ID CORIN_HUMAN Reviewed; 1042 AA.
AC Q9Y5Q5; B0ZBE3; Q2TBD2; Q4W5E5; Q4W5G6; Q9UHY2;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 27-MAR-2024, entry version 203.
DE RecName: Full=Atrial natriuretic peptide-converting enzyme;
DE EC=3.4.21.-;
DE AltName: Full=Corin;
DE AltName: Full=Heart-specific serine proteinase ATC2;
DE AltName: Full=Pro-ANP-converting enzyme;
DE AltName: Full=Transmembrane protease serine 10;
DE Contains:
DE RecName: Full=Atrial natriuretic peptide-converting enzyme, N-terminal propeptide;
DE Contains:
DE RecName: Full=Atrial natriuretic peptide-converting enzyme, activated protease fragment;
DE Contains:
DE RecName: Full=Atrial natriuretic peptide-converting enzyme, 180 kDa soluble fragment;
DE Contains:
DE RecName: Full=Atrial natriuretic peptide-converting enzyme, 160 kDa soluble fragment;
DE Contains:
DE RecName: Full=Atrial natriuretic peptide-converting enzyme, 100 kDa soluble fragment;
GN Name=CORIN; Synonyms=CRN, TMPRSS10;
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] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANTS
RP TYR-13 AND ARG-525.
RC TISSUE=Heart;
RX PubMed=10329693; DOI=10.1074/jbc.274.21.14926;
RA Yan W., Sheng N., Seto M., Morser J., Wu Q.;
RT "Corin, a mosaic transmembrane serine protease encoded by a novel cDNA from
RT human heart.";
RL J. Biol. Chem. 274:14926-14935(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS TYR-13 AND
RP ARG-525.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 734-1040.
RC TISSUE=Heart;
RX PubMed=11082206; DOI=10.1046/j.1432-1033.2000.01806.x;
RA Hooper J.D., Scarman A.L., Clarke B.E., Normyle J.F., Antalis T.M.;
RT "Localization of the mosaic transmembrane serine protease corin to heart
RT myocytes.";
RL Eur. J. Biochem. 267:6931-6937(2000).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF SER-985.
RX PubMed=10880574; DOI=10.1073/pnas.150149097;
RA Yan W., Wu F., Morser J., Wu Q.;
RT "Corin, a transmembrane cardiac serine protease, acts as a pro-atrial
RT natriuretic peptide-converting enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:8525-8529(2000).
RN [6]
RP ACTIVATION, MUTAGENESIS OF ARG-801 AND SER-985, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=14559895; DOI=10.1074/jbc.m309991200;
RA Knappe S., Wu F., Masikat M.R., Morser J., Wu Q.;
RT "Functional analysis of the transmembrane domain and activation cleavage of
RT human corin: design and characterization of a soluble corin.";
RL J. Biol. Chem. 278:52363-52370(2003).
RN [7]
RP PROTEOLYTIC PROCESSING, GLYCOSYLATION, AND DISULFIDE BONDS.
RX PubMed=17660514; DOI=10.1074/jbc.m703687200;
RA Liao X., Wang W., Chen S., Wu Q.;
RT "Role of glycosylation in corin zymogen activation.";
RL J. Biol. Chem. 282:27728-27735(2007).
RN [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19751717; DOI=10.1016/j.cca.2009.09.004;
RA Peleg A., Jaffe A.S., Hasin Y.;
RT "Enzyme-linked immunoabsorbent assay for detection of human serine protease
RT corin in blood.";
RL Clin. Chim. Acta 409:85-89(2009).
RN [9]
RP FUNCTION.
RX PubMed=20489134; DOI=10.1373/clinchem.2010.143883;
RA Semenov A.G., Tamm N.N., Seferian K.R., Postnikov A.B., Karpova N.S.,
RA Serebryanaya D.V., Koshkina E.V., Krasnoselsky M.I., Katrukha A.G.;
RT "Processing of pro-B-type natriuretic peptide: furin and corin as candidate
RT convertases.";
RL Clin. Chem. 56:1166-1176(2010).
RN [10]
RP FUNCTION.
