LOCUS       NP_001724                705 aa            linear   PRI 12-JUN-2025
DEFINITION  complement C1r subcomponent isoform 1 preproprotein [Homo sapiens].
ACCESSION   NP_001724 XP_930935 XP_935774
VERSION     NP_001724.4
DBSOURCE    REFSEQ: accession NM_001733.7
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 705)
  AUTHORS   Zhang,Q., Yue,Y., Wang,X., Cui,H., Liu,Y., Gao,M., Liu,T. and
            Xiao,L.
  TITLE     Tandem Mass Tag-Labeled Quantitative Proteome Analyses Identify C1R
            and A2M as Novel Serum Biomarkers in Pregnant Women with
            Obstructive Sleep Apnea
  JOURNAL   J Proteome Res 23 (4), 1232-1248 (2024)
   PUBMED   38407963
  REMARK    GeneRIF: Tandem Mass Tag-Labeled Quantitative Proteome Analyses
            Identify C1R and A2M as Novel Serum Biomarkers in Pregnant Women
            with Obstructive Sleep Apnea.
REFERENCE   2  (residues 1 to 705)
  AUTHORS   Yadav,M.K., Maharana,J., Yadav,R., Saha,S., Sarma,P., Soni,C.,
            Singh,V., Saha,S., Ganguly,M., Li,X.X., Mohapatra,S., Mishra,S.,
            Khant,H.A., Chami,M., Woodruff,T.M., Banerjee,R., Shukla,A.K. and
            Gati,C.
  TITLE     Molecular basis of anaphylatoxin binding, activation, and signaling
            bias at complement receptors
  JOURNAL   Cell 186 (22), 4956-4973 (2023)
   PUBMED   37852260
REFERENCE   3  (residues 1 to 705)
  AUTHORS   Nakajima,K., Suzuki,H., Yamamoto,M., Yamamoto,T., Kawai,T.,
            Nakabayashi,K., Hata,K., Kosaki,K., Nakajima,H., Sano,S. and
            Kubo,A.
  TITLE     A familial case of periodontal Ehlers-Danlos syndrome lacking skin
            extensibility and joint hypermobility with a missense mutation in
            C1R
  JOURNAL   J Dermatol 49 (7), 714-718 (2022)
   PUBMED   35365885
  REMARK    GeneRIF: A familial case of periodontal Ehlers-Danlos syndrome
            lacking skin extensibility and joint hypermobility with a missense
            mutation in C1R.
REFERENCE   4  (residues 1 to 705)
  AUTHORS   Wang,X., Yang,G., Wang,Q., Zhao,Y., Ding,K., Ji,C., Shi,Z., Li,H.,
            Li,Y. and Li,S.
  TITLE     C1R, CCL2, and TNFRSF1A Genes in Coronavirus Disease-COVID-19
            Pathway Serve as Novel Molecular Biomarkers of GBM Prognosis and
            Immune Infiltration
  JOURNAL   Dis Markers 2022, 8602068 (2022)
   PUBMED   35726234
  REMARK    GeneRIF: C1R, CCL2, and TNFRSF1A Genes in Coronavirus
            Disease-COVID-19 Pathway Serve as Novel Molecular Biomarkers of GBM
            Prognosis and Immune Infiltration.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 705)
  AUTHORS   Viiklepp,K., Nissinen,L., Ojalill,M., Riihila,P., Kallajoki,M.,
            Meri,S., Heino,J. and Kahari,V.M.
  TITLE     C1r Upregulates Production of Matrix Metalloproteinase-13 and
            Promotes Invasion of Cutaneous Squamous Cell Carcinoma
  JOURNAL   J Invest Dermatol 142 (5), 1478-1488 (2022)
   PUBMED   34756877
  REMARK    GeneRIF: C1r Upregulates Production of Matrix Metalloproteinase-13
            and Promotes Invasion of Cutaneous Squamous Cell Carcinoma.
REFERENCE   6  (residues 1 to 705)
  AUTHORS   Kapferer-Seebacher,I., van Dijk,F.S. and Zschocke,J.
