C2 complement C2 [Homo sapiens (human)] - Gene

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: mouse all
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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_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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?

Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.
Title: Proteomic analysis of diabetes genetic risk scores identifies complement C2 and neuropilin-2 as predictors of type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) Study.
Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein.
Title: Gain-of-Function Mutations R249C and S250C in Complement C2 Protein Increase C3 Deposition in the Presence of C-Reactive Protein.
Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity.
Title: Complement protein levels and MBL2 polymorphisms are associated with dengue and disease severity.
Hereditary Deficiency of the Second Component of Complement: Early Diagnosis and 21-Year Follow-Up of a Family.
Title: Hereditary Deficiency of the Second Component of Complement: Early Diagnosis and 21-Year Follow-Up of a Family.
Logistic regression analyses showed that six C2 single nucleotide polymorphisms had significant associations with the risk of chronic hepatitis B and chronic hepatitis B-related hepatocellular carcinoma among the Korean subjects. Stepwise analysis revealed that causal markers (rs9267665 and rs10947223) were identified among the C2 variants.
Title: Genetic association of complement component 2 variants with chronic hepatitis B in a Korean population.
The pooled ORs for rs551397, rs2274700, rs4151667, rs641153, rs1047286, rs9332739, and rs547154 in the heterozygote model were 0.53, 0.53 , 0.54, 0.48, 1.42, 0.50, and 0.52, respectively. We confirmed the protective role of C2/CFB/CFH polymorphisms in the development of Age-Related Macular Degeneration (AMD), and showed single nucleotide polymorphism in C3 was a high-risk factor for AMD
Title: Association Between Complement Factor C2/C3/CFB/CFH Polymorphisms and Age-Related Macular Degeneration: A Meta-Analysis.
Vag8 binding to human C1-inhibitor (C1-inh) interferes with the binding of C1-inh to C1s, C1r and MASP-2, resulting in the release of active proteases that subsequently cleave C2 and C4 away from the bacterial surface.
Title: Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface.
Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway-specific Mechanisms for Control and Activation of the Complement Proconvertases.
Title: Solution Structures of Complement C2 and Its C4 Complexes Propose Pathway-specific Mechanisms for Control and Activation of the Complement Proconvertases.
The rs2844455 A allele of C2 is a risk factor for systemic lupus erythematosus development in a Chinese population, whereas the G allele might be a protective factor.
Title: Genetic association of complement component 2 polymorphism with systemic lupus erythematosus.
our data indicate that C2 rs547154 polymorphism plays a protective role in the development of PCV.
Title: C2 rs547154 polymorphism and polypoidal choroidal vasculopathy susceptibility: a meta-analysis.

Submit: New GeneRIF Correction See all GeneRIFs (46)

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 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 EBI GWAS CatalogPubMed
Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis. 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
Genetic variations at loci involved in the immune response are risk factors for hepatocellular carcinoma. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia. 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
GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region. 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
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Seven new loci associated with age-related macular degeneration. EBI GWAS Catalog EBI GWAS CatalogPubMed
The genetic architecture of economic and political preferences. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

N3_3_3 (e-PCR)
- UniSTS:239180

C2_3011 (e-PCR)
- UniSTS:280470

WI-8686 (e-PCR)
- UniSTS:73117

RH18075 (e-PCR)
- UniSTS:72393

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 more info	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

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Preferred Names: complement C2

Names: C3/C5 convertase; complement component 2; complement component C2

NP_000054.2

EC 3.4.21.43

NP_001139375.1

EC 3.4.21.43

NP_001171534.1

EC 3.4.21.43

NP_001269386.1

EC 3.4.21.43

NP_001269387.1

EC 3.4.21.43

NP_001269388.1

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_011730.1 RefSeqGene

Range

4989..23186

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_26

mRNA and Protein(s)

NM_000063.6 → NP_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:473 → 742

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:253 → 450

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:24 → 204

CCP; Complement control protein (CCP) modules (aka short consensus repeats SCRs or SUSHI repeats) have been identified in several proteins of the complement system
NM_001145903.3 → NP_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:19 → 73

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:341 → 610

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:121 → 318

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 ...
NM_001178063.3 → NP_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:28 → 82

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:259 → 491

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:259 → 528

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:115 → 236

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 ...
NM_001282457.2 → NP_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:227 → 459

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:227 → 496

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:38 → 204

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 ...
NM_001282458.2 → NP_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:60 → 115

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:444 → 676

Tryp_SPc; Trypsin-like serine protease

cd00190
Location:444 → 713

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:224 → 421

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 ...
NM_001282459.2 → NP_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:89 → 144

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:253 → 284

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 ...