C1S_HUMAN
ID C1S_HUMAN Reviewed; 688 AA.
AC P09871; D3DUT4; Q9UCU7; Q9UCU8; Q9UCU9; Q9UCV0; Q9UCV1; Q9UCV2; Q9UCV3;
AC Q9UCV4; Q9UCV5; Q9UM14;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 250.
DE RecName: Full=Complement C1s subcomponent;
DE EC=3.4.21.42;
DE AltName: Full=C1 esterase;
DE AltName: Full=Complement component 1 subcomponent s;
DE Contains:
DE RecName: Full=Complement C1s subcomponent heavy chain;
DE Contains:
DE RecName: Full=Complement C1s subcomponent light chain;
DE Flags: Precursor;
GN Name=C1S;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=3500856; DOI=10.1111/j.1432-1033.1987.tb13644.x;
RA McKinnon C.M., Carter P.E., Smyth S.J., Dunbar B., Fothergill J.E.;
RT "Molecular cloning of cDNA for human complement component C1s. The complete
RT amino acid sequence.";
RL Eur. J. Biochem. 169:547-553(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2831944; DOI=10.1021/bi00400a004;
RA Tosi M., Duponchel C., Meo T., Julier C.;
RT "Complete cDNA sequence of human complement Cls and close physical linkage
RT of the homologous genes Cls and Clr.";
RL Biochemistry 26:8516-8524(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2459702; DOI=10.1073/pnas.85.19.7307;
RA Kusumoto H., Hirosawa S., Salier J.-P., Hagen F.S., Kurachi K.;
RT "Human genes for complement components C1r and C1s in a close tail-to-tail
RT arrangement.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7307-7311(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PNS;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-329.
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=9794427;
RA Endo Y., Takahashi M., Nakao M., Saiga H., Sekine H., Matsushita M.,
RA Nonaka M., Fujita T.;
RT "Two lineages of mannose-binding lectin-associated serine protease (MASP)
RT in vertebrates.";
RL J. Immunol. 161:4924-4930(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE OF 291-688.
RX PubMed=2553984; DOI=10.1016/0022-2836(89)90161-7;
RA Tosi M., Duponchel C., Meo T., Couture-Tosi E.;
RT "Complement genes C1r and C1s feature an intronless serine protease domain
RT closely related to haptoglobin.";
RL J. Mol. Biol. 208:709-714(1989).
RN [8]
RP PROTEIN SEQUENCE OF 16-61; 168-219; 287-334 AND 384-445.
RX PubMed=3007145; DOI=10.1111/j.1432-1033.1986.tb09546.x;
RA Spycher S.E., Nick H., Rickli E.E.;
RT "Human complement component C1s. Partial sequence determination of the
RT heavy chain and identification of the peptide bond cleaved during
RT activation.";
RL Eur. J. Biochem. 156:49-57(1986).
RN [9]
RP PROTEIN SEQUENCE OF 438-500; 503-534; 542-601; 617-623 AND 626-656.
RX PubMed=6362661; DOI=10.1042/bj2150565;
RA Carter P.E., Dunbar B., Fothergill J.E.;
RT "The serine proteinase chain of human complement component C1s. Cyanogen
RT bromide cleavage and N-terminal sequences of the fragments.";
RL Biochem. J. 215:565-571(1983).
RN [10]
RP PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-174, AND HYDROXYLATION AT
RP ASN-149.
RX PubMed=2141278; DOI=10.1021/bi00466a021;
RA Thielens N.M., van Dorsselaer A., Gagnon J., Arlaud G.J.;
RT "Chemical and functional characterization of a fragment of C1-s containing
RT the epidermal growth factor homology region.";
RL Biochemistry 29:3570-3578(1990).
RN [11]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Plasma;
RX PubMed=1854725; DOI=10.1021/bi00243a014;
RA Illy C., Thielens N.M., Gagnon J., Arlaud G.J.;
RT "Effect of lactoperoxidase-catalyzed iodination on the Ca(2+)-dependent
RT interactions of human C1s. Location of the iodination sites.";
RL Biochemistry 30:7135-7141(1991).
