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 24-JAN-2024, entry version 250. 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}. 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; 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; 15. DR ComplexPortal; CPX-1920; Complement C1 complex. DR IntAct; P00736; 11. DR MINT; P00736; -. DR STRING; 9606.ENSP00000444271; -. 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 GlyCosmos; P00736; 4 sites, 17 glycans. 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 PaxDb; 9606-ENSP00000438615; -. DR PeptideAtlas; P00736; -. DR ProteomicsDB; 51270; -. DR DNASU; 715; -. DR GeneID; 715; -. DR KEGG; hsa:715; -. DR UCSC; uc031ysf.2; human. DR AGR; HGNC:1246; -. 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; 5394076at2759; -. 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 240 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 GO; GO:0072562; C:blood microparticle; HDA:UniProtKB. 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:0140313; F:molecular sequestering activity; EXP:DisProt. 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; cd00054; EGF_CA; 1. DR CDD; cd00190; Tryp_SPc; 1. DR DisProt; DP00621; -. DR Gene3D; 2.10.70.10; Complement Module, domain 1; 2. DR Gene3D; 2.10.25.10; Laminin; 1. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 2. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 3. 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; IPR024175; Pept_S1A_C1r/C1S/mannan-bd. 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; COMPLEMENT C1R SUBCOMPONENT; 1. DR PANTHER; PTHR24255; COMPLEMENT COMPONENT 1, S SUBCOMPONENT-RELATED; 1. DR Pfam; PF00431; CUB; 2. DR Pfam; PF14670; FXa_inhibition; 1. 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; SM00181; EGF; 1. DR SMART; SM00179; EGF_CA; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57535; Complement control module/SCR domain; 2. DR SUPFAM; SSF57196; EGF/Laminin; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 2. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. 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. DR Genevisible; P00736; HS. 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; the mutant is not secreted but FT retained intracellularly; requires 2 nucleotide FT substitutions)" 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; uncertain significance; FT dbSNP:rs1057518643)" FT /evidence="ECO:0000269|PubMed:27745832" FT /id="VAR_077107" FT VARIANT 297 FT /note="G -> D (in EDSPD1; uncertain significance; FT dbSNP:rs1057519026)" FT /evidence="ECO:0000269|PubMed:27745832" FT /id="VAR_077108" FT VARIANT 300 FT /note="L -> P (in EDSPD1; uncertain significance; FT dbSNP:rs1057515579)" FT /evidence="ECO:0000269|PubMed:27745832" FT /id="VAR_077109" FT VARIANT 301 FT /note="R -> P (in EDSPD1; uncertain significance; FT 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; uncertain significance; FT 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:27745832" FT /id="VAR_077118" FT VARIANT 435 FT /note="W -> R (in EDSPD1; uncertain significance; FT 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 //