Tclin C5 Complement C5

Protein Classes

PANTHER Classes

Protein / Signaling Molecule / Cytokine / Complement C5

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Complement C5

Protein / Defense/immunity Protein / Complement Component / Complement C5

DTO Classes

Protein / Enzyme Modulator / Protease Inhibitor / Serine Protease Inhibitor / Complement C5

Protein Summary

Description

Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled. Derived from proteolytic degradation of complement C5, C5 anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes (PubMed:8182049). C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation. This gene encodes a component of the complement system, a part of the innate immune system that plays an important role in inflammation, host homeostasis, and host defense against pathogens. The encoded preproprotein is proteolytically processed to generate multiple protein products, including the C5 alpha chain, C5 beta chain, C5a anaphylatoxin and C5b. The C5 protein is comprised of the C5 alpha and beta chains, which are linked by a disulfide bridge. Cleavage of the alpha chain by a convertase enzyme results in the formation of the C5a anaphylatoxin, which possesses potent spasmogenic and chemotactic activity, and the C5b macromolecular cleavage product, a subunit of the membrane attack complex (MAC). Mutations in this gene cause complement component 5 deficiency, a disease characterized by recurrent bacterial infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

Uniprot Accession IDs

• P01031
• Q14CJ0
• Q27I61

Gene Name

• C5

Ensembl ID

• ENST00000223642
• ENSP00000223642
• ENSG00000106804

Symbol

• CPAMD4
• C5D
• C5a
• C5b
• ECLZB
• CPAMD4

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
protein domain	1
biological term	0.85
gene perturbation	0.76
disease	0.7

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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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: 448.07   (req: < 5)

Gene RIFs: 145   (req: <= 3)

Antibodies: 679   (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: 448.07   (req: >= 5)

Gene RIFs: 145   (req: > 3)

Antibodies: 679   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 17

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 Drugs: 6

Approved Drugs (6)

Explore Approved Drugs

1 – 6 of 6

raloxifene

C5Tclin

Kd : 6.15

sulindac

C5Tclin

Kd : 6.24

oxaprozin

C5Tclin

Kd : 6.19

carprofen

C5Tclin

Kd : 6.24

eculizumab

C5Tclin

ANTIBODY BINDING :

ravulizumab

C5Tclin

ANTIBODY BINDING Kd : 9.35654732

GWAS Traits (14)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 14

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
lymphocyte count	EFO_0004587	3	2	3		89.1
birth weight	EFO_0004344	4	3	4		77.8
rheumatoid arthritis	EFO_0000685	5	4	2	1.1	77.7
serum non-albumin protein measurement	EFO_0004568	1	1	1		64
myeloid white cell count	EFO_0007988	1	1	1		60.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
lymphocyte count	EFO_0004587	3		89.1
birth weight	EFO_0004344	4		77.8
rheumatoid arthritis	EFO_0000685	2	1.1	77.7
serum non-albumin protein measurement	EFO_0004568	1		64
myeloid white cell count	EFO_0007988	1		60.2

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Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	complement C5	VGNC:4628	464703
Macaque	complement C5		700467
Mouse	hemolytic complement	MGI:96031	15139
Dog	complement C5	VGNC:38595	474816
Cow	complement C5	VGNC:49997	512045

Species	Name	OMA	EggNOG	Inparanoid
Chimp	complement C5
Macaque	complement C5
Mouse	hemolytic complement
Dog	complement C5
Cow	complement C5

Protein Structure (20 Structures, 1 AlphaFold Model)

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Representation

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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-P01031-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 20

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 (44)

Reactome (13)

KEGG (7)

WikiPathways (24)

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

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Find Similar Targets

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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	Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Reactome	Complement cascade	133 targets	R-HSA-166658
Reactome	G alpha (i) signalling events	408 targets	R-HSA-418594
Reactome	GPCR downstream signalling	1152 targets	R-HSA-388396

Name	Explore in Pharos	Explore in Source
Activation of C3 and C5	6 targets	R-HSA-174577
Class A/1 (Rhodopsin-like receptors)	323 targets	R-HSA-373076
Complement cascade	133 targets	R-HSA-166658
G alpha (i) signalling events	408 targets	R-HSA-418594
GPCR downstream signalling	1152 targets	R-HSA-388396

Gene Ontology Terms (21)

Functions (3)

Components (4)

Processes (14)

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10

1 – 3 of 3

GO Term	Evidence	Assigned by
chemokine activity	Traceable Author Statement (TAS)	ProtInc
signaling receptor binding	Traceable Author Statement (TAS)	ProtInc
endopeptidase inhibitor activity	Inferred from Electronic Annotation (IEA)	InterPro

Protein-Protein Interactions (280)

Explore Interacting Targets

1 – 10 of 280

• See Interactions on String-DB

C6

Tbio

Novelty:  0.0132784

Score:  0.993

Data Source:  Reactome,STRINGDB

C5AR1

Tchem

Family:  GPCR

Novelty:  0.00188281

Score:  0.987

Data Source:  Reactome,STRINGDB

C8B

Tbio

Novelty:  0.00873524

Score:  0.978

Data Source:  Reactome,STRINGDB

C5AR2

Tbio

Family:  GPCR

Novelty:  0.01193736

Score:  0.972

Data Source:  Reactome,STRINGDB

C7

Tbio

Novelty:  0.01540501

Score:  0.968

Data Source:  Reactome,STRINGDB

CPB2

Tchem

Family:  Enzyme

Novelty:  0.00164543

Score:  0.966

Data Source:  Reactome,STRINGDB

C8A

Tbio

Novelty:  0.00429321

Score:  0.963

Data Source:  Reactome,STRINGDB

C2

Tchem

Novelty:  0.00974862

Score:  0.963

Data Source:  Reactome,STRINGDB

C3AR1

Tchem

Family:  GPCR

Novelty:  0.00527301

Score:  0.956

Data Source:  STRINGDB

C9

Tchem

Novelty:  0.00749298

Score:  0.954

Data Source:  Reactome,STRINGDB

Publication Statistics

PubMed Score  448.07

PubMed score by year

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PubTator Score  1356.65

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Cleavage on pair of basic residues
Complement alternate pathway
Complement pathway
Complete proteome
Cytolysis
Direct protein sequencing
Disulfide bond
Glycoprotein
Immunity

GWAS Trait Find Similar Targets

No Header	No Header
allergic rhinitis
allergy
asthma
birth weight
Eczema
eosinophil percentage of leukocytes
high density lipoprotein cholesterol measurement
leukocyte count
lymphocyte count
lymphocyte percentage of leukocytes

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype
respiratory system phenotype