C1S

Protein identityUniProt · HPA

UniProt accession

P09871

Gene

C1S

Ensembl

ENSG00000182326

Chromosome

12

Canonical length

688 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Nucleoplasm,Cytosol

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes a serine protease, which is a major constituent of the human complement subcomponent C1. C1s associates with two other complement components C1r and C1q in order to yield the first component of the serum complement system. Defects in this gene are the cause of selective C1s deficiency. [provided by RefSeq, Mar 2009]

Canonical amino-acid sequenceUniProt

688 residues, UniProt reviewed canonical sequence.

>P09871|C1S
     1  MWCIVLFSLL AWVYAEPTMY GEILSPNYPQ AYPSEVEKSW DIEVPEGYGI HLYFTHLDIE
    61  LSENCAYDSV QIISGDTEEG RLCGQRSSNN PHSPIVEEFQ VPYNKLQVIF KSDFSNEERF
   121  TGFAAYYVAT DINECTDFVD VPCSHFCNNF IGGYFCSCPP EYFLHDDMKN CGVNCSGDVF
   181  TALIGEIASP NYPKPYPENS RCEYQIRLEK GFQVVVTLRR EDFDVEAADS AGNCLDSLVF
   241  VAGDRQFGPY CGHGFPGPLN IETKSNALDI IFQTDLTGQK KGWKLRYHGD PMPCPKEDTP
   301  NSVWEPAKAK YVFRDVVQIT CLDGFEVVEG RVGATSFYST CQSNGKWSNS KLKCQPVDCG
   361  IPESIENGKV EDPESTLFGS VIRYTCEEPY YYMENGGGGE YHCAGNGSWV NEVLGPELPK
   421  CVPVCGVPRE PFEEKQRIIG GSDADIKNFP WQVFFDNPWA GGALINEYWV LTAAHVVEGN
   481  REPTMYVGST SVQTSRLAKS KMLTPEHVFI HPGWKLLEVP EGRTNFDNDI ALVRLKDPVK
   541  MGPTVSPICL PGTSSDYNLM DGDLGLISGW GRTEKRDRAV RLKAARLPVA PLRKCKEVKV
   601  EKPTADAEAY VFTPNMICAG GEKGMDSCKG DSGGAFAVQD PNDKTKFYAA GLVSWGPQCG
   661  TYGLYTRVKN YVDWIMKTMQ ENSTPRED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against C1S 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)

0.29

Highest tissue expression

2,663 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about C1S.

Disease | AllUniProt

Conditions C1S is implicated in, by any mechanism.

• Complement component C1s deficiency (C1SD) MIM:613783
• Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2) MIM:617174

Disease | GeneticClinVar

38 pathogenic / likely-pathogenic of 709 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Complement component C1s deficiency
• Ehlers-Danlos syndrome, periodontal type 2
• Ehlers-Danlos syndrome, periodontal type 1
• C1S-related disorder

Disease | ImmuneIEDB

Conditions an epitope on C1S was assayed in.

• rheumatoid arthritis B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against C1S are reported. Each links to that disease's full target list.

• Lupus Erythematosus, Systemic 3
• Lupus Nephritis 3

ReferencesPubMed · IEDB

Publications for C1S from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.6

gnomAD pLI

0

gnomAD missense Z

0.56

DepMap mean gene effect

-0.06

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

• complement activation, classical pathway
• innate immune response
• proteolysis

Molecular functions

• calcium ion binding
• identical protein binding
• serine-type endopeptidase activity

Cellular components

• blood microparticle
• cell surface
• complement component C1 complex
• extracellular region
• extracellular space
• symbiont cell surface

Protein domainsUniProt · Pfam · InterPro

• EGF-type aspartate/asparagine hydroxylation site
• Sushi/SCR/CCP domain
• CUB domain
• Serine proteases, trypsin domain
• Peptidase S1A, chymotrypsin family
• EGF-like calcium-binding domain
• Peptidase S1, PA clan
• EGF-like calcium-binding, conserved site
• Peptidase S1A, complement C1r/C1S/mannan-binding
• Serine proteases, trypsin family, serine active site
• Spermadhesin, CUB domain superfamily
• Sushi/SCR/CCP superfamily
• Sushi repeat (SCR repeat)
• Trypsin
• CUB domain
• Coagulation Factor Xa inhibitory site

KeywordsUniProt

• Calcium
• Complement pathway
• Disulfide bond
• EGF-like domain
• Ehlers-Danlos syndrome
• Glycoprotein
• Hydrolase
• Hydroxylation
• Immunity
• Innate immunity
• Metal-binding
• Protease
• Repeat
• Secreted
• Serine protease
• Signal
• Sushi