C1R_HUMAN
ID C1R_HUMAN Reviewed; 705 AA.
AC P00736; A6NJQ8; Q68D77; Q8J012;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 16-DEC-2008, sequence version 2.
DT 03-AUG-2022, entry version 243.
DE RecName: Full=Complement C1r subcomponent;
DE EC=3.4.21.41;
DE AltName: Full=Complement component 1 subcomponent r;
DE Contains:
DE RecName: Full=Complement C1r subcomponent heavy chain;
DE Contains:
DE RecName: Full=Complement C1r subcomponent light chain;
DE Flags: Precursor;
GN Name=C1R;
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], AND VARIANT ARG-186.
RX PubMed=3021205; DOI=10.1021/bi00365a020;
RA Leytus S.P., Kurachi K., Sakariassen K.S., Davie E.W.;
RT "Nucleotide sequence of the cDNA coding for human complement C1r.";
RL Biochemistry 25:4855-4863(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS LEU-152 AND ARG-186.
RX PubMed=3030286; DOI=10.1042/bj2400783;
RA Journet A., Tosi M.;
RT "Cloning and sequencing of full-length cDNA encoding the precursor of human
RT complement component C1r.";
RL Biochem. J. 240:783-787(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-131; LEU-152; TYR-163;
RP LYS-184; ARG-186 AND ARG-261.
RX PubMed=12914573; DOI=10.1046/j.1469-1809.2003.00019.x;
RA Nakagawa M., Yuasa I., Irizawa Y., Umetsu K.;
RT "The human complement component C1R gene: the exon-intron structure and the
RT molecular basis of allelic diversity.";
RL Ann. Hum. Genet. 67:207-215(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LEU-152 AND ARG-186.
RC TISSUE=Skin;
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 [7]
RP PROTEIN SEQUENCE OF 18-463.
RX PubMed=3036070; DOI=10.1042/bj2410711;
RA Arlaud G.J., Willis A.C., Gagnon J.;
RT "Complete amino acid sequence of the A chain of human complement-classical-
RT pathway enzyme C1r.";
RL Biochem. J. 241:711-720(1987).
RN [8]
RP PROTEIN SEQUENCE OF 464-705.
RX PubMed=6303394; DOI=10.1021/bi00277a003;
RA Arlaud G.J., Gagnon J.;
RT "Complete amino acid sequence of the catalytic chain of human complement
RT subcomponent C1-r.";
RL Biochemistry 22:1758-1764(1983).
RN [9]
RP PROTEIN SEQUENCE OF 152-186, AND HYDROXYLATION AT ASN-167.
RX PubMed=2820791; DOI=10.1016/0014-5793(87)80205-3;
RA Arlaud G.J., van Dorsselaer A., Bell A., Mancini M., Aude C., Gagnon J.;
RT "Identification of erythro-beta-hydroxyasparagine in the EGF-like domain of
RT human C1r.";
RL FEBS Lett. 222:129-134(1987).
RN [10]
RP PROTEIN SEQUENCE OF 133-137; 187-211 AND 609-613, AND PHOSPHORYLATION AT
RP SER-206 BY CK2.
RX PubMed=8635594; DOI=10.1016/0014-5793(96)00403-6;
RA Pelloux S., Thielens N.M., Hudry-Clergeon G., Petillot Y., Filhol O.,
RA Arlaud G.J.;
RT "Identification of a cryptic protein kinase CK2 phosphorylation site in
RT human complement protease Clr, and its use to probe intramolecular
RT interaction.";
RL FEBS Lett. 386:15-20(1996).
RN [11]
RP POSSIBLE INVOLVEMENT IN C1R DEFICIENCY.
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 [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-125; ASN-221 AND ASN-514.
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 [13]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-514.
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 [14]
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 [15]
RP SUBCELLULAR LOCATION, INVOLVEMENT IN EDSPD1, VARIANTS EDSPD1 ASP-50;
RP GLY-290; ASP-297; PRO-300; PRO-301; CYS-302; 306-ILE--CYS-309 DELINS
RP ARG-ARG; TRP-309; ARG-338; PHE-358; CYS-364; TRP-371; 401-ARG--TYR-405
RP DELINS HIS-VAL-ILE AND ARG-435, AND CHARACTERIZATION OF VARIANTS EDSPD1
RP ASP-50; TRP-309 AND TRP-371.
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 [16]
RP STRUCTURE BY NMR OF 140-192.
