ACE_MOUSE
ID ACE_MOUSE Reviewed; 1312 AA.
AC P09470; P22967; Q6GTS2;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 30-AUG-2005, sequence version 3.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:2545691};
DE Short=ACE {ECO:0000303|PubMed:2545691};
DE EC=3.4.15.1 {ECO:0000269|PubMed:16270063};
DE AltName: Full=Dipeptidyl carboxypeptidase I;
DE AltName: Full=Kininase II {ECO:0000250|UniProtKB:P12821};
DE AltName: CD_antigen=CD143;
DE Contains:
DE RecName: Full=Angiotensin-converting enzyme, soluble form {ECO:0000250|UniProtKB:P12821};
DE Flags: Precursor;
GN Name=Ace {ECO:0000303|PubMed:2545691, ECO:0000312|MGI:MGI:87874};
GN Synonyms=Dcp1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC).
RX PubMed=2545691; DOI=10.1016/s0021-9258(18)80158-2;
RA Bernstein K.E., Martin B.M., Edwards A.S., Bernstein E.A.;
RT "Mouse angiotensin-converting enzyme is a protein composed of two
RT homologous domains.";
RL J. Biol. Chem. 264:11945-11951(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND PARTIAL
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2164636; DOI=10.1128/mcb.10.8.4294-4302.1990;
RA Howard T.E., Shai S.-Y., Langford K.G., Martin B.M., Bernstein K.E.;
RT "Transcription of testicular angiotensin-converting enzyme (ACE) is
RT initiated within the 12th intron of the somatic ACE gene.";
RL Mol. Cell. Biol. 10:4294-4302(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SOMATIC).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-332 (ISOFORM SOMATIC), AND PARTIAL PROTEIN
RP SEQUENCE.
RX PubMed=2841312; DOI=10.1016/s0021-9258(18)37909-2;
RA Bernstein K.E., Martin B.M., Bernstein E.A., Linton J., Striker L.,
RA Striker G.;
RT "The isolation of angiotensin-converting enzyme cDNA.";
RL J. Biol. Chem. 263:11021-11024(1988).
RN [5]
RP PROTEIN SEQUENCE OF 35-54.
RC TISSUE=Kidney;
RX PubMed=2835538; DOI=10.1038/ki.1988.48;
RA Bernstein K.E., Martin B.M., Striker L., Striker G.;
RT "Partial protein sequence of mouse and bovine kidney angiotensin converting
RT enzyme.";
RL Kidney Int. 33:652-655(1988).
RN [6]
RP ALTERNATIVE PROMOTER USAGE, FUNCTION (ISOFORM TESTIS-SPECIFIC), AND TISSUE
RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC).
RX PubMed=1651914; DOI=10.1016/s0021-9258(18)98437-1;
RA Langford K.G., Shai S.Y., Howard T.E., Kovac M.J., Overbeek P.A.,
RA Bernstein K.E.;
RT "Transgenic mice demonstrate a testis-specific promoter for angiotensin-
RT converting enzyme.";
RL J. Biol. Chem. 266:15559-15562(1991).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=7753170; DOI=10.1038/375146a0;
RA Krege J.H., John S.W., Langenbach L.L., Hodgin J.B., Hagaman J.R.,
RA Bachman E.S., Jennette J.C., O'Brien D.A., Smithies O.;
RT "Male-female differences in fertility and blood pressure in ACE-deficient
RT mice.";
RL Nature 375:146-148(1995).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=8642790;
RA Esther C.R. Jr., Howard T.E., Marino E.M., Goddard J.M., Capecchi M.R.,
RA Bernstein K.E.;
RT "Mice lacking angiotensin-converting enzyme have low blood pressure, renal
RT pathology, and reduced male fertility.";
RL Lab. Invest. 74:953-965(1996).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9231832; DOI=10.1161/01.hyp.30.1.128;
RA Tian B., Meng Q.C., Chen Y.F., Krege J.H., Smithies O., Oparil S.;
RT "Blood pressures and cardiovascular homeostasis in mice having reduced or
RT absent angiotensin-converting enzyme gene function.";
RL Hypertension 30:128-133(1997).