RN [12]
RP DISULFIDE BONDS.
RX PubMed=2007122; DOI=10.1021/bi00225a014;
RA Hess D., Schaller J., Rickli E.E.;
RT "Identification of the disulfide bonds of human complement C1s.";
RL Biochemistry 30:2827-2833(1991).
RN [13]
RP PARTIAL PROTEIN SEQUENCE, AND 3D-STRUCTURE MODELING OF CATALYTIC DOMAIN.
RX PubMed=7779774; DOI=10.1021/bi00022a004;
RA Rossi V., Gaboriaud C., Lacroix M., Ulrich J., Fontecilla-Camps J.-C.,
RA Gagnon J., Arlaud G.J.;
RT "Structure of the catalytic region of human complement protease C1s: study
RT by chemical cross-linking and three-dimensional homology modeling.";
RL Biochemistry 34:7311-7321(1995).
RN [14]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=11527969; DOI=10.1074/jbc.m105934200;
RA Rossi V., Cseh S., Bally I., Thielens N.M., Jensenius J.C., Arlaud G.J.;
RT "Substrate specificities of recombinant mannan-binding lectin-associated
RT serine proteases-1 and -2.";
RL J. Biol. Chem. 276:40880-40887(2001).
RN [15]
RP INVOLVEMENT IN COMPLEMENT COMPONENT C1S DEFICIENCY.
RX PubMed=11390518; DOI=10.4049/jimmunol.166.12.7612;
RA Dragon-Durey M.-A., Quartier P., Fremeaux-Bacchi V., Blouin J.,
RA de Barace C., Prieur A.-M., Weiss L., Fridman W.-H.;
RT "Molecular basis of a selective C1s deficiency associated with early onset
RT multiple autoimmune diseases.";
RL J. Immunol. 166:7612-7616(2001).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-406.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [17]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-174 AND ASN-406.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP INVOLVEMENT IN EDSPD2, AND VARIANTS EDSPD2 ARG-294 AND VAL-316 DEL.
RX PubMed=27745832; DOI=10.1016/j.ajhg.2016.08.019;
RG Molecular Basis of Periodontal EDS Consortium;
RA Kapferer-Seebacher I., Pepin M., Werner R., Aitman T.J., Nordgren A.,
RA Stoiber H., Thielens N., Gaboriaud C., Amberger A., Schossig A., Gruber R.,
RA Giunta C., Bamshad M., Bjoerck E., Chen C., Chitayat D., Dorschner M.,
RA Schmitt-Egenolf M., Hale C.J., Hanna D., Hennies H.C.,
RA Heiss-Kisielewsky I., Lindstrand A., Lundberg P., Mitchell A.L.,
RA Nickerson D.A., Reinstein E., Rohrbach M., Romani N., Schmuth M.,
RA Silver R., Taylan F., Vandersteen A., Vandrovcova J., Weerakkody R.,
RA Yang M., Pope F.M., Byers P.H., Zschocke J.;
RT "Periodontal Ehlers-Danlos syndrome is caused by mutations in C1R and C1S,
RT which encode subcomponents C1r and C1s of complement.";
RL Am. J. Hum. Genet. 99:1005-1014(2016).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 358-688.
RX PubMed=10775260; DOI=10.1093/emboj/19.8.1755;
RA Gaboriaud C., Rossi V., Bally I., Arlaud G.J., Fontecilla-Camps J.-C.;
RT "Crystal structure of the catalytic domain of human complement c1s: a
RT serine protease with a handle.";
RL EMBO J. 19:1755-1765(2000).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING SITES, AND
RP GLYCOSYLATION AT ASN-406.
RX PubMed=12788922; DOI=10.1074/jbc.m305175200;
RA Gregory L.A., Thielens N.M., Arlaud G.J., Fontecilla-Camps J.-C.,
RA Gaboriaud C.;
RT "X-ray structure of the Ca2+-binding interaction domain of C1s. Insights
RT into the assembly of the C1 complex of complement.";
RL J. Biol. Chem. 278:32157-32164(2003).
