Full text data of C1S
C1S
[Confidence: low (only semi-automatic identification from reviews)]
Complement C1s subcomponent; 3.4.21.42 (C1 esterase; Complement component 1 subcomponent s; Complement C1s subcomponent heavy chain; Complement C1s subcomponent light chain; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Complement C1s subcomponent; 3.4.21.42 (C1 esterase; Complement component 1 subcomponent s; Complement C1s subcomponent heavy chain; Complement C1s subcomponent light chain; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P09871
ID C1S_HUMAN Reviewed; 688 AA.
AC P09871; D3DUT4; Q9UCU7; Q9UCU8; Q9UCU9; Q9UCV0; Q9UCV1; Q9UCV2;
read moreAC Q9UCV3; Q9UCV4; Q9UCV5; Q9UM14;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 180.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT complete 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
RT linkage 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-
RT tail 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT (MASP) 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
RT domain 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;
RA Carter P.E., Dunbar B., Fothergill J.E.;
RT "The serine proteinase chain of human complement component C1s.
RT Cyanogen 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
RP AT 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
RT containing 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+)-
RT dependent interactions of human C1s. Location of the iodination
RT 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
RP 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:
RT study by chemical cross-linking and three-dimensional homology
RT modeling.";
RL Biochemistry 34:7311-7321(1995).
RN [14]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME
RP REGULATION.
RX PubMed=11527969; DOI=10.1074/jbc.M105934200;
RA Rossi V., Cseh S., Bally I., Thielens N.M., Jensenius J.C.,
RA Arlaud G.J.;
RT "Substrate specificities of recombinant mannan-binding lectin-
RT associated 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;
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
RT onset multiple autoimmune diseases.";
RL J. Immunol. 166:7612-7616(2001).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-406, AND MASS
RP SPECTROMETRY.
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.,
RA Moore R.J., 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, AND MASS
RP SPECTROMETRY.
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
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING
RP SITES, AND 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.
RT Insights 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
CC and C1r to form C1, the first component of the classical pathway
CC of the complement system. C1r activates C1s so that it can, in
CC turn, activate C2 and C4.
CC -!- CATALYTIC ACTIVITY: Cleavage of Arg-|-Ala bond in complement
CC component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in
CC complement component C2 to form C2a and C2b: the 'classical'
CC pathway C3 convertase.
CC -!- ENZYME REGULATION: Inhibited by SERPING1.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.3 uM for complement component C2 (at 37 degrees Celsius);
CC KM=1.9 uM for complement component C4 (at 37 degrees Celsius);
CC Note=Less efficient than MASP2 in C4 cleavage;
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q,
CC C1r and C1s in the molar ration of 1:2:2. Activated C1s is an
CC disulfide-linked heterodimer of a heavy chain and a light chain.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-2810045, EBI-2810045;
CC P00736:C1R; NbExp=3; IntAct=EBI-2810045, EBI-3926504;
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC aspartate and asparagine is (R) stereospecific within EGF domains.
CC -!- DISEASE: Complement component C1s deficiency (C1SD) [MIM:613783]:
CC A rare defect resulting in C1 deficiency and impaired activation
CC of the complement classical pathway. C1 deficiency generally leads
CC to severe immune complex disease with features of systemic lupus
CC erythematosus and glomerulonephritis. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family.
CC -!- SIMILARITY: Contains 2 CUB domains.
CC -!- SIMILARITY: Contains 1 EGF-like domain.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SIMILARITY: Contains 2 Sushi (CCP/SCR) domains.
CC -!- WEB RESOURCE: Name=C1Sbase; Note=C1S mutation db;
CC URL="http://bioinf.uta.fi/C1Sbase/";
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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 PIR; A40496; C1HUS.
DR RefSeq; NP_001725.1; NM_001734.3.
DR RefSeq; NP_958850.1; NM_201442.2.
DR RefSeq; XP_005253817.1; XM_005253760.1.
DR RefSeq; XP_005277812.1; XM_005277755.1.
DR UniGene; Hs.458355; -.
DR PDB; 1ELV; X-ray; 1.70 A; A=358-688.
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 PDBsum; 1ELV; -.
DR PDBsum; 1NZI; -.
DR PDBsum; 4J1Y; -.
DR PDBsum; 4LMF; -.
DR PDBsum; 4LOR; -.
DR PDBsum; 4LOS; -.
DR PDBsum; 4LOT; -.
DR ProteinModelPortal; P09871; -.
DR SMR; P09871; 18-684.
DR IntAct; P09871; 8.
DR MINT; MINT-4655918; -.
DR BindingDB; P09871; -.
DR ChEMBL; CHEMBL3913; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00072; Trastuzumab.
DR MEROPS; S01.193; -.
DR PhosphoSite; P09871; -.
DR DMDM; 115205; -.
DR SWISS-2DPAGE; P09871; -.
DR PaxDb; P09871; -.
DR PeptideAtlas; P09871; -.
DR PRIDE; P09871; -.
DR Ensembl; ENST00000328916; ENSP00000328173; ENSG00000182326.
DR Ensembl; ENST00000360817; ENSP00000354057; ENSG00000182326.
DR Ensembl; ENST00000406697; ENSP00000385035; ENSG00000182326.
DR Ensembl; ENST00000594877; ENSP00000471707; ENSG00000269882.
DR Ensembl; ENST00000595575; ENSP00000469947; ENSG00000269882.