RN [10]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE.
RX PubMed=9664078; DOI=10.1172/jci3545;
RA Ramaraj P., Kessler S.P., Colmenares C., Sen G.C.;
RT "Selective restoration of male fertility in mice lacking angiotensin-
RT converting enzymes by sperm-specific expression of the testicular
RT isozyme.";
RL J. Clin. Invest. 102:371-378(1998).
RN [11]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE.
RX PubMed=9482924; DOI=10.1073/pnas.95.5.2552;
RA Hagaman J.R., Moyer J.S., Bachman E.S., Sibony M., Magyar P.L., Welch J.E.,
RA Smithies O., Krege J.H., O'Brien D.A.;
RT "Angiotensin-converting enzyme and male fertility.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2552-2557(1998).
RN [12]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE.
RX PubMed=10831599; DOI=10.1074/jbc.m004006200;
RA Kessler S.P., Rowe T.M., Gomos J.B., Kessler P.M., Sen G.C.;
RT "Physiological non-equivalence of the two isoforms of angiotensin-
RT converting enzyme.";
RL J. Biol. Chem. 275:26259-26264(2000).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=11303049;
RA Junot C., Gonzales M.F., Ezan E., Cotton J., Vazeux G., Michaud A.,
RA Azizi M., Vassiliou S., Yiotakis A., Corvol P., Dive V.;
RT "RXP 407, a selective inhibitor of the N-domain of angiotensin I-converting
RT enzyme, blocks in vivo the degradation of hemoregulatory peptide acetyl-
RT Ser-Asp-Lys-Pro with no effect on angiotensin I hydrolysis.";
RL J. Pharmacol. Exp. Ther. 297:606-611(2001).
RN [14]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE.
RX PubMed=11723129; DOI=10.1074/jbc.m109474200;
RA Kessler S.P., Gomos J.B., Scheidemantel T.S., Rowe T.M., Smith H.L.,
RA Sen G.C.;
RT "The germinal isozyme of angiotensin-converting enzyme can substitute for
RT the somatic isozyme in maintaining normal renal structure and functions.";
RL J. Biol. Chem. 277:4271-4276(2002).
RN [15]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), AND DISRUPTION PHENOTYPE.
RX PubMed=12777443; DOI=10.1074/jbc.m3023472000;
RA Kessler S.P., deS Senanayake P., Scheidemantel T.S., Gomos J.B., Rowe T.M.,
RA Sen G.C.;
RT "Maintenance of normal blood pressure and renal functions are independent
RT effects of angiotensin-converting enzyme.";
RL J. Biol. Chem. 278:21105-21112(2003).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF 395-HIS--HIS-399.
RX PubMed=14757757; DOI=10.1074/jbc.m400149200;
RA Fuchs S., Xiao H.D., Cole J.M., Adams J.W., Frenzel K., Michaud A.,
RA Zhao H., Keshelava G., Capecchi M.R., Corvol P., Bernstein K.E.;
RT "Role of the N-terminal catalytic domain of angiotensin-converting enzyme
RT investigated by targeted inactivation in mice.";
RL J. Biol. Chem. 279:15946-15953(2004).
RN [17]
RP TISSUE SPECIFICITY.
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 [18]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), ACTIVITY REGULATION (ISOFORM
RP TESTIS-SPECIFIC), ACTIVE SITE, AND MUTAGENESIS OF HIS-993; GLU-994 AND
RP HIS-997.
RX PubMed=15665832; DOI=10.1038/nm1179;
RA Kondoh G., Tojo H., Nakatani Y., Komazawa N., Murata C., Yamagata K.,
RA Maeda Y., Kinoshita T., Okabe M., Taguchi R., Takeda J.;
RT "Angiotensin-converting enzyme is a GPI-anchored protein releasing factor
RT crucial for fertilization.";
RL Nat. Med. 11:160-166(2005).
RN [19]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC), DISRUPTION PHENOTYPE, AND MUTAGENESIS
RP OF 413-LYS--LYS-417 (ISOFORM TESTIS-SPECIFIC).