CC -!- FUNCTION: C1s B chain is a serine protease that combines with C1q and
CC C1r to form C1, the first component of the classical pathway of the
CC complement system. C1r activates C1s so that it can, in turn, activate
CC C2 and C4.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleavage of Arg-|-Ala bond in complement component C4 to form
CC C4a and C4b, and Lys(or Arg)-|-Lys bond in complement component C2 to
CC form C2a and C2b: the 'classical' pathway C3 convertase.;
CC EC=3.4.21.42; Evidence={ECO:0000269|PubMed:11527969};
CC -!- ACTIVITY REGULATION: Inhibited by SERPING1.
CC {ECO:0000269|PubMed:11527969}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.3 uM for complement component C2 (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:11527969};
CC KM=1.9 uM for complement component C4 (at 37 degrees Celsius)
CC {ECO:0000269|PubMed:11527969};
CC Note=Less efficient than MASP2 in C4 cleavage.;
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, C1r and
CC C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked
CC heterodimer of a heavy chain and a light chain.
CC {ECO:0000269|PubMed:2007122}.
CC -!- INTERACTION:
CC P09871; P00736: C1R; NbExp=6; IntAct=EBI-2810045, EBI-3926504;
CC P09871; P09871: C1S; NbExp=2; IntAct=EBI-2810045, EBI-2810045;
CC P09871; P06681: C2; NbExp=3; IntAct=EBI-2810045, EBI-2835920;
CC P09871; O43889-2: CREB3; NbExp=3; IntAct=EBI-2810045, EBI-625022;
CC P09871; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-2810045, EBI-7545592;
CC P09871; P05155: SERPING1; NbExp=5; IntAct=EBI-2810045, EBI-1223454;
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate
CC and asparagine is (R) stereospecific within EGF domains.
CC {ECO:0000269|PubMed:2141278}.
CC -!- DISEASE: Complement component C1s deficiency (C1SD) [MIM:613783]: A
CC rare defect resulting in C1 deficiency and impaired activation of the
CC complement classical pathway. C1 deficiency generally leads to severe
CC immune complex disease with features of systemic lupus erythematosus
CC and glomerulonephritis. {ECO:0000269|PubMed:11390518}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Ehlers-Danlos syndrome, periodontal type, 2 (EDSPD2)
CC [MIM:617174]: A form of Ehlers-Danlos syndrome, a connective tissue
CC disorder characterized by hyperextensible skin, atrophic cutaneous
CC scars due to tissue fragility and joint hyperlaxity. EDSPD2 is
CC characterized by the association of typical features of Ehlers-Danlos
CC syndrome with gingival recession and severe early-onset periodontal
CC disease, leading to premature loss of permanent teeth. EDSPD2
CC transmission pattern is consistent with autosomal dominant inheritance.
CC {ECO:0000269|PubMed:27745832}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- WEB RESOURCE: Name=C1Sbase; Note=C1S mutation db;
CC URL="http://structure.bmc.lu.se/idbase/C1Sbase/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X06596; CAA29817.1; -; mRNA.
DR EMBL; M18767; AAA51853.1; -; mRNA.
DR EMBL; J04080; AAA51852.1; -; mRNA.
DR EMBL; CH471116; EAW88689.1; -; Genomic_DNA.
DR EMBL; CH471116; EAW88690.1; -; Genomic_DNA.
DR EMBL; BC056903; AAH56903.1; -; mRNA.
DR EMBL; AB009076; BAA86864.1; -; Genomic_DNA.
DR CCDS; CCDS31735.1; -.
DR PIR; A40496; C1HUS.
DR RefSeq; NP_001333779.1; NM_001346850.1.
DR RefSeq; NP_001725.1; NM_001734.4.
DR RefSeq; NP_958850.1; NM_201442.3.
DR RefSeq; XP_005253817.1; XM_005253760.1.
DR PDB; 1ELV; X-ray; 1.70 A; A=356-688.
DR PDB; 1NZI; X-ray; 1.50 A; A/B=16-174.