DR Ensembl; ENST00000600933; ENSP00000469899; ENSG00000269882.
DR GeneID; 716; -.
DR KEGG; hsa:716; -.
DR UCSC; uc001qsj.3; human.
DR CTD; 716; -.
DR GeneCards; GC12P007096; -.
DR HGNC; HGNC:1247; C1S.
DR HPA; CAB016722; -.
DR HPA; HPA018852; -.
DR MIM; 120580; gene.
DR MIM; 613783; phenotype.
DR neXtProt; NX_P09871; -.
DR Orphanet; 169147; Immunodeficiency due to an early component of complement deficiency.
DR PharmGKB; PA25636; -.
DR eggNOG; COG5640; -.
DR HOVERGEN; HBG000559; -.
DR InParanoid; P09871; -.
DR KO; K01331; -.
DR OMA; PTMYGEI; -.
DR PhylomeDB; P09871; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; C1S; human.
DR EvolutionaryTrace; P09871; -.
DR GeneWiki; C1S; -.
DR GenomeRNAi; 716; -.
DR NextBio; 2912; -.
DR PMAP-CutDB; P09871; -.
DR PRO; PR:P09871; -.
DR ArrayExpress; P09871; -.
DR Bgee; P09871; -.
DR Genevestigator; P09871; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.290; -; 2.
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; IPR024175; Pept_S1A_C1r/C1S/mannan-bd.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR018114; Peptidase_S1_AS.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR000436; Sushi_SCR_CCP.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
DR Pfam; PF00431; CUB; 2.
DR Pfam; PF00084; Sushi; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001155; C1r_C1s_MASP; 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; PS00022; EGF_1; FALSE_NEG.
DR PROSITE; PS01186; EGF_2; FALSE_NEG.
DR PROSITE; PS50026; EGF_3; FALSE_NEG.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50923; SUSHI; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; FALSE_NEG.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Complement pathway; Complete proteome;
KW Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Hydroxylation; Immunity; Innate immunity;
KW Metal-binding; Polymorphism; Protease; Reference proteome; Repeat;
KW Serine protease; Signal; Sushi.
FT SIGNAL 1 15
FT CHAIN 16 688 Complement C1s subcomponent.
FT /FTId=PRO_0000027586.
FT CHAIN 16 437 Complement C1s subcomponent heavy chain.
FT /FTId=PRO_0000027587.
FT CHAIN 438 688 Complement C1s subcomponent light chain.
FT /FTId=PRO_0000027588.
FT DOMAIN 16 130 CUB 1.
FT DOMAIN 131 172 EGF-like; calcium-binding.
FT DOMAIN 175 290 CUB 2.
FT DOMAIN 292 356 Sushi 1.
FT DOMAIN 357 423 Sushi 2.
FT DOMAIN 438 680 Peptidase S1.
FT ACT_SITE 475 475 Charge relay system.
FT ACT_SITE 529 529 Charge relay system.
FT ACT_SITE 632 632 Charge relay system.
FT METAL 60 60 Calcium.
FT METAL 68 68 Calcium.
FT METAL 113 113 Calcium.
FT METAL 131 131 Calcium.
FT METAL 132 132 Calcium; via carbonyl oxygen.
FT METAL 134 134 Calcium.
FT METAL 149 149 Calcium.
FT METAL 150 150 Calcium; via carbonyl oxygen.
FT METAL 153 153 Calcium; via carbonyl oxygen.
FT MOD_RES 149 149 (3R)-3-hydroxyasparagine.
FT CARBOHYD 174 174 N-linked (GlcNAc...).
FT CARBOHYD 406 406 N-linked (GlcNAc...).
FT DISULFID 65 83
FT DISULFID 135 147
FT DISULFID 143 156
FT DISULFID 158 171
FT DISULFID 175 202
FT DISULFID 234 251
FT DISULFID 294 341
FT DISULFID 321 354
FT DISULFID 359 403
FT DISULFID 386 421
FT DISULFID 425 549 Interchain (between heavy and light
FT chains).
FT DISULFID 595 618
FT DISULFID 628 659
FT VARIANT 119 119 R -> H (in dbSNP:rs12146727).
FT /FTId=VAR_033643.
FT VARIANT 327 327 V -> L (in dbSNP:rs2239170).
FT /FTId=VAR_033644.
FT VARIANT 383 383 R -> H (in dbSNP:rs20573).
FT /FTId=VAR_014565.
FT CONFLICT 294 294 C -> K (in Ref. 8; AA sequence).
FT CONFLICT 513 513 G -> GG (in Ref. 7).
FT CONFLICT 573 573 T -> A (in Ref. 9; AA sequence).
FT CONFLICT 645 646 TK -> GR (in Ref. 9; AA sequence).