RX PubMed=16270063; DOI=10.1038/nm1105-1140;
RA Fuchs S., Frenzel K., Hubert C., Lyng R., Muller L., Michaud A., Xiao H.D.,
RA Adams J.W., Capecchi M.R., Corvol P., Shur B.D., Bernstein K.E.;
RT "Male fertility is dependent on dipeptidase activity of testis ACE.";
RL Nat. Med. 11:1140-1142(2005).
RN [20]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-151.
RC STRAIN=C57BL/6J; TISSUE=Plasma;
RX PubMed=16944957; DOI=10.1021/pr060186m;
RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.;
RT "Proteome-wide characterization of N-glycosylation events by diagonal
RT chromatography.";
RL J. Proteome Res. 5:2438-2447(2006).
RN [21]
RP MUTAGENESIS OF 413-LYS--LYS-417 (ISOFORM TESTIS-SPECIFIC).
RX PubMed=17634445; DOI=10.1095/biolreprod.107.060004;
RA Deguchi E., Tani T., Watanabe H., Yamada S., Kondoh G.;
RT "Dipeptidase-inactivated tACE action in vivo: selective inhibition of
RT sperm-zona pellucida binding in the mouse.";
RL Biol. Reprod. 77:794-802(2007).
RN [22]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC).
RX PubMed=17135368; DOI=10.1096/fj.06-6678com;
RA Kessler S.P., Senanayake P.D., Gaughan C., Sen G.C.;
RT "Vascular expression of germinal ACE fails to maintain normal blood
RT pressure in ACE-/- mice.";
RL FASEB J. 21:156-166(2007).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain cortex;
RX PubMed=17114649; DOI=10.1074/mcp.m600046-mcp200;
RA Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F.,
RA Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B.,
RA Panse C., Schlapbach R., Mansuy I.M.;
RT "Qualitative and quantitative analyses of protein phosphorylation in naive
RT and stimulated mouse synaptosomal preparations.";
RL Mol. Cell. Proteomics 6:283-293(2007).
RN [24]
RP DISRUPTION PHENOTYPE.
RX PubMed=18443281; DOI=10.1073/pnas.0802690105;
RA Jayasooriya A.P., Mathai M.L., Walker L.L., Begg D.P., Denton D.A.,
RA Cameron-Smith D., Egan G.F., McKinley M.J., Rodger P.D., Sinclair A.J.,
RA Wark J.D., Weisinger H.S., Jois M., Weisinger R.S.;
RT "Mice lacking angiotensin-converting enzyme have increased energy
RT expenditure, with reduced fat mass and improved glucose clearance.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6531-6536(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1305, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [26]
RP SUBCELLULAR LOCATION.
RX PubMed=23535237; DOI=10.1152/ajpcell.00364.2012;
RA Xiao L., Haack K.K., Zucker I.H.;
RT "Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-
RT activated protein kinase and extracellular signal-regulated kinase 1/2
RT signaling.";
RL Am. J. Physiol. 304:C1073-C1079(2013).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=35201898; DOI=10.1126/science.abl5130;
RA Trieu B.H., Remmers B.C., Toddes C., Brandner D.D., Lefevre E.M.,
RA Kocharian A., Retzlaff C.L., Dick R.M., Mashal M.A., Gauthier E.A., Xie W.,
RA Zhang Y., More S.S., Rothwell P.E.;
RT "Angiotensin-converting enzyme gates brain circuit-specific plasticity via
RT an endogenous opioid.";
RL Science 2022:eabl5130-eabl5130(2022).
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:7753170, PubMed:8642790, PubMed:9231832, PubMed:11723129,
CC PubMed:12777443, PubMed:14757757, PubMed:16270063, PubMed:35201898).