DR PDB; 4J1Y; X-ray; 2.66 A; A/B=292-688.
DR PDB; 4LMF; X-ray; 2.92 A; A/B/C/D=17-292.
DR PDB; 4LOR; X-ray; 2.50 A; A=17-292.
DR PDB; 4LOS; X-ray; 2.00 A; A=172-358.
DR PDB; 4LOT; X-ray; 2.92 A; A=175-423.
DR PDB; 6F1C; X-ray; 4.20 A; B/D=16-292.
DR PDB; 6F1H; X-ray; 4.50 A; B/D=17-292.
DR PDBsum; 1ELV; -.
DR PDBsum; 1NZI; -.
DR PDBsum; 4J1Y; -.
DR PDBsum; 4LMF; -.
DR PDBsum; 4LOR; -.
DR PDBsum; 4LOS; -.
DR PDBsum; 4LOT; -.
DR PDBsum; 6F1C; -.
DR PDBsum; 6F1H; -.
DR AlphaFoldDB; P09871; -.
DR SASBDB; P09871; -.
DR SMR; P09871; -.
DR BioGRID; 107177; 13.
DR ComplexPortal; CPX-1920; Complement C1 complex.
DR IntAct; P09871; 17.
DR MINT; P09871; -.
DR STRING; 9606.ENSP00000385035; -.
DR BindingDB; P09871; -.
DR ChEMBL; CHEMBL3913; -.
DR DrugBank; DB02371; 2-(2-Hydroxy-1,1-Dihydroxymethyl-Ethylamino)-Ethanesulfonic Acid.
DR DrugBank; DB09228; Conestat alfa.
DR DrugBank; DB09130; Copper.
DR DrugBank; DB12831; Gabexate.
DR DrugBank; DB06404; Human C1-esterase inhibitor.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P09871; -.
DR GuidetoPHARMACOLOGY; 2335; -.
DR MEROPS; S01.193; -.
DR GlyConnect; 1144; 4 N-Linked glycans (2 sites).
DR GlyGen; P09871; 2 sites, 7 N-linked glycans (2 sites).
DR iPTMnet; P09871; -.
DR PhosphoSitePlus; P09871; -.
DR BioMuta; C1S; -.
DR DMDM; 115205; -.
DR SWISS-2DPAGE; P09871; -.
DR CPTAC; non-CPTAC-1103; -.
DR EPD; P09871; -.
DR jPOST; P09871; -.
DR MassIVE; P09871; -.
DR MaxQB; P09871; -.
DR PaxDb; P09871; -.
DR PeptideAtlas; P09871; -.
DR PRIDE; P09871; -.
DR ProteomicsDB; 52270; -.
DR ABCD; P09871; 28 sequenced antibodies.
DR Antibodypedia; 3384; 642 antibodies from 35 providers.
DR DNASU; 716; -.
DR Ensembl; ENST00000328916.7; ENSP00000328173.3; ENSG00000182326.16.
DR Ensembl; ENST00000360817.10; ENSP00000354057.5; ENSG00000182326.16.
DR Ensembl; ENST00000406697.5; ENSP00000385035.1; ENSG00000182326.16.
DR GeneID; 716; -.
DR KEGG; hsa:716; -.
DR MANE-Select; ENST00000360817.10; ENSP00000354057.5; NM_001734.5; NP_001725.1.
DR UCSC; uc001qsj.4; human.
DR CTD; 716; -.
DR DisGeNET; 716; -.
DR GeneCards; C1S; -.
DR GeneReviews; C1S; -.
DR HGNC; HGNC:1247; C1S.
DR HPA; ENSG00000182326; Tissue enriched (liver).
DR MalaCards; C1S; -.
DR MIM; 120580; gene.
DR MIM; 613783; phenotype.
DR MIM; 617174; phenotype.
DR neXtProt; NX_P09871; -.
DR OpenTargets; ENSG00000182326; -.
DR Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency.
DR Orphanet; 75392; Periodontal Ehlers-Danlos syndrome.
DR PharmGKB; PA25636; -.