RX PubMed=21763278; DOI=10.1016/j.bbrc.2011.06.192;
RA Peng J., Jiang J., Wang W., Qi X., Sun X.L., Wu Q.;
RT "Glycosylation and processing of pro-B-type natriuretic peptide in
RT cardiomyocytes.";
RL Biochem. Biophys. Res. Commun. 411:593-598(2011).
RN [11]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ARG-134;
RP ARG-164; ARG-180; ARG-213; ARG-239; ARG-244; ARG-427; ARG-801 AND SER-985.
RX PubMed=21288900; DOI=10.1074/jbc.m110.185082;
RA Jiang J., Wu S., Wang W., Chen S., Peng J., Zhang X., Wu Q.;
RT "Ectodomain shedding and autocleavage of the cardiac membrane protease
RT corin.";
RL J. Biol. Chem. 286:10066-10072(2011).
RN [12]
RP ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR LOCATION,
RP GLYCOSYLATION, AND MUTAGENESIS OF ASP-26 AND MET-30.
RX PubMed=21518754; DOI=10.1074/jbc.m110.217570;
RA Qi X., Jiang J., Zhu M., Wu Q.;
RT "Human corin isoforms with different cytoplasmic tails that alter cell
RT surface targeting.";
RL J. Biol. Chem. 286:20963-20969(2011).
RN [13]
RP FUNCTION, INVOLVEMENT IN PEE5, TISSUE SPECIFICITY, AND VARIANTS PEE5
RP GLU-317 AND GLY-472.
RX PubMed=22437503; DOI=10.1038/nature10897;
RA Cui Y., Wang W., Dong N., Lou J., Srinivasan D.K., Cheng W., Huang X.,
RA Liu M., Fang C., Peng J., Chen S., Wu S., Liu Z., Dong L., Zhou Y., Wu Q.;
RT "Role of corin in trophoblast invasion and uterine spiral artery
RT remodelling in pregnancy.";
RL Nature 484:246-250(2012).
RN [14]
RP VARIANT ARG-525.
RX PubMed=17918732; DOI=10.1002/humu.20617;
RA Guipponi M., Toh M.-Y., Tan J., Park D., Hanson K., Ballana E., Kwong D.,
RA Cannon P.Z.F., Wu Q., Gout A., Delorenzi M., Speed T.P., Smith R.J.H.,
RA Dahl H.-H.M., Petersen M., Teasdale R.D., Estivill X., Park W.J.,
RA Scott H.S.;
RT "An integrated genetic and functional analysis of the role of type II
RT transmembrane serine proteases (TMPRSSs) in hearing loss.";
RL Hum. Mutat. 29:130-141(2008).
CC -!- FUNCTION: Serine-type endopeptidase involved in atrial natriuretic
CC peptide (NPPA) and brain natriuretic peptide (NPPB) processing
CC (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278).
CC Converts through proteolytic cleavage the non-functional propeptides
CC NPPA and NPPB into their active hormones, ANP and BNP(1-32)
CC respectively, thereby regulating blood pressure in the heart and
CC promoting natriuresis, diuresis and vasodilation (PubMed:10880574,
CC PubMed:21288900, PubMed:20489134, PubMed:21763278). Proteolytic
CC cleavage of pro-NPPA also plays a role in female pregnancy by promoting
CC trophoblast invasion and spiral artery remodeling in uterus
CC (PubMed:22437503). Also acts as a regulator of sodium reabsorption in
CC kidney (By similarity). {ECO:0000250|UniProtKB:Q9Z319,
CC ECO:0000269|PubMed:10880574, ECO:0000269|PubMed:20489134,
CC ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21763278,
CC ECO:0000269|PubMed:22437503}.
CC -!- FUNCTION: [Isoform 2]: Has weaker endopeptidase activity compared to
CC isoform 1.
