ACE_HUMAN
ID ACE_HUMAN Reviewed; 1306 AA.
AC P12821; B0LPF0; B4DXI3; E7EU16; P22966; Q53YX9; Q59GY8; Q7M4L4;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 252.
DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:2849100};
DE Short=ACE {ECO:0000303|PubMed:2849100};
DE EC=3.4.15.1 {ECO:0000269|PubMed:10913258, ECO:0000269|PubMed:11076943, ECO:0000269|PubMed:12542396, ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:7961923};
DE AltName: Full=Dipeptidyl carboxypeptidase I {ECO:0000303|PubMed:4322742};
DE AltName: Full=Kininase II {ECO:0000303|PubMed:6055465};
DE AltName: CD_antigen=CD143;
DE Contains:
DE RecName: Full=Angiotensin-converting enzyme, soluble form;
DE Flags: Precursor;
GN Name=ACE {ECO:0000303|PubMed:2849100, ECO:0000312|HGNC:HGNC:2707};
GN Synonyms=DCP, DCP1;
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 SOMATIC-1).
RX PubMed=2849100; DOI=10.1073/pnas.85.24.9386;
RA Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G.,
RA Corbol P.;
RT "Two putative active centers in human angiotensin I-converting enzyme
RT revealed by molecular cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:9386-9390(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE
RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC).
RX PubMed=2547653; DOI=10.1016/0014-5793(89)80897-x;
RA Lattion A.L., Soubrier F., Allegrini J., Hubert C., Corvol P.,
RA Alhenc-Gelas F.;
RT "The testicular transcript of the angiotensin I-converting enzyme encodes
RT for the ancestral, non-duplicated form of the enzyme.";
RL FEBS Lett. 252:99-104(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE
RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC).
RX PubMed=2554286; DOI=10.1073/pnas.86.20.7741;
RA Ehlers M.R.W., Fox E.A., Strydom D.J., Riordan J.F.;
RT "Molecular cloning of human testicular angiotensin-converting enzyme: the
RT testis isozyme is identical to the C-terminal half of endothelial
RT angiotensin-converting enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:7741-7745(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-261; TRP-561 AND
RP SER-1286.
RX PubMed=10319862; DOI=10.1038/8760;
RA Rieder M.J., Taylor S.L., Clark A.G., Nickerson D.A.;
RT "Sequence variation in the human angiotensin converting enzyme.";
RL Nat. Genet. 22:59-62(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1239 (ISOFORM SOMATIC-1).
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [9]
RP PROTEIN SEQUENCE OF 30-46, FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Lung;
RX PubMed=2558109; DOI=10.1093/oxfordjournals.jbchem.a122871;
RA Takeuchi K., Shimizu T., Ohishi N., Seyama Y., Takaku F., Yotsumoto H.;
RT "Purification of human lung angiotensin-converting enzyme by high-
RT performance liquid chromatography: properties and N-terminal amino acid
RT sequence.";
RL J. Biochem. 106:442-445(1989).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1114-1306 (ISOFORM SOMATIC-2), AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Umbilical vein endothelial cell;
RX PubMed=9642152; DOI=10.1006/bbrc.1998.8813;
RA Sugimura K., Tian X.-L., Hoffmann S., Ganten D., Bader M.;
RT "Alternative splicing of the mRNA coding for the human endothelial
RT angiotensin-converting enzyme: a new mechanism for solubilization.";
RL Biochem. Biophys. Res. Commun. 247:466-472(1998).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=6055465; DOI=10.1038/2151402a0;
RA Yang H.Y., Erdoes E.G.;
RT "Second kininase in human blood plasma.";
RL Nature 215:1402-1403(1967).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=4322742; DOI=10.1016/0005-2795(70)90017-6;
RA Yang H.Y., Erdoes E.G., Levin Y.;
RT "A dipeptidyl carboxypeptidase that converts angiotensin I and inactivates
RT bradykinin.";
RL Biochim. Biophys. Acta 214:374-376(1970).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=656131; DOI=10.1016/0006-2952(78)90542-7;
RA Erdoes E.G., Johnson A.R., Boyden N.T.;
RT "Hydrolysis of enkephalin by cultured human endothelial cells and by
RT purified peptidyl dipeptidase.";
RL Biochem. Pharmacol. 27:843-848(1978).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=6270633; DOI=10.1016/s0196-9781(81)80027-7;
RA Stewart T.A., Weare J.A., Erdoes E.G.;
RT "Purification and characterization of human converting enzyme (kininase
RT II).";
RL Peptides 2:145-152(1981).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=6208535; DOI=10.1016/0196-9781(84)90020-2;
RA Skidgel R.A., Engelbrecht S., Johnson A.R., Erdoes E.G.;
RT "Hydrolysis of substance p and neurotensin by converting enzyme and neutral
RT endopeptidase.";
RL Peptides 5:769-776(1984).
RN [16]
RP FUNCTION.
RX PubMed=2982830; DOI=10.1016/s0021-9258(18)89410-8;
RA Norman J.A., Chang J.Y.;
RT "Proteolytic conversion of [Met]enkephalin-Arg6-Gly7-Leu8 by brain synaptic
RT membranes. Characterization of formed peptides and mechanism of
RT proteolysis.";
RL J. Biol. Chem. 260:2653-2656(1985).
RN [17]
RP FUNCTION.
RX PubMed=2983326; DOI=10.1073/pnas.82.4.1025;
RA Skidgel R.A., Erdoes E.G.;
RT "Novel activity of human angiotensin I converting enzyme: release of the
RT NH2- and COOH-terminal tripeptides from the luteinizing hormone-releasing
RT hormone.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:1025-1029(1985).
RN [18]
RP COFACTOR, AND ZINC-BINDING.
RX PubMed=1649623; DOI=10.1021/bi00243a012;
RA Ehlers M.R.W., Riordan J.F.;
RT "Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries
RT of the somatic and testis isozymes.";
RL Biochemistry 30:7118-7126(1991).
RN [19]
RP ALTERNATIVE PROMOTER USAGE, AND FUNCTION (ISOFORM TESTIS-SPECIFIC).
RX PubMed=1651327; DOI=10.1016/s0021-9258(18)98626-6;
RA Hubert C., Houot A.M., Corvol P., Soubrier F.;
RT "Structure of the angiotensin I-converting enzyme gene. Two alternate
RT promoters correspond to evolutionary steps of a duplicated gene.";
RL J. Biol. Chem. 266:15377-15383(1991).
RN [20]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), CATALYTIC ACTIVITY (ISOFORM
RP TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC), AND
RP SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC).
RX PubMed=1668266; DOI=10.1016/1046-5928(91)90001-y;
RA Ehlers M.R., Chen Y.N., Riordan J.F.;
RT "Purification and characterization of recombinant human testis angiotensin-
RT converting enzyme expressed in Chinese hamster ovary cells.";
RL Protein Expr. Purif. 2:1-9(1991).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992.
RX PubMed=1851160; DOI=10.1016/s0021-9258(18)31543-6;
RA Wei L., Alhenc-Gelas F., Corvol P., Clauser E.;
RT "The two homologous domains of human angiotensin I-converting enzyme are
RT both catalytically active.";
RL J. Biol. Chem. 266:9002-9008(1991).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP 390-HIS--HIS-394 AND 988-HIS--HIS-992.
RX PubMed=1320019; DOI=10.1016/s0021-9258(18)42224-7;
RA Wei L., Clauser E., Alhenc-Gelas F., Corvol P.;
RT "The two homologous domains of human angiotensin I-converting enzyme
RT interact differently with competitive inhibitors.";
RL J. Biol. Chem. 267:13398-13405(1992).
RN [23]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8257427; DOI=10.1042/bj2960373;
RA Rieger K.J., Saez-Servent N., Papet M.P., Wdzieczak-Bakala J., Morgat J.L.,
RA Thierry J., Voelter W., Lenfant M.;
RT "Involvement of human plasma angiotensin I-converting enzyme in the
RT degradation of the haemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-
RT proline.";
RL Biochem. J. 296:373-378(1993).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND
RP MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992.
RX PubMed=7683654; DOI=10.1016/s0021-9258(18)98378-x;
RA Jaspard E., Wei L., Alhenc-Gelas F.;
RT "Differences in the properties and enzymatic specificities of the two
RT active sites of angiotensin I-converting enzyme (kininase II). Studies with
RT bradykinin and other natural peptides.";
RL J. Biol. Chem. 268:9496-9503(1993).
RN [25]
RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE
RP FORM), AND MUTAGENESIS OF ARG-1166.
RX PubMed=8253769; DOI=10.1016/s0021-9258(19)74332-4;
RA Beldent V., Michaud A., Wei L., Chauvet M.T., Corvol P.;
RT "Proteolytic release of human angiotensin-converting enzyme. Localization
RT of the cleavage site.";
RL J. Biol. Chem. 268:26428-26434(1993).
RN [26]
RP FUNCTION.
RX PubMed=7523412; DOI=10.1016/s0021-9258(18)47091-3;
RA Danilov S., Jaspard E., Churakova T., Towbin H., Savoie F., Wei L.,
RA Alhenc-Gelas F.;
RT "Structure-function analysis of angiotensin I-converting enzyme using
RT monoclonal antibodies. Selective inhibition of the amino-terminal active
RT site.";
RL J. Biol. Chem. 269:26806-26814(1994).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF
RP 390-HIS--HIS-394; GLU-1016 AND ASP-1020.
RX PubMed=7961923; DOI=10.1016/s0021-9258(18)43897-5;
RA Williams T.A., Corvol P., Soubrier F.;
RT "Identification of two active site residues in human angiotensin I-
RT converting enzyme.";
RL J. Biol. Chem. 269:29430-29434(1994).
RN [28]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF 390-HIS--HIS-394.
RX PubMed=7876104; DOI=10.1074/jbc.270.8.3656;
RA Rousseau A., Michaud A., Chauvet M.T., Lenfant M., Corvol P.;
RT "The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and
RT specific substrate of the N-terminal active site of human angiotensin-
RT converting enzyme.";
RL J. Biol. Chem. 270:3656-3661(1995).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE
RP FORM), PROTEOLYTIC CLEAVAGE, AND CLEAVAGE SITE.
RX PubMed=7499427; DOI=10.1074/jbc.270.48.28962;
RA Beldent V., Michaud A., Bonnefoy C., Chauvet M.T., Corvol P.;
RT "Cell surface localization of proteolysis of human endothelial angiotensin
RT I-converting enzyme. Effect of the amino-terminal domain in the
RT solubilization process.";
RL J. Biol. Chem. 270:28962-28969(1995).
RN [30]
RP DISULFIDE BONDS.
RX PubMed=8755737; DOI=10.1021/bi960243x;
RA Sturrock E.D., Yu X.C., Wu Z., Biemann K., Riordan J.F.;
RT "Assignment of free and disulfide-bonded cysteine residues in testis
RT angiotensin-converting enzyme: functional implications.";
RL Biochemistry 35:9560-9566(1996).
