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    C3 complement C3 [ Homo sapiens (human) ]

    Gene ID: 718, updated on 6-May-2024

    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
    NEW
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    Try the new Transcript table

    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_000019.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13850 Neighboring gene ribosomal protein L7 pseudogene 50 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13851 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13852 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:6631163-6631664 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13853 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13854 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13855 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13856 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13857 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9960 Neighboring gene TNF superfamily member 14 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6674384-6674960 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6674961-6675535 Neighboring gene Sharpr-MPRA regulatory region 11629 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6697003-6697504 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6697505-6698004 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13859 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6727893-6728394 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6728395-6728894 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9961 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:6735174-6735942 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:6736406-6736560 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:6736926-6737087 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9962 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9963 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13861 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6738248-6739016 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13862 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13863 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9964 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:6739785-6740552 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6742783-6743702 Neighboring gene G protein-coupled receptor 108 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:6745754-6746254 Neighboring gene microRNA 6791 Neighboring gene uncharacterized LOC124904623 Neighboring gene thyroid hormone receptor interactor 10

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    EBI GWAS Catalog

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

    HIV-1 interactions

    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

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    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
     

    General protein information

    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

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_009557.1 RefSeqGene

      Range
      4970..47817
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_27

    mRNA and Protein(s)

    1. NM_000064.4NP_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:678747
      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:9961282
      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:15131661
      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:770866
      A2M; Alpha-2-macroglobulin family
      pfam01835
      Location:129224
      A2M_N; MG2 domain
      pfam07677
      Location:13981493
      A2M_recep; A-macroglobulin receptor
      pfam07678
      Location:10511282
      A2M_comp; A-macroglobulin complement component
      pfam07703
      Location:458604
      A2M_N_2; Alpha-2-macroglobulin family N-terminal region

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      6677704..6720650 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      6667334..6710056 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)