  TITLE     Periodontal Ehlers-Danlos Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   34324282
REFERENCE   7  (residues 1 to 705)
  AUTHORS   Luo,C., Thielens,N.M., Gagnon,J., Gal,P., Sarvari,M., Tseng,Y.,
            Tosi,M., Zavodszky,P., Arlaud,G.J. and Schumaker,V.N.
  TITLE     Recombinant human complement subcomponent C1s lacking
            beta-hydroxyasparagine, sialic acid, and one of its two
            carbohydrate chains still reassembles with C1q and C1r to form a
            functional C1 complex
  JOURNAL   Biochemistry 31 (17), 4254-4262 (1992)
   PUBMED   1533159
REFERENCE   8  (residues 1 to 705)
  AUTHORS   Lee,S.L., Wallace,S.L., Barone,R., Blum,L. and Chase,P.H.
  TITLE     Familial deficiency of two subunits of the first component of
            complement. C1r and C1s associated with a lupus erythematosus-like
            disease
  JOURNAL   Arthritis Rheum 21 (8), 958-967 (1978)
   PUBMED   737019
REFERENCE   9  (residues 1 to 705)
  AUTHORS   Ziccardi,R.J. and Cooper,N.R.
  TITLE     Activation of C1r by proteolytic cleavage
  JOURNAL   J Immunol 116 (2), 504-509 (1976)
   PUBMED   1249422
REFERENCE   10 (residues 1 to 705)
  AUTHORS   Ziccardi,R.J. and Cooper,N.R.
  TITLE     Physicochemical and functional characterization of the C1r subunit
            of the first complement component
  JOURNAL   J Immunol 116 (2), 496-503 (1976)
   PUBMED   814163
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC035220.1 and M14058.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 29, 2017 this sequence version replaced NP_001724.3.
            
            Summary: This gene encodes a member of the peptidase S1 protein
            family. The encoded protein is a proteolytic subunit in the
            complement system C1 complex. The complement system acts as a
            mediator in the innate immune response by ultimately triggering
            phagocytosis, inflammation, and rupturing the bacterial cell wall.
            Mutations in this gene are associated with Ehlers-Danlos Syndrome.
            [provided by RefSeq, Dec 2018].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC035220.1, SRR1803617.180836.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2467144, SAMEA2467148
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000647956.2/ ENSP00000497341.1
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..705
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12p13.31"
     Protein         1..705
                     /product="complement C1r subcomponent isoform 1
                     preproprotein"
                     /EC_number="3.4.21.41"
                     /note="complement component 1, r subcomponent; complement
                     C1r subcomponent"
                     /calculated_mol_wt=78269
     sig_peptide     1..17
                     /note="/evidence=ECO:0000269|PubMed:3036070; propagated
                     from UniProtKB/Swiss-Prot (P00736.2)"
                     /calculated_mol_wt=1923
     mat_peptide     18..705
                     /product="Complement C1r subcomponent. /id=PRO_0000027577"
                     /note="propagated from UniProtKB/Swiss-Prot (P00736.2)"
                     /calculated_mol_wt=78269
     mat_peptide     18..463
                     /product="Complement C1r subcomponent heavy chain.
                     /id=PRO_0000027578"
                     /note="propagated from UniProtKB/Swiss-Prot (P00736.2)"
                     /calculated_mol_wt=51191
     Site            order(26,28,30,57,62,104,135,137,139..140)
                     /site_type="other"
                     /note="heterodimerization interface [polypeptide binding]"
                     /db_xref="CDD:238001"
     Region          27..138
                     /region_name="CUB"
                     /note="Domain first found in C1r, C1s, uEGF, and bone
                     morphogenetic protein; smart00042"
                     /db_xref="CDD:214483"
     Site            125
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Region          161..189
                     /region_name="FXa_inhibition"
                     /note="Coagulation Factor Xa inhibitory site; pfam14670"
                     /db_xref="CDD:464251"
     Site            167
                     /site_type="hydroxylation"
                     /note="(3R)-3-hydroxyasparagine.