CC Composed of two similar catalytic domains, each possessing a functional
CC active site, with different selectivity for substrates
CC (PubMed:11303049). Plays a major role in the angiotensin-renin system
CC that regulates blood pressure and sodium retention by the kidney by
CC converting angiotensin I to angiotensin II, resulting in an increase of
CC the vasoconstrictor activity of angiotensin (PubMed:9231832,
CC PubMed:11303049, PubMed:14757757). Also able to inactivate bradykinin,
CC a potent vasodilator, and therefore enhance the blood pressure response
CC (By similarity). Acts as a regulator of synaptic transmission by
CC mediating cleavage of neuropeptide hormones, such as substance P,
CC neurotensin or enkephalins (By similarity). Catalyzes degradation of
CC different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin,
CC Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu)
CC (PubMed:35201898). 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 (PubMed:35201898). Met-enkephalin-Arg-Phe cleavage by ACE
CC decreases activation of OPRM1, leading to long-term synaptic
CC potentiation of glutamate release (PubMed:35201898). Also acts as a
CC regulator of hematopoietic stem cell differentiation by mediating
CC degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP)
CC (PubMed:11303049). Acts as a regulator of cannabinoid signaling pathway
CC by mediating degradation of hemopressin, an antagonist peptide of the
CC cannabinoid receptor CNR1 (By similarity). Involved in amyloid-beta
CC metabolism by catalyzing degradation of Amyloid-beta protein 40 and
CC Amyloid-beta protein 42 peptides, thereby preventing plaque formation
CC (By similarity). Catalyzes cleavage of cholecystokinin (maturation of
CC Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both
CC maturation and degradation) hormones (By similarity). Degradation of
CC hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins
CC is mediated by the N-terminal catalytic domain, while angiotensin I and
CC cholecystokinin cleavage is mediated by the C-terminal catalytic region
CC (PubMed:11303049). {ECO:0000250|UniProtKB:P12821,
CC ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:11723129,
CC ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:14757757,
CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:35201898,
CC ECO:0000269|PubMed:7753170, ECO:0000269|PubMed:8642790,
CC ECO:0000269|PubMed:9231832}.
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:0000250|UniProtKB:P12821}.
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:1651914,
CC PubMed:9482924). In contrast to somatic isoforms, only contains one
CC catalytic domain (PubMed:16270063). Acts as a dipeptidyl
CC carboxypeptidase that removes dipeptides from the C-terminus of
CC substrates (PubMed:16270063). The identity of substrates that are
CC needed for male fertility is unknown (PubMed:16270063). Isoform Testis-
CC specific and isoform Somatic have distinct activities and cannot
CC completely compensate for the loss of the other when expressed in
CC somatic tissues or testis (PubMed:9664078, PubMed:10831599,
CC PubMed:11723129, PubMed:12777443, PubMed:16270063). May also have a
CC glycosidase activity which releases GPI-anchored proteins from the
CC membrane by cleaving the mannose linkage in the GPI moiety
CC (PubMed:15665832). The GPIase activity was reported to be essential for
CC the egg-binding ability of the sperm (PubMed:15665832). This activity
CC is however unclear and has been challenged by other groups, suggesting
CC that it may be indirect (PubMed:16270063).
CC {ECO:0000269|PubMed:10831599, ECO:0000269|PubMed:11723129,
CC ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:15665832,
CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:1651914,
CC ECO:0000269|PubMed:9482924, ECO:0000269|PubMed:9664078}.
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:11303049};
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:11303049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561;
CC Evidence={ECO:0000269|PubMed:11303049};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71452;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71460;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71464;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71472;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71476;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:11303049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71456;
CC Evidence={ECO:0000269|PubMed:11303049};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71484;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71488;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000269|PubMed:35201898};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70676;
CC Evidence={ECO:0000269|PubMed:35201898};
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:16270063};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P12821};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P12821};
CC -!- COFACTOR: [Isoform Testis-specific]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P12821};
CC Note=Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.
CC {ECO:0000250|UniProtKB:P12821};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000250|UniProtKB:P12821};
CC Note=Binds 3 chloride ions per subunit. {ECO:0000250|UniProtKB:P12821};
CC -!- COFACTOR: [Isoform Testis-specific]:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Evidence={ECO:0000250|UniProtKB:P12821};
CC -!- ACTIVITY REGULATION: The dipeptidyl carboxypeptidase activity is
CC specifically inhibited by lisinopril, captopril and enalaprilat
CC (PubMed:15665832, PubMed:35201898). The N-terminal catalytic domain,
CC but not the C-terminal catalytic domain, is specifically inhibited by
CC the phosphinic peptide RXP 407 (PubMed:11303049).