FT STRAND 19 24
FT TURN 26 29
FT STRAND 34 43
FT STRAND 48 58
FT HELIX 63 65
FT STRAND 67 73
FT STRAND 80 82
FT STRAND 84 86
FT STRAND 96 112
FT STRAND 122 131
FT TURN 134 136
FT STRAND 137 140
FT STRAND 143 150
FT STRAND 153 157
FT STRAND 162 164
FT STRAND 171 173
FT STRAND 176 180
FT STRAND 182 188
FT TURN 190 193
FT STRAND 201 207
FT STRAND 212 217
FT HELIX 220 222
FT STRAND 223 225
FT STRAND 235 242
FT STRAND 245 250
FT STRAND 252 254
FT STRAND 259 262
FT STRAND 265 273
FT STRAND 282 291
FT STRAND 300 306
FT STRAND 309 312
FT STRAND 316 321
FT STRAND 325 331
FT STRAND 334 341
FT TURN 348 351
FT STRAND 353 356
FT STRAND 368 370
FT STRAND 381 386
FT TURN 388 390
FT STRAND 391 393
FT STRAND 399 403
FT STRAND 409 411
FT TURN 412 414
FT STRAND 421 423
FT HELIX 446 448
FT STRAND 452 455
FT TURN 456 459
FT STRAND 460 466
FT STRAND 469 472
FT HELIX 474 477
FT STRAND 490 492
FT HELIX 494 499
FT STRAND 505 510
FT HELIX 520 522
FT STRAND 531 537
FT HELIX 555 557
FT STRAND 564 570
FT STRAND 576 578
FT STRAND 583 590
FT HELIX 592 596
FT STRAND 616 620
FT HELIX 627 629
FT STRAND 635 639
FT STRAND 647 655
FT STRAND 661 667
FT HELIX 668 671
FT HELIX 672 681
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
//
ID C1S_HUMAN Reviewed; 688 AA.
AC P09871; D3DUT4; Q9UCU7; Q9UCU8; Q9UCU9; Q9UCV0; Q9UCV1; Q9UCV2;
read moreAC Q9UCV3; Q9UCV4; Q9UCV5; Q9UM14;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 22-JAN-2014, entry version 180.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT complete 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
RT linkage 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-
RT tail 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT (MASP) 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
RT domain 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;
RA Carter P.E., Dunbar B., Fothergill J.E.;
RT "The serine proteinase chain of human complement component C1s.
RT Cyanogen 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
RP AT 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
RT containing 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+)-
RT dependent interactions of human C1s. Location of the iodination
RT 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
RP 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:
RT study by chemical cross-linking and three-dimensional homology
RT modeling.";
RL Biochemistry 34:7311-7321(1995).
RN [14]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME
RP REGULATION.
RX PubMed=11527969; DOI=10.1074/jbc.M105934200;
RA Rossi V., Cseh S., Bally I., Thielens N.M., Jensenius J.C.,
RA Arlaud G.J.;
RT "Substrate specificities of recombinant mannan-binding lectin-
RT associated 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;
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
RT onset multiple autoimmune diseases.";
RL J. Immunol. 166:7612-7616(2001).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-406, AND MASS
RP SPECTROMETRY.
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.,
RA Moore R.J., 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, AND MASS
RP SPECTROMETRY.
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
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [18]
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 [19]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 16-174, CALCIUM-BINDING
RP SITES, AND 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.
RT Insights 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
CC and C1r to form C1, the first component of the classical pathway
CC of the complement system. C1r activates C1s so that it can, in
CC turn, activate C2 and C4.
CC -!- CATALYTIC ACTIVITY: Cleavage of Arg-|-Ala bond in complement
CC component C4 to form C4a and C4b, and Lys(or Arg)-|-Lys bond in
CC complement component C2 to form C2a and C2b: the 'classical'
CC pathway C3 convertase.
CC -!- ENZYME REGULATION: Inhibited by SERPING1.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=12.3 uM for complement component C2 (at 37 degrees Celsius);
CC KM=1.9 uM for complement component C4 (at 37 degrees Celsius);
CC Note=Less efficient than MASP2 in C4 cleavage;
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q,
CC C1r and C1s in the molar ration of 1:2:2. Activated C1s is an
CC disulfide-linked heterodimer of a heavy chain and a light chain.
CC -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-2810045, EBI-2810045;
CC P00736:C1R; NbExp=3; IntAct=EBI-2810045, EBI-3926504;
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC aspartate and asparagine is (R) stereospecific within EGF domains.
CC -!- DISEASE: Complement component C1s deficiency (C1SD) [MIM:613783]:
CC A rare defect resulting in C1 deficiency and impaired activation
CC of the complement classical pathway. C1 deficiency generally leads
CC to severe immune complex disease with features of systemic lupus
CC erythematosus and glomerulonephritis. Note=The disease is caused
CC by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family.
CC -!- SIMILARITY: Contains 2 CUB domains.
CC -!- SIMILARITY: Contains 1 EGF-like domain.
CC -!- SIMILARITY: Contains 1 peptidase S1 domain.
CC -!- SIMILARITY: Contains 2 Sushi (CCP/SCR) domains.
CC -!- WEB RESOURCE: Name=C1Sbase; Note=C1S mutation db;
CC URL="http://bioinf.uta.fi/C1Sbase/";
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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 PIR; A40496; C1HUS.
DR RefSeq; NP_001725.1; NM_001734.3.
DR RefSeq; NP_958850.1; NM_201442.2.
DR RefSeq; XP_005253817.1; XM_005253760.1.
DR RefSeq; XP_005277812.1; XM_005277755.1.
DR UniGene; Hs.458355; -.
DR PDB; 1ELV; X-ray; 1.70 A; A=358-688.
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 PDBsum; 1ELV; -.
DR PDBsum; 1NZI; -.
DR PDBsum; 4J1Y; -.
DR PDBsum; 4LMF; -.
DR PDBsum; 4LOR; -.
DR PDBsum; 4LOS; -.
DR PDBsum; 4LOT; -.
DR ProteinModelPortal; P09871; -.
