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P09871 (C1S_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 186. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Complement C1s subcomponent

EC=3.4.21.42
Alternative name(s):
C1 esterase
Complement component 1 subcomponent s
Gene names
Name:C1S
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length688 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.

Catalytic activity

Cleavage of Arg-|-Ala bond in complement component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in complement component C2 to form C2a and C2b: the 'classical' pathway C3 convertase. Ref.14

Enzyme regulation

Inhibited by SERPING1. Ref.14

Subunit structure

C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain. Ref.12

Post-translational modification

The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

Involvement in disease

Complement component C1s deficiency (C1SD) [MIM:613783]: A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Sequence similarities

Belongs to the peptidase S1 family.

Contains 2 CUB domains.

Contains 1 EGF-like domain.

Contains 1 peptidase S1 domain.

Contains 2 Sushi (CCP/SCR) domains.

Biophysicochemical properties

Kinetic parameters:

Less efficient than MASP2 in C4 cleavage.

KM=12.3 µM for complement component C2 (at 37 degrees Celsius) Ref.14

KM=1.9 µM for complement component C4 (at 37 degrees Celsius)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

itself2EBI-2810045,EBI-2810045
C1RP007363EBI-2810045,EBI-3926504

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1515 Ref.8
Chain16 – 688673Complement C1s subcomponent
PRO_0000027586
Chain16 – 437422Complement C1s subcomponent heavy chain
PRO_0000027587
Chain438 – 688251Complement C1s subcomponent light chain
PRO_0000027588

Regions

Domain16 – 130115CUB 1
Domain131 – 17242EGF-like; calcium-binding
Domain175 – 290116CUB 2
Domain292 – 35665Sushi 1
Domain357 – 42367Sushi 2
Domain438 – 680243Peptidase S1

Sites

Active site4751Charge relay system
Active site5291Charge relay system
Active site6321Charge relay system
Metal binding601Calcium
Metal binding681Calcium
Metal binding1131Calcium
Metal binding1311Calcium
Metal binding1321Calcium; via carbonyl oxygen
Metal binding1341Calcium
Metal binding1491Calcium
Metal binding1501Calcium; via carbonyl oxygen
Metal binding1531Calcium; via carbonyl oxygen

Amino acid modifications

Modified residue1491(3R)-3-hydroxyasparagine Ref.10
Glycosylation1741N-linked (GlcNAc...) Ref.10 Ref.17
Glycosylation4061N-linked (GlcNAc...) Ref.16 Ref.17 Ref.19
Disulfide bond65 ↔ 83 Ref.12
Disulfide bond135 ↔ 147 Ref.12
Disulfide bond143 ↔ 156 Ref.12
Disulfide bond158 ↔ 171 Ref.12
Disulfide bond175 ↔ 202 Ref.12
Disulfide bond234 ↔ 251 Ref.12
Disulfide bond294 ↔ 341 Ref.12
Disulfide bond321 ↔ 354 Ref.12
Disulfide bond359 ↔ 403 Ref.12
Disulfide bond386 ↔ 421 Ref.12
Disulfide bond425 ↔ 549Interchain (between heavy and light chains) Ref.12
Disulfide bond595 ↔ 618 Ref.12
Disulfide bond628 ↔ 659 Ref.12

Natural variations

Natural variant1191R → H.
Corresponds to variant rs12146727 [ dbSNP | Ensembl ].
VAR_033643
Natural variant3271V → L.
Corresponds to variant rs2239170 [ dbSNP | Ensembl ].
VAR_033644
Natural variant3831R → H.
Corresponds to variant rs20573 [ dbSNP | Ensembl ].
VAR_014565

Experimental info

Sequence conflict2941C → K AA sequence Ref.8
Sequence conflict5131G → GG Ref.7
Sequence conflict5731T → A AA sequence Ref.9
Sequence conflict645 – 6462TK → GR AA sequence Ref.9

Secondary structure

................................................................................................................................... 688
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09871 [UniParc].

Last modified July 1, 1989. Version 1.
Checksum: 85522647A4C47205

FASTA68876,684
        10         20         30         40         50         60 
MWCIVLFSLL AWVYAEPTMY GEILSPNYPQ AYPSEVEKSW DIEVPEGYGI HLYFTHLDIE 

        70         80         90        100        110        120 
LSENCAYDSV QIISGDTEEG RLCGQRSSNN PHSPIVEEFQ VPYNKLQVIF KSDFSNEERF 

       130        140        150        160        170        180 
TGFAAYYVAT DINECTDFVD VPCSHFCNNF IGGYFCSCPP EYFLHDDMKN CGVNCSGDVF 

       190        200        210        220        230        240 
TALIGEIASP NYPKPYPENS RCEYQIRLEK GFQVVVTLRR EDFDVEAADS AGNCLDSLVF 

       250        260        270        280        290        300 
VAGDRQFGPY CGHGFPGPLN IETKSNALDI IFQTDLTGQK KGWKLRYHGD PMPCPKEDTP 