DR VEuPathDB; HostDB:ENSG00000182326; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000157473; -.
DR HOGENOM; CLU_006842_14_1_1; -.
DR InParanoid; P09871; -.
DR OMA; DFADAPC; -.
DR OrthoDB; 6580at2759; -.
DR PhylomeDB; P09871; -.
DR TreeFam; TF330373; -.
DR BRENDA; 3.4.21.42; 2681.
DR PathwayCommons; P09871; -.
DR Reactome; R-HSA-166663; Initial triggering of complement.
DR Reactome; R-HSA-173623; Classical antibody-mediated complement activation.
DR Reactome; R-HSA-977606; Regulation of Complement cascade.
DR SABIO-RK; P09871; -.
DR SignaLink; P09871; -.
DR SIGNOR; P09871; -.
DR BioGRID-ORCS; 716; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; C1S; human.
DR EvolutionaryTrace; P09871; -.
DR GeneWiki; C1S; -.
DR GenomeRNAi; 716; -.
DR Pharos; P09871; Tchem.
DR PRO; PR:P09871; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P09871; protein.
DR Bgee; ENSG00000182326; Expressed in pericardium and 199 other tissues.
DR ExpressionAtlas; P09871; baseline and differential.
DR Genevisible; P09871; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0005602; C:complement component C1 complex; IC:ComplexPortal.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; IC:ComplexPortal.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00033; CCP; 2.
DR CDD; cd00041; CUB; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.120.290; -; 2.
DR InterPro; IPR035708; Complement_C1s_subcomponent.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR035914; Sperma_CUB_dom_sf.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24255:SF18; PTHR24255:SF18; 1.
DR Pfam; PF00431; CUB; 2.
DR Pfam; PF00084; Sushi; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00032; CCP; 2.
DR SMART; SM00042; CUB; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF49854; SSF49854; 2.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 2.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS01180; CUB; 2.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50923; SUSHI; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Complement pathway; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain; Ehlers-Danlos syndrome;
KW Glycoprotein; Hydrolase; Hydroxylation; Immunity; Innate immunity;
KW Metal-binding; Protease; Reference proteome; Repeat; Serine protease;
KW Signal; Sushi.
FT SIGNAL 1..15
FT /evidence="ECO:0000269|PubMed:3007145"
FT CHAIN 16..688
FT /note="Complement C1s subcomponent"
FT /id="PRO_0000027586"
FT CHAIN 16..437
FT /note="Complement C1s subcomponent heavy chain"
FT /id="PRO_0000027587"
FT CHAIN 438..688
FT /note="Complement C1s subcomponent light chain"
FT /id="PRO_0000027588"
FT DOMAIN 16..130
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 131..172
FT /note="EGF-like; calcium-binding"
FT DOMAIN 175..290
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 292..356
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 357..423
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 438..680
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 475
FT /note="Charge relay system"
FT ACT_SITE 529
FT /note="Charge relay system"
FT ACT_SITE 632
FT /note="Charge relay system"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 113
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 149
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT BINDING 153
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT MOD_RES 149
FT /note="(3R)-3-hydroxyasparagine"
FT /evidence="ECO:0000269|PubMed:2141278"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:2141278"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12788922,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT DISULFID 65..83
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 135..147
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 143..156
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 158..171
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 175..202
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 234..251
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 294..341
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 321..354
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 359..403
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 386..421
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 425..549
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00302, ECO:0000269|PubMed:2007122"
FT DISULFID 595..618
FT /evidence="ECO:0000269|PubMed:2007122"
FT DISULFID 628..659
FT /evidence="ECO:0000269|PubMed:2007122"
FT VARIANT 119
FT /note="R -> H (in dbSNP:rs12146727)"
FT /id="VAR_033643"
FT VARIANT 294