DR SMR; P09871; 18-684.
DR IntAct; P09871; 8.
DR MINT; MINT-4655918; -.
DR BindingDB; P09871; -.
DR ChEMBL; CHEMBL3913; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00072; Trastuzumab.
DR MEROPS; S01.193; -.
DR PhosphoSite; P09871; -.
DR DMDM; 115205; -.
DR SWISS-2DPAGE; P09871; -.
DR PaxDb; P09871; -.
DR PeptideAtlas; P09871; -.
DR PRIDE; P09871; -.
DR Ensembl; ENST00000328916; ENSP00000328173; ENSG00000182326.
DR Ensembl; ENST00000360817; ENSP00000354057; ENSG00000182326.
DR Ensembl; ENST00000406697; ENSP00000385035; ENSG00000182326.
DR Ensembl; ENST00000594877; ENSP00000471707; ENSG00000269882.
DR Ensembl; ENST00000595575; ENSP00000469947; ENSG00000269882.
DR Ensembl; ENST00000600933; ENSP00000469899; ENSG00000269882.
DR GeneID; 716; -.
DR KEGG; hsa:716; -.
DR UCSC; uc001qsj.3; human.
DR CTD; 716; -.
DR GeneCards; GC12P007096; -.
DR HGNC; HGNC:1247; C1S.
DR HPA; CAB016722; -.
DR HPA; HPA018852; -.
DR MIM; 120580; gene.
DR MIM; 613783; phenotype.
DR neXtProt; NX_P09871; -.
DR Orphanet; 169147; Immunodeficiency due to an early component of complement deficiency.
DR PharmGKB; PA25636; -.
DR eggNOG; COG5640; -.
DR HOVERGEN; HBG000559; -.
DR InParanoid; P09871; -.
DR KO; K01331; -.
DR OMA; PTMYGEI; -.
DR PhylomeDB; P09871; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; C1S; human.
DR EvolutionaryTrace; P09871; -.
DR GeneWiki; C1S; -.
DR GenomeRNAi; 716; -.
DR NextBio; 2912; -.
DR PMAP-CutDB; P09871; -.
DR PRO; PR:P09871; -.
DR ArrayExpress; P09871; -.
DR Bgee; P09871; -.
DR Genevestigator; P09871; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 2.60.120.290; -; 2.
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; IPR024175; Pept_S1A_C1r/C1S/mannan-bd.
DR InterPro; IPR001254; Peptidase_S1.
DR InterPro; IPR018114; Peptidase_S1_AS.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR000436; Sushi_SCR_CCP.
DR InterPro; IPR009003; Trypsin-like_Pept_dom.
DR Pfam; PF00431; CUB; 2.
DR Pfam; PF00084; Sushi; 2.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001155; C1r_C1s_MASP; 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; PS00022; EGF_1; FALSE_NEG.
DR PROSITE; PS01186; EGF_2; FALSE_NEG.
DR PROSITE; PS50026; EGF_3; FALSE_NEG.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS50923; SUSHI; 2.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; FALSE_NEG.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Complement pathway; Complete proteome;
KW Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Glycoprotein; Hydrolase; Hydroxylation; Immunity; Innate immunity;
KW Metal-binding; Polymorphism; Protease; Reference proteome; Repeat;
KW Serine protease; Signal; Sushi.
FT SIGNAL 1 15
FT CHAIN 16 688 Complement C1s subcomponent.
FT /FTId=PRO_0000027586.
FT CHAIN 16 437 Complement C1s subcomponent heavy chain.
FT /FTId=PRO_0000027587.
FT CHAIN 438 688 Complement C1s subcomponent light chain.
FT /FTId=PRO_0000027588.
FT DOMAIN 16 130 CUB 1.
FT DOMAIN 131 172 EGF-like; calcium-binding.
FT DOMAIN 175 290 CUB 2.
FT DOMAIN 292 356 Sushi 1.
FT DOMAIN 357 423 Sushi 2.
FT DOMAIN 438 680 Peptidase S1.
FT ACT_SITE 475 475 Charge relay system.
FT ACT_SITE 529 529 Charge relay system.
FT ACT_SITE 632 632 Charge relay system.
FT METAL 60 60 Calcium.
FT METAL 68 68 Calcium.
FT METAL 113 113 Calcium.
FT METAL 131 131 Calcium.
FT METAL 132 132 Calcium; via carbonyl oxygen.
FT METAL 134 134 Calcium.
FT METAL 149 149 Calcium.
FT METAL 150 150 Calcium; via carbonyl oxygen.
FT METAL 153 153 Calcium; via carbonyl oxygen.
FT MOD_RES 149 149 (3R)-3-hydroxyasparagine.
FT CARBOHYD 174 174 N-linked (GlcNAc...).
FT CARBOHYD 406 406 N-linked (GlcNAc...).
FT DISULFID 65 83
FT DISULFID 135 147
FT DISULFID 143 156
FT DISULFID 158 171
FT DISULFID 175 202
FT DISULFID 234 251
FT DISULFID 294 341
FT DISULFID 321 354
FT DISULFID 359 403
FT DISULFID 386 421
FT DISULFID 425 549 Interchain (between heavy and light
FT chains).
FT DISULFID 595 618
FT DISULFID 628 659
FT VARIANT 119 119 R -> H (in dbSNP:rs12146727).
FT /FTId=VAR_033643.
FT VARIANT 327 327 V -> L (in dbSNP:rs2239170).
