Seroatlas · Human Serome Atlas

C4A

Complement C4-A

Also known as: C4, C4A2, C4A3, C4A4, C4A6, C4B, C4S, CO4, CO4A_HUMAN, CPAMD2, RG

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

Protein identityUniProt · HPA

UniProt accession: P0C0L4
Gene: C4A
Ensembl: ENSG00000244731
Chromosome: 6
Canonical length: 1744 aa
Protein class: Blood group antigen proteins, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted secreted proteins
Secretome location: Secreted to blood

OverviewNCBI Gene

This gene encodes the acidic form of complement factor 4, part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain is cleaved to release C4 anaphylatoxin, an antimicrobial peptide and a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus and type I diabetes mellitus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]

Canonical amino-acid sequenceUniProt

1744 residues, UniProt reviewed canonical sequence.

>P0C0L4|C4A
     1  MRLLWGLIWA SSFFTLSLQK PRLLLFSPSV VHLGVPLSVG VQLQDVPRGQ VVKGSVFLRN
    61  PSRNNVPCSP KVDFTLSSER DFALLSLQVP LKDAKSCGLH QLLRGPEVQL VAHSPWLKDS
   121  LSRTTNIQGI NLLFSSRRGH LFLQTDQPIY NPGQRVRYRV FALDQKMRPS TDTITVMVEN
   181  SHGLRVRKKE VYMPSSIFQD DFVIPDISEP GTWKISARFS DGLESNSSTQ FEVKKYVLPN
   241  FEVKITPGKP YILTVPGHLD EMQLDIQARY IYGKPVQGVA YVRFGLLDED GKKTFFRGLE
   301  SQTKLVNGQS HISLSKAEFQ DALEKLNMGI TDLQGLRLYV AAAIIESPGG EMEEAELTSW
   361  YFVSSPFSLD LSKTKRHLVP GAPFLLQALV REMSGSPASG IPVKVSATVS SPGSVPEVQD
   421  IQQNTDGSGQ VSIPIIIPQT ISELQLSVSA GSPHPAIARL TVAAPPSGGP GFLSIERPDS
   481  RPPRVGDTLN LNLRAVGSGA TFSHYYYMIL SRGQIVFMNR EPKRTLTSVS VFVDHHLAPS
   541  FYFVAFYYHG DHPVANSLRV DVQAGACEGK LELSVDGAKQ YRNGESVKLH LETDSLALVA
   601  LGALDTALYA AGSKSHKPLN MGKVFEAMNS YDLGCGPGGG DSALQVFQAA GLAFSDGDQW
   661  TLSRKRLSCP KEKTTRKKRN VNFQKAINEK LGQYASPTAK RCCQDGVTRL PMMRSCEQRA
   721  ARVQQPDCRE PFLSCCQFAE SLRKKSRDKG QAGLQRALEI LQEEDLIDED DIPVRSFFPE
   781  NWLWRVETVD RFQILTLWLP DSLTTWEIHG LSLSKTKGLC VATPVQLRVF REFHLHLRLP
   841  MSVRRFEQLE LRPVLYNYLD KNLTVSVHVS PVEGLCLAGG GGLAQQVLVP AGSARPVAFS
   901  VVPTAAAAVS LKVVARGSFE FPVGDAVSKV LQIEKEGAIH REELVYELNP LDHRGRTLEI
   961  PGNSDPNMIP DGDFNSYVRV TASDPLDTLG SEGALSPGGV ASLLRLPRGC GEQTMIYLAP
  1021  TLAASRYLDK TEQWSTLPPE TKDHAVDLIQ KGYMRIQQFR KADGSYAAWL SRDSSTWLTA
  1081  FVLKVLSLAQ EQVGGSPEKL QETSNWLLSQ QQADGSFQDP CPVLDRSMQG GLVGNDETVA
  1141  LTAFVTIALH HGLAVFQDEG AEPLKQRVEA SISKANSFLG EKASAGLLGA HAAAITAYAL
  1201  TLTKAPVDLL GVAHNNLMAM AQETGDNLYW GSVTGSQSNA VSPTPAPRNP SDPMPQAPAL
  1261  WIETTAYALL HLLLHEGKAE MADQASAWLT RQGSFQGGFR STQDTVIALD ALSAYWIASH
  1321  TTEERGLNVT LSSTGRNGFK SHALQLNNRQ IRGLEEELQF SLGSKINVKV GGNSKGTLKV
  1381  LRTYNVLDMK NTTCQDLQIE VTVKGHVEYT MEANEDYEDY EYDELPAKDD PDAPLQPVTP
  1441  LQLFEGRRNR RRREAPKVVE EQESRVHYTV CIWRNGKVGL SGMAIADVTL LSGFHALRAD
  1501  LEKLTSLSDR YVSHFETEGP HVLLYFDSVP TSRECVGFEA VQEVPVGLVQ PASATLYDYY
  1561  NPERRCSVFY GAPSKSRLLA TLCSAEVCQC AEGKCPRQRR ALERGLQDED GYRMKFACYY
  1621  PRVEYGFQVK VLREDSRAAF RLFETKITQV LHFTKDVKAA ANQMRNFLVR ASCRLRLEPG
  1681  KEYLIMGLDG ATYDLEGHPQ YLLDSNSWIE EMPSERLCRS TRQRAACAQL NDFLQEYGTQ
  1741  GCQV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C4A 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): 0.26
Highest tissue expression: 342 nTPM

Expression across tissuesHPA

Tissue

liver: 342 nTPM
adrenal gland: 118 nTPM
ovary: 58 nTPM
kidney: 47 nTPM
thyroid gland: 46 nTPM
colon: 32 nTPM

Single-cell type

conjunctival goblet cells: 1 nCPM
cardiomyocytes: 0.7 nCPM
prostatic club cells: 0.4 nCPM
proximal tubule cells: 0.4 nCPM
basal prostatic cells: 0.3 nCPM
prostatic glandular cells: 0.3 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

medulla oblongata: 9.2 nTPM
thalamus: 4.1 nTPM
basal ganglia: 3.9 nTPM
midbrain: 3.5 nTPM
pons: 3.5 nTPM
cerebral cortex: 3 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C4A.

Disease | AllUniProt

Conditions C4A is implicated in, by any mechanism.

Complement component 4A deficiency (C4AD) MIM:614380
Systemic lupus erythematosus (SLE) MIM:152700

Disease | ImmuneIEDB

Conditions an epitope on C4A 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): 1.45
gnomAD pLI: 0
gnomAD missense Z: 1.92

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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

InteractionsUniProt · HPA

Protein binding partners of C4A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

PINK1

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads C4A as an antibody target. Whether an autoantibody or antibody against C4A could matter depends on whether native C4A is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

C4A is annotated at the cell surface, where native C4A 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.

The trimer provides a surface for interaction between the antigen-antibody complex and other complement components.

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