CC -!- ACTIVITY REGULATION: Inhibited in a dose-dependent manner by non-
CC specific trypsin-like serine protease inhibitors including benzamidine.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.28 mM for pyroGlu-Phe-Lys-pNA.HCl {ECO:0000269|PubMed:14559895};
CC KM=3.52 mM for pyroGlu-Pro-Arg-pNA.HCl {ECO:0000269|PubMed:14559895};
CC KM=2.95 mM for H-D-Pro-Phe-Arg-pNA.2HCl
CC {ECO:0000269|PubMed:14559895};
CC KM=1.92 mM for Bz-Ile-Glu-(gamma-OR)-Gly-Arg-pNA.HCl
CC {ECO:0000269|PubMed:14559895};
CC KM=16 mM for pyroGlu-Gly-Arg-pNA.HCl {ECO:0000269|PubMed:14559895};
CC -!- INTERACTION:
CC Q9Y5Q5; Q13520: AQP6; NbExp=3; IntAct=EBI-17876114, EBI-13059134;
CC Q9Y5Q5; O00501: CLDN5; NbExp=3; IntAct=EBI-17876114, EBI-18400628;
CC Q9Y5Q5; P54849: EMP1; NbExp=3; IntAct=EBI-17876114, EBI-4319440;
CC Q9Y5Q5; Q8TED1: GPX8; NbExp=3; IntAct=EBI-17876114, EBI-11721746;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19751717,
CC ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21518754}; Single-pass
CC type II membrane protein {ECO:0000269|PubMed:19751717,
CC ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:21518754}. Note=May
CC easily detach from the endothelial cell membrane.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cell membrane; Single-pass type II
CC membrane protein. Note=Less efficiently targeted to the cell membrane
CC compared to isoform 1.
CC -!- SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme,
CC 180 kDa soluble fragment]: Secreted. Note=Soluble form produced
CC following cleavage by ADAM10.
CC -!- SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme,
CC 160 kDa soluble fragment]: Secreted. Note=Soluble form produced
CC following autocatalytic cleavage.
CC -!- SUBCELLULAR LOCATION: [Atrial natriuretic peptide-converting enzyme,
CC 100 kDa soluble fragment]: Secreted. Note=Soluble form produced
CC following autocatalytic cleavage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=E1, hE1;
CC IsoId=Q9Y5Q5-1; Sequence=Displayed;
CC Name=2; Synonyms=E1a, hE1a;
CC IsoId=Q9Y5Q5-2; Sequence=VSP_043952;
CC -!- TISSUE SPECIFICITY: Highly expressed in heart. Expressed in heart
CC myocytes. Also expressed in pregnant uterus. Detected in blood, in
CC plasma as well as in serum (at protein level).
CC {ECO:0000269|PubMed:10329693, ECO:0000269|PubMed:19751717,
CC ECO:0000269|PubMed:22437503}.
CC -!- DOMAIN: The DDNN motif is required for targeting to the cell membrane
CC and enzyme activation. {ECO:0000269|PubMed:21518754}.
CC -!- PTM: N-glycosylated; required for processing and activation.
CC {ECO:0000269|PubMed:17660514, ECO:0000269|PubMed:21518754}.
CC -!- PTM: Activated through proteolytic processing by a trypsin-like
CC protease; cleaved into a N-terminal propeptide and an activated corin
CC protease fragment. Different soluble forms are produced by cleavage and
CC autocatalytic cleavage: Atrial natriuretic peptide-converting enzyme,
CC 180 kDa soluble fragment is produced by cleavage by ADAM10, while 160
CC kDa and 100 kDa soluble fragments are produced by autocatalytic
CC cleavage. Cleavage by ADAM10 to produce soluble 180 kDa soluble
CC fragment takes place after the transmembrane region and before FZ 1.
CC -!- PTM: A disulfide bond links the activated corin protease fragment and
CC the N-terminal propeptide. The disulfide bond also links the activated
CC corin protease fragment with soluble fragments (100 kDa, 160 kDa and
CC 180 kDa fragments).
CC -!- DISEASE: Pre-eclampsia/eclampsia 5 (PEE5) [MIM:614595]: A hypertensive
CC disorder of pregnancy characterized by new hypertension (blood pressure
CC 140/90 or greater) presenting after 20 weeks' gestation with clinically
CC relevant proteinuria. It impacts 2 individuals, the mother and her
CC child, both of whom can be severely affected. Preeclampsia is one of
CC the causes of maternal mortality and morbidity worldwide.
