprot Accession IDs

• P0C0L4
• A6H8M8
• A6NHJ5
• A7E2V2
• B0QZR6
• B0V2C8
• B2RUT6
• B7ZVZ6
• P01028
• P78445
• Q13160
• Q13906
• Q14033
• Q14835
• Q4LE82
• Q5JNX2
• Q5JQM8
• Q6P4R1
• Q6U2E5
• Q6U2E8
• Q6U2F0
• Q6U2F3
• Q6U2F4
• Q6U2F6
• Q6U2F8
• Q6U2G0
• Q96EG2
• Q96SA8
• Q9NPK5
• Q9UIP5

Gene Name

• C4A

Ensembl ID

• ENST00000383325
• ENSP00000372815
• ENSG00000206340
• ENST00000421274
• ENSP00000388662
• ENSG00000227746
• ENST00000428956
• ENSP00000396688
• ENSG00000244731
• ENST00000498271
• ENSP00000420212

Symbol

• CO4
• CPAMD2
• C4
• RG
• C4S
• CO4
• C4A2
• C4A3
• C4A4
• C4A6
• C4AD
• CPAMD2

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

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Complement C4-a

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Complement C4-a

Protein / Defense/immunity Protein / Complement Component / Complement C4-a

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Complement C4-a

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: 2356.27   (req: < 5)

Gene RIFs: 89   (req: <= 3)

Antibodies: 584   (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: 2356.27   (req: >= 5)

Gene RIFs: 89   (req: > 3)

Antibodies: 584   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 11

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

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

Find Targets by Sequence

Show Full Sequence

ProtVista Viewer

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.

Go To Tool

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.

Go To Tool

GlyGen

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

Go To Tool

ARCHS4

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

Go To Tool

Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (311)

Explore Interacting Targets

1 – 10 of 311

• See Interactions on String-DB

SNX27

Tbio

Novelty:  0.02419724

p_int:  0.999978144

p_ni:  0.000021856

Data Source:  BioPlex

PVR

Tbio

Novelty:  0.00215811

p_int:  0.999917355

p_ni:  0.000082645

p_wrong:  1e-9

Score:  0.199

Data Source:  BioPlex,STRINGDB

GDPD1

Tbio

Family:  Enzyme

Novelty:  0.28722153

p_int:  0.999543977

p_ni:  0.00039224

p_wrong:  0.000063782

Score:  0.153

Data Source:  BioPlex,STRINGDB

SLC15A1

Tchem

Family:  Transporter

Novelty:  0.00149723

p_int:  0.999390947

p_ni:  0.000609053

Data Source:  BioPlex

MSMB

Tbio

Novelty:  0.00241546

p_int:  0.999372886

p_ni:  0.000382114

p_wrong:  0.000245

Data Source:  BioPlex

FAM171B

Tdark

Novelty:  0.38456365

p_int:  0.998677987

p_ni:  0.001322012

Score:  0.161

Data Source:  BioPlex,STRINGDB

SCN2B

Tbio

Family:  IC

Novelty:  0.03773629

p_int:  0.998492802

p_ni:  0.001507148

p_wrong:  5e-8

Data Source:  BioPlex

OCLN

Tbio

Novelty:  0.00047671

p_int:  0.997900461

p_ni:  0.001475763

p_wrong:  0.000623776

Score:  0.155

Data Source:  BioPlex,STRINGDB

CCL5

Tchem

Novelty:  0.00032607

p_int:  0.996994267

p_ni:  0.002485949

p_wrong:  0.000519783

Score:  0.357

Data Source:  BioPlex,STRINGDB

LGALS8

Tchem

Novelty:  0.00623836

p_int:  0.996479377

p_ni:  0.003520384

p_wrong:  2.39e-7

Score:  0.168

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (40)

Reactome (10)

KEGG (4)

WikiPathways (26)

Activation of C3 and C5 (R-HSA-174577)

Click on a row in the table to change the structure displayed.

Find Similar Targets

Items per page:

5

1 – 5 of 10

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of C3 and C5	6 targets	R-HSA-174577
Reactome	Complement cascade	133 targets	R-HSA-166658
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Initial triggering of complement	98 targets	R-HSA-166663
Reactome	Innate Immune System	1188 targets	R-HSA-168249

Name	Explore in Pharos	Explore in Source
Activation of C3 and C5	6 targets	R-HSA-174577
Complement cascade	133 targets	R-HSA-166658
Immune System	2246 targets	R-HSA-168256
Initial triggering of complement	98 targets	R-HSA-166663
Innate Immune System	1188 targets	R-HSA-168249

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (22)

Functions (3)

Components (11)

Processes (8)

Find Similar Targets

Items per page:

10

1 – 3 of 3

GO Term	Evidence	Assigned by
complement component C1q binding	Inferred from Direct Assay (IDA)	BHF-UCL
serine-type endopeptidase activity	Traceable Author Statement (TAS)	Reactome
endopeptidase inhibitor activity	Inferred from Electronic Annotation (IEA)	InterPro

Disease Associations (null)

No disease associations found

GWAS Traits (270)

Items per page:

5

1 – 5 of 270

GWAS Trait	EFO ID	ENSG ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
age-related macular degeneration	EFO_0001365	ENSG00000206340	9	10	0	1.9	99.7
age-related macular degeneration	EFO_0001365	ENSG00000227746	9	10	0	1.9	99.7
age-related macular degeneration	EFO_0001365	ENSG00000244731	9	10	0	1.9	99.7
systemic lupus erythematosus	EFO_0002690	ENSG00000206340	6	5	0	2.3	99.4
systemic lupus erythematosus	EFO_0002690	ENSG00000227746	6	5	0	2.3	99.4

Items per page:

5

1 – 5 of 270

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
age-related macular degeneration	EFO_0001365	0	1.9	99.7
age-related macular degeneration	EFO_0001365	0	1.9	99.7
age-related macular degeneration	EFO_0001365	0	1.9	99.7
systemic lupus erythematosus	EFO_0002690	0	2.3	99.4
systemic lupus erythematosus	EFO_0002690	0	2.3	99.4

Reset Zoom  Beta Count   Odds Ratio

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Blood group antigen
Cell junction
Cell projection
Cleavage on pair of basic residues
Complement pathway
Complete proteome
Direct protein sequencing
Disease mutation

GWAS Trait Find Similar Targets

No Header	No Header
age at first sexual intercourse measurement
age-related macular degeneration
antinuclear antibody measurement
appendicular lean mass
AQP4-IgG-positive neuromyelitis optica
atopic eczema
atrophic macular degeneration
autism spectrum disorder
autoimmune thyroid disease
blood metabolite measurement

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
digestive/alimentary phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
mortality/aging
renal/urinary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (1)

1 – 1 of 1

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Xenopus	complement component 4A (Rodgers blood group)	XB-GENE-478881	100135012

Species	Name	OMA	EggNOG	Inparanoid
Xenopus	complement component 4A (Rodgers blood group)

Publication Statistics

PubMed Score 2356.27

PubMed score by year

Reset Zoom

PubTator Score 2652.34

PubTator score by year

Reset Zoom

Related Publications

Text Mined References (157)

GeneRif Annotations (89)

Items per page:

10

0 of 0

PMID	Year	Title