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    C2 complement C2 [ Homo sapiens (human) ]

    Gene ID: 717, updated on 27-Nov-2024

    Summary

    Official Symbol
    C2provided by HGNC
    Official Full Name
    complement C2provided by HGNC
    Primary source
    HGNC:HGNC:1248
    See related
    Ensembl:ENSG00000166278 MIM:613927; AllianceGenome:HGNC:1248
    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
    CO2; ARMD14
    Summary
    Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]
    Expression
    Biased expression in liver (RPKM 95.8), lung (RPKM 36.7) and 11 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    Location:
    6p21.33
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (31897783..31945672)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (31751025..31798877)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31865560..31913449)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:31830779-31831404 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31831405-31832028 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31832029-31832653 Neighboring gene solute carrier family 44 member 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:31838055-31838988 Neighboring gene EHMT2 and SLC44A4 antisense RNA 1 Neighboring gene euchromatic histone lysine methyltransferase 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:31864618-31865314 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:31865398-31865992 Neighboring gene zinc finger and BTB domain containing 12 Neighboring gene C2 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:31915103-31915602 Neighboring gene complement factor B Neighboring gene negative elongation factor complex member E Neighboring gene microRNA 1236

    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

    Associated conditions

    Description Tests
    Age related macular degeneration 14
    MedGen: C3809653 OMIM: 615489 GeneReviews: Not available
    not available
    Complement component 2 deficiency
    MedGen: C3150275 OMIM: 217000 GeneReviews: Not available
    not available

    EBI GWAS Catalog

    Description
    A genome-wide association study of hepatitis B vaccine response in an Indonesian population reveals multiple independent risk variants in the HLA region.
    EBI GWAS Catalog
    Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
    EBI GWAS Catalog
    Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.
    EBI GWAS Catalog
    Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
    EBI GWAS Catalog
    Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma.
    EBI GWAS Catalog
    Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.
    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
    GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.
    EBI GWAS Catalog
    Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog
    Seven new loci associated with age-related macular degeneration.
    EBI GWAS Catalog
    The genetic architecture of economic and political preferences.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Potential readthrough

    Included gene: CFB

    Clone Names

    • DKFZp779M0311

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables serine-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    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, classical pathway IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in innate immune response 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 proteolysis IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to bacterium IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to nutrient IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to thyroid hormone IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in extracellular exosome HDA PubMed 
    located_in extracellular region TAS
    Traceable Author Statement
    more info
     
    located_in extracellular space TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    complement C2
    Names
    C3/C5 convertase
    complement component 2
    complement component C2
    NP_000054.2
    NP_001139375.1
    NP_001171534.1
    NP_001269386.1
    NP_001269387.1
    NP_001269388.1

    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_011730.1 RefSeqGene

      Range
      4989..23186
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_26

    mRNA and Protein(s)

    1. NM_000063.6NP_000054.2  complement C2 isoform 1 preproprotein

      See identical proteins and their annotated locations for NP_000054.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AK222537, AK312581
      Consensus CDS
      CCDS4728.1
      UniProtKB/Swiss-Prot
      B4DPF3, B4DV20, E9PFN7, O19694, P06681, Q13904
      UniProtKB/TrEMBL
      A0A1U9X8W4, A0A1U9X8X3, A0A1U9X8X9, Q53HP3, Q5JP69
      Related
      ENSP00000299367.5, ENST00000299367.10
      Conserved Domains (3) summary
      cd00190
      Location:473742
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      cd01470
      Location:253450
      vWA_complement_factors; Complement factors B and C2 are two critical proteases for complement activation. They both contain three CCP or Sushi domains, a trypsin-type serine protease domain and a single VWA domain with a conserved metal ion dependent adhesion site referred ...
      cl27761
      Location:24204
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
    2. NM_001145903.3NP_001139375.1  complement C2 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two in-frame exons in the 5' coding region, compared to variant 1, that results in an isoform (2) with a shorter N-terminus that lacks one of two SUSHI repeat domains, compared to isoform 1.
      Source sequence(s)
      AK222537, AK300892, AL645922, DC349268
      Consensus CDS
      CCDS54991.1
      UniProtKB/TrEMBL
      A0A8Q3WKN5
      Related
      ENSP00000395683.2, ENST00000442278.6
      Conserved Domains (3) summary
      cd00033
      Location:1973
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      cd00190
      Location:341610
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      cd01470
      Location:121318
      vWA_complement_factors; Complement factors B and C2 are two critical proteases for complement activation. They both contain three CCP or Sushi domains, a trypsin-type serine protease domain and a single VWA domain with a conserved metal ion dependent adhesion site referred ...
    3. NM_001178063.3NP_001171534.1  complement C2 isoform 3