CC {ECO:0000269|PubMed:22437503}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Initially named CORIN due to its abundant expression in
CC the heart. {ECO:0000305|PubMed:10329693}.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU00274}.
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DR EMBL; AF133845; AAD31850.1; -; mRNA.
DR EMBL; AC092597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC104646; AAY40991.1; -; Genomic_DNA.
DR EMBL; AC107068; AAY40917.1; -; Genomic_DNA.
DR EMBL; EU326305; ACA05911.1; -; Genomic_DNA.
DR EMBL; BC110451; AAI10452.1; -; mRNA.
DR EMBL; AF113248; AAF21966.1; -; mRNA.
DR CCDS; CCDS3477.1; -. [Q9Y5Q5-1]
DR RefSeq; NP_001265514.1; NM_001278585.1.
DR RefSeq; NP_006578.2; NM_006587.3. [Q9Y5Q5-1]
DR AlphaFoldDB; Q9Y5Q5; -.
DR SMR; Q9Y5Q5; -.
DR BioGRID; 115937; 4.
DR IntAct; Q9Y5Q5; 4.
DR STRING; 9606.ENSP00000273857; -.
DR MEROPS; S01.019; -.
DR TCDB; 8.A.131.1.8; the transmembrane protease serine 3 (tmprss3) family.
DR GlyCosmos; Q9Y5Q5; 19 sites, No reported glycans.
DR GlyGen; Q9Y5Q5; 19 sites.
DR iPTMnet; Q9Y5Q5; -.
DR PhosphoSitePlus; Q9Y5Q5; -.
DR BioMuta; CORIN; -.
DR DMDM; 317373348; -.
DR MassIVE; Q9Y5Q5; -.
DR PaxDb; 9606-ENSP00000273857; -.
DR PeptideAtlas; Q9Y5Q5; -.
DR ProteomicsDB; 86472; -. [Q9Y5Q5-1]
DR ProteomicsDB; 86473; -. [Q9Y5Q5-2]
DR Antibodypedia; 23775; 382 antibodies from 27 providers.
DR DNASU; 10699; -.
DR Ensembl; ENST00000273857.9; ENSP00000273857.4; ENSG00000145244.12. [Q9Y5Q5-1]
DR GeneID; 10699; -.
DR KEGG; hsa:10699; -.
DR MANE-Select; ENST00000273857.9; ENSP00000273857.4; NM_006587.4; NP_006578.2.
DR UCSC; uc003gxm.5; human. [Q9Y5Q5-1]
DR AGR; HGNC:19012; -.
DR CTD; 10699; -.
DR DisGeNET; 10699; -.
DR GeneCards; CORIN; -.
DR HGNC; HGNC:19012; CORIN.
DR HPA; ENSG00000145244; Tissue enriched (heart).
DR MalaCards; CORIN; -.
DR MIM; 605236; gene.
DR MIM; 614595; phenotype.
DR neXtProt; NX_Q9Y5Q5; -.
DR OpenTargets; ENSG00000145244; -.
DR Orphanet; 275555; Preeclampsia.
DR PharmGKB; PA134972424; -.
DR VEuPathDB; HostDB:ENSG00000145244; -.
DR eggNOG; KOG3577; Eukaryota.
DR eggNOG; KOG3627; Eukaryota.
DR GeneTree; ENSGT00940000157103; -.
DR InParanoid; Q9Y5Q5; -.
DR OMA; HCSREQT; -.
DR OrthoDB; 4252799at2759; -.
DR PhylomeDB; Q9Y5Q5; -.
DR TreeFam; TF351678; -.
DR PathwayCommons; Q9Y5Q5; -.
DR Reactome; R-HSA-5578768; Physiological factors.
DR SABIO-RK; Q9Y5Q5; -.
DR SignaLink; Q9Y5Q5; -.
DR BioGRID-ORCS; 10699; 7 hits in 1149 CRISPR screens.
DR ChiTaRS; CORIN; human.
DR GeneWiki; CORIN; -.