FT /note="C -> R (in EDSPD2; dbSNP:rs886040975)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077120"
FT VARIANT 316
FT /note="Missing (in EDSPD2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077121"
FT VARIANT 327
FT /note="V -> L (in dbSNP:rs2239170)"
FT /id="VAR_033644"
FT VARIANT 383
FT /note="R -> H (in dbSNP:rs20573)"
FT /id="VAR_014565"
FT CONFLICT 294
FT /note="C -> K (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="G -> GG (in Ref. 7)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="T -> A (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 645..646
FT /note="TK -> GR (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:1NZI"
FT TURN 26..29
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 34..43
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 48..58
FT /evidence="ECO:0007829|PDB:1NZI"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 96..112
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 122..131
FT /evidence="ECO:0007829|PDB:1NZI"
FT TURN 134..136
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:4LOR"
FT STRAND 143..150
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:1NZI"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:4LOR"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:4LOR"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:4LOS"
FT TURN 190..193
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 201..207
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 212..217
FT /evidence="ECO:0007829|PDB:4LOS"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 235..242
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 245..250
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 265..273
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 282..291
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 300..306
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:4J1Y"
FT STRAND 316..321
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 325..331
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 334..341
FT /evidence="ECO:0007829|PDB:4LOS"
FT TURN 348..351
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:4LOS"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 381..386
FT /evidence="ECO:0007829|PDB:1ELV"
FT TURN 388..390
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:4LOT"
FT STRAND 399..403
FT /evidence="ECO:0007829|PDB:1ELV"
FT TURN 405..407
FT /evidence="ECO:0007829|PDB:4LOT"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:1ELV"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 421..423
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:1ELV"
FT TURN 456..459
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 460..466
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 469..472
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 474..477
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:4J1Y"
FT HELIX 494..499
FT /evidence="ECO:0007829|PDB:4J1Y"
FT STRAND 505..510
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 520..522
FT /evidence="ECO:0007829|PDB:4J1Y"
FT STRAND 531..537
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 564..570
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 576..578
FT /evidence="ECO:0007829|PDB:4J1Y"
FT STRAND 583..590
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 592..596
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 616..620
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 627..629
FT /evidence="ECO:0007829|PDB:4J1Y"
FT STRAND 635..639
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 647..655
FT /evidence="ECO:0007829|PDB:1ELV"
FT STRAND 661..667
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 668..671
FT /evidence="ECO:0007829|PDB:1ELV"
FT HELIX 672..681
FT /evidence="ECO:0007829|PDB:1ELV"
SQ SEQUENCE 688 AA; 76684 MW; 85522647A4C47205 CRC64;
MWCIVLFSLL AWVYAEPTMY GEILSPNYPQ AYPSEVEKSW DIEVPEGYGI HLYFTHLDIE
LSENCAYDSV QIISGDTEEG RLCGQRSSNN PHSPIVEEFQ VPYNKLQVIF KSDFSNEERF
TGFAAYYVAT DINECTDFVD VPCSHFCNNF IGGYFCSCPP EYFLHDDMKN CGVNCSGDVF
TALIGEIASP NYPKPYPENS RCEYQIRLEK GFQVVVTLRR EDFDVEAADS AGNCLDSLVF
VAGDRQFGPY CGHGFPGPLN IETKSNALDI IFQTDLTGQK KGWKLRYHGD PMPCPKEDTP
NSVWEPAKAK YVFRDVVQIT CLDGFEVVEG RVGATSFYST CQSNGKWSNS KLKCQPVDCG
IPESIENGKV EDPESTLFGS VIRYTCEEPY YYMENGGGGE YHCAGNGSWV NEVLGPELPK
CVPVCGVPRE PFEEKQRIIG GSDADIKNFP WQVFFDNPWA GGALINEYWV LTAAHVVEGN
REPTMYVGST SVQTSRLAKS KMLTPEHVFI HPGWKLLEVP EGRTNFDNDI ALVRLKDPVK
MGPTVSPICL PGTSSDYNLM DGDLGLISGW GRTEKRDRAV RLKAARLPVA PLRKCKEVKV
EKPTADAEAY VFTPNMICAG GEKGMDSCKG DSGGAFAVQD PNDKTKFYAA GLVSWGPQCG
TYGLYTRVKN YVDWIMKTMQ ENSTPRED