FT /FTId=VAR_033644.
FT VARIANT 383 383 R -> H (in dbSNP:rs20573).
FT /FTId=VAR_014565.
FT CONFLICT 294 294 C -> K (in Ref. 8; AA sequence).
FT CONFLICT 513 513 G -> GG (in Ref. 7).
FT CONFLICT 573 573 T -> A (in Ref. 9; AA sequence).
FT CONFLICT 645 646 TK -> GR (in Ref. 9; AA sequence).
FT STRAND 19 24
FT TURN 26 29
FT STRAND 34 43
FT STRAND 48 58
FT HELIX 63 65
FT STRAND 67 73
FT STRAND 80 82
FT STRAND 84 86
FT STRAND 96 112
FT STRAND 122 131
FT TURN 134 136
FT STRAND 137 140
FT STRAND 143 150
FT STRAND 153 157
FT STRAND 162 164
FT STRAND 171 173
FT STRAND 176 180
FT STRAND 182 188
FT TURN 190 193
FT STRAND 201 207
FT STRAND 212 217
FT HELIX 220 222
FT STRAND 223 225
FT STRAND 235 242
FT STRAND 245 250
FT STRAND 252 254
FT STRAND 259 262
FT STRAND 265 273
FT STRAND 282 291
FT STRAND 300 306
FT STRAND 309 312
FT STRAND 316 321
FT STRAND 325 331
FT STRAND 334 341
FT TURN 348 351
FT STRAND 353 356
FT STRAND 368 370
FT STRAND 381 386
FT TURN 388 390
FT STRAND 391 393
FT STRAND 399 403
FT STRAND 409 411
FT TURN 412 414
FT STRAND 421 423
FT HELIX 446 448
FT STRAND 452 455
FT TURN 456 459
FT STRAND 460 466
FT STRAND 469 472
FT HELIX 474 477
FT STRAND 490 492
FT HELIX 494 499
FT STRAND 505 510
FT HELIX 520 522
FT STRAND 531 537
FT HELIX 555 557
FT STRAND 564 570
FT STRAND 576 578
FT STRAND 583 590
FT HELIX 592 596
FT STRAND 616 620
FT HELIX 627 629
FT STRAND 635 639
FT STRAND 647 655
FT STRAND 661 667
FT HELIX 668 671
FT HELIX 672 681
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
//
MIM
120580
*RECORD*
*FIELD* NO
120580
*FIELD* TI
*120580 COMPLEMENT COMPONENT 1, s SUBCOMPONENT; C1S
;;COMPLEMENT COMPONENT C1s
*FIELD* TX
read more
CLONING
MacKinnon et al. (1987) derived the complete amino acid sequence of C1s
from molecular cloning of cDNA. Tosi et al. (1987) presented the
complete cDNA sequence of C1s. Kusumoto et al. (1988) found that the
amino acid sequence of C1s was 40.5% identical to that of C1r (216950),
with excellent matches of tentative disulfide bond locations conserving
the overall domain structure of C1r.
MAPPING
By means of a cDNA in somatic cell hybrids, Cohen-Haguenauer et al.
(1986) assigned the C1S and C1R (216950) genes to chromosome 12.
Leppert et al. (1987) found a maximum lod score of 5.99 at theta = 0.038
for linkage between C1S and one of the PRP loci (see 168710); the
maximum lod score between C1R and another PRP locus was 4.21 at theta =
0.001. Although C1r and C1s are structurally and functionally similar,
with a significant degree of sequence homology suggesting origin by gene
duplication, cDNA probes for human C1r and C1s do not cross-hybridize
even at mild stringency conditions and are therefore gene-specific.
Using a panel of human-rodent cell hybrids, Van Cong et al. (1988)
independently assigned the C1r and C1s genes to chromosome 12. In situ
hybridization confirmed these assignments and localized the genes to
12p13.
By hybridization of C1r and C1s probes to restriction endonuclease
fragments of genomic DNA, Tosi et al. (1987) demonstrated close physical
linkage of the genes. This finding was consistent with their evolution
through tandem gene duplication and was also consistent with the
previously observed combined hereditary deficiencies of C1r and C1s (see
216950). Their coordinate expression may depend on the close linkage.
The 2 genes lie in a DNA stretch not longer than 50 kb.
By DNA blotting and sequencing analyses of genomic DNA and of an
isolated genomic DNA clone, Kusumoto et al. (1988) showed that the C1r
and C1s genes are closely located in a 'tail-to-tail' arrangement at a
distance of about 9.5 kb.
MOLECULAR GENETICS
Inoue et al. (1998) reported a patient with selective C1s deficiency
(613783) resulting from a homozygous mutation in the C1S gene
(120580.0001).
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) detected selective C1S deficiency (613783) resulting from
a homozygous nonsense mutation in exon 12 of the C1S gene (120580.0002).
*FIELD* AV
.0001
C1s DEFICIENCY
C1S, 4-BP DEL, NT1087
In a patient with systemic lupus erythematosus-like syndrome and chronic
glomerulonephritis, Inoue et al. (1998) reported the molecular basis of
selective C1s deficiency (613783). No C1s protein was detectable by
immunoblot. By Northern blot and RT-PCR analysis, C1s mRNA was of
appropriate size, but only 10% of the level detected in HCS2/8, a human
chondrosarcoma cell line. Levels of beta-actin and C1r mRNA were similar
to levels detected in HCS2/8. The patient was homozygous for a 4-bp
deletion in exon 10 of the C1S gene, 1087-1090delTTTG. This deletion
resulted in a premature termination codon 94 bp downstream.