DR GenomeRNAi; 10699; -.
DR Pharos; Q9Y5Q5; Tbio.
DR PRO; PR:Q9Y5Q5; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9Y5Q5; Protein.
DR Bgee; ENSG00000145244; Expressed in cardiac muscle of right atrium and 118 other cell types or tissues.
DR ExpressionAtlas; Q9Y5Q5; baseline and differential.
DR Genevisible; Q9Y5Q5; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0007565; P:female pregnancy; IMP:UniProtKB.
DR GO; GO:0016486; P:peptide hormone processing; IDA:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR GO; GO:0035813; P:regulation of renal sodium excretion; ISS:UniProtKB.
DR GO; GO:0003050; P:regulation of systemic arterial blood pressure by atrial natriuretic peptide; IMP:UniProtKB.
DR CDD; cd07445; CRD_corin_1; 1.
DR CDD; cd07888; CRD_corin_2; 1.
DR CDD; cd00112; LDLa; 7.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 2.
DR Gene3D; 4.10.400.10; Low-density Lipoprotein Receptor; 7.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 1.
DR InterPro; IPR017052; Corin.
DR InterPro; IPR041762; Corin_CRD_1.
DR InterPro; IPR041763; Corin_CRD_2.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR017448; SRCR-like_dom.
DR InterPro; IPR036772; SRCR-like_dom_sf.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR033116; TRYPSIN_SER.
DR PANTHER; PTHR24252; ACROSIN-RELATED; 1.
DR PANTHER; PTHR24252:SF9; ATRIAL NATRIURETIC PEPTIDE-CONVERTING ENZYME ISOFORM X1; 1.
DR Pfam; PF01392; Fz; 2.
DR Pfam; PF00057; Ldl_recept_a; 6.
DR Pfam; PF15494; SRCR_2; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF036376; Corin; 1.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00063; FRI; 2.
DR SMART; SM00192; LDLa; 7.
DR SMART; SM00202; SR; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF63501; Frizzled cysteine-rich domain; 2.
DR SUPFAM; SSF57424; LDL receptor-like module; 7.
DR SUPFAM; SSF56487; SRCR-like; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1.
DR PROSITE; PS50038; FZ; 2.
DR PROSITE; PS01209; LDLRA_1; 6.
DR PROSITE; PS50068; LDLRA_2; 7.
DR PROSITE; PS00420; SRCR_1; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Autocatalytic cleavage; Cell membrane;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Protease;
KW Reference proteome; Repeat; Secreted; Serine protease; Signal-anchor;
KW Transmembrane; Transmembrane helix; Zymogen.
FT CHAIN 1..1042
FT /note="Atrial natriuretic peptide-converting enzyme"
FT /id="PRO_0000088673"
FT CHAIN 1..801
FT /note="Atrial natriuretic peptide-converting enzyme, N-
FT terminal propeptide"
FT /evidence="ECO:0000305"
FT /id="PRO_0000391765"
FT CHAIN 165..801
FT /note="Atrial natriuretic peptide-converting enzyme, 160
FT kDa soluble fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000417984"
FT CHAIN 428..801
FT /note="Atrial natriuretic peptide-converting enzyme, 100
FT kDa soluble fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000417985"
FT CHAIN ?..801
FT /note="Atrial natriuretic peptide-converting enzyme, 180
FT kDa soluble fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000417986"
FT CHAIN 802..1042
FT /note="Atrial natriuretic peptide-converting enzyme,
FT activated protease fragment"
FT /evidence="ECO:0000305"
FT /id="PRO_0000391766"
FT TOPO_DOM 1..45
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 46..66
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 67..1042
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT DOMAIN 134..259
FT /note="FZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 268..304
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 305..340
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 341..377
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 378..415
FT /note="LDL-receptor class A 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 450..573
FT /note="FZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 579..614
FT /note="LDL-receptor class A 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 615..653