RN [31]
RP SUBCELLULAR LOCATION (ISOFORM TESTIS-SPECIFIC), GLYCOSYLATION AT ASN-103;
RP ASN-121; ASN-140; ASN-368 AND ASN-617 (ISOFORM TESTIS-SPECIFIC), AND
RP MUTAGENESIS OF ASN-103; ASN-121; ASN-140; ASN-186 AND ASN-617 (ISOFORM
RP TESTIS-SPECIFIC).
RX PubMed=8626443; DOI=10.1074/jbc.271.11.6429;
RA Sadhukhan R., Sen I.;
RT "Different glycosylation requirements for the synthesis of enzymatically
RT active angiotensin-converting enzyme in mammalian cells and yeast.";
RL J. Biol. Chem. 271:6429-6434(1996).
RN [32]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=8609242; DOI=10.1172/jci118484;
RA Azizi M., Rousseau A., Ezan E., Guyene T.T., Michelet S., Grognet J.M.,
RA Lenfant M., Corvol P., Menard J.;
RT "Acute angiotensin-converting enzyme inhibition increases the plasma level
RT of the natural stem cell regulator N-acetyl-seryl-aspartyl-lysyl-proline.";
RL J. Clin. Invest. 97:839-844(1996).
RN [33]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9371719; DOI=10.1042/bj3280587;
RA Isaac R.E., Williams T.A., Sajid M., Corvol P., Coates D.;
RT "Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of
RT pro-hormone peptides by human germinal angiotensin I-converting enzyme
RT (ACE) and the C-domain of human somatic ACE.";
RL Biochem. J. 328:587-591(1997).
RN [34]
RP GLYCOSYLATION AT ASN-38; ASN-54; ASN-111; ASN-146; ASN-509; ASN-695;
RP ASN-714; ASN-760; ASN-942 AND ASN-1191, LACK OF GLYCOSYLATION AT ASN-1225,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=9013598; DOI=10.1074/jbc.272.6.3511;
RA Yu X.C., Sturrock E.D., Wu Z., Biemann K., Ehlers M.R.W., Riordan J.F.;
RT "Identification of N-linked glycosylation sites in human testis
RT angiotensin-converting enzyme and expression of an active deglycosylated
RT form.";
RL J. Biol. Chem. 272:3511-3519(1997).
RN [35]
RP FUNCTION, AND MUTAGENESIS OF 390-HIS--HIS-394 AND 988-HIS--HIS-992.
RX PubMed=10336644; DOI=10.1046/j.1432-1327.1999.00419.x;
RA Isaac R.E., Michaud A., Keen J.N., Williams T.A., Coates D., Wetsel W.C.,
RA Corvol P.;
RT "Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides
RT from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-
RT terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.";
RL Eur. J. Biochem. 262:569-574(1999).
RN [36]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10913258; DOI=10.1021/bi9928905;
RA Araujo M.C., Melo R.L., Cesari M.H., Juliano M.A., Juliano L.,
RA Carmona A.K.;
RT "Peptidase specificity characterization of C- and N-terminal catalytic
RT sites of angiotensin I-converting enzyme.";
RL Biochemistry 39:8519-8525(2000).
RN [37]
RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE
RP FORM), PROTEOLYTIC CLEAVAGE, CLEAVAGE SITE, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=10769174; DOI=10.1042/bj3470711;
RA Woodman Z.L., Oppong S.Y., Cook S., Hooper N.M., Schwager S.L.U.,
RA Brandt W.F., Ehlers M.R.W., Sturrock E.D.;
RT "Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient
RT compared with testis ACE despite cleavage at identical stalk sites.";
RL Biochem. J. 347:711-718(2000).
RN [38]
RP TISSUE SPECIFICITY.
RX PubMed=10969042; DOI=10.1161/01.res.87.5.e1;
RA Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N.,
RA Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.;
RT "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2)
RT converts angiotensin I to angiotensin 1-9.";
RL Circ. Res. 87:E1-E9(2000).
RN [39]
RP TISSUE SPECIFICITY.
RX PubMed=10924499; DOI=10.1074/jbc.m002615200;
RA Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.;
RT "A human homolog of angiotensin-converting enzyme. Cloning and functional
RT expression as a captopril-insensitive carboxypeptidase.";
RL J. Biol. Chem. 275:33238-33243(2000).
RN [40]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND CHARACTERIZATION OF
RP VARIANT LEU-1228.
RX PubMed=11076943; DOI=10.1074/jbc.m007706200;
RA Eyries M., Michaud A., Deinum J., Agrapart M., Chomilier J., Kramers C.,
RA Soubrier F.;
RT "Increased shedding of angiotensin-converting enzyme by a mutation
RT identified in the stalk region.";
RL J. Biol. Chem. 276:5525-5532(2001).
RN [41]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND
RP MUTAGENESIS OF ARG-529 AND ARG-1127.
RX PubMed=11432860; DOI=10.1074/jbc.m101495200;
RA Liu X., Fernandez M., Wouters M.A., Heyberger S., Husain A.;
RT "Arg(1098) is critical for the chloride dependence of human angiotensin I-
RT converting enzyme C-domain catalytic activity.";
RL J. Biol. Chem. 276:33518-33525(2001).
RN [42]
RP FUNCTION, SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE
RP FORM), PROTEOLYTIC CLEAVAGE, CLEAVAGE SITE, AND MUTAGENESIS OF ASN-1229.
RX PubMed=11274151; DOI=10.1074/jbc.m100339200;
RA Alfalah M., Parkin E.T., Jacob R., Sturrock E.D., Mentele R., Turner A.J.,
RA Hooper N.M., Naim H.Y.;
RT "A point mutation in the juxtamembrane stalk of human angiotensin I-
RT converting enzyme invokes the action of a distinct secretase.";
RL J. Biol. Chem. 276:21105-21109(2001).
RN [43]
RP FUNCTION.
RX PubMed=11604391; DOI=10.1074/jbc.m104068200;
RA Hu J., Igarashi A., Kamata M., Nakagawa H.;
RT "Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A
RT beta); retards A beta aggregation, deposition, fibril formation; and
RT inhibits cytotoxicity.";
RL J. Biol. Chem. 276:47863-47868(2001).
RN [44]
RP PHOSPHORYLATION AT SER-1299, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-1299.
RX PubMed=12386153; DOI=10.1161/01.res.0000038114.17939.c8;
RA Kohlstedt K., Shoghi F., Mueller-Esterl W., Busse R., Fleming I.;
RT "CK2 phosphorylates the angiotensin-converting enzyme and regulates its
RT retention in the endothelial cell plasma membrane.";
RL Circ. Res. 91:749-756(2002).
RN [45]
RP TISSUE SPECIFICITY.
RX PubMed=12459472; DOI=10.1016/s0014-5793(02)03640-2;
RA Harmer D., Gilbert M., Borman R., Clark K.L.;
RT "Quantitative mRNA expression profiling of ACE 2, a novel homologue of
RT angiotensin converting enzyme.";
RL FEBS Lett. 532:107-110(2002).
RN [46]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND CLEAVAGE SITE.
RX PubMed=12542396; DOI=10.1042/bj20021842;
RA Gordon K., Redelinghuys P., Schwager S.L.U., Ehlers M.R.W.,
RA Papageorgiou A.C., Natesh R., Acharya K.R., Sturrock E.D.;
RT "Deglycosylation, processing and crystallization of human testis
RT angiotensin-converting enzyme.";
RL Biochem. J. 371:437-442(2003).
RN [47]
RP INDUCTION.
RX PubMed=15151696; DOI=10.1186/1741-7015-2-19;
RA Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.;
RT "ACE2 gene expression is up-regulated in the human failing heart.";
RL BMC Med. 2:19-19(2004).
RN [48]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15671045; DOI=10.1093/eurheartj/ehi114;
RA Burrell L.M., Risvanis J., Kubota E., Dean R.G., MacDonald P.S., Lu S.,
RA Tikellis C., Grant S.L., Lew R.A., Smith A.I., Cooper M.E., Johnston C.I.;
RT "Myocardial infarction increases ACE2 expression in rat and humans.";
RL Eur. Heart J. 26:369-375(2005).
RN [49]
RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-1116 AND TYR-1125.
RX PubMed=15615692; DOI=10.1074/jbc.m412638200;
RA Naqvi N., Liu K., Graham R.M., Husain A.;
RT "Molecular basis of exopeptidase activity in the C-terminal domain of human
RT angiotensin I-converting enzyme: insights into the origins of its
RT exopeptidase activity.";
RL J. Biol. Chem. 280:6669-6675(2005).
RN [50]
RP FUNCTION, ACTIVE SITES, AND MUTAGENESIS OF GLU-391 AND GLU-989.
RX PubMed=16154999; DOI=10.1074/jbc.m508460200;
RA Hemming M.L., Selkoe D.J.;
RT "Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme
RT (ACE) and elevated by an ACE inhibitor.";
RL J. Biol. Chem. 280:37644-37650(2005).
RN [51]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-509; ASN-695 AND ASN-714.
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 [52]
RP SUBUNIT.
RX PubMed=16476786; DOI=10.1124/mol.105.020636;
RA Kohlstedt K., Gershome C., Friedrich M., Mueller-Esterl W.,
RA Alhenc-Gelas F., Busse R., Fleming I.;
RT "Angiotensin-converting enzyme (ACE) dimerization is the initial step in
RT the ACE inhibitor-induced ACE signaling cascade in endothelial cells.";
RL Mol. Pharmacol. 69:1725-1732(2006).
RN [53]
RP FUNCTION.
RX PubMed=18077343; DOI=10.1073/pnas.0706980105;
RA Heimann A.S., Gomes I., Dale C.S., Pagano R.L., Gupta A., de Souza L.L.,
RA Luchessi A.D., Castro L.M., Giorgi R., Rioli V., Ferro E.S., Devi L.A.;
RT "Hemopressin is an inverse agonist of CB1 cannabinoid receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:20588-20593(2007).
RN [54]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITES, AND MUTAGENESIS OF GLU-391 AND
RP GLU-989.
RX PubMed=19773553; DOI=10.1074/jbc.m109.011437;
RA Zou K., Maeda T., Watanabe A., Liu J., Liu S., Oba R., Satoh Y., Komano H.,
RA Michikawa M.;
RT "Abeta42-to-Abeta40- and angiotensin-converting activities in different
RT domains of angiotensin-converting enzyme.";
RL J. Biol. Chem. 284:31914-31920(2009).
RN [55]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-111; ASN-445 AND ASN-714.
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 [56]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [57]
RP PHOSPHORYLATION AT SER-1299, AND MUTAGENESIS OF SER-1299.
RX PubMed=21901117; DOI=10.1371/journal.pone.0022803;
RA Barauna V.G., Campos L.C., Miyakawa A.A., Krieger J.E.;
RT "ACE as a mechanosensor to shear stress influences the control of its own
RT regulation via phosphorylation of cytoplasmic Ser(1270).";
RL PLoS ONE 6:e22803-e22803(2011).
RN [58] {ECO:0007744|PDB:1O86, ECO:0007744|PDB:1O8A}
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230, X-RAY CRYSTALLOGRAPHY
RP (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH CHLORIDE AND LISINOPRIL, ACTIVE
RP SITE, AND ACTIVITY REGULATION.