RX PubMed=9477945; DOI=10.1021/bi971851v;
RA Bersch B., Hernandez J.-F., Marion D., Arlaud G.J.;
RT "Solution structure of the epidermal growth factor (EGF)-like module of
RT human complement protease C1r, an atypical member of the EGF family.";
RL Biochemistry 37:1204-1214(1998).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 307-702.
RX PubMed=11823416; DOI=10.1093/emboj/21.3.231;
RA Budayova-Spano M., Lacroix M., Thielens N.M., Arlaud G.J.,
RA Fontecilla-Camps J.-C., Gaboriaud C.;
RT "The crystal structure of the zymogen catalytic domain of complement
RT protease C1r reveals that a disruptive mechanical stress is required to
RT trigger activation of the C1 complex.";
RL EMBO J. 21:231-239(2002).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 375-702.
RX PubMed=12429092; DOI=10.1016/s0969-2126(02)00881-x;
RA Budayova-Spano M., Grabarse W., Thielens N.M., Hillen H., Lacroix M.,
RA Schmidt M., Fontecilla-Camps J.-C., Arlaud G.J., Gaboriaud C.;
RT "Monomeric structures of the zymogen and active catalytic domain of
RT complement protease c1r: further insights into the c1 activation
RT mechanism.";
RL Structure 10:1509-1519(2002).
RN [19]
RP VARIANT LEU-152.
RX PubMed=8162045; DOI=10.1093/hmg/3.1.217-a;
RA Nothen M.M., Dewald G.;
RT "A common amino acid polymorphism in complement component C1R.";
RL Hum. Mol. Genet. 3:217-217(1994).
RN [20]
RP VARIANTS LYS-184 AND ARG-261, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22028381; DOI=10.1093/jmcb/mjr024;
RA Su Z.D., Sun L., Yu D.X., Li R.X., Li H.X., Yu Z.J., Sheng Q.H., Lin X.,
RA Zeng R., Wu J.R.;
RT "Quantitative detection of single amino acid polymorphisms by targeted
RT proteomics.";
RL J. Mol. Cell Biol. 3:309-315(2011).
CC -!- FUNCTION: C1r B chain is a serine protease that combines with C1q and
CC C1s to form C1, the first component of the classical pathway of the
CC complement system.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Lys(or Arg)-|-Ile bond in complement
CC subcomponent C1s to form the active form of C1s (EC 3.4.21.42).;
CC EC=3.4.21.41;
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, C1r and
CC C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains,
CC each of which is activated by cleavage into two chains, A and B,
CC connected by disulfide bonds.
CC -!- INTERACTION:
CC P00736; P00736: C1R; NbExp=2; IntAct=EBI-3926504, EBI-3926504;
CC P00736; P09871: C1S; NbExp=6; IntAct=EBI-3926504, EBI-2810045;
CC P00736; P05155: SERPING1; NbExp=2; IntAct=EBI-3926504, EBI-1223454;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27745832}.
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:2820791}.
CC -!- POLYMORPHISM: Complement component C1r deficiency [MIM:216950] leads to
CC the failure of the classical complement system activation pathway (C1
CC deficiency). Individuals with C1 deficiency are highly susceptible to
CC infections by microorganisms and have greater risk in developing
CC autoimmune diseases such as systemic lupus erythematosus (SLE).
CC {ECO:0000269|PubMed:2831944}.
CC -!- DISEASE: Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1)
CC [MIM:130080]: 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. EDSPD1 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. EDSPD1
CC inheritance is autosomal dominant. {ECO:0000269|PubMed:27745832}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; M14058; AAA51851.1; -; mRNA.
DR EMBL; X04701; CAA28407.1; -; mRNA.
DR EMBL; AB083037; BAC19850.2; -; Genomic_DNA.
DR EMBL; AC094008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140077; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR749540; CAH18343.1; -; mRNA.
DR EMBL; BC035220; AAH35220.1; -; mRNA.
DR CCDS; CCDS81658.1; -.
DR PIR; A24170; C1HURB.
DR RefSeq; NP_001724.3; NM_001733.4.
DR PDB; 1APQ; NMR; -; A=140-192.
DR PDB; 1GPZ; X-ray; 2.90 A; A/B=307-705.
DR PDB; 1MD7; X-ray; 3.20 A; A=375-702.
DR PDB; 1MD8; X-ray; 2.80 A; A=375-703.
DR PDB; 2QY0; X-ray; 2.60 A; A/C=309-463, B/D=464-705.
DR PDB; 6F1C; X-ray; 4.20 A; A/C=18-308.