.0002
C1s DEFICIENCY
C1S, ARG534TER
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) determined that an absence of plasma C1s (613783)
accounted for a lack of classic complement (CH50) pathway activity.
Microsatellite and sequence analyses revealed a C-to-T transition in
codon 534 in exon 12 of the C1S gene, resulting in an arg-to-ter
substitution and premature termination. DNA analysis indicated that both
parents were heterozygous for the mutation. Restriction enzyme analysis
showed that the propositus was homozygous for the mutation, while a
paternal grandmother, maternal grandfather, and aunts on both sides of
the family were heterozygous. The mutation was not detected in systemic
lupus erythematosus (152700) patients or unrelated Caucasian controls,
including some from the same geographic region. At age 5, the child was
alive and well while receiving immunosuppressive drugs daily and
penicillin.
*FIELD* RF
1. Cohen-Haguenauer, O.; Serero, S.; Tosi, M.; Van Cong, N.; Stubnicer,
A.-C.; de Tand, M.-F.; Meo, T.; Frezal, J.: Chromosomal assignment
of human C1R, C1S genes on chromosome 12 and C1 inhibitor gene on
chromosome 11. (Abstract) 7th Int. Cong. Hum. Genet., Berlin 617
only, 1986.
2. Dragon-Durey, M.-A.; Quartier, P.; Fremeaux-Bacchi, V.; Blouin,
J.; de Barace, C.; Prieur, A.-M.; Weiss, L.; Fridman, W.-H.: Molecular
basis of a selective C1s deficiency associated with early onset multiple
autoimmune diseases. J. Immun. 166: 7612-7616, 2001.
3. Inoue, N.; Saito, T.; Masuda, R.; Suzuki, Y.; Ohtomi, M.; Sakiyama,
H.: Selective complement C1s deficiency caused by homozygous four-base
deletion in the C1s gene. Hum. Genet. 103: 415-418, 1998.
4. Kusumoto, H.; Hirosawa, S.; Salier, J. P.; Hagen, F. S.; Kurachi,
K.: Human genes for complement components C1r and C1s in a close
tail-to-tail arrangement. Proc. Nat. Acad. Sci. 85: 7307-7311, 1988.
5. Leppert, M.; Ferrell, R.; Kamboh, M. I.; Beasley, J.; O'Connell,
P.; Lathrop, M.; Lalouel, J. M.; White, R.: Linkage of the polymorphic
protein markers F13B, C1S, C1R, and blood group antigen Kidd in CEPH
reference families. (Abstract) Cytogenet. Cell Genet. 46: 647 only,
1987.
6. MacKinnon, C. M.; Carter, P. E.; Smyth, S. J.; Dunbar, B.; Fothergill,
J. E.: Molecular cloning of cDNA for human complement component C1s:
the complete amino acid sequence. Europ. J. Biochem. 169: 547-553,
1987.
7. Tosi, M.; Duponchel, C.; Meo, T.; Julier, C.: Complete cDNA sequence
of human complement C1s and close physical linkage of the homologous
genes C1s and C1r. Biochemistry 26: 8516-8524, 1987.
8. Van Cong, N.; Tosi, M.; Gross, M. S.; Cohen-Haguenauer, O.; Jegou-Foubert,
C.; de Tand, M. F.; Meo, T.; Frezal, J.: Assignment of the complement
serine protease genes C1r and C1s to chromosome 12 region 12p13. Hum.
Genet. 78: 363-368, 1988.
*FIELD* CN
Paul J. Converse - updated: 10/17/2001
Ada Hamosh - updated: 3/9/1999
*FIELD* CD
Victor A. McKusick: 10/16/1986
*FIELD* ED
carol: 03/03/2011
carol: 3/2/2011
carol: 3/1/2011
joanna: 3/17/2004
mgross: 10/17/2001
alopez: 3/12/1999
alopez: 3/9/1999
dkim: 6/30/1998
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 10/17/1988
root: 10/12/1988
root: 4/29/1988
*RECORD*
*FIELD* NO
120580
*FIELD* TI
*120580 COMPLEMENT COMPONENT 1, s SUBCOMPONENT; C1S
;;COMPLEMENT COMPONENT C1s
*FIELD* TX
read more
CLONING
MacKinnon et al. (1987) derived the complete amino acid sequence of C1s
from molecular cloning of cDNA. Tosi et al. (1987) presented the
complete cDNA sequence of C1s. Kusumoto et al. (1988) found that the
amino acid sequence of C1s was 40.5% identical to that of C1r (216950),
with excellent matches of tentative disulfide bond locations conserving
the overall domain structure of C1r.
MAPPING
By means of a cDNA in somatic cell hybrids, Cohen-Haguenauer et al.
(1986) assigned the C1S and C1R (216950) genes to chromosome 12.
Leppert et al. (1987) found a maximum lod score of 5.99 at theta = 0.038
for linkage between C1S and one of the PRP loci (see 168710); the
maximum lod score between C1R and another PRP locus was 4.21 at theta =
0.001. Although C1r and C1s are structurally and functionally similar,
with a significant degree of sequence homology suggesting origin by gene
duplication, cDNA probes for human C1r and C1s do not cross-hybridize
even at mild stringency conditions and are therefore gene-specific.