CC {ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:15665832,
CC ECO:0000269|PubMed:35201898}.
CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: The putative GPIase
CC activity is nearly insensitive to captopril.
CC {ECO:0000269|PubMed:15665832}.
CC -!- SUBUNIT: Monomer and homodimer; homodimerizes following binding to an
CC inhibitor (By similarity). 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:P12821, ECO:0000250|UniProtKB:P12822}.
CC -!- SUBCELLULAR LOCATION: [Isoform Somatic]: Cell membrane
CC {ECO:0000269|PubMed:23535237}; Single-pass type I membrane protein
CC {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:23535237}. Note=Detected
CC in both cell membrane and cytoplasm in neurons.
CC {ECO:0000269|PubMed:23535237}.
CC -!- SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]:
CC Secreted {ECO:0000250|UniProtKB:P12821}.
CC -!- SUBCELLULAR LOCATION: [Isoform Testis-specific]: Cell membrane
CC {ECO:0000250|UniProtKB:P12821}; Single-pass type I membrane protein
CC {ECO:0000255}. Secreted {ECO:0000250|UniProtKB:P12821}. Note=The
CC testis-specific isoform can be cleaved before the transmembrane region,
CC releasing a soluble form. {ECO:0000250|UniProtKB:P12821}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=Somatic; Synonyms=sACE {ECO:0000303|PubMed:16270063};
CC IsoId=P09470-1; Sequence=Displayed;
CC Name=Testis-specific; Synonyms=ACE-T, tACE
CC {ECO:0000303|PubMed:16270063}, germinal ACE
CC {ECO:0000303|PubMed:11723129}, gACE {ECO:0000303|PubMed:11723129};
CC IsoId=P09470-2, P22967-1;
CC Sequence=VSP_037638, VSP_037639;
CC -!- TISSUE SPECIFICITY: [Isoform Somatic]: Highly expressed in kidney and
CC lung; not expressed in the liver (PubMed:16154999). In the brain,
CC expressed in the cerebral cortex, hippocampus, cerebellum and basal
CC ganglia/brainstem (PubMed:16154999). Highly expressed in dopamine
CC receptor DRD1-expressing neurons in the dorsal striatum and the nucleus
CC accumbens of the brain (PubMed:35201898). {ECO:0000269|PubMed:16154999,
CC ECO:0000269|PubMed:35201898}.
CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Specifically expressed
CC in spermatocytes, adult testis. {ECO:0000269|PubMed:1651914}.
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. Cleavage can take place at different sites of the juxtamembrane
CC stalk region. {ECO:0000250|UniProtKB:P12821}.
CC -!- PTM: Phosphorylated by CK2 on Ser-1305; which allows membrane retention
CC (By similarity). 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:P12821,
CC ECO:0000250|UniProtKB:P12822}.
CC -!- DISRUPTION PHENOTYPE: Mice display low blood pressure (hypotension),
CC elevated serum potassium, anemia, urine concentration defects and gross
CC renal structural defects (PubMed:8642790, PubMed:9231832,
CC PubMed:11723129, PubMed:12777443). Male mice also have reduced
CC fertility: sperm show defects in transport within the oviducts and in
CC binding to zonae pellucidae (PubMed:7753170, PubMed:9482924). Mice also
CC show impaired metabolism, characterized by increased energy
CC expenditure, reduced fat mass and improved glucose clearance
CC (PubMed:18443281). Expression of isoform Somatic in testis in knockout
CC mice does not restore male fertility (PubMed:10831599). In contrast,
CC expression of isoform Testis-specific in the sperm of knockout mice
CC only restores fertility without curing other defects (PubMed:9664078).
CC Isoform Testis-specific can substitute for isoform Somatic for normal
CC kidney structure but not for normal blood pressure when expressed in
CC vascular cells of knockout mice (PubMed:11723129, PubMed:12777443,
CC PubMed:16270063). {ECO:0000269|PubMed:10831599,
CC ECO:0000269|PubMed:11723129, ECO:0000269|PubMed:12777443,
CC ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:18443281,
CC ECO:0000269|PubMed:7753170, ECO:0000269|PubMed:8642790,
CC ECO:0000269|PubMed:9231832, ECO:0000269|PubMed:9482924,
CC ECO:0000269|PubMed:9664078}.
