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C2 complement C2 [ Homo sapiens (human) ]

Gene ID: 717, updated on 5-Aug-2018
Official Symbol
C2provided by HGNC
Official Full Name
complement C2provided by HGNC
Primary source
HGNC:HGNC:1248
See related
Ensembl:ENSG00000166278 MIM:613927; Vega:OTTHUMG00000031190
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
Location:
6p21.33
Exon count:
20
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 6 NC_000006.12 (31897785..31945674)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (31865562..31913449)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 44 member 4 Neighboring gene uncharacterized LOC107986588 Neighboring gene euchromatic histone lysine methyltransferase 2 Neighboring gene zinc finger and BTB domain containing 12 Neighboring gene C2 antisense RNA 1 Neighboring gene complement factor B Neighboring gene negative elongation factor complex member E Neighboring gene microRNA 1236

  • 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

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

NHGRI 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.
NHGRI GWA Catalog
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
NHGRI GWA Catalog
Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.
NHGRI GWA Catalog
Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration.
NHGRI GWA Catalog
Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma.
NHGRI GWA Catalog
Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia.
NHGRI GWA Catalog
Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC).
NHGRI GWA Catalog
GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.
NHGRI GWA Catalog
Heritability and genome-wide association study to assess genetic differences between advanced age-related macular degeneration subtypes.
NHGRI GWA Catalog
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
NHGRI GWA Catalog
Seven new loci associated with age-related macular degeneration.
NHGRI GWA Catalog
The genetic architecture of economic and political preferences.
NHGRI GWA Catalog
  • Activation of C3 and C5, organism-specific biosystem (from REACTOME)
    Activation of C3 and C5, organism-specific biosystemThe 3 pathways of complement activation converge on the cleavage of C3 by C3 convertases. C3 convertase cleaves C3 into C3a and C3b - a central step of complement activation. C3a remains in the flu...
  • Complement Activation, organism-specific biosystem (from WikiPathways)
    Complement Activation, organism-specific biosystemThe complement system is a biochemical cascade that helps, or complements, the ability of antibodies to clear pathogens from an organism. It is part of the immune system called the innate immune syst...
  • Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
    Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
  • Complement and coagulation cascades, organism-specific biosystem (from KEGG)
    Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement and coagulation cascades, conserved biosystem (from KEGG)
    Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
  • Complement cascade, organism-specific biosystem (from REACTOME)
    Complement cascade, organism-specific biosystemIn the complement cascade, a panel of soluble molecules rapidly and effectively senses a danger or damage and triggers reactions to provide a response that discriminates among foreign intruders, cell...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Initial triggering of complement, organism-specific biosystem (from REACTOME)
    Initial triggering of complement, organism-specific biosystemComplement activation is due to a cascade of proteolytic steps, performed by serine protease domains in some of the components. Three different pathways of activation are distinguished triggered by t...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Pertussis, organism-specific biosystem (from KEGG)
    Pertussis, organism-specific biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Pertussis, conserved biosystem (from KEGG)
    Pertussis, conserved biosystemPertussis, also known as whooping cough, is an acute respiratory infectious disease caused by a bacteria called Bordetella Pertussis. The characteristic symptoms are paroxysmal cough, inspiratory whe...
  • Regulation of Complement cascade, organism-specific biosystem (from REACTOME)
    Regulation of Complement cascade, organism-specific biosystemTwo inherent features of complement activation make its regulation very important: 1. There is an inherent positive feedback loop because the product of C3 activation forms part of an enzyme that cau...
  • Staphylococcus aureus infection, organism-specific biosystem (from KEGG)
    Staphylococcus aureus infection, organism-specific biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
  • Staphylococcus aureus infection, conserved biosystem (from KEGG)
    Staphylococcus aureus infection, conserved biosystemStaphylococcus aureus can cause multiple forms of infections ranging from superficial skin infections to food poisoning and life-threatening infections. The organism has several ways to divert the ef...
  • Systemic lupus erythematosus, organism-specific biosystem (from KEGG)
    Systemic lupus erythematosus, organism-specific biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
  • Systemic lupus erythematosus, conserved biosystem (from KEGG)
    Systemic lupus erythematosus, conserved biosystemSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by the production of IgG autoantibodies that are specific for self-antigens, such as DNA, nuclear proteins and cert...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Potential readthrough

