C1RL_HUMAN
ID C1RL_HUMAN Reviewed; 487 AA.
AC Q9NZP8; Q53GX9;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Complement C1r subcomponent-like protein;
DE Short=C1r-LP;
DE Short=C1r-like protein;
DE EC=3.4.21.-;
DE AltName: Full=C1r-like serine protease analog protein;
DE Short=CLSPa;
DE Flags: Precursor;
GN Name=C1RL; Synonyms=C1RL1, C1RLP, CLSPA;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND VARIANT VAL-285.
RC TISSUE=Dendritic cell;
RX PubMed=15358180; DOI=10.1016/j.bbrc.2004.06.127;
RA Lin N., Liu S., Li N., Wu P., An H., Yu Y., Wan T., Cao X.;
RT "A novel human dendritic cell-derived C1r-like serine protease analog
RT inhibits complement-mediated cytotoxicity.";
RL Biochem. Biophys. Res. Commun. 321:329-336(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15527420; DOI=10.1042/bj20041196;
RA Ligoudistianou C., Xu Y., Garnier G., Circolo A., Volanakis J.E.;
RT "A novel human complement-related protein, C1r-like protease (C1r-LP),
RT specifically cleaves pro-C1s.";
RL Biochem. J. 387:165-173(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
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 [5]
RP FUNCTION, AND MUTAGENESIS OF SER-436.
RX PubMed=15385675; DOI=10.1073/pnas.0405692101;
RA Wicher K.B., Fries E.;
RT "Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by
RT the complement C1r-like protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14390-14395(2004).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-166; ASN-242 AND ASN-296.
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 [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-147; ASN-242 AND ASN-296.
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 [8]
RP GLYCOSYLATION AT ASN-242.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
CC -!- FUNCTION: Mediates the proteolytic cleavage of HP/haptoglobin in the
CC endoplasmic reticulum. {ECO:0000269|PubMed:15358180,
CC ECO:0000269|PubMed:15385675, ECO:0000269|PubMed:15527420}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15358180}.
CC -!- TISSUE SPECIFICITY: Highly expressed in placenta, liver, kidney,
CC pancreas, moderately in lung, spleen, prostate, ovary, colon, and PBL,
CC and weakly in heart, skeletal muscle, thymus, testis, and small
CC intestine. Expressed in PC-3 (prostate adenocarcinoma) and SK-OV-3
CC (ovary adenocarcinoma) cells, but not in LoVo and HT-29 (colon
CC adenocarcinoma), SMMC7721 (hepatocellular carcinoma), CaoV-3 (ovary
CC adenocarcinoma), HeLa (cervix epithelioid carcinoma), MCF-7 (breast
CC adenocarcinoma), U-251MG (glioma) or A-549 (lung carcinoma) cells.
CC Widely expressed in myeloid leukemia cell lines, including K-562
CC (chronic myelogenous leukemia), THP-1 (myelomonocytic leukemia), HL-60
CC and NB4 (promyelocytic leukemia), and KG-1 (acute myelogenous leukemia)
CC cells. Expressed mainly in the liver and in serum (at protein level).
CC {ECO:0000269|PubMed:15358180, ECO:0000269|PubMed:15527420}.
CC -!- INDUCTION: Up-regulated in monocytes and dendritic cells (DC)
CC undergoing maturation or activation. {ECO:0000269|PubMed:15358180}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
CC -!- CAUTION: Does not associate with the C1 complex. According to
CC PubMed:15385675, doesn't cleave the proform of complement C1s.
CC {ECO:0000305}.
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DR EMBL; AF178985; AAF44349.1; -; mRNA.
DR EMBL; AK222802; BAD96522.1; -; mRNA.
DR EMBL; AC018653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC094008; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC233309; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS8573.1; -.
DR RefSeq; NP_001284569.1; NM_001297640.1.
DR RefSeq; NP_057630.2; NM_016546.3.
DR AlphaFoldDB; Q9NZP8; -.
DR SMR; Q9NZP8; -.
DR BioGRID; 119431; 10.
DR IntAct; Q9NZP8; 1.
DR STRING; 9606.ENSP00000266542; -.
DR MEROPS; S01.189; -.
DR GlyConnect; 1143; 11 N-Linked glycans (3 sites).
DR GlyGen; Q9NZP8; 6 sites, 12 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q9NZP8; -.
DR PhosphoSitePlus; Q9NZP8; -.
DR BioMuta; C1RL; -.
DR DMDM; 182705204; -.
DR CPTAC; non-CPTAC-1102; -.
DR EPD; Q9NZP8; -.
DR jPOST; Q9NZP8; -.
DR MassIVE; Q9NZP8; -.
DR PaxDb; Q9NZP8; -.
DR PeptideAtlas; Q9NZP8; -.
DR PRIDE; Q9NZP8; -.
DR ProteomicsDB; 83474; -.
DR Antibodypedia; 1734; 120 antibodies from 22 providers.