DR PDB; 6F1D; X-ray; 1.95 A; A=191-307.
DR PDB; 6F1H; X-ray; 4.50 A; A/C=18-308.
DR PDB; 6F39; X-ray; 5.80 A; A/B=22-306.
DR PDBsum; 1APQ; -.
DR PDBsum; 1GPZ; -.
DR PDBsum; 1MD7; -.
DR PDBsum; 1MD8; -.
DR PDBsum; 2QY0; -.
DR PDBsum; 6F1C; -.
DR PDBsum; 6F1D; -.
DR PDBsum; 6F1H; -.
DR PDBsum; 6F39; -.
DR AlphaFoldDB; P00736; -.
DR SASBDB; P00736; -.
DR SMR; P00736; -.
DR BioGRID; 107176; 13.
DR ComplexPortal; CPX-1920; Complement C1 complex.
DR IntAct; P00736; 11.
DR MINT; P00736; -.
DR STRING; 9606.ENSP00000438615; -.
DR BindingDB; P00736; -.
DR ChEMBL; CHEMBL4611; -.
DR DrugBank; DB09228; Conestat alfa.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB12831; Gabexate.
DR DrugBank; DB06404; Human C1-esterase inhibitor.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR DrugCentral; P00736; -.
DR GuidetoPHARMACOLOGY; 2334; -.
DR MEROPS; S01.192; -.
DR GlyConnect; 713; 17 N-Linked glycans (3 sites).
DR GlyGen; P00736; 4 sites, 17 N-linked glycans (3 sites).
DR iPTMnet; P00736; -.
DR PhosphoSitePlus; P00736; -.
DR BioMuta; C1R; -.
DR DMDM; 218511956; -.
DR EPD; P00736; -.
DR jPOST; P00736; -.
DR MassIVE; P00736; -.
DR PeptideAtlas; P00736; -.
DR PRIDE; P00736; -.
DR ProteomicsDB; 51270; -.
DR DNASU; 715; -.
DR GeneID; 715; -.
DR KEGG; hsa:715; -.
DR UCSC; uc031ysf.2; human.
DR CTD; 715; -.
DR DisGeNET; 715; -.
DR GeneCards; C1R; -.
DR GeneReviews; C1R; -.
DR HGNC; HGNC:1246; C1R.
DR MalaCards; C1R; -.
DR MIM; 130080; phenotype.
DR MIM; 216950; phenotype.
DR MIM; 613785; gene.
DR neXtProt; NX_P00736; -.
DR Orphanet; 300345; Autosomal systemic lupus erythematosus.
DR Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency.
DR Orphanet; 75392; Periodontal Ehlers-Danlos syndrome.
DR PharmGKB; PA25635; -.
DR eggNOG; KOG3627; Eukaryota.
DR InParanoid; P00736; -.
DR OrthoDB; 156878at2759; -.
DR PhylomeDB; P00736; -.
DR TreeFam; TF330373; -.
DR BRENDA; 3.4.21.41; 2681.
DR PathwayCommons; P00736; -.
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; P00736; -.
DR SignaLink; P00736; -.
DR SIGNOR; P00736; -.
DR BioGRID-ORCS; 715; 5 hits in 207 CRISPR screens.
DR ChiTaRS; C1R; human.
DR EvolutionaryTrace; P00736; -.
DR GeneWiki; C1R_(gene); -.
DR GenomeRNAi; 715; -.
DR Pharos; P00736; Tclin.
DR PRO; PR:P00736; -.
DR Proteomes; UP000005640; Unplaced.
DR RNAct; P00736; protein.
DR Genevisible; P00736; HS.
DR GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR GO; GO:0005602; C:complement component C1 complex; IC:ComplexPortal.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:CAFA.
DR GO; GO:0005509; F:calcium ion binding; IDA:CAFA.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004252; F:serine-type endopeptidase activity; EXP:Reactome.
DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031638; P:zymogen activation; IDA:CAFA.
DR CDD; cd00033; CCP; 2.
DR CDD; cd00041; CUB; 2.
DR CDD; cd00190; Tryp_SPc; 1.
DR DisProt; DP00621; -.
DR Gene3D; 2.40.10.10; -; 3.
DR Gene3D; 2.60.120.290; -; 2.
DR InterPro; IPR035707; Complement_C1r.
DR InterPro; IPR000859; CUB_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
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:SF25; PTHR24255:SF25; 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; SM00181; EGF; 1.
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; PS01186; EGF_2; 1.