       310        320        330        340        350        360 
NSVWEPAKAK YVFRDVVQIT CLDGFEVVEG RVGATSFYST CQSNGKWSNS KLKCQPVDCG 

       370        380        390        400        410        420 
IPESIENGKV EDPESTLFGS VIRYTCEEPY YYMENGGGGE YHCAGNGSWV NEVLGPELPK 

       430        440        450        460        470        480 
CVPVCGVPRE PFEEKQRIIG GSDADIKNFP WQVFFDNPWA GGALINEYWV LTAAHVVEGN 

       490        500        510        520        530        540 
REPTMYVGST SVQTSRLAKS KMLTPEHVFI HPGWKLLEVP EGRTNFDNDI ALVRLKDPVK 

       550        560        570        580        590        600 
MGPTVSPICL PGTSSDYNLM DGDLGLISGW GRTEKRDRAV RLKAARLPVA PLRKCKEVKV 

       610        620        630        640        650        660 
EKPTADAEAY VFTPNMICAG GEKGMDSCKG DSGGAFAVQD PNDKTKFYAA GLVSWGPQCG 

       670        680 
TYGLYTRVKN YVDWIMKTMQ ENSTPRED 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNA for human complement component C1s. The complete amino acid sequence."
McKinnon C.M., Carter P.E., Smyth S.J., Dunbar B., Fothergill J.E.
Eur. J. Biochem. 169:547-553(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Liver.
[2]"Complete cDNA sequence of human complement Cls and close physical linkage of the homologous genes Cls and Clr."
Tosi M., Duponchel C., Meo T., Julier C.
Biochemistry 26:8516-8524(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Human genes for complement components C1r and C1s in a close tail-to-tail arrangement."
Kusumoto H., Hirosawa S., Salier J.-P., Hagen F.S., Kurachi K.
Proc. Natl. Acad. Sci. U.S.A. 85:7307-7311(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: PNS.
[6]"Two lineages of mannose-binding lectin-associated serine protease (MASP) in vertebrates."
Endo Y., Takahashi M., Nakao M., Saiga H., Sekine H., Matsushita M., Nonaka M., Fujita T.
J. Immunol. 161:4924-4930(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-329.
Tissue: Peripheral blood leukocyte.
[7]"Complement genes C1r and C1s feature an intronless serine protease domain closely related to haptoglobin."
Tosi M., Duponchel C., Meo T., Couture-Tosi E.
J. Mol. Biol. 208:709-714(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 291-688.
[8]"Human complement component C1s. Partial sequence determination of the heavy chain and identification of the peptide bond cleaved during activation."
Spycher S.E., Nick H., Rickli E.E.
Eur. J. Biochem. 156:49-57(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 16-61; 168-219; 287-334 AND 384-445.
[9]"The serine proteinase chain of human complement component C1s. Cyanogen bromide cleavage and N-terminal sequences of the fragments."
Carter P.E., Dunbar B., Fothergill J.E.
Biochem. J. 215:565-571(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 438-500; 503-534; 542-601; 617-623 AND 626-656.
[10]"Chemical and functional characterization of a fragment of C1-s containing the epidermal growth factor homology region."
Thielens N.M., van Dorsselaer A., Gagnon J., Arlaud G.J.
Biochemistry 29:3570-3578(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-174, HYDROXYLATION AT ASN-149.
[11]"Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)-dependent interactions of human C1s. Location of the iodination sites."
Illy C., Thielens N.M., Gagnon J., Arlaud G.J.
Biochemistry 30:7135-7141(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE.
Tissue: Plasma.
[12]"Identification of the disulfide bonds of human complement C1s."
Hess D., Schaller J., Rickli E.E.
Biochemistry 30:2827-2833(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[13]"Structure of the catalytic region of human complement protease C1s: study by chemical cross-linking and three-dimensional homology modeling."
Rossi V., Gaboriaud C., Lacroix M., Ulrich J., Fontecilla-Camps J.-C., Gagnon J., Arlaud G.J.
Biochemistry 34:7311-7321(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, 3D-STRUCTURE MODELING OF CATALYTIC DOMAIN.
[14]"Substrate specificities of recombinant mannan-binding lectin-associated serine proteases-1 and -2."
Rossi V., Cseh S., Bally I., Thielens N.M., Jensenius J.C., Arlaud G.J.
J. Biol. Chem. 276:40880-40887(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[15]"Molecular basis of a selective C1s deficiency associated with early onset multiple autoimmune diseases."
Dragon-Durey M.-A., Quartier P., Fremeaux-Bacchi V., Blouin J., de Barace C., Prieur A.-M., Weiss L., Fridman W.-H.
J. Immunol. 166:7612-7616(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN COMPLEMENT COMPONENT C1S DEFICIENCY.
[16]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-406.
Tissue: Plasma.
[17]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-174 AND ASN-406.
Tissue: Liver.
[18]"Crystal structure of the catalytic domain of human complement c1s: a serine protease with a handle."
Gaboriaud C., Rossi V., Bally I., Arlaud G.J., Fontecilla-Camps J.-C.
EMBO J. 19:1755-1765(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 358-688.
[19]"X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement."
Gregory L.A., Thielens N.M., Arlaud G.J., Fontecilla-Camps J.-C., Gaboriaud C.
J. Biol. Chem. 278:32157-32164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING SITES, GLYCOSYLATION AT ASN-406.
+Additional computationally mapped references.