      See identical proteins and their annotated locations for NP_001171534.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate 5' sequence and lacks an in-frame internal segment, as compared to variant 1. The resulting isoform (3) is shorter; it has a distinct N-terminus and lacks an internal segment, as compared to isoform 1.
      Source sequence(s)
      AK298311, AW515583
      Consensus CDS
      CCDS56416.1
      UniProtKB/TrEMBL
      A0A0G2JIE7
      Related
      ENSP00000392322.2, ENST00000452323.7
      Conserved Domains (4) summary
      cd00033
      Location:2882
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00020
      Location:259491
      Tryp_SPc; Trypsin-like serine protease
      cd00190
      Location:259528
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      cl00057
      Location:115236
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
    4. NM_001282457.2NP_001269386.1  complement C2 isoform 4

      See identical proteins and their annotated locations for NP_001269386.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) represents use of an alternate promoter and has multiple differences in the coding region compared to variant 1. The resulting protein (isoform 4) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AK222537, AK298808, AL671762
      Consensus CDS
      CCDS75428.1
      UniProtKB/TrEMBL
      B4DQI1, E9PDZ0
      Related
      ENSP00000418923.1, ENST00000469372.5
      Conserved Domains (3) summary
      smart00020
      Location:227459
      Tryp_SPc; Trypsin-like serine protease
      cd00190
      Location:227496
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      cl00057
      Location:38204
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
    5. NM_001282458.2NP_001269387.1  complement C2 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (5) has a shorter and distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AA740316, AK300930, AL645922, DC358441
      UniProtKB/TrEMBL
      A0A0G2JL69, B4DV48
      Related
      ENSP00000512074.1, ENST00000695637.1
      Conserved Domains (4) summary
      cd00033
      Location:60115
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      smart00020
      Location:444676
      Tryp_SPc; Trypsin-like serine protease
      cd00190
      Location:444713
      Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...
      cd01470
      Location:224421
      vWA_complement_factors; Complement factors B and C2 are two critical proteases for complement activation. They both contain three CCP or Sushi domains, a trypsin-type serine protease domain and a single VWA domain with a conserved metal ion dependent adhesion site referred ...
    6. NM_001282459.2NP_001269388.1  complement C2 isoform 6 precursor

      See identical proteins and their annotated locations for NP_001269388.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) uses an alternate 3' exon structure, and thus differs in the 3' coding region and 3' UTR compared to variant 1. It encodes isoform 6 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL645922, BC029781
      Consensus CDS
      CCDS75427.1
      UniProtKB/TrEMBL
      Q8N6L6
      Related
      ENSP00000406190.2, ENST00000418949.6
      Conserved Domains (2) summary
      cd00033
      Location:89144
      CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
      cl00057
      Location:253284
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      31897783..31945672
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_2

    Genomic

    1. NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

      Range
      3375208..3423099
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_3

    Genomic

    1. NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

      Range
      3145557..3193452
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_4

    Genomic

    1. NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

      Range
      3232932..3250649
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_5

    Genomic

    1. NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

      Range
      3239855..3287708
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_6

    Genomic

    1. NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

      Range
      3153755..3201647
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_7

    Genomic

    1. NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

      Range
      3228956..3246861
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      31751025..31798877
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)