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 13-FEB-2019, entry version 223. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT human complement component C1r."; RL Biochem. J. 240:783-787(1986). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-131; LEU-152; RP TYR-163; 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 RT and the 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., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., 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., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA 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., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA 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., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., 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 RP 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 RT project: 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- RT classical-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 RT complement 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., RA Gagnon J.; RT "Identification of erythro-beta-hydroxyasparagine in the EGF-like RT domain of human C1r."; RL FEBS Lett. 222:129-134(1987). RN [10] RP PROTEIN SEQUENCE OF 133-137; 187-211 AND 609-613, AND PHOSPHORYLATION RP AT 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 RT in 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 RT linkage 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., 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 [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 RT multiple 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver 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 RP EDSPD1 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., RA Gruber R., Giunta C., Bamshad M., Bjoerck E., Chen C., Chitayat D., RA Dorschner M., 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 RT C1S, 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 RT of human complement protease C1r, an atypical member of the EGF RT 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 RT to 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., RA Lin X., 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 CC and C1s to form C1, the first component of the classical pathway CC of the complement system. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective cleavage of Lys(or Arg)-|-Ile bond in CC complement subcomponent C1s to form the active form of C1s (EC CC 3.4.21.42).; EC=3.4.21.41; CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q, CC C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of CC identical chains, each of which is activated by cleavage into two CC chains, A and B, connected by disulfide bonds. CC -!- INTERACTION: CC P09871:C1S; NbExp=4; IntAct=EBI-3926504, EBI-2810045; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27745832}. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of CC aspartate and asparagine is (R) stereospecific within EGF domains. CC {ECO:0000269|PubMed:2820791}. CC -!- POLYMORPHISM: Complement component C1r deficiency [MIM:216950] CC leads to the failure of the classical complement system activation CC pathway (C1 deficiency). Individuals with C1 deficiency are highly CC susceptible to infections by microorganisms and have greater risk CC in developing autoimmune diseases such as systemic lupus CC erythematosus (SLE). {ECO:0000269|PubMed:2831944}. CC -!