CC -!- DISRUPTION PHENOTYPE: [Isoform Somatic]: Mice lacking somatic isoform
CC display normal male fertility. {ECO:0000269|PubMed:9482924}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; J04946; AAA37147.1; -; mRNA.
DR EMBL; J04947; AAA37148.1; -; mRNA.
DR EMBL; M55333; AAA37149.1; -; mRNA.
DR EMBL; M61094; AAA37150.1; -; Genomic_DNA.
DR EMBL; BC040404; AAH40404.1; -; mRNA.
DR EMBL; J03940; AAA37146.1; -; mRNA.
DR CCDS; CCDS25543.1; -. [P09470-1]
DR CCDS; CCDS25544.1; -. [P09470-2]
DR PIR; A34171; A34171.
DR PIR; A35655; A35655.
DR RefSeq; NP_033728.1; NM_009598.2. [P09470-2]
DR RefSeq; NP_997507.1; NM_207624.5. [P09470-1]
DR AlphaFoldDB; P09470; -.
DR SMR; P09470; -.
DR BioGRID; 197920; 3.
DR STRING; 10090.ENSMUSP00000001963; -.
DR BindingDB; P09470; -.
DR ChEMBL; CHEMBL2994; -.
DR MEROPS; M02.001; -.
DR MEROPS; M02.004; -.
DR GlyConnect; 2129; 9 N-Linked glycans (5 sites).
DR GlyGen; P09470; 14 sites, 9 N-linked glycans (5 sites).
DR iPTMnet; P09470; -.
DR PhosphoSitePlus; P09470; -.
DR jPOST; P09470; -.
DR MaxQB; P09470; -.
DR PaxDb; P09470; -.
DR PeptideAtlas; P09470; -.
DR PRIDE; P09470; -.
DR ProteomicsDB; 285580; -. [P09470-1]
DR ProteomicsDB; 285581; -. [P09470-2]
DR Antibodypedia; 31288; 873 antibodies from 43 providers.
DR DNASU; 11421; -.
DR Ensembl; ENSMUST00000001963; ENSMUSP00000001963; ENSMUSG00000020681. [P09470-1]
DR Ensembl; ENSMUST00000001964; ENSMUSP00000001964; ENSMUSG00000020681. [P09470-2]
DR GeneID; 11421; -.
DR KEGG; mmu:11421; -.
DR UCSC; uc007lxu.2; mouse. [P09470-1]
DR UCSC; uc007lxw.2; mouse. [P09470-2]
DR CTD; 1636; -.
DR MGI; MGI:87874; Ace.
DR VEuPathDB; HostDB:ENSMUSG00000020681; -.
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000162051; -.
DR HOGENOM; CLU_014364_3_0_1; -.
DR InParanoid; P09470; -.
DR OMA; WEGWHNV; -.
DR PhylomeDB; P09470; -.
DR TreeFam; TF312861; -.
DR BRENDA; 3.4.15.1; 3474.
DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR BioGRID-ORCS; 11421; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Ace; mouse.
DR PRO; PR:P09470; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P09470; protein.
DR Bgee; ENSMUSG00000020681; Expressed in small intestine Peyer's patch and 191 other tissues.
DR ExpressionAtlas; P09470; baseline and differential.
DR Genevisible; P09470; MM.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; ISO:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0031711; F:bradykinin receptor binding; ISO:MGI.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0031404; F:chloride ion binding; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISO:MGI.
DR GO; GO:0008238; F:exopeptidase activity; ISO:MGI.
DR GO; GO:1901363; F:heterocyclic compound binding; ISO:MGI.
DR GO; GO:0070573; F:metallodipeptidase activity; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IMP:MGI.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB.
DR GO; GO:0008240; F:tripeptidyl-peptidase activity; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:MGI.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; ISO:MGI.
DR GO; GO:0002003; P:angiotensin maturation; IDA:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; ISO:MGI.
DR GO; GO:0050482; P:arachidonic acid secretion; ISO:MGI.