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; Complement pathway; Direct protein sequencing;
KW Disease variant; Disulfide bond; EGF-like domain; Ehlers-Danlos syndrome;
KW Glycoprotein; Hydrolase; Hydroxylation; Immunity; Innate immunity;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Secreted;
KW Serine protease; Signal; Sushi.
FT SIGNAL 1..17
FT /evidence="ECO:0000269|PubMed:3036070"
FT CHAIN 18..705
FT /note="Complement C1r subcomponent"
FT /id="PRO_0000027577"
FT CHAIN 18..463
FT /note="Complement C1r subcomponent heavy chain"
FT /id="PRO_0000027578"
FT CHAIN 464..705
FT /note="Complement C1r subcomponent light chain"
FT /id="PRO_0000027579"
FT DOMAIN 18..141
FT /note="CUB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 142..190
FT /note="EGF-like; calcium-binding"
FT /evidence="ECO:0000255"
FT DOMAIN 193..305
FT /note="CUB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 307..373
FT /note="Sushi 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 374..449
FT /note="Sushi 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 464..702
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 502
FT /note="Charge relay system"
FT ACT_SITE 557
FT /note="Charge relay system"
FT ACT_SITE 654
FT /note="Charge relay system"
FT MOD_RES 167
FT /note="(3R)-3-hydroxyasparagine"
FT /evidence="ECO:0000269|PubMed:2820791"
FT MOD_RES 206
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000269|PubMed:8635594"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 581
FT /note="N-linked (GlcNAc...) asparagine"
FT DISULFID 71..89
FT /evidence="ECO:0000305"
FT DISULFID 146..165
FT DISULFID 161..174
FT DISULFID 176..189
FT DISULFID 193..220
FT /evidence="ECO:0000305"
FT DISULFID 250..268
FT /evidence="ECO:0000305"
FT DISULFID 309..358
FT DISULFID 338..371
FT DISULFID 376..429
FT DISULFID 406..447
FT DISULFID 451..577
FT /note="Interchain (between heavy and light chains)"
FT DISULFID 620..639
FT DISULFID 650..680
FT VARIANT 50
FT /note="V -> D (in EDSPD1; requires 2 nucleotide
FT substitutions; the mutant is not secreted but retained
FT intracellularly)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077106"
FT VARIANT 131
FT /note="Y -> H (in dbSNP:rs1278295523)"
FT /evidence="ECO:0000269|PubMed:12914573"
FT /id="VAR_018667"
FT VARIANT 152
FT /note="S -> L (in dbSNP:rs1801046)"
FT /evidence="ECO:0000269|PubMed:12914573,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:3030286,
FT ECO:0000269|PubMed:8162045"
FT /id="VAR_016103"
FT VARIANT 163
FT /note="H -> Y (in dbSNP:rs144141261)"
FT /evidence="ECO:0000269|PubMed:12914573"
FT /id="VAR_018668"
FT VARIANT 184
FT /note="E -> K (confirmed at protein level;
FT dbSNP:rs1126605)"
FT /evidence="ECO:0000269|PubMed:12914573,
FT ECO:0000269|PubMed:22028381"
FT /id="VAR_018669"
FT VARIANT 186
FT /note="T -> R (in dbSNP:rs4519167)"
FT /evidence="ECO:0000269|PubMed:12914573,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:3021205,
FT ECO:0000269|PubMed:3030286"
FT /id="VAR_047933"
FT VARIANT 261
FT /note="G -> R (confirmed at protein level;
FT dbSNP:rs3813728)"
FT /evidence="ECO:0000269|PubMed:12914573,
FT ECO:0000269|PubMed:22028381"
FT /id="VAR_018670"
FT VARIANT 290
FT /note="D -> G (in EDSPD1; unknown pathological
FT significance; dbSNP:rs1057518643)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077107"
FT VARIANT 297
FT /note="G -> D (in EDSPD1; unknown pathological
FT significance; dbSNP:rs1057519026)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077108"
FT VARIANT 300
FT /note="L -> P (in EDSPD1; unknown pathological
FT significance; dbSNP:rs1057515579)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077109"
FT VARIANT 301
FT /note="R -> P (in EDSPD1; unknown pathological
FT significance; dbSNP:rs760277934)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077110"
FT VARIANT 302
FT /note="Y -> C (in EDSPD1; dbSNP:rs1057519576)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077111"
FT VARIANT 306..309
FT /note="IIKC -> RR (in EDSPD1)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077112"
FT VARIANT 309
FT /note="C -> W (in EDSPD1; the mutant is not secreted but
FT retained intracellularly; dbSNP:rs769707492)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077113"
FT VARIANT 338
FT /note="C -> R (in EDSPD1; dbSNP:rs1057519577)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077114"
