U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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
Compare labs
Complement component 2 deficiency
MedGen: C3150275 OMIM: 217000 GeneReviews: Not available
Compare labs

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)