DR GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0071838; P:cell proliferation in bone marrow; IMP: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; ISO:MGI.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; ISO:MGI.
DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl.
DR GO; GO:0060047; P:heart contraction; IMP:MGI.
DR GO; GO:0042447; P:hormone catabolic process; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; IMP:UniProtKB.
DR GO; GO:0048286; P:lung alveolus development; ISO:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:UniProtKB.
DR GO; GO:0090281; P:negative regulation of calcium ion import; ISO:MGI.
DR GO; GO:1903597; P:negative regulation of gap junction assembly; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0046325; P:negative regulation of glucose import; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IMP:BHF-UCL.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; ISO:MGI.
DR GO; GO:0002446; P:neutrophil mediated immunity; IMP:MGI.
DR GO; GO:0043171; P:peptide catabolic process; ISO:MGI.
DR GO; GO:0006518; P:peptide metabolic process; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:MGI.
DR GO; GO:2000170; P:positive regulation of peptidyl-cysteine S-nitrosylation; IMP:BHF-UCL.
DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; IMP:BHF-UCL.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:BHF-UCL.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IMP:BHF-UCL.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0060177; P:regulation of angiotensin metabolic process; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; IDA:BHF-UCL.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; IMP:BHF-UCL.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IDA:UniProtKB.
DR GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; ISO:MGI.
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; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR GO; GO:0010814; P:substance P catabolic process; ISS:UniProtKB.
DR GO; GO:0042310; P:vasoconstriction; ISO:MGI.
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 Alternative promoter usage; Calmodulin-binding; Carboxypeptidase;
KW Cell membrane; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Phosphoprotein; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..34
FT /evidence="ECO:0000269|PubMed:2835538"
FT CHAIN 35..1312
FT /note="Angiotensin-converting enzyme"
FT /id="PRO_0000028539"
FT CHAIN 35..1237
FT /note="Angiotensin-converting enzyme, soluble form"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT /id="PRO_0000028540"
FT TOPO_DOM 35..1264
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1265..1281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1282..1312
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 35..635
FT /note="Peptidase M2 1"
FT REGION 636..1237
FT /note="Peptidase M2 2"
FT REGION 1220..1261
FT /note="Juxtamembrane stalk"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT ACT_SITE 396
FT /note="Proton acceptor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 525
FT /note="Proton donor 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 994
FT /note="Proton acceptor 2"
FT /evidence="ECO:0000305|PubMed:15665832"
FT ACT_SITE 1123
FT /note="Proton donor 2"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 236
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 395
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 423
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 534
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 796
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 834
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 993
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:15665832"
FT BINDING 997
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:15665832"
FT BINDING 1021
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1095
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1099
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1132
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT MOD_RES 1305
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 59
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16944957"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 323
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 682
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 700
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT CARBOHYD 719
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT CARBOHYD 765
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 947
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1196
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 162..170
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 762..768
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 962..980
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 1148..1160
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT VAR_SEQ 1..580
FT /note="Missing (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:2164636"
FT /id="VSP_037638"
FT VAR_SEQ 581..646
FT /note="GCSRPWQEVLKDLVGSDALDAKALLEYFQPVSQWLEEQNQRNGEVLGWPENQ
FT WRPPLPDNYPEGID -> MGQGWATPGLPSFLFLLLCCGHHLLVLSQVATDHVTANQGI
FT TNQATTRSQTTTHQATIDQTTQIPN (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:2164636"
FT /id="VSP_037639"
FT MUTAGEN 395..399
FT /note="HEMGH->KEMGK: In ACE(7/7) mutant; knockin mice have
FT normal blood pressure, renal function, and hematocrit.
FT Knockin mice show normal plasma levels of angiotensin II
FT but an elevation of plasma and urine peptide N-acetyl-SDKP
FT (AcSDKP)."
FT /evidence="ECO:0000269|PubMed:14757757"
FT MUTAGEN 993
FT /note="H->K: Abolishes peptidase activity but no effect on
FT GPIase activity; when associated with K-997."
FT /evidence="ECO:0000269|PubMed:15665832"
FT MUTAGEN 994
FT /note="E->D: Abolishes peptidase activity but no effect on
FT GPIase activity."