RX PubMed=12540854; DOI=10.1038/nature01370;
RA Natesh R., Schwager S.L.U., Sturrock E.D., Acharya K.R.;
RT "Crystal structure of the human angiotensin-converting enzyme-lisinopril
RT complex.";
RL Nature 421:551-554(2003).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 642-1230 IN COMPLEX WITH
RP ENALAPRILAT, AND X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN
RP COMPLEX WITH CAPTOPRIL.
RX PubMed=15236580; DOI=10.1021/bi049480n;
RA Natesh R., Schwager S.L.U., Evans H.R., Sturrock E.D., Acharya K.R.;
RT "Structural details on the binding of antihypertensive drugs captopril and
RT enalaprilat to human testicular angiotensin I-converting enzyme.";
RL Biochemistry 43:8718-8724(2004).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 30-641 IN COMPLEX WITH LISINOPRIL;
RP ZINC AND CHLORIDE IONS, ACTIVITY REGULATION, AND GLYCOSYLATION AT ASN-54;
RP ASN-74; ASN-146; ASN-318 AND ASN-509.
RX PubMed=16476442; DOI=10.1016/j.jmb.2006.01.048;
RA Corradi H.R., Schwager S.L.U., Nchinda A.T., Sturrock E.D., Acharya K.R.;
RT "Crystal structure of the N domain of human somatic angiotensin I-
RT converting enzyme provides a structural basis for domain-specific inhibitor
RT design.";
RL J. Mol. Biol. 357:964-974(2006).
RN [61] {ECO:0007744|PDB:2OC2, ECO:0007744|PDB:3NXQ}
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 30-658 IN COMPLEX WITH ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, GLYCOSYLATION AT ASN-38; ASN-54;
RP ASN-74; ASN-111 ASN-146; ASN-160; ASN-445 AND ASN-509, LACK OF
RP GLYCOSYLATION AT ASN-523, AND MUTAGENESIS OF ASN-318; ASN-445 AND ASN-509.
RX PubMed=20826823; DOI=10.1074/jbc.m110.167866;
RA Anthony C.S., Corradi H.R., Schwager S.L., Redelinghuys P., Georgiadis D.,
RA Dive V., Acharya K.R., Sturrock E.D.;
RT "The N domain of human angiotensin-I-converting enzyme: the role of N-
RT glycosylation and the crystal structure in complex with an N domain-
RT specific phosphinic inhibitor, RXP407.";
RL J. Biol. Chem. 285:35685-35693(2010).
RN [62] {ECO:0007744|PDB:2YDM}
RP X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC
RP (ISOFORM TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM TESTIS-SPECIFIC),
RP COFACTOR, AND GLYCOSYLATION AT ASN-103 AND ASN-140 (ISOFORM
RP TESTIS-SPECIFIC).
RX PubMed=21810173; DOI=10.1111/j.1742-4658.2011.08276.x;
RA Akif M., Masuyer G., Schwager S.L., Bhuyan B.J., Mugesh G., Isaac R.E.,
RA Sturrock E.D., Acharya K.R.;
RT "Structural characterization of angiotensin I-converting enzyme in complex
RT with a selenium analogue of captopril.";
RL FEBS J. 278:3644-3650(2011).
RN [63] {ECO:0007744|PDB:4APH, ECO:0007744|PDB:4APJ}
RP X-RAY CRYSTALLOGRAPHY (1.99 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND GLYCOSYLATION AT ASN-677 AND
RP ASN-714.
RX PubMed=23056909; DOI=10.1038/srep00717;
RA Masuyer G., Schwager S.L., Sturrock E.D., Isaac R.E., Acharya K.R.;
RT "Molecular recognition and regulation of human angiotensin-I converting
RT enzyme (ACE) activity by natural inhibitory peptides.";
RL Sci. Rep. 2:717-717(2012).
RN [64] {ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2O, ECO:0007744|PDB:4C2P, ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 69-732 IN COMPLEX WITH ZINC
RP (ISOFORM TESTIS-SPECIFIC), FUNCTION, COFACTOR, GLYCOSYLATION AT ASN-103 AND
RP ASN-140 (ISOFORM TESTIS-SPECIFIC), AND MUTAGENESIS OF ARG-553 (ISOFORM
RP TESTIS-SPECIFIC).
RX PubMed=24297181; DOI=10.1074/jbc.m113.512335;
RA Yates C.J., Masuyer G., Schwager S.L., Akif M., Sturrock E.D.,
RA Acharya K.R.;
RT "Molecular and thermodynamic mechanisms of the chloride-dependent human
RT angiotensin-I-converting enzyme (ACE).";
RL J. Biol. Chem. 289:1798-1814(2014).
RN [65] {ECO:0007744|PDB:4UFA, ECO:0007744|PDB:4UFB}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 30-657 IN COMPLEX WITH ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND GLYCOSYLATION AT ASN-74;
RP ASN-445 AND ASN-509.
RX PubMed=26403559; DOI=10.1038/srep13742;
RA Masuyer G., Douglas R.G., Sturrock E.D., Acharya K.R.;
RT "Structural basis of Ac-SDKP hydrolysis by Angiotensin-I converting
RT enzyme.";
RL Sci. Rep. 5:13742-13742(2015).
RN [66]
RP INVOLVEMENT IN MVCD3.
RX PubMed=10099885;
RA Vleming L.J., van der Pijl J.W., Lemkes H.H.P.J., Westendorp R.G.J.,
RA Maassen J.A., Daha M.R., van Es L.A., van Kooten C.;
RT "The DD genotype of the ACE gene polymorphism is associated with
RT progression of diabetic nephropathy to end stage renal failure in IDDM.";
RL Clin. Nephrol. 51:133-140(1999).
RN [67]
RP VARIANTS THR-1018; VAL-1051; GLN-1279; SER-1286 AND PRO-1296.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [68]
RP VARIANT LEU-1228, AND ASSOCIATION WITH BENIGN SERUM INCREASE OF
RP ANGIOTENSIN-CONVERTING ENZYME.
RX PubMed=11551873; DOI=10.1161/hc3601.095932;
RA Kramers C., Danilov S.M., Deinum J., Balyasnikova I.V., Scharenborg N.,
RA Looman M., Boomsma F., de Keijzer M.H., van Duijn C., Martin S.,
RA Soubrier F., Adema G.J.;
RT "Point mutation in the stalk of angiotensin-converting enzyme causes a
RT dramatic increase in serum angiotensin-converting enzyme but no
RT cardiovascular disease.";
RL Circulation 104:1236-1240(2001).
RN [69]
RP VARIANT LEU-1228, AND ASSOCIATION WITH BENIGN SERUM INCREASE OF
RP ANGIOTENSIN-CONVERTING ENZYME.
RX PubMed=14694062; DOI=10.1212/01.wnl.0000098990.12845.da;
RA Linnebank M., Kesper K., Jeub M., Urbach H., Wuellner U., Klockgether T.,
RA Schmidt S.;
RT "Hereditary elevation of angiotensin converting enzyme suggesting
RT neurosarcoidosis.";
RL Neurology 61:1819-1820(2003).
RN [70]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR.
RX PubMed=15534175; DOI=10.1001/archneur.61.11.1652;
RA Casas J.P., Hingorani A.D., Bautista L.E., Sharma P.;
RT "Meta-analysis of genetic studies in ischemic stroke: thirty-two genes
RT involving approximately 18,000 cases and 58,000 controls.";
RL Arch. Neurol. 61:1652-1661(2004).
RN [71]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ICH.
RX PubMed=15277638; DOI=10.1212/01.wnl.0000130200.12993.0c;
RA Slowik A., Turaj W., Dziedzic T., Haefele A., Pera J., Malecki M.T.,
RA Glodzik-Sobanska L., Szermer P., Figlewicz D.A., Szczudlik A.;
RT "DD genotype of ACE gene is a risk factor for intracerebral hemorrhage.";
RL Neurology 63:359-361(2004).
RN [72]
RP INVOLVEMENT IN RTD, AND VARIANT ARG-354.
RX PubMed=16116425; DOI=10.1038/ng1623;
RA Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N.,
RA Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., Delezoide A.-L.,
RA Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M.,
RA Antignac C., Gubler M.-C.;
RT "Mutations in genes in the renin-angiotensin system are associated with
RT autosomal recessive renal tubular dysgenesis.";
RL Nat. Genet. 37:964-968(2005).
RN [73]
RP VARIANT ASN-295.
RX PubMed=25787250; DOI=10.1073/pnas.1503696112;
RA Cromer M.K., Choi M., Nelson-Williams C., Fonseca A.L., Kunstman J.W.,
RA Korah R.M., Overton J.D., Mane S., Kenney B., Malchoff C.D., Stalberg P.,
RA Akerstroem G., Westin G., Hellman P., Carling T., Bjoerklund P.,
RA Lifton R.P.;
RT "Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in
RT insulin-producing adenomas.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:4062-4067(2015).
CC -!- FUNCTION: Dipeptidyl carboxypeptidase that removes dipeptides from the
CC C-terminus of a variety of circulating hormones, such as angiotensin I,
CC bradykinin or enkephalins, thereby playing a key role in the regulation
CC of blood pressure, electrolyte homeostasis or synaptic plasticity
CC (PubMed:2558109, PubMed:4322742, PubMed:7683654, PubMed:7523412,
CC PubMed:15615692, PubMed:20826823). Composed of two similar catalytic
CC domains, each possessing a functional active site, with different
CC selectivity for substrates (PubMed:1851160, PubMed:1320019,
CC PubMed:7683654, PubMed:7876104, PubMed:10913258, PubMed:19773553).
CC Plays a major role in the angiotensin-renin system that regulates blood
CC pressure and sodium retention by the kidney by converting angiotensin I
CC to angiotensin II, resulting in an increase of the vasoconstrictor
CC activity of angiotensin (PubMed:4322742, PubMed:1851160,
CC PubMed:11432860, PubMed:19773553, PubMed:23056909). Also able to
CC inactivate bradykinin, a potent vasodilator, and therefore enhance the
CC blood pressure response (PubMed:2558109, PubMed:6055465,
CC PubMed:4322742, PubMed:6270633, PubMed:7683654, PubMed:15615692). Acts
CC as a regulator of synaptic transmission by mediating cleavage of
CC neuropeptide hormones, such as substance P, neurotensin or enkephalins
CC (PubMed:656131, PubMed:6270633, PubMed:6208535, PubMed:15615692).