FT VARIANT 358
FT /note="C -> F (in EDSPD1; dbSNP:rs1057518645)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077115"
FT VARIANT 364
FT /note="W -> C (in EDSPD1; unknown pathological
FT significance; dbSNP:rs1057519578)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077116"
FT VARIANT 371
FT /note="C -> W (in EDSPD1; the mutant is not secreted but
FT retained intracellularly; dbSNP:rs1057519579)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077117"
FT VARIANT 401..405
FT /note="RIQYY -> HVI (in EDSPD1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077118"
FT VARIANT 435
FT /note="W -> R (in EDSPD1; unknown pathological
FT significance; dbSNP:rs1060499554)"
FT /evidence="ECO:0000269|PubMed:27745832"
FT /id="VAR_077119"
FT TURN 145..147
FT /evidence="ECO:0007829|PDB:1APQ"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:1APQ"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:1APQ"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:1APQ"
FT STRAND 171..175
FT /evidence="ECO:0007829|PDB:1APQ"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:6F1D"
FT TURN 208..211
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 281..288
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 299..306
FT /evidence="ECO:0007829|PDB:6F1D"
FT STRAND 319..322
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:1GPZ"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 342..346
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 349..352
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 370..373
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 385..392
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 401..406
FT /evidence="ECO:0007829|PDB:2QY0"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 411..413
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 426..429
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 433..437
FT /evidence="ECO:0007829|PDB:2QY0"
FT TURN 438..440
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 447..449
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 478..492
FT /evidence="ECO:0007829|PDB:2QY0"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 501..504
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 518..522
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 526..532
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 537..542
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 548..552
FT /evidence="ECO:0007829|PDB:1GPZ"
FT STRAND 559..565
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:1MD7"
FT HELIX 582..585
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 590..595
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 600..602
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 608..614
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 617..626
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 637..641
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 643..650
FT /evidence="ECO:0007829|PDB:1GPZ"
FT TURN 651..655
FT /evidence="ECO:0007829|PDB:1MD8"
FT STRAND 657..661
FT /evidence="ECO:0007829|PDB:2QY0"
FT TURN 663..665
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 668..676
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 678..683
FT /evidence="ECO:0007829|PDB:2QY0"
FT STRAND 685..689
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 690..693
FT /evidence="ECO:0007829|PDB:2QY0"
FT HELIX 694..700
FT /evidence="ECO:0007829|PDB:2QY0"
SQ SEQUENCE 705 AA; 80119 MW; B45D120201061462 CRC64;
MWLLYLLVPA LFCRAGGSIP IPQKLFGEVT SPLFPKPYPN NFETTTVITV PTGYRVKLVF
QQFDLEPSEG CFYDYVKISA DKKSLGRFCG QLGSPLGNPP GKKEFMSQGN KMLLTFHTDF
SNEENGTIMF YKGFLAYYQA VDLDECASRS KSGEEDPQPQ CQHLCHNYVG GYFCSCRPGY
ELQEDTHSCQ AECSSELYTE ASGYISSLEY PRSYPPDLRC NYSIRVERGL TLHLKFLEPF
DIDDHQQVHC PYDQLQIYAN GKNIGEFCGK QRPPDLDTSS NAVDLLFFTD ESGDSRGWKL
RYTTEIIKCP QPKTLDEFTI IQNLQPQYQF RDYFIATCKQ GYQLIEGNQV LHSFTAVCQD
DGTWHRAMPR CKIKDCGQPR NLPNGDFRYT TTMGVNTYKA RIQYYCHEPY YKMQTRAGSR
ESEQGVYTCT AQGIWKNEQK GEKIPRCLPV CGKPVNPVEQ RQRIIGGQKA KMGNFPWQVF
TNIHGRGGGA LLGDRWILTA AHTLYPKEHE AQSNASLDVF LGHTNVEELM KLGNHPIRRV
SVHPDYRQDE SYNFEGDIAL LELENSVTLG PNLLPICLPD NDTFYDLGLM GYVSGFGVME
EKIAHDLRFV RLPVANPQAC ENWLRGKNRM DVFSQNMFCA GHPSLKQDAC QGDSGGVFAV
RDPNTDRWVA TGIVSWGIGC SRGYGFYTKV LNYVDWIKKE MEEED
