Tbio C4B Complement C4-B

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Complement C4-b

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

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

DTO Classes

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

Protein Summary

Description

Non-enzymatic component of the 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 basic 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 may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. 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. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P0C0L5
• A2BHY4
• P01028
• P78445
• Q13160
• Q13906
• Q14033
• Q14835
• Q6U2E9
• Q6U2G1
• Q6U2I5
• Q6U2L1
• Q6U2L7
• Q6U2L9
• Q6U2M5
• Q6VCV8
• Q96SA7
• Q9NPK5
• Q9UIP5

Gene Name

• C4B

Ensembl ID

• ENST00000375177
• ENSP00000364321
• ENSG00000228454
• ENST00000411583
• ENSP00000407942
• ENSG00000228267
• ENST00000435363
• ENSP00000415941
• ENSG00000224389
• ENST00000435500
• ENSP00000412786
• ENSG00000233312
• ENST00000449788
• ENSP00000414200
• ENSG00000236625

Symbol

• CO4
• CPAMD3
• CH
• C4F
• CO4
• C4B1
• C4B2
• C4B3
• C4B5
• C4BD
• C4B12
• C4B_2
• CPAMD3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein complex	1
biological term	0.82
small molecule perturbation	0.81
cell line	0.68
disease	0.67

Related Tools

Target Illumination GWAS Analytics (TIGA)

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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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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: 1541.33   (req: < 5)

Gene RIFs: 116   (req: <= 3)

Antibodies: 296   (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: 1541.33   (req: >= 5)

Gene RIFs: 116   (req: > 3)

Antibodies: 296   (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

GWAS Traits (284)

Items per page:

5

1 – 5 of 284

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	ENSG00000228267	9	10	0	1.9	99.3
age-related macular degeneration	EFO_0001365	ENSG00000224389	9	10	0	1.9	99.3
age-related macular degeneration	EFO_0001365	ENSG00000236625	9	10	0	1.9	99.3
age-related macular degeneration	EFO_0001365	ENSG00000233312	9	9	0	1.9	99.3
systemic lupus erythematosus	EFO_0002690	ENSG00000224389	6	5	0	2.3	99

Items per page:

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1 – 5 of 284

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
age-related macular degeneration	EFO_0001365	0	1.9	99.3
age-related macular degeneration	EFO_0001365	0	1.9	99.3
age-related macular degeneration	EFO_0001365	0	1.9	99.3
age-related macular degeneration	EFO_0001365	0	1.9	99.3
systemic lupus erythematosus	EFO_0002690	0	2.3	99

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Orthologs (7)

1 – 5 of 7

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Mouse	complement component 4B (Chido blood group)	MGI:88228	12268
Rat	complement C4-like	RGD:9245878	103689965
Dog	complement C4-A		481722
Horse	complement C4-A		100059239
Cow	Bos taurus complement component 4A (C4A), mRNA. [Source:RefSeq mRNA;Acc:NM_001166485]

Species	Name	OMA	EggNOG	Inparanoid
Mouse	complement component 4B (Chido blood group)
Rat	complement C4-like
Dog	complement C4-A
Horse	complement C4-A
Cow	Bos taurus complement component 4A (C4A), mRNA. [Source:RefSeq mRNA;Acc:NM_001166485]

Protein Structure (1 Structure, 1 AlphaFold Model)

tutorial

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P0C0L5-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 1 of 1

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (148)

Reactome (6)

KEGG (4)

WikiPathways (138)

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

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Find Similar Targets

Items per page:

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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

Gene Ontology Terms (22)

Functions (4)

Components (10)

Processes (8)

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1 – 4 of 4

GO Term	Evidence	Assigned by
carbohydrate binding	Inferred from Direct Assay (IDA)	BHF-UCL
complement 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

Protein-Protein Interactions (189)

Explore Interacting Targets

1 – 10 of 189

• See Interactions on String-DB

C4A

Tbio

Novelty:  0.00062793

Score:  0.995

Data Source:  Reactome,STRINGDB

CD46

Tbio

Novelty:  0.00098341

Score:  0.992

Data Source:  Reactome,STRINGDB

CR1

Tbio

Novelty:  0.00157449

Score:  0.991

Data Source:  Reactome,STRINGDB

MASP2

Tchem

Family:  Enzyme

Novelty:  0.00466852

Score:  0.986

Data Source:  Reactome,STRINGDB

C1S

Tchem

Novelty:  0.00043003

Score:  0.983

Data Source:  Reactome,STRINGDB

CFB

Tchem

Novelty:  0.00102672

Score:  0.982

Data Source:  STRINGDB

C4BPA

Tbio

Novelty:  0.00319944

Score:  0.977

Data Source:  Reactome,STRINGDB

C1R

Tclin

Novelty:  0.00210654

Score:  0.977

Data Source:  Reactome,STRINGDB

C2

Tchem

Novelty:  0.00974862

Score:  0.976

Data Source:  Reactome,STRINGDB

MASP1

Tchem

Family:  Enzyme

Novelty:  0.0029019

Score:  0.975

Data Source:  Reactome,STRINGDB

Publication Statistics

PubMed Score  1541.33

PubMed score by year

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PubTator Score  737.47

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

ProtVista Viewer

Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Blood group antigen
Cell junction
Cell projection
Cleavage on pair of basic residues
Complement pathway
Complete proteome
Direct protein sequencing
Disulfide bond
Glycoprotein

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