CC Catalyzes degradation of different enkephalin neuropeptides (Met-
CC enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-
CC enkephalin-Arg-Gly-Leu) (PubMed:656131, PubMed:6270633,
CC PubMed:2982830). Acts as a regulator of synaptic plasticity in the
CC nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-
CC Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-
CC enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE
CC decreases activation of OPRM1, leading to long-term synaptic
CC potentiation of glutamate release (By similarity). Also acts as a
CC regulator of hematopoietic stem cell differentiation by mediating
CC degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP)
CC (PubMed:8257427, PubMed:7876104, PubMed:8609242, PubMed:26403559). Acts
CC as a regulator of cannabinoid signaling pathway by mediating
CC degradation of hemopressin, an antagonist peptide of the cannabinoid
CC receptor CNR1 (PubMed:18077343). Involved in amyloid-beta metabolism by
CC catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta
CC protein 42 peptides, thereby preventing plaque formation
CC (PubMed:11604391, PubMed:16154999, PubMed:19773553). Catalyzes cleavage
CC of cholecystokinin (maturation of Cholecystokinin-8 and
CC Cholecystokinin-5) and Gonadoliberin-1 (both maturation and
CC degradation) hormones (PubMed:2983326, PubMed:7683654, PubMed:9371719,
CC PubMed:10336644). Degradation of hemoregulatory peptide N-acetyl-SDKP
CC (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal
CC catalytic domain, while angiotensin I and cholecystokinin cleavage is
CC mediated by the C-terminal catalytic region (PubMed:7876104,
CC PubMed:10336644, PubMed:19773553). {ECO:0000250|UniProtKB:P09470,
CC ECO:0000269|PubMed:10336644, ECO:0000269|PubMed:10913258,
CC ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:11604391,
CC ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:15615692,
CC ECO:0000269|PubMed:16154999, ECO:0000269|PubMed:18077343,
CC ECO:0000269|PubMed:1851160, ECO:0000269|PubMed:19773553,
CC ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:23056909,
CC ECO:0000269|PubMed:2558109, ECO:0000269|PubMed:26403559,
CC ECO:0000269|PubMed:2982830, ECO:0000269|PubMed:2983326,
CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465,
CC ECO:0000269|PubMed:6208535, ECO:0000269|PubMed:6270633,
CC ECO:0000269|PubMed:656131, ECO:0000269|PubMed:7523412,
CC ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104,
CC ECO:0000269|PubMed:8257427, ECO:0000269|PubMed:8609242,
CC ECO:0000269|PubMed:9371719}.
CC -!- FUNCTION: [Angiotensin-converting enzyme, soluble form]: Soluble form
CC that is released in blood plasma and other body fluids following
CC proteolytic cleavage in the juxtamembrane stalk region.
CC {ECO:0000269|PubMed:10769174, ECO:0000269|PubMed:11274151,
CC ECO:0000269|PubMed:7499427, ECO:0000269|PubMed:8253769}.
CC -!- FUNCTION: [Isoform Testis-specific]: Isoform produced by alternative
CC promoter usage that is specifically expressed in spermatocytes and
CC adult testis, and which is required for male fertility (PubMed:1651327,
CC PubMed:1668266). In contrast to somatic isoforms, only contains one
CC catalytic domain (PubMed:1651327, PubMed:1668266). Acts as a dipeptidyl
CC carboxypeptidase that removes dipeptides from the C-terminus of
CC substrates (PubMed:1668266, PubMed:24297181). The identity of
CC substrates that are needed for male fertility is unknown (By
CC similarity). May also have a glycosidase activity which releases GPI-
CC anchored proteins from the membrane by cleaving the mannose linkage in
CC the GPI moiety. The GPIase activity was reported to be essential for
CC the egg-binding ability of the sperm (By similarity). This activity is
CC however unclear and has been challenged by other groups, suggesting
CC that it may be indirect (By similarity). {ECO:0000250|UniProtKB:P09470,
CC ECO:0000269|PubMed:1651327, ECO:0000269|PubMed:1668266,
CC ECO:0000269|PubMed:24297181}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa,
CC when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion
CC of angiotensin I to angiotensin II, with increase in vasoconstrictor
CC activity, but no action on angiotensin II.; EC=3.4.15.1;
CC Evidence={ECO:0000269|PubMed:10913258, ECO:0000269|PubMed:11076943,
CC ECO:0000269|PubMed:12542396, ECO:0000269|PubMed:1320019,
CC ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:2558109,
CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:7961923};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=angiotensin I + H2O = angiotensin II + L-histidyl-L-leucine;
CC Xref=Rhea:RHEA:63560, ChEBI:CHEBI:15377, ChEBI:CHEBI:58506,
CC ChEBI:CHEBI:147350, ChEBI:CHEBI:147392; EC=3.4.15.1;
CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:1851160,
CC ECO:0000269|PubMed:19773553, ECO:0000269|PubMed:23056909,
CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6270633};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561;
CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:1851160,
CC ECO:0000269|PubMed:19773553, ECO:0000269|PubMed:23056909,
CC ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6270633};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bradykinin + H2O = bradykinin(1-7) + L-Phe-L-Arg;
CC Xref=Rhea:RHEA:71451, ChEBI:CHEBI:15377, ChEBI:CHEBI:132988,
CC ChEBI:CHEBI:133147, ChEBI:CHEBI:147352;
CC Evidence={ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465,
CC ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7683654,
CC ECO:0000305|PubMed:2558109};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71452;
CC Evidence={ECO:0000269|PubMed:4322742, ECO:0000269|PubMed:6055465,
CC ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7683654,
CC ECO:0000305|PubMed:2558109};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + substance P = L-Leu-L-Met-NH2 + substance P(1-9);
CC Xref=Rhea:RHEA:71459, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692,
CC ChEBI:CHEBI:190693, ChEBI:CHEBI:190700;
CC Evidence={ECO:0000269|PubMed:6208535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460;
CC Evidence={ECO:0000269|PubMed:6208535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + substance P = Gly-L-Leu-L-Met-NH2 + substance P(1-8);
CC Xref=Rhea:RHEA:71463, ChEBI:CHEBI:15377, ChEBI:CHEBI:190692,
CC ChEBI:CHEBI:190694, ChEBI:CHEBI:190699;
CC Evidence={ECO:0000269|PubMed:6208535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71464;
CC Evidence={ECO:0000269|PubMed:6208535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + substance P = L-Phe-L-Phe-Gly-L-Leu-L-Met-NH2 +
CC substance P(1-6); Xref=Rhea:RHEA:71471, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:190692, ChEBI:CHEBI:190696, ChEBI:CHEBI:190697;
CC Evidence={ECO:0000269|PubMed:6208535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71472;
CC Evidence={ECO:0000269|PubMed:6208535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + neurotensin = L-isoleucyl-L-leucine + neurotensin(1-11);
CC Xref=Rhea:RHEA:71475, ChEBI:CHEBI:15377, ChEBI:CHEBI:147362,
CC ChEBI:CHEBI:190704, ChEBI:CHEBI:190706;
CC Evidence={ECO:0000269|PubMed:6208535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476;
CC Evidence={ECO:0000269|PubMed:6208535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=goralatide + H2O = L-lysyl-L-proline + N-acetyl-L-seryl-L-
CC aspartate; Xref=Rhea:RHEA:71455, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:190701, ChEBI:CHEBI:190702, ChEBI:CHEBI:190703;
CC Evidence={ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:7876104,
CC ECO:0000269|PubMed:8257427};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71456;
CC Evidence={ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:7876104,
CC ECO:0000269|PubMed:8257427};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + Met-enkephalin = L-phenylalanyl-L-methionine + L-
CC tyrosylglycylglycine; Xref=Rhea:RHEA:71483, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:189868, ChEBI:CHEBI:190708, ChEBI:CHEBI:190709;
CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71484;
CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + Leu-enkephalin = L-phenylalanyl-L-leucine + L-
CC tyrosylglycylglycine; Xref=Rhea:RHEA:71487, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:190689, ChEBI:CHEBI:190708, ChEBI:CHEBI:190710;
CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71488;
CC Evidence={ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:656131};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + Met-enkephalin-Arg-Phe = L-arginyl-L-phenylalanine +
CC Met-enkephalin; Xref=Rhea:RHEA:70675, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:189868, ChEBI:CHEBI:189869, ChEBI:CHEBI:189870;
CC Evidence={ECO:0000250|UniProtKB:P09470};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70676;
CC Evidence={ECO:0000250|UniProtKB:P09470};
CC -!- CATALYTIC ACTIVITY: [Isoform Testis-specific]:
CC Reaction=Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa,
CC when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion
CC of angiotensin I to angiotensin II, with increase in vasoconstrictor
CC activity, but no action on angiotensin II.; EC=3.4.15.1;
CC Evidence={ECO:0000269|PubMed:1668266};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:16476442,
CC ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:20826823,
CC ECO:0000269|PubMed:23056909, ECO:0000269|PubMed:26403559,
CC ECO:0000269|PubMed:7961923};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:12540854,
CC ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:1649623};
CC -!- COFACTOR: [Isoform Testis-specific]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:21810173,
CC ECO:0000269|PubMed:24297181};
CC Note=Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.
CC {ECO:0000269|PubMed:1649623, ECO:0000269|PubMed:21810173,
CC ECO:0000269|PubMed:24297181};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:11432860, ECO:0000269|PubMed:12540854,
CC ECO:0000269|PubMed:16476442};
CC Note=Binds 3 chloride ions per subunit. {ECO:0000269|PubMed:12540854,
CC ECO:0000269|PubMed:16476442};
CC -!- COFACTOR: [Isoform Testis-specific]:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000269|PubMed:24297181};
CC -!- ACTIVITY REGULATION: The dipeptidyl carboxypeptidase activity is
CC strongly activated by chloride (PubMed:7683654, PubMed:11432860,
CC PubMed:15615692, PubMed:12540854, PubMed:16476442). The dipeptidyl
CC carboxypeptidase activity is specifically inhibited by lisinopril,
CC captopril and enalaprilat (PubMed:6270633, PubMed:6208535,
CC PubMed:1320019, PubMed:7876104, PubMed:8609242, PubMed:12540854,
CC PubMed:16476442). {ECO:0000269|PubMed:11432860,
CC ECO:0000269|PubMed:12540854, ECO:0000269|PubMed:1320019,
CC ECO:0000269|PubMed:15615692, ECO:0000269|PubMed:16476442,
CC ECO:0000269|PubMed:6208535, ECO:0000269|PubMed:6270633,
CC ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104,
CC ECO:0000269|PubMed:8609242}.
CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: Strongly inhibited by
CC lisinopril and captopril. {ECO:0000269|PubMed:1668266,
CC ECO:0000269|PubMed:21810173}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.51 mM for Hip-His-Leu {ECO:0000269|PubMed:11076943,
CC ECO:0000269|PubMed:12542396};
CC KM=30 uM for angiotensin I {ECO:0000305|PubMed:6270633};
CC KM=16 uM for angiotensin I {ECO:0000269|PubMed:1851160};
CC KM=1 uM for bradykinin {ECO:0000305|PubMed:6270633};
CC KM=0.18 uM for bradykinin {ECO:0000269|PubMed:7683654};
CC KM=1000 uM for Met-enkephalin {ECO:0000269|PubMed:6270633};
CC KM=1000 uM for Leu-enkephalin {ECO:0000269|PubMed:6270633};
CC KM=41 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP)
CC {ECO:0000269|PubMed:7876104};
CC KM=31 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the
CC active site at the N-terminus {ECO:0000269|PubMed:7876104};
CC KM=39 uM for hemoregulatory peptide N-acetyl-SDKP (AcSDKP) for the
CC active site at the C-terminus {ECO:0000269|PubMed:7876104};
CC KM=9 uM for GWMDFGRR peptide (Cholecystokinin-5-GRR)
CC {ECO:0000269|PubMed:9371719};
CC Note=kcat is 500 min(-1) for angiotensin I (PubMed:6270633). kcat is
CC 500 min(-1) for bradykinin (PubMed:6270633). kcat is 3500 min(-1) for
CC Met-enkephalin (PubMed:6270633). kcat is 700 min(-1) for Leu-
CC enkephalin (PubMed:6270633). kcat is 12 sec(-1) for the
CC hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:7876104).