Included gene: CFB

Homology

Clone Names

  • DKFZp779M0311

Gene Ontology Provided by GOA

Function Evidence Code Pubs
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
serine-type endopeptidase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
complement activation IMP
Inferred from Mutant Phenotype
more info
PubMed 
complement activation TAS
Traceable Author Statement
more info
 
complement activation, classical pathway IEA
Inferred from Electronic Annotation
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic cell clearance IMP
Inferred from Mutant Phenotype
more info
PubMed 
proteolysis IEA
Inferred from Electronic Annotation
more info
 
regulation of complement activation TAS
Traceable Author Statement
more info
 
response to nutrient IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space TAS
Traceable Author Statement
more info
PubMed 
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

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_000063.5NP_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, AW515583, DC358441
    Consensus CDS
    CCDS4728.1
    UniProtKB/Swiss-Prot
    P06681
    UniProtKB/TrEMBL
    Q53HP3, Q5JP69
    Related
    ENSP00000299367.5, OTTHUMP00000029277, ENST00000299367.9, OTTHUMT00000076379
    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_001145903.2NP_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, AW515583, DC349268, DC358441
    Consensus CDS
    CCDS54991.1
    UniProtKB/Swiss-Prot
    P06681
    UniProtKB/TrEMBL
    Q53HP3
    Related
    ENSP00000395683.2, OTTHUMP00000174694, ENST00000442278.6, OTTHUMT00000076376
    Conserved Domains (4) 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
    smart00020
    Location:341573
    Tryp_SPc; Trypsin-like serine protease
    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_001178063.2NP_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/Swiss-Prot
    P06681
    Related
    ENSP00000392322.2, OTTHUMP00000174692, ENST00000452323.6, OTTHUMT00000268608
    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_001282457.1NP_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, AW515583
    Consensus CDS
    CCDS75428.1
    UniProtKB/TrEMBL
    B4DQI1, Q53HP3
    Related
    ENSP00000418923.1, OTTHUMP00000215942, ENST00000469372.5, OTTHUMT00000356430
    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_001282458.1NP_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, AW515583, DC358441
    UniProtKB/TrEMBL
    A0A0G2JL69, B4DV48
    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_001282459.1NP_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, DC358441
    Consensus CDS
    CCDS75427.1
    UniProtKB/TrEMBL
    Q8N6L6
    Related
    ENSP00000406190.2, OTTHUMP00000215944, ENST00000418949.6, OTTHUMT00000076374
    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: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p12 Primary Assembly

    Range
    31897785..31945674
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_2

Genomic

  1. NT_113891.3 Reference GRCh38.p12 ALT_REF_LOCI_2

    Range
    3375210..3423101
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_3

Genomic

  1. NT_167245.2 Reference GRCh38.p12 ALT_REF_LOCI_3

    Range
    3145559..3193454
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_4

Genomic

  1. NT_167246.2 Reference GRCh38.p12 ALT_REF_LOCI_4

    Range
    3232692..3250651
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_5

Genomic

  1. NT_167247.2 Reference GRCh38.p12 ALT_REF_LOCI_5

    Range
    3239857..3287710
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_6

Genomic

  1. NT_167248.2 Reference GRCh38.p12 ALT_REF_LOCI_6

    Range
    3153757..3201649
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p12 ALT_REF_LOCI_7

Genomic

  1. NT_167249.2 Reference GRCh38.p12 ALT_REF_LOCI_7

    Range
    3228716..3246863
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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