Using a panel of human-rodent cell hybrids, Van Cong et al. (1988)
independently assigned the C1r and C1s genes to chromosome 12. In situ
hybridization confirmed these assignments and localized the genes to
12p13.
By hybridization of C1r and C1s probes to restriction endonuclease
fragments of genomic DNA, Tosi et al. (1987) demonstrated close physical
linkage of the genes. This finding was consistent with their evolution
through tandem gene duplication and was also consistent with the
previously observed combined hereditary deficiencies of C1r and C1s (see
216950). Their coordinate expression may depend on the close linkage.
The 2 genes lie in a DNA stretch not longer than 50 kb.
By DNA blotting and sequencing analyses of genomic DNA and of an
isolated genomic DNA clone, Kusumoto et al. (1988) showed that the C1r
and C1s genes are closely located in a 'tail-to-tail' arrangement at a
distance of about 9.5 kb.
MOLECULAR GENETICS
Inoue et al. (1998) reported a patient with selective C1s deficiency
(613783) resulting from a homozygous mutation in the C1S gene
(120580.0001).
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) detected selective C1S deficiency (613783) resulting from
a homozygous nonsense mutation in exon 12 of the C1S gene (120580.0002).
*FIELD* AV
.0001
C1s DEFICIENCY
C1S, 4-BP DEL, NT1087
In a patient with systemic lupus erythematosus-like syndrome and chronic
glomerulonephritis, Inoue et al. (1998) reported the molecular basis of
selective C1s deficiency (613783). No C1s protein was detectable by
immunoblot. By Northern blot and RT-PCR analysis, C1s mRNA was of
appropriate size, but only 10% of the level detected in HCS2/8, a human
chondrosarcoma cell line. Levels of beta-actin and C1r mRNA were similar
to levels detected in HCS2/8. The patient was homozygous for a 4-bp
deletion in exon 10 of the C1S gene, 1087-1090delTTTG. This deletion
resulted in a premature termination codon 94 bp downstream.
.0002
C1s DEFICIENCY
C1S, ARG534TER
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) determined that an absence of plasma C1s (613783)
accounted for a lack of classic complement (CH50) pathway activity.
Microsatellite and sequence analyses revealed a C-to-T transition in
codon 534 in exon 12 of the C1S gene, resulting in an arg-to-ter
substitution and premature termination. DNA analysis indicated that both
parents were heterozygous for the mutation. Restriction enzyme analysis
showed that the propositus was homozygous for the mutation, while a
paternal grandmother, maternal grandfather, and aunts on both sides of
the family were heterozygous. The mutation was not detected in systemic
lupus erythematosus (152700) patients or unrelated Caucasian controls,
including some from the same geographic region. At age 5, the child was
alive and well while receiving immunosuppressive drugs daily and
penicillin.
*FIELD* RF
1. Cohen-Haguenauer, O.; Serero, S.; Tosi, M.; Van Cong, N.; Stubnicer,
A.-C.; de Tand, M.-F.; Meo, T.; Frezal, J.: Chromosomal assignment
of human C1R, C1S genes on chromosome 12 and C1 inhibitor gene on
chromosome 11. (Abstract) 7th Int. Cong. Hum. Genet., Berlin 617
only, 1986.
2. Dragon-Durey, M.-A.; Quartier, P.; Fremeaux-Bacchi, V.; Blouin,
J.; de Barace, C.; Prieur, A.-M.; Weiss, L.; Fridman, W.-H.: Molecular
basis of a selective C1s deficiency associated with early onset multiple
autoimmune diseases. J. Immun. 166: 7612-7616, 2001.
3. Inoue, N.; Saito, T.; Masuda, R.; Suzuki, Y.; Ohtomi, M.; Sakiyama,
H.: Selective complement C1s deficiency caused by homozygous four-base
deletion in the C1s gene. Hum. Genet. 103: 415-418, 1998.
4. Kusumoto, H.; Hirosawa, S.; Salier, J. P.; Hagen, F. S.; Kurachi,
K.: Human genes for complement components C1r and C1s in a close
tail-to-tail arrangement. Proc. Nat. Acad. Sci. 85: 7307-7311, 1988.
5. Leppert, M.; Ferrell, R.; Kamboh, M. I.; Beasley, J.; O'Connell,
P.; Lathrop, M.; Lalouel, J. M.; White, R.: Linkage of the polymorphic
protein markers F13B, C1S, C1R, and blood group antigen Kidd in CEPH
reference families. (Abstract) Cytogenet. Cell Genet. 46: 647 only,
1987.
6. MacKinnon, C. M.; Carter, P. E.; Smyth, S. J.; Dunbar, B.; Fothergill,
J. E.: Molecular cloning of cDNA for human complement component C1s:
the complete amino acid sequence. Europ. J. Biochem. 169: 547-553,
1987.
7. Tosi, M.; Duponchel, C.; Meo, T.; Julier, C.: Complete cDNA sequence
of human complement C1s and close physical linkage of the homologous
genes C1s and C1r. Biochemistry 26: 8516-8524, 1987.
8. Van Cong, N.; Tosi, M.; Gross, M. S.; Cohen-Haguenauer, O.; Jegou-Foubert,
C.; de Tand, M. F.; Meo, T.; Frezal, J.: Assignment of the complement
serine protease genes C1r and C1s to chromosome 12 region 12p13. Hum.
Genet. 78: 363-368, 1988.