CC {ECO:0000269|PubMed:6270633, ECO:0000269|PubMed:7876104};
CC -!- SUBUNIT: Monomer and homodimer; homodimerizes following binding to an
CC inhibitor (PubMed:16476786). Interacts with calmodulin (CALM1, CALM2 or
CC CALM3); interaction takes place in the cytoplasmic region and regulates
CC phosphorylation and proteolytic cleavage (By similarity).
CC {ECO:0000250|UniProtKB:P12822, ECO:0000269|PubMed:16476786}.
CC -!- INTERACTION:
CC P12821-3; P05556: ITGB1; NbExp=2; IntAct=EBI-25497695, EBI-703066;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12386153};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:P09470}. Note=Detected in both cell membrane and
CC cytoplasm in neurons. {ECO:0000250|UniProtKB:P09470}.
CC -!- SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]:
CC Secreted {ECO:0000269|PubMed:10769174, ECO:0000269|PubMed:11274151,
CC ECO:0000269|PubMed:7499427, ECO:0000269|PubMed:8253769}.
CC -!- SUBCELLULAR LOCATION: [Isoform Testis-specific]: Cell membrane
CC {ECO:0000269|PubMed:1668266, ECO:0000269|PubMed:8626443}; Single-pass
CC type I membrane protein {ECO:0000255}. Secreted
CC {ECO:0000269|PubMed:1668266}. Note=The testis-specific isoform can be
CC cleaved before the transmembrane region, releasing a soluble form.
CC {ECO:0000269|PubMed:1668266}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=4;
CC Name=Somatic-1;
CC IsoId=P12821-1; Sequence=Displayed;
CC Name=Somatic-2; Synonyms=Soluble;
CC IsoId=P12821-2; Sequence=VSP_029932, VSP_029933;
CC Name=Testis-specific; Synonyms=ACE-T, ACEt
CC {ECO:0000303|PubMed:8626443}, tACE {ECO:0000303|PubMed:1668266,
CC ECO:0000303|PubMed:21810173}, hTACE {ECO:0000303|PubMed:1668266};
CC IsoId=P12821-3, P22966-1;
CC Sequence=VSP_035120, VSP_035121;
CC Name=4;
CC IsoId=P12821-4; Sequence=VSP_054836, VSP_054837;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in
CC lung, kidney, heart, gastrointestinal system and prostate.
CC {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042,
CC ECO:0000269|PubMed:12459472, ECO:0000269|PubMed:15671045}.
CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Specifically expressed
CC in spermatocytes and adult testis. {ECO:0000269|PubMed:2547653,
CC ECO:0000269|PubMed:2554286}.
CC -!- INDUCTION: Up-regulated in failing heart. {ECO:0000269|PubMed:15151696,
CC ECO:0000269|PubMed:15671045}.
CC -!- PTM: [Angiotensin-converting enzyme, soluble form]: Produced following
CC proteolytic cleavage by secretase enzymes that cleave the transmembrane
CC form in the juxtamembrane stalk region upstream of the transmembrane
CC region (PubMed:8253769, PubMed:7499427, PubMed:10769174,
CC PubMed:11274151). Cleavage can take place at different sites of the
CC juxtamembrane stalk region (PubMed:8253769, PubMed:7499427,
CC PubMed:10769174, PubMed:11274151). {ECO:0000269|PubMed:10769174,
CC ECO:0000269|PubMed:11274151, ECO:0000269|PubMed:7499427,
CC ECO:0000269|PubMed:8253769}.
CC -!- PTM: Phosphorylated by CK2 on Ser-1299; which allows membrane retention
CC (PubMed:12386153). Phosphorylated on tyrosine residues on its
CC extracellular part, promoting cleavage by secretase enzymes and
CC formation of the soluble form (Angiotensin-converting enzyme, soluble
CC form) (By similarity). {ECO:0000250|UniProtKB:P12822,
CC ECO:0000269|PubMed:12386153}.
CC -!- DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute
CC neurologic event leading to death of neural tissue of the brain and
CC resulting in loss of motor, sensory and/or cognitive function. Ischemic
CC strokes, resulting from vascular occlusion, is considered to be a
CC highly complex disease consisting of a group of heterogeneous disorders
CC with multiple genetic and environmental risk factors.
CC {ECO:0000269|PubMed:15534175}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal
CC recessive severe disorder of renal tubular development characterized by
CC persistent fetal anuria and perinatal death, probably due to pulmonary
CC hypoplasia from early-onset oligohydramnios (the Potter phenotype).
CC {ECO:0000269|PubMed:16116425}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Microvascular complications of diabetes 3 (MVCD3)
CC [MIM:612624]: Pathological conditions that develop in numerous tissues
CC and organs as a consequence of diabetes mellitus. They include diabetic
CC retinopathy, diabetic nephropathy leading to end-stage renal disease,
CC and diabetic neuropathy. Diabetic retinopathy remains the major cause
CC of new-onset blindness among diabetic adults. It is characterized by
CC vascular permeability and increased tissue ischemia and angiogenesis.
CC {ECO:0000269|PubMed:10099885}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- DISEASE: Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological
CC condition characterized by bleeding into one or both cerebral
CC hemispheres including the basal ganglia and the cerebral cortex. It is
CC often associated with hypertension and craniocerebral trauma.
CC Intracerebral bleeding is a common cause of stroke.
CC {ECO:0000269|PubMed:15277638}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Inhibitors of ACE are commonly used to treat
CC hypertension and some types of renal and cardiac dysfunction.
CC -!- MISCELLANEOUS: [Isoform Somatic-2]: Incomplete sequence. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92208.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; J04144; AAA51684.1; -; mRNA.
DR EMBL; M26657; AAA60611.1; -; mRNA.
DR EMBL; X16295; CAA34362.1; -; mRNA.
DR EMBL; AF118569; AAD28560.1; -; Genomic_DNA.
DR EMBL; AY436326; AAR03504.1; -; Genomic_DNA.
DR EMBL; AK301988; BAG63395.1; -; mRNA.
DR EMBL; EU332840; ABY87529.1; -; Genomic_DNA.
DR EMBL; AB208971; BAD92208.1; ALT_INIT; mRNA.
DR EMBL; AC113554; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS11637.1; -. [P12821-1]
DR CCDS; CCDS45755.1; -. [P12821-3]
DR CCDS; CCDS54155.1; -. [P12821-4]
DR PIR; A31759; A31759.
DR PIR; PW0053; PW0053.
DR PIR; S05238; S05238.
DR RefSeq; NP_000780.1; NM_000789.3. [P12821-1]
DR RefSeq; NP_001171528.1; NM_001178057.1. [P12821-4]
DR RefSeq; NP_690043.1; NM_152830.2. [P12821-3]
DR PDB; 1O86; X-ray; 2.00 A; A=642-1230.
DR PDB; 1O8A; X-ray; 2.00 A; A=642-1230.
DR PDB; 1UZE; X-ray; 1.82 A; A=642-1230.
DR PDB; 1UZF; X-ray; 2.00 A; A=642-1230.
DR PDB; 2C6F; X-ray; 3.01 A; A/B=30-641.
DR PDB; 2C6N; X-ray; 3.00 A; A/B=30-641.
DR PDB; 2IUL; X-ray; 2.01 A; A=642-1232.
DR PDB; 2IUX; X-ray; 2.80 A; A=642-1232.
DR PDB; 2OC2; X-ray; 2.25 A; A=642-1232.
DR PDB; 2XY9; X-ray; 1.97 A; A=645-1228.
DR PDB; 2XYD; X-ray; 2.15 A; A/B=30-639.
DR PDB; 2YDM; X-ray; 2.44 A; A=642-1230.
DR PDB; 3BKK; X-ray; 2.17 A; A=642-1232.
DR PDB; 3BKL; X-ray; 2.18 A; A=642-1232.
DR PDB; 3L3N; X-ray; 2.30 A; A=642-1232.
DR PDB; 3NXQ; X-ray; 1.99 A; A/B=30-658.
DR PDB; 4APH; X-ray; 1.99 A; A=642-1230.
DR PDB; 4APJ; X-ray; 2.60 A; A=642-1230.
DR PDB; 4BXK; X-ray; 2.20 A; A/B=30-657.
DR PDB; 4BZR; X-ray; 1.84 A; A=642-1230.
DR PDB; 4BZS; X-ray; 2.10 A; A/B=30-657.
DR PDB; 4C2N; X-ray; 2.59 A; A=642-1230.
DR PDB; 4C2O; X-ray; 1.80 A; A=642-1230.
DR PDB; 4C2P; X-ray; 1.99 A; A=642-1230.
DR PDB; 4C2Q; X-ray; 2.40 A; A=642-1230.
DR PDB; 4C2R; X-ray; 2.30 A; A=642-1230.
DR PDB; 4CA5; X-ray; 1.85 A; A=642-1230.
DR PDB; 4CA6; X-ray; 1.91 A; A/B=30-639.
DR PDB; 4UFA; X-ray; 1.80 A; A/B=30-657.
DR PDB; 4UFB; X-ray; 1.80 A; A/B/C/D=30-657.
DR PDB; 5AM8; X-ray; 1.90 A; A/B/C/D=30-658.
DR PDB; 5AM9; X-ray; 1.80 A; A/B/C/D=30-658.
DR PDB; 5AMA; X-ray; 1.80 A; A/B/C/D=30-658.
DR PDB; 5AMB; X-ray; 1.55 A; A/B=30-658.
DR PDB; 5AMC; X-ray; 1.65 A; A/B=30-658.
DR PDB; 6EN5; X-ray; 1.75 A; A/B/C/D=30-657.
DR PDB; 6EN6; X-ray; 1.80 A; A/B/C/D=30-657.
DR PDB; 6F9R; X-ray; 1.85 A; A/B=30-657.
DR PDB; 6F9T; X-ray; 1.60 A; A=642-1232.
DR PDB; 6F9U; X-ray; 1.90 A; A=642-1232.
DR PDB; 6F9V; X-ray; 1.69 A; A/B=30-657.
DR PDB; 6H5W; X-ray; 1.37 A; A=642-1232.
DR PDB; 6H5X; X-ray; 1.80 A; A/B=30-657.
DR PDB; 6QS1; X-ray; 1.80 A; A/B=30-657.
DR PDB; 6TT1; X-ray; 1.80 A; A/B=30-657.
DR PDB; 6TT3; X-ray; 1.70 A; A/B=30-657.
DR PDB; 6TT4; X-ray; 1.80 A; A/B=30-657.
DR PDB; 6ZPQ; X-ray; 1.85 A; A/B/C/D=30-657.
DR PDB; 6ZPT; X-ray; 2.80 A; A/B/C/D=30-657.
DR PDB; 6ZPU; X-ray; 2.00 A; A=642-1238.
DR PDB; 7Q24; X-ray; 2.00 A; A/B=30-657.
DR PDB; 7Q25; X-ray; 1.60 A; A/B=30-657.
DR PDB; 7Q26; X-ray; 1.70 A; A/B=30-657.