                     /evidence=ECO:0000269|PubMed:2820791; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Region          193..302
                     /region_name="CUB"
                     /note="CUB domain; pfam00431"
                     /db_xref="CDD:395345"
     Site            order(202,204,206,233,238,275,299,301,303..304)
                     /site_type="other"
                     /note="heterodimerization interface [polypeptide binding]"
                     /db_xref="CDD:238001"
     Site            206
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by CK2.
                     /evidence=ECO:0000269|PubMed:8635594; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Site            221
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Region          309..371
                     /region_name="Sushi"
                     /note="Sushi repeat (SCR repeat); pfam00084"
                     /db_xref="CDD:459664"
     Region          376..447
                     /region_name="CCP"
                     /note="Complement control protein (CCP) modules (aka short
                     consensus repeats SCRs or SUSHI repeats) have been
                     identified in several proteins of the complement system;
                     cd00033"
                     /db_xref="CDD:153056"
     Site            order(386,407)
                     /site_type="active"
                     /note="receptor-ligand interactions [active]"
                     /db_xref="CDD:153056"
     Region          463..697
                     /region_name="Tryp_SPc"
                     /note="Trypsin-like serine protease; smart00020"
                     /db_xref="CDD:214473"
     mat_peptide     464..705
                     /product="Complement C1r subcomponent light chain.
                     /id=PRO_0000027579"
                     /note="propagated from UniProtKB/Swiss-Prot (P00736.2)"
                     /calculated_mol_wt=27096
     Site            464
                     /site_type="active"
                     /note="cleavage site [active]"
                     /db_xref="CDD:238113"
     Site            order(502,557,654)
                     /site_type="active"
                     /db_xref="CDD:238113"
     Site            514
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:16335952,
                     ECO:0000269|PubMed:19159218; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Site            581
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine; propagated from
                     UniProtKB/Swiss-Prot (P00736.2)"
     Site            order(648,675,677)
                     /site_type="other"
                     /note="substrate binding sites [chemical binding]"
                     /db_xref="CDD:238113"
     CDS             1..705
                     /gene="C1R"
                     /gene_synonym="EDS8; EDSPD1"
                     /coded_by="NM_001733.7:58..2175"
                     /note="isoform 1 preproprotein is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS81658.1"
                     /db_xref="GeneID:715"
                     /db_xref="HGNC:HGNC:1246"
                     /db_xref="MIM:613785"
ORIGIN      
        1 mwllyllvpa lfcraggsip ipqklfgevt splfpkpypn nfetttvitv ptgyrvklvf
       61 qqfdlepseg cfydyvkisa dkkslgrfcg qlgsplgnpp gkkefmsqgn kmlltfhtdf
      121 sneengtimf ykgflayyqa vdldecasrs ksgeedpqpq cqhlchnyvg gyfcscrpgy
      181 elqedrhscq aecsselyte asgyissley prsyppdlrc nysirvergl tlhlkflepf
      241 diddhqqvhc pydqlqiyan gknigefcgk qrppdldtss navdllfftd esgdsrgwkl
      301 rytteiikcp qpktldefti iqnlqpqyqf rdyfiatckq gyqliegnqv lhsftavcqd
      361 dgtwhrampr ckikdcgqpr nlpngdfryt ttmgvntyka riqyychepy ykmqtragsr
      421 eseqgvytct aqgiwkneqk gekiprclpv cgkpvnpveq rqriiggqka kmgnfpwqvf
      481 tnihgrggga llgdrwilta ahtlypkehe aqsnasldvf lghtnveelm klgnhpirrv
      541 svhpdyrqde synfegdial lelensvtlg pnllpiclpd ndtfydlglm gyvsgfgvme
      601 ekiahdlrfv rlpvanpqac enwlrgknrm dvfsqnmfca ghpslkqdac qgdsggvfav
      661 rdpntdrwva tgivswgigc srgygfytkv lnyvdwikke meeed
//