FT /evidence="ECO:0000269|PubMed:15665832"
FT MUTAGEN 997
FT /note="H->K: Abolishes peptidase activity but no effect on
FT GPIase activity; when associated with K-993."
FT /evidence="ECO:0000269|PubMed:15665832"
FT CONFLICT 568
FT /note="A -> T (in Ref. 1; AAA37147)"
FT /evidence="ECO:0000305"
FT MUTAGEN P09470-2:413..417
FT /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase
FT activity. Knockin mice expressed in a knockout background
FT display defects in male fertility. They however show normal
FT blood pressure and kidney morphology."
FT /evidence="ECO:0000269|PubMed:16270063,
FT ECO:0000269|PubMed:17135368"
SQ SEQUENCE 1312 AA; 150918 MW; 7DF9F5BE91762DFF CRC64;
MGAASGQRGR WPLSPPLLML SLLVLLLQPS PAPALDPGLQ PGNFSPDEAG AQLFAESYNS
SAEVVMFQST VASWAHDTNI TEENARRQEE AALVSQEFAE VWGKKAKELY ESIWQNFTDS
KLRRIIGSIR TLGPANLPLA QRQQYNSLLS NMSRIYSTGK VCFPNKTATC WSLDPELTNI
LASSRSYAKL LFAWEGWHDA VGIPLKPLYQ DFTAISNEAY RQDDFSDTGA FWRSWYESPS
FEESLEHIYH QLEPLYLNLH AYVRRALHRR YGDKYVNLRG PIPAHLLGDM WAQSWENIYD
MVVPFPDKPN LDVTSTMVQK GWNATHMFRV SEEFFTSLGL SPMPPEFWAE SMLEKPTDGR
EVVCHASAWD FYNRKDFRIK QCTRVTMEQL ATVHHEMGHV QYYLQYKDLH VSLRRGANPG
FHEAIGDVLA LSVSTPAHLH KIGLLDHVTN DIESDINYLL KMALEKIAFL PFGYLVDQWR
WGVFSGRTPP SRYNFDWWYL RTKYQGICPP VARNETHFDA GAKFHIPNVT PYIRYFVSFV
LQFQFHQALC KEAGHQGPLH QCDIYQSAQA GAKLKQVLQA GCSRPWQEVL KDLVGSDALD
AKALLEYFQP VSQWLEEQNQ RNGEVLGWPE NQWRPPLPDN YPEGIDLETD EAKADRFVEE
YDRTAQVLLN EYAEANWQYN TNITIEGSKI LLEKSTEVSN HTLKYGTRAK TFDVSNFQNS
SIKRIIKKLQ NLDRAVLPPK ELEEYNQILL DMETTYSLSN ICYTNGTCMP LEPDLTNMMA
TSRKYEELLW AWKSWRDKVG RAILPFFPKY VEFSNKIAKL NGYTDAGDSW RSLYESDNLE
QDLEKLYQEL QPLYLNLHAY VRRSLHRHYG SEYINLDGPI PAHLLGNMWA QTWSNIYDLV
APFPSAPNID ATEAMIKQGW TPRRIFKEAD NFFTSLGLLP VPPEFWNKSM LEKPTDGREV
VCHPSAWDFY NGKDFRIKQC TSVNMEDLVI AHHEMGHIQY FMQYKDLPVT FREGANPGFH
EAIGDIMALS VSTPKHLYSL NLLSTEGSGY EYDINFLMKM ALDKIAFIPF SYLIDQWRWR
VFDGSITKEN YNQEWWSLRL KYQGLCPPVP RSQGDFDPGS KFHVPANVPY VRYFVSFIIQ
FQFHEALCRA AGHTGPLHKC DIYQSKEAGK LLADAMKLGY SKPWPEAMKL ITGQPNMSAS
AMMNYFKPLT EWLVTENRRH GETLGWPEYN WAPNTARAEG STAESNRVNF LGLYLEPQQA
RVGQWVLLFL GVALLVATVG LAHRLYNIRN HHSLRRPHRG PQFGSEVELR HS