DR PDB; 7Q27; X-ray; 1.50 A; A=642-1238.
DR PDB; 7Q28; X-ray; 1.65 A; A=642-1238.
DR PDB; 7Q29; X-ray; 1.60 A; A=642-1238.
DR PDBsum; 1O86; -.
DR PDBsum; 1O8A; -.
DR PDBsum; 1UZE; -.
DR PDBsum; 1UZF; -.
DR PDBsum; 2C6F; -.
DR PDBsum; 2C6N; -.
DR PDBsum; 2IUL; -.
DR PDBsum; 2IUX; -.
DR PDBsum; 2OC2; -.
DR PDBsum; 2XY9; -.
DR PDBsum; 2XYD; -.
DR PDBsum; 2YDM; -.
DR PDBsum; 3BKK; -.
DR PDBsum; 3BKL; -.
DR PDBsum; 3L3N; -.
DR PDBsum; 3NXQ; -.
DR PDBsum; 4APH; -.
DR PDBsum; 4APJ; -.
DR PDBsum; 4BXK; -.
DR PDBsum; 4BZR; -.
DR PDBsum; 4BZS; -.
DR PDBsum; 4C2N; -.
DR PDBsum; 4C2O; -.
DR PDBsum; 4C2P; -.
DR PDBsum; 4C2Q; -.
DR PDBsum; 4C2R; -.
DR PDBsum; 4CA5; -.
DR PDBsum; 4CA6; -.
DR PDBsum; 4UFA; -.
DR PDBsum; 4UFB; -.
DR PDBsum; 5AM8; -.
DR PDBsum; 5AM9; -.
DR PDBsum; 5AMA; -.
DR PDBsum; 5AMB; -.
DR PDBsum; 5AMC; -.
DR PDBsum; 6EN5; -.
DR PDBsum; 6EN6; -.
DR PDBsum; 6F9R; -.
DR PDBsum; 6F9T; -.
DR PDBsum; 6F9U; -.
DR PDBsum; 6F9V; -.
DR PDBsum; 6H5W; -.
DR PDBsum; 6H5X; -.
DR PDBsum; 6QS1; -.
DR PDBsum; 6TT1; -.
DR PDBsum; 6TT3; -.
DR PDBsum; 6TT4; -.
DR PDBsum; 6ZPQ; -.
DR PDBsum; 6ZPT; -.
DR PDBsum; 6ZPU; -.
DR PDBsum; 7Q24; -.
DR PDBsum; 7Q25; -.
DR PDBsum; 7Q26; -.
DR PDBsum; 7Q27; -.
DR PDBsum; 7Q28; -.
DR PDBsum; 7Q29; -.
DR AlphaFoldDB; P12821; -.
DR SMR; P12821; -.
DR BioGRID; 108004; 15.
DR CORUM; P12821; -.
DR IntAct; P12821; 5.
DR MINT; P12821; -.
DR STRING; 9606.ENSP00000290866; -.
DR BindingDB; P12821; -.
DR ChEMBL; CHEMBL1808; -.
DR DrugBank; DB00542; Benazepril.
DR DrugBank; DB00616; Candoxatril.
DR DrugBank; DB01197; Captopril.
DR DrugBank; DB01340; Cilazapril.
DR DrugBank; DB15565; Cilazaprilat.
DR DrugBank; DB00584; Enalapril.
DR DrugBank; DB09477; Enalaprilat.
DR DrugBank; DB02032; Epicaptopril.
DR DrugBank; DB00492; Fosinopril.
DR DrugBank; DB00722; Lisinopril.
DR DrugBank; DB00691; Moexipril.
DR DrugBank; DB03740; N-acetyl-alpha-D-glucosamine.
DR DrugBank; DB00886; Omapatrilat.
DR DrugBank; DB00790; Perindopril.
DR DrugBank; DB00881; Quinapril.
DR DrugBank; DB00178; Ramipril.
DR DrugBank; DB01180; Rescinnamine.
DR DrugBank; DB01348; Spirapril.
DR DrugBank; DB08836; Temocapril.
DR DrugBank; DB00519; Trandolapril.
DR DrugBank; DB13166; Zofenopril.
DR DrugCentral; P12821; -.
DR GuidetoPHARMACOLOGY; 1613; -.
DR MEROPS; M02.001; -.
DR MEROPS; M02.004; -.
DR GlyConnect; 1011; 24 N-Linked glycans (7 sites).
DR GlyGen; P12821; 18 sites, 25 N-linked glycans (7 sites).
DR iPTMnet; P12821; -.
DR PhosphoSitePlus; P12821; -.
DR BioMuta; ACE; -.
DR DMDM; 113045; -.
DR CPTAC; CPTAC-2597; -.
DR jPOST; P12821; -.
DR MassIVE; P12821; -.
DR MaxQB; P12821; -.
DR PaxDb; P12821; -.
DR PeptideAtlas; P12821; -.
DR PRIDE; P12821; -.
DR ProteomicsDB; 52874; -. [P12821-1]
DR ProteomicsDB; 52875; -. [P12821-2]
DR ProteomicsDB; 52876; -. [P12821-3]
DR ProteomicsDB; 52877; -. [P12821-4]
DR ABCD; P12821; 1 sequenced antibody.
DR Antibodypedia; 31288; 873 antibodies from 43 providers.
DR DNASU; 1636; -.
DR Ensembl; ENST00000290863.10; ENSP00000290863.6; ENSG00000159640.17. [P12821-3]
DR Ensembl; ENST00000290866.10; ENSP00000290866.4; ENSG00000159640.17. [P12821-1]
DR Ensembl; ENST00000413513.7; ENSP00000392247.3; ENSG00000159640.17. [P12821-4]
DR GeneID; 1636; -.
DR KEGG; hsa:1636; -.
DR MANE-Select; ENST00000290866.10; ENSP00000290866.4; NM_000789.4; NP_000780.1.
DR UCSC; uc002jau.3; human. [P12821-1]
DR CTD; 1636; -.
DR DisGeNET; 1636; -.
DR GeneCards; ACE; -.
DR HGNC; HGNC:2707; ACE.
DR HPA; ENSG00000159640; Tissue enhanced (intestine, testis).
DR MalaCards; ACE; -.
DR MIM; 106180; gene+phenotype.
DR MIM; 267430; phenotype.
DR MIM; 601367; phenotype.
DR MIM; 612624; phenotype.
DR MIM; 614519; phenotype.
DR neXtProt; NX_P12821; -.
DR OpenTargets; ENSG00000159640; -.
DR Orphanet; 34145; NON RARE IN EUROPE: Berger disease.
DR Orphanet; 97369; Renal tubular dysgenesis of genetic origin.
DR PharmGKB; PA139; -.
DR VEuPathDB; HostDB:ENSG00000159640; -.
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000162051; -.
DR HOGENOM; CLU_014364_3_0_1; -.
DR InParanoid; P12821; -.
DR OMA; WEGWHNV; -.
DR OrthoDB; 238880at2759; -.
DR PhylomeDB; P12821; -.
DR TreeFam; TF312861; -.
DR BioCyc; MetaCyc:HS08412-MON; -.
DR BRENDA; 3.4.15.1; 2681.
DR PathwayCommons; P12821; -.
DR Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SABIO-RK; P12821; -.
DR SignaLink; P12821; -.
DR SIGNOR; P12821; -.
DR BioGRID-ORCS; 1636; 12 hits in 1072 CRISPR screens.
DR ChiTaRS; ACE; human.
DR EvolutionaryTrace; P12821; -.
DR GeneWiki; Angiotensin-converting_enzyme; -.
DR GenomeRNAi; 1636; -.
DR Pharos; P12821; Tclin.
DR PRO; PR:P12821; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P12821; protein.
DR Bgee; ENSG00000159640; Expressed in ileal mucosa and 107 other tissues.
DR ExpressionAtlas; P12821; baseline and differential.
DR Genevisible; P12821; HS.
DR GO; GO:0009925; C:basal plasma membrane; IEA:Ensembl.
DR GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR GO; GO:0005768; C:endosome; IDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0097225; C:sperm midpiece; IEA:Ensembl.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0031711; F:bradykinin receptor binding; IPI:BHF-UCL.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0031404; F:chloride ion binding; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008238; F:exopeptidase activity; IDA:BHF-UCL.
DR GO; GO:1901363; F:heterocyclic compound binding; IEA:Ensembl.
DR GO; GO:0070573; F:metallodipeptidase activity; IDA:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:BHF-UCL.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0050435; P:amyloid-beta metabolic process; IDA:BHF-UCL.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; IEA:Ensembl.
DR GO; GO:0002003; P:angiotensin maturation; IDA:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:BHF-UCL.
DR GO; GO:0050482; P:arachidonic acid secretion; IDA:BHF-UCL.
DR GO; GO:0097746; P:blood vessel diameter maintenance; IC:BHF-UCL.
DR GO; GO:0001974; P:blood vessel remodeling; IC:BHF-UCL.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071838; P:cell proliferation in bone marrow; ISS:BHF-UCL.
DR GO; GO:1904045; P:cellular response to aldosterone; IEA:Ensembl.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0042755; P:eating behavior; IEA:Ensembl.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IEA:Ensembl.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; ISS:BHF-UCL.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IC:BHF-UCL.
DR GO; GO:0042447; P:hormone catabolic process; IDA:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0032943; P:mononuclear cell proliferation; IC:BHF-UCL.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IEA:Ensembl.
DR GO; GO:1903597; P:negative regulation of gap junction assembly; ISS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; IEA:Ensembl.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; IEA:Ensembl.
DR GO; GO:0002446; P:neutrophil mediated immunity; ISS:BHF-UCL.
DR GO; GO:0043171; P:peptide catabolic process; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:Ensembl.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IEA:Ensembl.
DR GO; GO:2000170; P:positive regulation of peptidyl-cysteine S-nitrosylation; ISS:BHF-UCL.
DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; ISS:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISS:BHF-UCL.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IBA:GO_Central.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IEA:Ensembl.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; TAS:UniProtKB.
DR GO; GO:0060177; P:regulation of angiotensin metabolic process; IDA:BHF-UCL.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:BHF-UCL.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; ISS:BHF-UCL.
DR GO; GO:0002019; P:regulation of renal output by angiotensin; IC:BHF-UCL.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISS:BHF-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; IMP:BHF-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IC:UniProtKB.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; ISS:BHF-UCL.
DR GO; GO:0010814; P:substance P catabolic process; IDA:UniProtKB.
DR GO; GO:0042310; P:vasoconstriction; IEA:Ensembl.
DR CDD; cd06461; M2_ACE; 2.
DR InterPro; IPR001548; Peptidase_M2.
DR PANTHER; PTHR10514; PTHR10514; 2.
DR Pfam; PF01401; Peptidase_M2; 2.
DR PRINTS; PR00791; PEPDIPTASEA.
DR PROSITE; PS00142; ZINC_PROTEASE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing;
KW Calmodulin-binding; Carboxypeptidase; Cell membrane; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Phosphoprotein; Protease;
KW Reference proteome; Repeat; Secreted; Signal; Transmembrane;
KW Transmembrane helix; Zinc.
FT SIGNAL 1..29
FT /evidence="ECO:0000269|PubMed:2558109"
FT CHAIN 30..1306
FT /note="Angiotensin-converting enzyme"
FT /id="PRO_0000028530"
FT CHAIN 30..1232
FT /note="Angiotensin-converting enzyme, soluble form"
FT /evidence="ECO:0000305|PubMed:10769174"
FT /id="PRO_0000028531"
FT TOPO_DOM 30..1256
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1257..1277
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1278..1306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 30..630
FT /note="Peptidase M2 1"
FT REGION 631..1232
FT /note="Peptidase M2 2"
FT REGION 1215..1256
FT /note="Juxtamembrane stalk"
FT /evidence="ECO:0000269|PubMed:11274151"
FT ACT_SITE 391
FT /note="Proton acceptor 1"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000305|PubMed:16154999, ECO:0000305|PubMed:19773553"
FT ACT_SITE 520
FT /note="Proton donor 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 989
FT /note="Proton acceptor 2"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000305|PubMed:16154999, ECO:0000305|PubMed:19773553"
FT ACT_SITE 1118
FT /note="Proton donor 2"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 231
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16476442"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559,
FT ECO:0007744|PDB:2OC2, ECO:0007744|PDB:3NXQ"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559,
FT ECO:0007744|PDB:2OC2, ECO:0007744|PDB:3NXQ"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559,
FT ECO:0007744|PDB:2OC2, ECO:0007744|PDB:3NXQ"
FT BINDING 529
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:16476442"
FT BINDING 791
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12540854"
FT BINDING 829
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12540854"
FT BINDING 988
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:23056909,
FT ECO:0007744|PDB:4APH"
FT BINDING 992
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:23056909,
FT ECO:0007744|PDB:4APH"
FT BINDING 1016
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:23056909,
FT ECO:0000269|PubMed:7961923, ECO:0007744|PDB:4APH"
FT BINDING 1090
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12540854"
FT BINDING 1094
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:12540854"
FT BINDING 1127
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000269|PubMed:12540854,
FT ECO:0000305|PubMed:11432860"
FT SITE 523
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:20826823"
FT SITE 1166..1167
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:7499427,
FT ECO:0000269|PubMed:8253769"
FT SITE 1225
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:9013598"
FT SITE 1232..1233
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:10769174"
FT MOD_RES 1299
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12386153,
FT ECO:0000269|PubMed:21901117"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20826823,
FT ECO:0000305|PubMed:9013598"
FT CARBOHYD 54
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559,
FT ECO:0007744|PDB:3NXQ"
FT CARBOHYD 111
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16476442,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:9013598"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:20826823"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16476442"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:20826823, ECO:0000269|PubMed:26403559,
FT ECO:0007744|PDB:3NXQ"
FT CARBOHYD 509
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:16476442, ECO:0000269|PubMed:20826823,
FT ECO:0000269|PubMed:26403559, ECO:0000269|PubMed:9013598,
FT ECO:0007744|PDB:3NXQ"
FT CARBOHYD 677
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23056909,
FT ECO:0007744|PDB:4APH"
FT CARBOHYD 695
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:9013598"
FT CARBOHYD 714
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:23056909,
FT ECO:0000269|PubMed:9013598, ECO:0007744|PDB:4APH"
FT CARBOHYD 760
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:9013598"
FT CARBOHYD 942
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:9013598"
FT CARBOHYD 1191
FT /note="N-linked (GlcNAc...) asparagine; partial"
FT /evidence="ECO:0000269|PubMed:9013598"
FT DISULFID 157..165
FT /evidence="ECO:0000269|PubMed:8755737"
FT DISULFID 757..763
FT /evidence="ECO:0000269|PubMed:8755737"
FT DISULFID 957..975
FT /evidence="ECO:0000269|PubMed:8755737"
FT DISULFID 1143..1155
FT /evidence="ECO:0000269|PubMed:8755737"
FT VAR_SEQ 1..641
FT /note="MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQS
FT YNSSAEQVLFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQN
FT FTDPQLRRIIGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDP
FT DLTNILASSRSYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRS
FT WYNSPTFEDDLEHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQ
FT SWENIYDMVVPFPDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSM
FT LEKPADGREVVCHASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPV
FT SLRRGANPGFHEAIGDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFL
FT PFGYLVDQWRWGVFSGRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNV
FT TPYIRYFVSFVLQFQFHEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQE
FT VLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGID
FT -> MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHGTSSQATTSSQTTTHQA
FT TAHQTSAQSPN (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054836"
FT VAR_SEQ 1..574
FT /note="Missing (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:2547653,
FT ECO:0000303|PubMed:2554286"
FT /id="VSP_035120"
FT VAR_SEQ 575..641
FT /note="AGSSRPWQEVLKDMVGLDALDAQPLLKYFQPVTQWLQEQNQQNGEVLGWPEY
FT QWHPPLPDNYPEGID -> MGQGWATAGLPSLLFLLLCYGHPLLVPSQEASQQVTVTHG
FT TSSQATTSSQTTTHQATAHQTSAQSPN (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:2547653,
FT ECO:0000303|PubMed:2554286"
FT /id="VSP_035121"
FT VAR_SEQ 1128..1168
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054837"
FT VAR_SEQ 1137..1145
FT /note="QFHEALCQA -> HPFSQHTAA (in isoform Somatic-2)"
FT /evidence="ECO:0000303|PubMed:9642152"
FT /id="VSP_029932"
FT VAR_SEQ 1146..1306
FT /note="Missing (in isoform Somatic-2)"
FT /evidence="ECO:0000303|PubMed:9642152"
FT /id="VSP_029933"
FT VARIANT 154
FT /note="A -> T (in dbSNP:rs13306087)"
FT /id="VAR_029139"
FT VARIANT 183
FT /note="A -> T (in dbSNP:rs12720754)"
FT /id="VAR_029140"
FT VARIANT 244
FT /note="Y -> C (in dbSNP:rs3730025)"
FT /id="VAR_023430"
FT VARIANT 260
FT /note="R -> C (in dbSNP:rs4302)"
FT /id="VAR_054000"
FT VARIANT 260
FT /note="R -> L (in dbSNP:rs4303)"
FT /id="VAR_054001"
FT VARIANT 261
FT /note="A -> S (in dbSNP:rs4303)"
FT /evidence="ECO:0000269|PubMed:10319862"
FT /id="VAR_011707"
FT VARIANT 295
FT /note="D -> N (in dbSNP:rs989500910)"
FT /evidence="ECO:0000269|PubMed:25787250"
FT /id="VAR_074173"
FT VARIANT 351
FT /note="P -> L (in dbSNP:rs2229839)"
FT /id="VAR_023431"
FT VARIANT 354
FT /note="G -> R (in dbSNP:rs56394458)"
FT /evidence="ECO:0000269|PubMed:16116425"
FT /id="VAR_035434"
FT VARIANT 379
FT /note="R -> Q (in dbSNP:rs13306085)"
FT /id="VAR_029141"
FT VARIANT 524
FT /note="V -> A (in dbSNP:rs12720746)"
FT /id="VAR_029142"
FT VARIANT 561
FT /note="R -> W (in dbSNP:rs4314)"
FT /evidence="ECO:0000269|PubMed:10319862"
FT /id="VAR_011708"
FT VARIANT 592
FT /note="D -> G (in dbSNP:rs12709426)"
FT /id="VAR_020053"
FT VARIANT 828
FT /note="M -> T (in dbSNP:rs13306091)"
FT /id="VAR_034602"
FT VARIANT 916
FT /note="T -> M (in dbSNP:rs3730043)"
FT /id="VAR_023432"
FT VARIANT 1018
FT /note="I -> T (in dbSNP:rs4976)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014189"
FT VARIANT 1051
FT /note="F -> V (in dbSNP:rs4977)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014190"
FT VARIANT 1187
FT /note="T -> M (in dbSNP:rs12709442)"
FT /id="VAR_023433"
FT VARIANT 1228
FT /note="P -> L (no effect on activity; increases secretion;
FT rate of solubilization is 2.5-fold higher than wild-type;
FT dbSNP:rs121912703)"
FT /evidence="ECO:0000269|PubMed:11076943,
FT ECO:0000269|PubMed:11551873, ECO:0000269|PubMed:14694062"
FT /id="VAR_023434"
FT VARIANT 1279
FT /note="R -> Q (in dbSNP:rs4980)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014191"
FT VARIANT 1286
FT /note="R -> S (in dbSNP:rs4364)"
FT /evidence="ECO:0000269|PubMed:10319862,
FT ECO:0000269|PubMed:10391210"
FT /id="VAR_011709"
FT VARIANT 1296
FT /note="Q -> P (in dbSNP:rs4981)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014192"
FT MUTAGEN 318
FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl
FT carboxypeptidase activity; when associated with D-445 and
FT D-509. In Ndom1234569 mutant; does not affect dipeptidyl
FT carboxypeptidase activity; when associated with D-445."
FT /evidence="ECO:0000269|PubMed:20826823"
FT MUTAGEN 390..394
FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase
FT activity; when associated with 988-K--K-992. Abolished N-
FT terminal active sites, leading to impaired ability to
FT degrade the hemoregulatory peptide N-acetyl-SDKP (AcSDKP).
FT In contrast, does not affect cleavage of other substrates,
FT such as Cholecystokinin-5."
FT /evidence="ECO:0000269|PubMed:10336644,
FT ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:1851160,
FT ECO:0000269|PubMed:7683654, ECO:0000269|PubMed:7876104,
FT ECO:0000269|PubMed:7961923"
FT MUTAGEN 391
FT /note="E->D: Abolished peptidase activity, leading to
FT increased levels of amyloid-beta; when associated with D-
FT 989."
FT /evidence="ECO:0000269|PubMed:16154999,
FT ECO:0000269|PubMed:19773553"
FT MUTAGEN 445
FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl
FT carboxypeptidase activity; when associated with D-318 and
FT D-445. In Ndom1234569 mutant; does not affect dipeptidyl
FT carboxypeptidase activity; when associated with D-318."
FT /evidence="ECO:0000269|PubMed:20826823"
FT MUTAGEN 509
FT /note="N->D: In Ndom123456 mutant; abolished dipeptidyl
FT carboxypeptidase activity; when associated with D-318 and
FT D-445."
FT /evidence="ECO:0000269|PubMed:20826823"
FT MUTAGEN 529
FT /note="R->Q: Abolished dependence to chloride, leading to
FT reduced peptidyl dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:11432860"
FT MUTAGEN 988..992
FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase
FT activity; when associated with 390-K--K-394. Abolishes the
FT second active site, preventing maturation of
FT Cholecystokinin-5."
FT /evidence="ECO:0000269|PubMed:10336644,
FT ECO:0000269|PubMed:1320019, ECO:0000269|PubMed:1851160,
FT ECO:0000269|PubMed:7683654"
FT MUTAGEN 989
FT /note="E->D: Abolished peptidase activity, leading to
FT increased levels of amyloid-beta; when associated with D-
FT 391."
FT /evidence="ECO:0000269|PubMed:16154999,
FT ECO:0000269|PubMed:19773553"
FT MUTAGEN 1016
FT /note="E->D: Strongly decreased dipeptidyl carboxypeptidase
FT activity; when associated with 390-K--K-394."
FT /evidence="ECO:0000269|PubMed:7961923"
FT MUTAGEN 1016
FT /note="E->V: Abolished dipeptidyl carboxypeptidase
FT activity; when associated with 390-K--K-394."
FT /evidence="ECO:0000269|PubMed:7961923"
FT MUTAGEN 1020
FT /note="D->E,A: Decreased dipeptidyl carboxypeptidase
FT activity; when associated with 390-K--K-394."
FT /evidence="ECO:0000269|PubMed:7961923"
FT MUTAGEN 1116
FT /note="K->A: Decreased ability to cleave substance P and
FT bradykinin. Reduced binding to captopril inhibitor."
FT /evidence="ECO:0000269|PubMed:15615692"
FT MUTAGEN 1125
FT /note="Y->F: Decreased ability to cleave substance P and
FT captopril inhibitor."
FT /evidence="ECO:0000269|PubMed:15615692"
FT MUTAGEN 1127
FT /note="R->Q: Abolished dependence to chloride, leading to
FT reduced peptidyl dipeptidase activity."
FT /evidence="ECO:0000269|PubMed:11432860"
FT MUTAGEN 1166
FT /note="R->Q: Does not prevent cleavage and secretion of the
FT soluble form, suggesting that processing can take place at
FT different sites."
FT /evidence="ECO:0000269|PubMed:8253769"
FT MUTAGEN 1229
FT /note="N->Q: Increased cleavage and secretion of the
FT soluble form by generating a new cleavage site."
FT /evidence="ECO:0000269|PubMed:11274151"
FT MUTAGEN 1299
FT /note="S->A: Abolishes phosphorylation and decreases
FT membrane retention."
FT /evidence="ECO:0000269|PubMed:12386153,
FT ECO:0000269|PubMed:21901117"
FT CONFLICT 35
FT /note="Q -> E (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 42
FT /note="D -> R (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 32..34
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 43..72
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 77..105
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 106..108
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 109..111
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 115..124
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 128..131
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 134..153
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:4BZS"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 168..170
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 171..178
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 182..216
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 223..229
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 236..266
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 281..284
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 294..297
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 309..314
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 319..332
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 340..345
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:6TT3"
FT STRAND 362..365
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 367..370
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 372..375
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 382..401
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 406..408
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 414..428
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 431..436
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 447..461
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 464..479
FT /evidence="ECO:0007829|PDB:5AMB"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:6TT1"
FT HELIX 485..487
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 488..500
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 514..517
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 519..524
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 528..547
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 563..575
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 581..589
FT /evidence="ECO:0007829|PDB:5AMB"
FT HELIX 597..617
FT /evidence="ECO:0007829|PDB:5AMB"
FT TURN 634..638
FT /evidence="ECO:0007829|PDB:5AMC"
FT HELIX 641..643
FT /evidence="ECO:0007829|PDB:5AM9"
FT HELIX 646..675
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 680..704
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 709..711
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 715..724
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 728..731
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 734..753
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 755..757
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 759..761
FT /evidence="ECO:0007829|PDB:1UZE"
FT STRAND 763..765
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 766..768
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 769..776
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 780..793
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 795..798
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 799..801
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 802..815
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 821..827
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 834..844
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 846..864
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 866..868
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 879..882
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 889..891
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 892..895
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 906..912
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 917..930
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 938..943
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 945..947
FT /evidence="ECO:0007829|PDB:4APJ"
FT STRAND 950..952
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 960..963
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 965..968
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 970..973
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 980..998
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 999..1001
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1004..1006
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1012..1026
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1029..1034
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1045..1059
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1062..1077
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 1083..1085
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1086..1098
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1112..1115
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 1117..1122
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1126..1145
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1152..1154
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1161..1171
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 1172..1175
FT /evidence="ECO:0007829|PDB:6H5W"
FT HELIX 1179..1187
FT /evidence="ECO:0007829|PDB:6H5W"
FT STRAND 1188..1191
FT /evidence="ECO:0007829|PDB:3BKL"
FT HELIX 1195..1215
FT /evidence="ECO:0007829|PDB:6H5W"
FT TURN 1222..1225
FT /evidence="ECO:0007829|PDB:6F9T"
FT BINDING P12821-3:414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24297181,
FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P,
FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R"
FT BINDING P12821-3:418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24297181,
FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P,
FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R"
FT BINDING P12821-3:442
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:24297181,
FT ECO:0007744|PDB:4C2N, ECO:0007744|PDB:4C2P,
FT ECO:0007744|PDB:4C2Q, ECO:0007744|PDB:4C2R"
FT CARBOHYD P12821-3:103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21810173,
FT ECO:0000269|PubMed:24297181, ECO:0000269|PubMed:8626443,
FT ECO:0007744|PDB:4C2O"
FT CARBOHYD P12821-3:121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8626443"
FT CARBOHYD P12821-3:140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21810173,
FT ECO:0000269|PubMed:24297181, ECO:0000269|PubMed:8626443,
FT ECO:0007744|PDB:4C2O"
FT CARBOHYD P12821-3:368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8626443"
FT CARBOHYD P12821-3:617
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:8626443"
FT VARIANT P12821-3:32
FT /note="S -> P (in dbSNP:rs4317)"
FT /evidence="ECO:0000305"
FT /id="VAR_082898"
FT VARIANT P12821-3:49
FT /note="S -> G (in dbSNP:rs4318)"
FT /evidence="ECO:0000305"
FT /id="VAR_082899"
FT MUTAGEN P12821-3:103
FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-121, D-140, D-368 and D-617. In ACE(t)g2
FT mutant; decreased N-glycosylation without affecting
FT stability; when associated with D-140, D-368 and D-617. In
FT ACE(t)g3 mutant; decreased N-glycosylation leading to
FT impaired stability and degradation; when associated with D-
FT 121, D-368 and D-617."
FT /evidence="ECO:0000269|PubMed:8626443"
FT MUTAGEN P12821-3:121
FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-140, D-368 and D-617. In ACE(t)g1
FT mutant; decreased N-glycosylation without affecting
FT stability; when associated with D-140, D-368 and D-617. In
FT ACE(t)g3 mutant; decreased N-glycosylation leading to
FT impaired stability and degradation; when associated with D-
FT 103, D-368 and D-617."
FT /evidence="ECO:0000269|PubMed:8626443"
FT MUTAGEN P12821-3:140
FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-121, D-368 and D-617. In ACE(t)g1
FT mutant; decreased N-glycosylation without affecting
FT stability; when associated with D-121, D-368 and D-617. In
FT ACE(t)g2 mutant; decreased N-glycosylation without
FT affecting stability; when associated with D-103, D-368 and
FT D-617."
FT /evidence="ECO:0000269|PubMed:8626443"
FT MUTAGEN P12821-3:368
FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-121, D-140 and D-617. In ACE(t)g1
FT mutant; decreased N-glycosylation without affecting
FT stability; when associated with D-121, D-140 and D-617. In
FT ACE(t)g2 mutant; decreased N-glycosylation without
FT affecting stability; when associated with D-103, D-140 and
FT D-617. In ACE(t)g3 mutant; decreased N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-121 and D-617."
FT /evidence="ECO:0000269|PubMed:8626443"
FT MUTAGEN P12821-3:553
FT /note="R->K,Q: Abolished binding to chloride ion."
FT /evidence="ECO:0000269|PubMed:24297181"
FT MUTAGEN P12821-3:617
FT /note="N->D: In ACE(t)g0 mutant; abolished N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-121, D-140 and D-368. In ACE(t)g1
FT mutant; decreased N-glycosylation without affecting
FT stability; when associated with D-121, D-140 and D-368. In
FT ACE(t)g2 mutant; decreased N-glycosylation without
FT affecting stability; when associated with D-103, D-140 and
FT D-368. In ACE(t)g3 mutant; decreased N-glycosylation
FT leading to impaired stability and degradation; when
FT associated with D-103, D-121 and D-368."
FT /evidence="ECO:0000269|PubMed:8626443"
SQ SEQUENCE 1306 AA; 149715 MW; 1B33BCA7301A26AA CRC64;
MGAASGRRGP GLLLPLPLLL LLPPQPALAL DPGLQPGNFS ADEAGAQLFA QSYNSSAEQV
LFQSVAASWA HDTNITAENA RRQEEAALLS QEFAEAWGQK AKELYEPIWQ NFTDPQLRRI
IGAVRTLGSA NLPLAKRQQY NALLSNMSRI YSTAKVCLPN KTATCWSLDP DLTNILASSR
SYAMLLFAWE GWHNAAGIPL KPLYEDFTAL SNEAYKQDGF TDTGAYWRSW YNSPTFEDDL
EHLYQQLEPL YLNLHAFVRR ALHRRYGDRY INLRGPIPAH LLGDMWAQSW ENIYDMVVPF
PDKPNLDVTS TMLQQGWNAT HMFRVAEEFF TSLELSPMPP EFWEGSMLEK PADGREVVCH
ASAWDFYNRK DFRIKQCTRV TMDQLSTVHH EMGHIQYYLQ YKDLPVSLRR GANPGFHEAI
GDVLALSVST PEHLHKIGLL DRVTNDTESD INYLLKMALE KIAFLPFGYL VDQWRWGVFS
GRTPPSRYNF DWWYLRTKYQ GICPPVTRNE THFDAGAKFH VPNVTPYIRY FVSFVLQFQF
HEALCKEAGY EGPLHQCDIY RSTKAGAKLR KVLQAGSSRP WQEVLKDMVG LDALDAQPLL
KYFQPVTQWL QEQNQQNGEV LGWPEYQWHP PLPDNYPEGI DLVTDEAEAS KFVEEYDRTS
QVVWNEYAEA NWNYNTNITT ETSKILLQKN MQIANHTLKY GTQARKFDVN QLQNTTIKRI
IKKVQDLERA ALPAQELEEY NKILLDMETT YSVATVCHPN GSCLQLEPDL TNVMATSRKY
EDLLWAWEGW RDKAGRAILQ FYPKYVELIN QAARLNGYVD AGDSWRSMYE TPSLEQDLER
LFQELQPLYL NLHAYVRRAL HRHYGAQHIN LEGPIPAHLL GNMWAQTWSN IYDLVVPFPS
APSMDTTEAM LKQGWTPRRM FKEADDFFTS LGLLPVPPEF WNKSMLEKPT DGREVVCHAS
AWDFYNGKDF RIKQCTTVNL EDLVVAHHEM GHIQYFMQYK DLPVALREGA NPGFHEAIGD
VLALSVSTPK HLHSLNLLSS EGGSDEHDIN FLMKMALDKI AFIPFSYLVD QWRWRVFDGS
ITKENYNQEW WSLRLKYQGL CPPVPRTQGD FDPGAKFHIP SSVPYIRYFV SFIIQFQFHE
ALCQAAGHTG PLHKCDIYQS KEAGQRLATA MKLGFSRPWP EAMQLITGQP NMSASAMLSY
FKPLLDWLRT ENELHGEKLG WPQYNWTPNS ARSEGPLPDS GRVSFLGLDL DAQQARVGQW
LLLFLGIALL VATLGLSQRL FSIRHRSLHR HSHGPQFGSE VELRHS