- DISEASE: Ehlers-Danlos syndrome, periodontal type, 1 (EDSPD1) CC [MIM:130080]: A form of Ehlers-Danlos syndrome, a connective CC tissue disorder characterized by hyperextensible skin, atrophic CC cutaneous scars due to tissue fragility and joint hyperlaxity. CC EDSPD1 is characterized by the association of typical features of CC Ehlers-Danlos syndrome with gingival recession and severe early- CC onset periodontal disease, leading to premature loss of permanent CC teeth. EDSPD1 inheritance is autosomal dominant. CC {ECO:0000269|PubMed:27745832}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC {ECO:0000255|PROSITE-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 UniGene; Hs.524224; -. DR UniGene; Hs.731679; -. 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 DisProt; DP00621; -. DR ProteinModelPortal; P00736; -. DR SMR; P00736; -. DR BioGrid; 107176; 10. DR IntAct; P00736; 3. DR MINT; P00736; -. DR BindingDB; P00736; -. DR ChEMBL; CHEMBL4611; -. DR DrugBank; DB00054; Abciximab. DR DrugBank; DB00051; Adalimumab. DR DrugBank; DB00092; Alefacept. DR DrugBank; DB00087; Alemtuzumab. DR DrugBank; DB00074; Basiliximab. DR DrugBank; DB00112; Bevacizumab. DR DrugBank; DB06404; C1 Esterase Inhibitor (Human). DR DrugBank; DB09228; C1 Esterase Inhibitor (Recombinant). DR DrugBank; DB00002; Cetuximab. DR DrugBank; DB00111; Daclizumab. DR DrugBank; DB00095; Efalizumab. DR DrugBank; DB00005; Etanercept. DR DrugBank; DB00056; Gemtuzumab ozogamicin. DR DrugBank; DB00078; Ibritumomab tiuxetan. DR DrugBank; DB00075; Muromonab. DR DrugBank; DB00108; Natalizumab. DR DrugBank; DB00110; Palivizumab. DR DrugBank; DB00073; Rituximab. DR DrugBank; DB00081; Tositumomab. DR DrugBank; DB00072; Trastuzumab. DR GuidetoPHARMACOLOGY; 2334; -. DR MEROPS; S01.192; -. DR GlyConnect; 713; -. DR iPTMnet; P00736; -. DR PhosphoSitePlus; P00736; -. DR BioMuta; C1R; -. DR DMDM; 218511956; -. DR EPD; P00736; -. DR jPOST; P00736; -. DR PeptideAtlas; P00736; -. DR PRIDE; P00736; -. DR ProteomicsDB; 51270; -. DR DNASU; 715; -. DR Ensembl; ENST00000542285; ENSP00000438615; ENSG00000159403. DR GeneID; 715; -. DR KEGG; hsa:715; -. DR UCSC; uc031ysf.2; human. DR CTD; 715; -. DR DisGeNET; 715; -. DR EuPathDB; HostDB:ENSG00000159403.15; -. DR GeneCards; C1R; -. DR HGNC; HGNC:1246; C1R. DR HPA; HPA001251; -. DR HPA; HPA001551; -. DR MalaCards; C1R; -. DR MIM; 130080; phenotype. DR MIM; 216950; phenotype. DR MIM; 613785; gene. DR neXtProt; NX_P00736; -. DR Orphanet; 75392; Ehlers-Danlos syndrome, periodontitis type. DR Orphanet; 169147; Immunodeficiency due to a classical component pathway complement deficiency. DR Orphanet; 93552; Pediatric systemic lupus erythematosus. DR PharmGKB; PA25635; -. DR HOVERGEN; HBG000559; -. DR InParanoid; P00736; -. DR KO; K01330; -. DR OrthoDB; 558558at2759; -. DR PhylomeDB; P00736; -. DR TreeFam; TF330373; -. DR BRENDA; 3.4.21.41; 2681. 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 SIGNOR; P00736; -. DR ChiTaRS; C1R; human. DR EvolutionaryTrace; P00736; -. DR GeneWiki; C1R_(gene); -. DR GenomeRNAi; 715; -. DR PRO; PR:P00736; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; ENSG00000159403; Expressed in 221 organ(s), highest expression level in liver. DR ExpressionAtlas; P00736; baseline and differential. DR Genevisible; P00736; HS. 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:0004252; F:serine-type endopeptidase activity; EXP:Reactome. DR GO; GO:0008236; F:serine-type peptidase activity; TAS:ProtInc. DR GO; GO:0006956; P:complement activation; TAS:Reactome. 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:0030449; P:regulation of complement activation; TAS:Reactome. 