DR DNASU; 51279; -.
DR Ensembl; ENST00000266542.9; ENSP00000266542.4; ENSG00000139178.12.
DR Ensembl; ENST00000671752.1; ENSP00000500804.1; ENSG00000288124.1.
DR GeneID; 51279; -.
DR KEGG; hsa:51279; -.
DR MANE-Select; ENST00000266542.9; ENSP00000266542.4; NM_016546.4; NP_057630.2.
DR UCSC; uc001qsn.4; human.
DR CTD; 51279; -.
DR DisGeNET; 51279; -.
DR GeneCards; C1RL; -.
DR HGNC; HGNC:21265; C1RL.
DR HPA; ENSG00000139178; Tissue enhanced (liver).
DR MIM; 608974; gene.
DR neXtProt; NX_Q9NZP8; -.
DR OpenTargets; ENSG00000139178; -.
DR PharmGKB; PA134957759; -.
DR VEuPathDB; HostDB:ENSG00000139178; -.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000162495; -.
DR HOGENOM; CLU_006842_0_0_1; -.
DR InParanoid; Q9NZP8; -.
DR OMA; NMFCVGD; -.
DR OrthoDB; 518015at2759; -.
DR PhylomeDB; Q9NZP8; -.
DR TreeFam; TF330373; -.
DR BRENDA; 3.4.21.41; 2681.
DR PathwayCommons; Q9NZP8; -.
DR SignaLink; Q9NZP8; -.
DR SIGNOR; Q9NZP8; -.
DR BioGRID-ORCS; 51279; 6 hits in 1073 CRISPR screens.
DR ChiTaRS; C1RL; human.
DR GenomeRNAi; 51279; -.
DR Pharos; Q9NZP8; Tbio.
DR PRO; PR:Q9NZP8; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9NZP8; protein.
DR Bgee; ENSG00000139178; Expressed in right lobe of liver and 98 other tissues.
DR ExpressionAtlas; Q9NZP8; baseline and differential.
DR Genevisible; Q9NZP8; HS.
DR GO; GO:0072562; C:blood microparticle; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031638; P:zymogen activation; IBA:GO_Central.
DR CDD; cd00041; CUB; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 2.60.120.290; -; 1.
DR InterPro; IPR000859; CUB_dom.
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; IPR001254; Trypsin_dom.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00431; CUB; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00042; CUB; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF49854; SSF49854; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS01180; CUB; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Complement pathway; Disulfide bond; Glycoprotein; Hydrolase; Immunity;
KW Innate immunity; Protease; Reference proteome; Secreted; Serine protease;
KW Signal; Sushi.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..487
FT /note="Complement C1r subcomponent-like protein"
FT /id="PRO_0000318678"
FT DOMAIN 39..163
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 165..230
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 245..484
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 283
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 339
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 436
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:19159218"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 363
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 94..112
FT /evidence="ECO:0000250"
FT DISULFID 195..228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DISULFID 402..421
FT /evidence="ECO:0000250"
FT DISULFID 432..462
FT /evidence="ECO:0000250"
FT VARIANT 285
FT /note="I -> V (in dbSNP:rs3742089)"
FT /evidence="ECO:0000269|PubMed:15358180"
FT /id="VAR_038852"
FT MUTAGEN 436
FT /note="S->A: Unable to cleave HP."
FT /evidence="ECO:0000269|PubMed:15385675"
FT CONFLICT 94
FT /note="C -> R (in Ref. 3; BAD96522)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="V -> A (in Ref. 3; BAD96522)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="I -> M (in Ref. 3; BAD96522)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 487 AA; 53498 MW; 6DE7CE9EA08C7990 CRC64;
MPGPRVWGKY LWRSPHSKGC PGAMWWLLLW GVLQACPTRG SVLLAQELPQ QLTSPGYPEP
YGKGQESSTD IKAPEGFAVR LVFQDFDLEP SQDCAGDSVT ISFVGSDPSQ FCGQQGSPLG
RPPGQREFVS SGRSLRLTFR TQPSSENKTA HLHKGFLALY QTVAVNYSQP ISEASRGSEA
INAPGDNPAK VQNHCQEPYY QAAAAGALTC ATPGTWKDRQ DGEEVLQCMP VCGRPVTPIA
QNQTTLGSSR AKLGNFPWQA FTSIHGRGGG ALLGDRWILT AAHTIYPKDS VSLRKNQSVN
VFLGHTAIDE MLKLGNHPVH RVVVHPDYRQ NESHNFSGDI ALLELQHSIP LGPNVLPVCL
PDNETLYRSG LLGYVSGFGM EMGWLTTELK YSRLPVAPRE ACNAWLQKRQ RPEVFSDNMF
CVGDETQRHS VCQGDSGSVY VVWDNHAHHW VATGIVSWGI GCGEGYDFYT KVLSYVDWIK
GVMNGKN
