Seroatlas · Human Serome Atlas

C2

Complement C2

Also known as: CO2_HUMAN

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P06681
Gene: C2
Ensembl: ENSG00000166278
Chromosome: 6
Canonical length: 752 aa
Protein class: Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted secreted proteins
Secretome location: Secreted to blood

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

752 residues, UniProt reviewed canonical sequence.

>P06681|C2
     1  MGPLMVLFCL LFLYPGLADS APSCPQNVNI SGGTFTLSHG WAPGSLLTYS CPQGLYPSPA
    61  SRLCKSSGQW QTPGATRSLS KAVCKPVRCP APVSFENGIY TPRLGSYPVG GNVSFECEDG
   121  FILRGSPVRQ CRPNGMWDGE TAVCDNGAGH CPNPGISLGA VRTGFRFGHG DKVRYRCSSN
   181  LVLTGSSERE CQGNGVWSGT EPICRQPYSY DFPEDVAPAL GTSFSHMLGA TNPTQKTKES
   241  LGRKIQIQRS GHLNLYLLLD CSQSVSENDF LIFKESASLM VDRIFSFEIN VSVAIITFAS
   301  EPKVLMSVLN DNSRDMTEVI SSLENANYKD HENGTGTNTY AALNSVYLMM NNQMRLLGME
   361  TMAWQEIRHA IILLTDGKSN MGGSPKTAVD HIREILNINQ KRNDYLDIYA IGVGKLDVDW
   421  RELNELGSKK DGERHAFILQ DTKALHQVFE HMLDVSKLTD TICGVGNMSA NASDQERTPW
   481  HVTIKPKSQE TCRGALISDQ WVLTAAHCFR DGNDHSLWRV NVGDPKSQWG KEFLIEKAVI
   541  SPGFDVFAKK NQGILEFYGD DIALLKLAQK VKMSTHARPI CLPCTMEANL ALRRPQGSTC
   601  RDHENELLNK QSVPAHFVAL NGSKLNINLK MGVEWTSCAE VVSQEKTMFP NLTDVREVVT
   661  DQFLCSGTQE DESPCKGESG GAVFLERRFR FFQVGLVSWG LYNPCLGSAD KNSRKRAPRS
   721  KVPPPRDFHI NLFRMQPWLR QHLGDVLNFL PL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.25
Highest tissue expression: 455 nTPM

Expression across tissuesHPA

Tissue

liver: 455 nTPM
lung: 77 nTPM
placenta: 46 nTPM
spleen: 44 nTPM
adipose tissue: 41 nTPM
small intestine: 29 nTPM

Single-cell type

hofbauer cells: 16 nCPM
alveolar cells type 2: 12 nCPM
podocytes: 12 nCPM
brain inhibitory neurons: 12 nCPM
proximal tubule cells: 11 nCPM
distal convoluted tubule cells: 10 nCPM

Immune cell

non-classical monocyte: 26 nTPM
intermediate monocyte: 21 nTPM
classical monocyte: 5.9 nTPM
total PBMC: 2.1 nTPM
myeloid DC: 0.7 nTPM
neutrophil: 0.5 nTPM

Brain region

thalamus: 8.5 nTPM
pons: 7.8 nTPM
medulla oblongata: 7.2 nTPM
white matter: 5.9 nTPM
spinal cord: 5.3 nTPM
cerebral cortex: 5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C2.

Disease | AllUniProt

Conditions C2 is implicated in, by any mechanism.

Macular degeneration, age-related, 14 (ARMD14) MIM:615489
Complement component 2 deficiency (C2D) MIM:217000

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 483 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Complement component 2 deficiency
C2 deficiency, type II
Age related macular degeneration 14
C2 deficiency, type I
C2-related disorder

Disease | ImmuneIEDB

Conditions an epitope on C2 was assayed in.

rheumatoid arthritis B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 1.03
gnomAD pLI: 0
gnomAD missense Z: 1.12
DepMap mean gene effect: -0.09
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads C2 as an antibody target. Whether an autoantibody or antibody against C2 could matter depends on whether native C2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

C2 is annotated at the cell surface, where native C2 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

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.

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