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 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; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; 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; PTHR45206; PTHR45206; 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; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW EGF-like domain; Ehlers-Danlos syndrome; Glycoprotein; Hydrolase; KW Hydroxylation; Immunity; Innate immunity; Phosphoprotein; KW Polymorphism; Protease; Reference proteome; Repeat; Secreted; KW Serine protease; Signal; Sushi. FT SIGNAL 1 17 {ECO:0000269|PubMed:3036070}. FT CHAIN 18 705 Complement C1r subcomponent. FT /FTId=PRO_0000027577. FT CHAIN 18 463 Complement C1r subcomponent heavy chain. FT /FTId=PRO_0000027578. FT CHAIN 464 705 Complement C1r subcomponent light chain. FT /FTId=PRO_0000027579. FT DOMAIN 18 141 CUB 1. {ECO:0000255|PROSITE- FT ProRule:PRU00059}. FT DOMAIN 142 190 EGF-like; calcium-binding. {ECO:0000255}. FT DOMAIN 193 305 CUB 2. {ECO:0000255|PROSITE- FT ProRule:PRU00059}. FT DOMAIN 307 373 Sushi 1. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 374 449 Sushi 2. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 464 702 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT ACT_SITE 502 502 Charge relay system. FT ACT_SITE 557 557 Charge relay system. FT ACT_SITE 654 654 Charge relay system. FT MOD_RES 167 167 (3R)-3-hydroxyasparagine. FT {ECO:0000269|PubMed:2820791}. FT MOD_RES 206 206 Phosphoserine; by CK2. FT {ECO:0000269|PubMed:8635594}. FT CARBOHYD 125 125 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 221 221 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952}. FT CARBOHYD 514 514 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16335952, FT ECO:0000269|PubMed:19159218}. FT CARBOHYD 581 581 N-linked (GlcNAc...) asparagine. FT DISULFID 71 89 {ECO:0000305}. FT DISULFID 146 165 FT DISULFID 161 174 FT DISULFID 176 189 FT DISULFID 193 220 {ECO:0000305}. FT DISULFID 250 268 {ECO:0000305}. FT DISULFID 309 358 FT DISULFID 338 371 FT DISULFID 376 429 FT DISULFID 406 447 FT DISULFID 451 577 Interchain (between heavy and light FT chains). FT DISULFID 620 639 FT DISULFID 650 680 FT VARIANT 50 50 V -> D (in EDSPD1; requires 2 nucleotide FT substitutions; the mutant is not secreted FT but retained intracellularly). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077106. FT VARIANT 131 131 Y -> H. {ECO:0000269|PubMed:12914573}. FT /FTId=VAR_018667. FT VARIANT 152 152 S -> L (common polymorphism; FT dbSNP:rs1801046). FT {ECO:0000269|PubMed:12914573, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:3030286, FT ECO:0000269|PubMed:8162045}. FT /FTId=VAR_016103. FT VARIANT 163 163 H -> Y. {ECO:0000269|PubMed:12914573}. FT /FTId=VAR_018668. FT VARIANT 184 184 E -> K (polymorphism; confirmed at FT protein level; dbSNP:rs1126605). FT {ECO:0000269|PubMed:12914573, FT ECO:0000269|PubMed:22028381}. FT /FTId=VAR_018669. FT VARIANT 186 186 T -> R (in dbSNP:rs4519167). FT {ECO:0000269|PubMed:12914573, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:3021205, FT ECO:0000269|PubMed:3030286}. FT /FTId=VAR_047933. FT VARIANT 261 261 G -> R (polymorphism; confirmed at FT protein level; dbSNP:rs3813728). FT {ECO:0000269|PubMed:12914573, FT ECO:0000269|PubMed:22028381}. FT /FTId=VAR_018670. FT VARIANT 290 290 D -> G (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077107. FT VARIANT 297 297 G -> D (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077108. FT VARIANT 300 300 L -> P (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077109. FT VARIANT 301 301 R -> P (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077110. FT VARIANT 302 302 Y -> C (in EDSPD1). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077111. FT VARIANT 306 309 IIKC -> RR (in EDSPD1). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077112. FT VARIANT 309 309 C -> W (in EDSPD1; the mutant is not FT secreted but retained intracellularly). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077113. FT VARIANT 338 338 C -> R (in EDSPD1). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077114. FT VARIANT 358 358 C -> F (in EDSPD1). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077115. FT VARIANT 364 364 W -> C (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077116. FT VARIANT 371 371 C -> W (in EDSPD1; the mutant is not FT secreted but retained intracellularly). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077117. FT VARIANT 401 405 RIQYY -> HVI (in EDSPD1; unknown FT pathological significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077118. FT VARIANT 435 435 W -> R (in EDSPD1; unknown pathological FT significance). FT {ECO:0000269|PubMed:27745832}. FT /FTId=VAR_077119. FT TURN 145 147 {ECO:0000244|PDB:1APQ}. FT TURN 150 152 {ECO:0000244|PDB:1APQ}. FT STRAND 156 158 {ECO:0000244|PDB:1APQ}. FT STRAND 162 168 {ECO:0000244|PDB:1APQ}. FT STRAND 171 175 {ECO:0000244|PDB:1APQ}. FT STRAND 196 198 {ECO:0000244|PDB:6F1D}. FT STRAND 200 206 {ECO:0000244|PDB:6F1D}. FT TURN 208 211 {ECO:0000244|PDB:6F1D}. FT STRAND 219 225 {ECO:0000244|PDB:6F1D}. FT STRAND 230 236 {ECO:0000244|PDB:6F1D}. FT STRAND 246 250 {ECO:0000244|PDB:6F1D}. FT STRAND 254 259 {ECO:0000244|PDB:6F1D}. FT STRAND 262 267 {ECO:0000244|PDB:6F1D}. FT STRAND 269 271 {ECO:0000244|PDB:6F1D}. FT STRAND 281 288 {ECO:0000244|PDB:6F1D}. FT STRAND 299 306 {ECO:0000244|PDB:6F1D}. FT STRAND 319 322 {ECO:0000244|PDB:2QY0}. FT STRAND 326 328 {ECO:0000244|PDB:1GPZ}. FT STRAND 333 338 {ECO:0000244|PDB:2QY0}. FT STRAND 342 346 {ECO:0000244|PDB:2QY0}. FT STRAND 349 352 {ECO:0000244|PDB:2QY0}. FT STRAND 355 358 {ECO:0000244|PDB:2QY0}. FT STRAND 364 366 {ECO:0000244|PDB:2QY0}. FT STRAND 370 373 {ECO:0000244|PDB:2QY0}. FT STRAND 385 392 {ECO:0000244|PDB:2QY0}. FT STRAND 401 406 {ECO:0000244|PDB:2QY0}. FT TURN 408 410 {ECO:0000244|PDB:2QY0}. FT STRAND 411 413 {ECO:0000244|PDB:2QY0}. FT STRAND 426 429 {ECO:0000244|PDB:2QY0}. FT STRAND 433 437 {ECO:0000244|PDB:2QY0}. FT TURN 438 440 {ECO:0000244|PDB:2QY0}. FT STRAND 447 449 {ECO:0000244|PDB:2QY0}. FT STRAND 478 492 {ECO:0000244|PDB:2QY0}. FT TURN 493 495 {ECO:0000244|PDB:2QY0}. FT STRAND 496 499 {ECO:0000244|PDB:2QY0}. FT HELIX 501 504 {ECO:0000244|PDB:2QY0}. FT STRAND 518 522 {ECO:0000244|PDB:2QY0}. FT HELIX 526 532 {ECO:0000244|PDB:2QY0}. FT STRAND 537 542 {ECO:0000244|PDB:2QY0}. FT STRAND 548 552 {ECO:0000244|PDB:1GPZ}. FT STRAND 559 565 {ECO:0000244|PDB:2QY0}. FT STRAND 571 573 {ECO:0000244|PDB:1MD7}. FT HELIX 582 585 {ECO:0000244|PDB:2QY0}. FT STRAND 590 595 {ECO:0000244|PDB:2QY0}. FT STRAND 600 602 {ECO:0000244|PDB:2QY0}. FT STRAND 608 614 {ECO:0000244|PDB:2QY0}. FT HELIX 617 626 {ECO:0000244|PDB:2QY0}. FT STRAND 637 641 {ECO:0000244|PDB:2QY0}. FT HELIX 643 650 {ECO:0000244|PDB:1GPZ}. FT TURN 651 655 {ECO:0000244|PDB:1MD8}. FT STRAND 657 661 {ECO:0000244|PDB:2QY0}. FT TURN 663 665 {ECO:0000244|PDB:2QY0}. FT STRAND 668 676 {ECO:0000244|PDB:2QY0}. FT STRAND 678 683 {ECO:0000244|PDB:2QY0}. FT STRAND 685 689 {ECO:0000244|PDB:2QY0}. FT HELIX 690 693 {ECO:0000244|PDB:2QY0}. FT HELIX 694 700 {ECO:0000244|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 //