Web resources

C1Sbase

C1S mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X06596 mRNA. Translation: CAA29817.1.
M18767 mRNA. Translation: AAA51853.1.
J04080 mRNA. Translation: AAA51852.1.
CH471116 Genomic DNA. Translation: EAW88689.1.
CH471116 Genomic DNA. Translation: EAW88690.1.
BC056903 mRNA. Translation: AAH56903.1.
AB009076 Genomic DNA. Translation: BAA86864.1.
CCDSCCDS31735.1.
PIRC1HUS. A40496.
RefSeqNP_001725.1. NM_001734.3.
NP_958850.1. NM_201442.2.
XP_005253817.1. XM_005253760.1.
UniGeneHs.458355.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ELVX-ray1.70A356-688[»]
1NZIX-ray1.50A/B16-174[»]
4J1YX-ray2.66A/B292-688[»]
4LMFX-ray2.92A/B/C/D17-292[»]
4LORX-ray2.50A17-292[»]
4LOSX-ray2.00A172-358[»]
4LOTX-ray2.92A175-423[»]
ProteinModelPortalP09871.
SMRP09871. Positions 17-684.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107177. 7 interactions.
IntActP09871. 8 interactions.
MINTMINT-4655918.

Chemistry

BindingDBP09871.
ChEMBLCHEMBL3913.
DrugBankDB00054. Abciximab.
DB00051. Adalimumab.
DB00074. Basiliximab.
DB00002. Cetuximab.
DB00005. Etanercept.
DB00056. Gemtuzumab ozogamicin.
DB00078. Ibritumomab.
DB00028. Immune globulin.
DB00075. Muromonab.
DB00073. Rituximab.
DB00072. Trastuzumab.

Protein family/group databases

MEROPSS01.193.

PTM databases

PhosphoSiteP09871.

Polymorphism databases

DMDM115205.

2D gel databases

SWISS-2DPAGEP09871.

Proteomic databases

MaxQBP09871.
PaxDbP09871.
PeptideAtlasP09871.
PRIDEP09871.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328916; ENSP00000328173; ENSG00000182326.
ENST00000360817; ENSP00000354057; ENSG00000182326.
ENST00000406697; ENSP00000385035; ENSG00000182326.
ENST00000594877; ENSP00000471707; ENSG00000269882.
ENST00000595575; ENSP00000469947; ENSG00000269882.
ENST00000600933; ENSP00000469899; ENSG00000269882.
GeneID716.
KEGGhsa:716.
UCSCuc001qsj.3. human.

Organism-specific databases

CTD716.
GeneCardsGC12P007096.
HGNCHGNC:1247. C1S.
HPACAB016722.
HPA018852.
MIM120580. gene.
613783. phenotype.
neXtProtNX_P09871.
Orphanet169147. Immunodeficiency due to an early component of complement deficiency.
PharmGKBPA25636.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOVERGENHBG000559.
InParanoidP09871.
KOK01331.
OMAPTMYGEI.
PhylomeDBP09871.
TreeFamTF330373.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressP09871.
BgeeP09871.
GenevestigatorP09871.

Family and domain databases

Gene3D2.60.120.290. 2 hits.
InterProIPR000859. CUB_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR024175. Pept_S1A_C1r/C1S/mannan-bd.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR000436. Sushi_SCR_CCP.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00431. CUB. 2 hits.
PF00084. Sushi. 2 hits.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001155. C1r_C1s_MASP. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00032. CCP. 2 hits.
SM00042. CUB. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF49854. SSF49854. 2 hits.
SSF50494. SSF50494. 1 hit.
SSF57535. SSF57535. 2 hits.
PROSITEPS00010. ASX_HYDROXYL. 1 hit.
PS01180. CUB. 2 hits.
PS01187. EGF_CA. 1 hit.
PS50923. SUSHI. 2 hits.
PS50240. TRYPSIN_DOM. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSC1S. human.
EvolutionaryTraceP09871.
GeneWikiC1S.
GenomeRNAi716.
NextBio2912.
PMAP-CutDBP09871.
PROP09871.
SOURCESearch...

Entry information

Entry nameC1S_HUMAN
AccessionPrimary (citable) accession number: P09871
Secondary accession number(s): D3DUT4 expand/collapse secondary AC list , Q9UCU7, Q9UCU8, Q9UCU9, Q9UCV0, Q9UCV1, Q9UCV2, Q9UCV3, Q9UCV4, Q9UCV5, Q9UM14
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: July 9, 2014
This is version 186 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM