C3 complement C3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: C3provided by HGNC
Official Full Name: complement C3provided by HGNC
Primary source: HGNC:HGNC:1318
See related: Ensembl:ENSG00000125730 MIM:120700; AllianceGenome:HGNC:1318
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ASP; C3a; C3b; AHUS5; ARMD9; CPAMD1; HEL-S-62p
Summary: Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]
Expression: Biased expression in liver (RPKM 1676.7), gall bladder (RPKM 250.0) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19p13.3

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (6677704..6720650, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (6667334..6710056, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (6677715..6720661, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Defective C3d caused by C3 p.W1034R in inherited atypical hemolytic uremic syndrome.
Title: Defective C3d caused by C3 p.W1034R in inherited atypical hemolytic uremic syndrome.
HylS', a fragment of truncated hyaluronidase of Streptococcus suis, contributes to immune evasion by interaction with host complement factor C3b.
Title: HylS', a fragment of truncated hyaluronidase of Streptococcus suis, contributes to immune evasion by interaction with host complement factor C3b.
Serum Uric Acid Associates with Systemic Complement C3 Activation in Severe ANCA-Associated Renal Vasculitides.
Title: Serum Uric Acid Associates with Systemic Complement C3 Activation in Severe ANCA-Associated Renal Vasculitides.
Complement C3 as a potential drug target in periodontitis: Evidence from the cis-Mendelian randomization approach.
Title: Complement C3 as a potential drug target in periodontitis: Evidence from the cis-Mendelian randomization approach.
Trypanosoma brucei Invariant Surface gp65 Inhibits the Alternative Pathway of Complement by Accelerating C3b Degradation.
Title: Trypanosoma brucei Invariant Surface gp65 Inhibits the Alternative Pathway of Complement by Accelerating C3b Degradation.
Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma.
Title: Serum complement component 3, complement component 4 and complement component 1q levels predict progressive visual field loss in older women with primary angle closure glaucoma.
Roles of mesangial C3 and C1q deposition in the clinical manifestations and prognosis of IgAN.
Title: Roles of mesangial C3 and C1q deposition in the clinical manifestations and prognosis of IgAN.
Complement protein C3a enhances adaptive immune responses towards FVIII products.
Title: Complement protein C3a enhances adaptive immune responses towards FVIII products.
Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Title: Cryo-EM structures of Trypanosoma brucei gambiense ISG65 with human complement C3 and C3b and their roles in alternative pathway restriction.
Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study.
Title: Association of Complement C3 With Incident Type 2 Diabetes and the Mediating Role of BMI: A 10-Year Follow-Up Study.

Submit: New GeneRIF Correction See all GeneRIFs (492)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Age related macular degeneration 9 MedGen: C1969651 OMIM: 611378 GeneReviews: Not available	Compare labs
Atypical hemolytic-uremic syndrome with C3 anomaly MedGen: C2752037 OMIM: 612925 GeneReviews: Genetic Atypical Hemolytic-Uremic Syndrome	Compare labs
Complement component 3 deficiency MedGen: C3151071 OMIM: 613779 GeneReviews: C3 Glomerulopathy	Compare labs

EBI GWAS Catalog

Description
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study for serum complement C3 and C4 levels in healthy Chinese subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC). EBI GWAS Catalog EBI GWAS CatalogPubMed
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven new loci associated with age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Preincubation of HIV-1 gp41 with either factor H or properdin, and of HIV-1 gp120 with C3b or C4b affect the interaction between HIV-1 gp41 and gp120	PubMed
	env	A synthetic peptide covering positions 233-251 of the HIV-1 gp120 protein binds to complement proteins C3, C4, C5, C9, and properdin	PubMed
	env	Complexes of recombinant HIV-1 gp120 with anti-HIV-1 antibodies cleave C3 and present generated C3 fragments on the cell surface	PubMed
	env	Inhibition of DAF or use of factor H depleted sera significantly increases C3 deposition on recombinant HIV-1 gp120 coated CD4 cells	PubMed
	env	Complement proteins C4, C3d, C5b-9, and properdin bind to HIV-1 gp120-coated CD4+ T cells of healthy individuals when incubated in autologous serum	PubMed
	env	Amino acid residues 100-129, 161-190, 231-250, 301-328, 410-449, and 470-499 of HIV-1 gp120 are involved in its binding to C3	PubMed
Envelope surface glycoprotein gp160, precursor	env	Complement component 3 (C3) production is upregulated by HIV-1 gp160	PubMed
Nef	nef	HIV-1 induces the upregulation of complement factor C3 in astrocytes and neurons through signaling pathways that involve protein kinase C and adenylate cyclase activation, which is an effect that may contribute to the pathogenesis of AIDS in the brain	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of complement component 3 (C3) in primary human brain microvascular endothelial cells	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:177904 (e-PCR)
- UniSTS:154979