FT /note="LDL-receptor class A 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 654..689
FT /note="LDL-receptor class A 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 690..801
FT /note="SRCR"
FT DOMAIN 802..1035
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 26..29
FT /note="DDNN motif"
FT COMPBIAS 7..21
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 843
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 892
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 985
FT /note="Charge relay system"
FT SITE 164..165
FT /note="Cleavage; by autolysis"
FT SITE 427..428
FT /note="Cleavage; by autolysis"
FT SITE 801..802
FT /note="Cleavage"
FT /evidence="ECO:0000305"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 231
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 376
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 413
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 446
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 451
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 469
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 651
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 697
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 761
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1022
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 139..199
FT /evidence="ECO:0000250"
FT DISULFID 147..192
FT /evidence="ECO:0000250"
FT DISULFID 183..223
FT /evidence="ECO:0000250"
FT DISULFID 212..256
FT /evidence="ECO:0000250"
FT DISULFID 216..240
FT /evidence="ECO:0000250"
FT DISULFID 269..282
FT /evidence="ECO:0000250"
FT DISULFID 277..295
FT /evidence="ECO:0000250"
FT DISULFID 289..304
FT /evidence="ECO:0000250"
FT DISULFID 306..318
FT /evidence="ECO:0000250"
FT DISULFID 313..331
FT /evidence="ECO:0000250"
FT DISULFID 325..340
FT /evidence="ECO:0000250"
FT DISULFID 342..355
FT /evidence="ECO:0000250"
FT DISULFID 350..368
FT /evidence="ECO:0000250"
FT DISULFID 362..377
FT /evidence="ECO:0000250"
FT DISULFID 379..392
FT /evidence="ECO:0000250"
FT DISULFID 387..405
FT /evidence="ECO:0000250"
FT DISULFID 399..414
FT /evidence="ECO:0000250"
FT DISULFID 455..518
FT /evidence="ECO:0000250"
FT DISULFID 463..511
FT /evidence="ECO:0000250"
FT DISULFID 502..540
FT /evidence="ECO:0000250"
FT DISULFID 529..570
FT /evidence="ECO:0000250"
FT DISULFID 533..557
FT /evidence="ECO:0000250"
FT DISULFID 580..592
FT /evidence="ECO:0000250"
FT DISULFID 587..605
FT /evidence="ECO:0000250"
FT DISULFID 599..614
FT /evidence="ECO:0000250"
FT DISULFID 616..630
FT /evidence="ECO:0000250"
FT DISULFID 624..643
FT /evidence="ECO:0000250"
FT DISULFID 637..652
FT /evidence="ECO:0000250"
FT DISULFID 655..667
FT /evidence="ECO:0000250"
FT DISULFID 662..680
FT /evidence="ECO:0000250"
FT DISULFID 674..689
FT /evidence="ECO:0000250"
FT DISULFID 790..912
FT /note="Interchain (between N-terminal propeptide and
FT activated protease fragment chains)"
FT /evidence="ECO:0000305|PubMed:17660514"
FT DISULFID 828..844
FT /evidence="ECO:0000250"
FT DISULFID 926..991
FT /evidence="ECO:0000250"
FT DISULFID 955..970
FT /evidence="ECO:0000250"
FT DISULFID 981..1010
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_043952"
FT VARIANT 13
FT /note="C -> Y (in dbSNP:rs2289433)"
FT /evidence="ECO:0000269|PubMed:10329693,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_038000"
FT VARIANT 317
FT /note="K -> E (in PEE5; dbSNP:rs387906894)"
FT /evidence="ECO:0000269|PubMed:22437503"
FT /id="VAR_067795"
FT VARIANT 444
FT /note="D -> G (in dbSNP:rs13105608)"
FT /id="VAR_067796"
FT VARIANT 472
FT /note="S -> G (in PEE5; dbSNP:rs387906895)"
FT /evidence="ECO:0000269|PubMed:22437503"
FT /id="VAR_067797"
FT VARIANT 525
FT /note="H -> R (in dbSNP:rs11934749)"
FT /evidence="ECO:0000269|PubMed:10329693,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17918732"
FT /id="VAR_038001"
FT MUTAGEN 26
FT /note="D->A: Impairs cell membrane targeting; when
FT associated with A-30."