*FIELD* CN
Paul J. Converse - updated: 10/17/2001
Ada Hamosh - updated: 3/9/1999
*FIELD* CD
Victor A. McKusick: 10/16/1986
*FIELD* ED
carol: 03/03/2011
carol: 3/2/2011
carol: 3/1/2011
joanna: 3/17/2004
mgross: 10/17/2001
alopez: 3/12/1999
alopez: 3/9/1999
dkim: 6/30/1998
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/26/1989
root: 10/17/1988
root: 10/12/1988
root: 4/29/1988
MIM
613783
*RECORD*
*FIELD* NO
613783
*FIELD* TI
#613783 COMPLEMENT COMPONENT C1s DEFICIENCY; C1SD
;;C1s DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because selective complement
read morecomponent C1s deficiency can be caused by homozygous mutation in the C1S
gene (120580) on chromosome 12p13.
CLINICAL FEATURES
Inoue et al. (1998) reported a patient with a systemic lupus
erythematosus-like syndrome and chronic glomerulonephritis in whom no
C1s protein was detectable by immunoblot. By Northern blot and RT-PCR
analysis, C1s mRNA was of appropriate size, but only 10% of the level
detected in HCS2/8, a human chondrosarcoma cell line. Levels of
beta-actin and C1r (216950) mRNA were similar to levels detected in
HCS2/8.
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) determined that an absence of plasma C1S accounted for a
lack of classic complement (CH50) pathway activity. At age 5, the child
was alive and well while receiving immunosuppressive drugs daily and
penicillin.
MOLECULAR GENETICS
Inoue et al. (1998) reported a patient with selective C1s deficiency
resulting from a homozygous mutation in the C1S gene (120580.0001).
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) detected selective C1S deficiency resulting from a
nonsense mutation in exon 12 of the C1S gene (120580.0002). Restriction
enzyme analysis showed that the propositus was homozygous for the
mutation, while a paternal grandmother, maternal grandfather, and aunts
on both sides of the family were heterozygous. The mutation was not
detected in systemic lupus erythematosus (152700) patients or unrelated
Caucasian controls, including some from the same geographic region.
*FIELD* RF
1. Dragon-Durey, M.-A.; Quartier, P.; Fremeaux-Bacchi, V.; Blouin,
J.; de Barace, C.; Prieur, A.-M.; Weiss, L.; Fridman, W.-H.: Molecular
basis of a selective C1s deficiency associated with early onset multiple
autoimmune diseases. J. Immun. 166: 7612-7616, 2001.
2. Inoue, N.; Saito, T.; Masuda, R.; Suzuki, Y.; Ohtomi, M.; Sakiyama,
H.: Selective complement C1s deficiency caused by homozygous four-base
deletion in the C1s gene. Hum. Genet. 103: 415-418, 1998.
*FIELD* CD
Carol A. Bocchini: 3/1/2011
*FIELD* ED
carol: 04/22/2011
carol: 3/1/2011
*RECORD*
*FIELD* NO
613783
*FIELD* TI
#613783 COMPLEMENT COMPONENT C1s DEFICIENCY; C1SD
;;C1s DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because selective complement
read morecomponent C1s deficiency can be caused by homozygous mutation in the C1S
gene (120580) on chromosome 12p13.
CLINICAL FEATURES
Inoue et al. (1998) reported a patient with a systemic lupus
erythematosus-like syndrome and chronic glomerulonephritis in whom no
C1s protein was detectable by immunoblot. By Northern blot and RT-PCR
analysis, C1s mRNA was of appropriate size, but only 10% of the level
detected in HCS2/8, a human chondrosarcoma cell line. Levels of
beta-actin and C1r (216950) mRNA were similar to levels detected in
HCS2/8.
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) determined that an absence of plasma C1S accounted for a
lack of classic complement (CH50) pathway activity. At age 5, the child
was alive and well while receiving immunosuppressive drugs daily and
penicillin.
MOLECULAR GENETICS
Inoue et al. (1998) reported a patient with selective C1s deficiency
resulting from a homozygous mutation in the C1S gene (120580.0001).
In a 27-month-old girl with multiple autoimmune diseases, Dragon-Durey
et al. (2001) detected selective C1S deficiency resulting from a
nonsense mutation in exon 12 of the C1S gene (120580.0002). Restriction
enzyme analysis showed that the propositus was homozygous for the
mutation, while a paternal grandmother, maternal grandfather, and aunts
on both sides of the family were heterozygous. The mutation was not
detected in systemic lupus erythematosus (152700) patients or unrelated
Caucasian controls, including some from the same geographic region.
*FIELD* RF
1. Dragon-Durey, M.-A.; Quartier, P.; Fremeaux-Bacchi, V.; Blouin,
J.; de Barace, C.; Prieur, A.-M.; Weiss, L.; Fridman, W.-H.: Molecular
basis of a selective C1s deficiency associated with early onset multiple
autoimmune diseases. J. Immun. 166: 7612-7616, 2001.
2. Inoue, N.; Saito, T.; Masuda, R.; Suzuki, Y.; Ohtomi, M.; Sakiyama,
H.: Selective complement C1s deficiency caused by homozygous four-base
deletion in the C1s gene. Hum. Genet. 103: 415-418, 1998.
*FIELD* CD
Carol A. Bocchini: 3/1/2011
*FIELD* ED
carol: 04/22/2011
carol: 3/1/2011