RH80210 (e-PCR)
- UniSTS:85903

RH45403 (e-PCR)
- UniSTS:3742

SGC31874 (e-PCR)
- UniSTS:37846

RH11718 (e-PCR)
- UniSTS:39138

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables C5L2 anaphylatoxin chemotactic receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in amyloid-beta clearance	ISS Inferred from Sequence or Structural Similarity more info
involved_in complement activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in complement activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in complement activation, alternative pathway	IEA Inferred from Electronic Annotation more info
involved_in complement activation, classical pathway	IEA Inferred from Electronic Annotation more info
involved_in complement receptor mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in complement-dependent cytotoxicity	IEA Inferred from Electronic Annotation more info
involved_in complement-mediated synapse pruning	ISS Inferred from Sequence or Structural Similarity more info
involved_in fatty acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in neuron remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in oviduct epithelium development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of activation of membrane attack complex	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic cell clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glucose transmembrane transport	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lipid storage	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phagocytosis, engulfment	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type IIa hypersensitivity	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular endothelial growth factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of triglyceride biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in vertebrate eye-specific patterning	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in azurophil granule lumen	TAS Traceable Author Statement more info
located_in blood microparticle	HDA more info	PubMed
located_in cell surface	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IEA Inferred from Electronic Annotation more info
located_in secretory granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: complement C3

Names: C3 and PZP-like alpha-2-macroglobulin domain-containing protein 1; C3a anaphylatoxin; acylation-stimulating protein cleavage product; complement component 3; complement component C3a; complement component C3b; epididymis secretory sperm binding protein Li 62p; prepro-C3

NP_000055.2

EC 3.4.21.43

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009557.1 RefSeqGene

Range

4970..47817

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_27

mRNA and Protein(s)

NM_000064.4 → NP_000055.2 complement C3 preproprotein

See identical proteins and their annotated locations for NP_000055.2

Status: REVIEWED

Source sequence(s)

AA025232, AC008760, AK299114, BC150179, BC150299, K02765

Consensus CDS

CCDS32883.1

UniProtKB/Swiss-Prot

A7E236, P01024

UniProtKB/TrEMBL

A0A8Q3SI05, V9HWA9

Related

ENSP00000245907.4, ENST00000245907.11

Conserved Domains (8) summary

cd00017
Location:678 → 747

ANATO; Anaphylatoxin homologous domain; C3a, C4a and C5a anaphylatoxins are protein fragments generated enzymatically in serum during activation of complement molecules C3, C4, and C5. They induce smooth muscle contraction. These fragments are homologous to ...

cd02896
Location:996 → 1282

complement_C3_C4_C5; Proteins similar to C3, C4 and C5 of vertebrate complement. The vertebrate complement system, comprised of a large number of distinct plasma proteins, is an effector of both the acquired and innate immune systems. The point of convergence of the ...

cd03583
Location:1513 → 1661

NTR_complement_C3; NTR/C345C domain, complement C3 subfamily; The NTR domain found in complement C3 is also known as the C345C domain because it occurs at the C-terminus of complement C3, C4 and C5. Complement C3 plays a pivotal role in the activation of the complement ...

pfam00207
Location:770 → 866

A2M; Alpha-2-macroglobulin family

pfam01835
Location:129 → 224

A2M_N; MG2 domain

pfam07677
Location:1398 → 1493

A2M_recep; A-macroglobulin receptor

pfam07678
Location:1051 → 1282

A2M_comp; A-macroglobulin complement component

pfam07703
Location:458 → 604

A2M_N_2; Alpha-2-macroglobulin family N-terminal region