FT /evidence="ECO:0000269|PubMed:21518754"
FT MUTAGEN 30
FT /note="M->A: Impairs cell membrane targeting; when
FT associated with A-26."
FT /evidence="ECO:0000269|PubMed:21518754"
FT MUTAGEN 134
FT /note="R->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 164
FT /note="R->A: Affects autocatalytic cleavage and production
FT of Atrial natriuretic peptide-converting enzyme, 160 kDa
FT soluble fragment."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 180
FT /note="R->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 213
FT /note="R->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 239
FT /note="R->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 244
FT /note="R->A: Does not affect autocatalytic cleavage."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 427
FT /note="R->A: Affects autocatalytic cleavage and production
FT of Atrial natriuretic peptide-converting enzyme, 100 kDa
FT soluble fragment."
FT /evidence="ECO:0000269|PubMed:21288900"
FT MUTAGEN 801
FT /note="R->A: Loss of activity towards NPPA."
FT /evidence="ECO:0000269|PubMed:14559895,
FT ECO:0000269|PubMed:21288900"
FT MUTAGEN 985
FT /note="S->A: Loss of activity towards NPPA."
FT /evidence="ECO:0000269|PubMed:10880574,
FT ECO:0000269|PubMed:14559895, ECO:0000269|PubMed:21288900"
FT CONFLICT 854
FT /note="W -> R (in Ref. 4; AAF21966)"
FT /evidence="ECO:0000305"
FT CONFLICT 876
FT /note="K -> R (in Ref. 4; AAF21966)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1042 AA; 116486 MW; A3F1CB8EBB676F78 CRC64;
MKQSPALAPE ERCRRAGSPK PVLRADDNNM GNGCSQKLAT ANLLRFLLLV LIPCICALVL
LLVILLSYVG TLQKVYFKSN GSEPLVTDGE IQGSDVILTN TIYNQSTVVS TAHPDQHVPA
WTTDASLPGD QSHRNTSACM NITHSQCQML PYHATLTPLL SVVRNMEMEK FLKFFTYLHR
LSCYQHIMLF GCTLAFPECI IDGDDSHGLL PCRSFCEAAK EGCESVLGMV NYSWPDFLRC
SQFRNQTESS NVSRICFSPQ QENGKQLLCG RGENFLCASG ICIPGKLQCN GYNDCDDWSD
EAHCNCSENL FHCHTGKCLN YSLVCDGYDD CGDLSDEQNC DCNPTTEHRC GDGRCIAMEW
VCDGDHDCVD KSDEVNCSCH SQGLVECRNG QCIPSTFQCD GDEDCKDGSD EENCSVIQTS
CQEGDQRCLY NPCLDSCGGS SLCDPNNSLN NCSQCEPITL ELCMNLPYNS TSYPNYFGHR
TQKEASISWE SSLFPALVQT NCYKYLMFFS CTILVPKCDV NTGEHIPPCR ALCEHSKERC
ESVLGIVGLQ WPEDTDCSQF PEENSDNQTC LMPDEYVEEC SPSHFKCRSG QCVLASRRCD
GQADCDDDSD EENCGCKERD LWECPSNKQC LKHTVICDGF PDCPDYMDEK NCSFCQDDEL
ECANHACVSR DLWCDGEADC SDSSDEWDCV TLSINVNSSS FLMVHRAATE HHVCADGWQE
ILSQLACKQM GLGEPSVTKL IQEQEKEPRW LTLHSNWESL NGTTLHELLV NGQSCESRSK
ISLLCTKQDC GRRPAARMNK RILGGRTSRP GRWPWQCSLQ SEPSGHICGC VLIAKKWVLT
VAHCFEGREN AAVWKVVLGI NNLDHPSVFM QTRFVKTIIL HPRYSRAVVD YDISIVELSE
DISETGYVRP VCLPNPEQWL EPDTYCYITG WGHMGNKMPF KLQEGEVRII SLEHCQSYFD
MKTITTRMIC AGYESGTVDS CMGDSGGPLV CEKPGGRWTL FGLTSWGSVC FSKVLGPGVY
SNVSYFVEWI KRQIYIQTFL LN
//
