ACE_RABIT
ID ACE_RABIT Reviewed; 1310 AA.
AC P12822; O02852; P22968;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 3.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:1311831};
DE Short=ACE {ECO:0000303|PubMed:1311831};
DE EC=3.4.15.1 {ECO:0000269|PubMed:7902354};
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:0000305|PubMed:8294466};
DE Flags: Precursor;
GN Name=ACE {ECO:0000303|PubMed:1311831}; Synonyms=DCP1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC).
RC TISSUE=Lung;
RX PubMed=1311831; DOI=10.1093/nar/20.4.683;
RA Thekkumkara T.J., Livingston W. III, Kumar R.S., Sen G.C.;
RT "Use of alternative polyadenylation sites for tissue-specific transcription
RT of two angiotensin-converting enzyme mRNAs.";
RL Nucleic Acids Res. 20:683-687(1992).
RN [2]
RP SEQUENCE REVISION.
RA Sen G.C.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE
RP SPECIFICITY (ISOFORM TESTIS-SPECIFIC).
RC STRAIN=New Zealand white; TISSUE=Testis;
RX PubMed=2550457; DOI=10.1016/s0021-9258(19)84769-5;
RA Kumar R.S., Kusari J., Roy S.N., Soffer R.L., Sen G.C.;
RT "Structure of testicular angiotensin-converting enzyme. A segmental mosaic
RT isozyme.";
RL J. Biol. Chem. 264:16754-16758(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88, AND ALTERNATIVE SPLICING.
RC TISSUE=Liver;
RX PubMed=1847388; DOI=10.1016/s0021-9258(19)67872-5;
RA Kumar R.S., Thekkumkara T.J., Sen G.C.;
RT "The mRNAs encoding the two angiotensin-converting isozymes are transcribed
RT from the same gene by a tissue-specific choice of alternative transcription
RT initiation sites.";
RL J. Biol. Chem. 266:3854-3862(1991).
RN [5]
RP PROTEIN SEQUENCE OF 34-44 AND 755-758.
RX PubMed=6291514; DOI=10.1016/0006-291x(82)90634-9;
RA Iwata K., Lai C.Y., El-Dorry H.A., Soffer R.L.;
RT "The NH2- and COOH-terminal sequences of the angiotensin-converting enzyme
RT isozymes from rabbit lung and testis.";
RL Biochem. Biophys. Res. Commun. 107:1097-1103(1982).
RN [6]
RP PROTEIN SEQUENCE OF 34-55.
RC TISSUE=Lung;
RX PubMed=6314908; DOI=10.1016/0003-9861(83)90362-4;
RA Iwata K., Blacher R., Soffer R.L., Lai C.Y.;
RT "Rabbit pulmonary angiotensin-converting enzyme: the NH2-terminal fragment
RT with enzymatic activity and its formation from the native enzyme by NH4OH
RT treatment.";
RL Arch. Biochem. Biophys. 227:188-201(1983).
RN [7]
RP PROTEIN SEQUENCE OF 34-55, AND GLYCOSYLATION.
RX PubMed=1654880; DOI=10.1042/bj2780375;
RA Kirley T.L.;
RT "The Mg(2+)-ATPase of rabbit skeletal-muscle transverse tubule is a highly
RT glycosylated multiple-subunit enzyme.";
RL Biochem. J. 278:375-380(1991).
RN [8]
RP NUCLEOTIDE SEQUENCE OF 646-746.
RX PubMed=1705622;
RA Sen G.C., Thekkumkara T.J., Kumar R.S.;
RT "Angiotensin-converting enzyme: structural relationship of the testicular
RT and the pulmonary forms.";
RL J. Cardiovasc. Pharmacol. 16:S14-S18(1990).
RN [9]
RP PROTEIN SEQUENCE OF 727-733 AND 809-815.
RX PubMed=2176870; DOI=10.1021/bi00498a011;
RA Chen Y.N., Riordan J.F.;
RT "Identification of essential tyrosine and lysine residues in angiotensin
RT converting enzyme: evidence for a single active site.";
RL Biochemistry 29:10493-10498(1990).
RN [10]
RP PROTEIN SEQUENCE OF 1237-1259, AND CLEAVAGE SITE.
RX PubMed=8294466; DOI=10.1016/s0021-9258(17)42144-2;
RA Ramchandran R., Sen G.C., Misono K., Sen I.;
RT "Regulated cleavage-secretion of the membrane-bound angiotensin-converting
RT enzyme.";
RL J. Biol. Chem. 269:2125-2130(1994).
RN [11]
RP FUNCTION.
RX PubMed=2554881; DOI=10.1042/bj2620125;
RA Dubreuil P., Fulcrand P., Rodriguez M., Fulcrand H., Laur J., Martinez J.;
RT "Novel activity of angiotensin-converting enzyme. Hydrolysis of
RT cholecystokinin and gastrin analogues with release of the amidated C-
RT terminal dipeptide.";
RL Biochem. J. 262:125-130(1989).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF LYS-727 AND TYR-809.
RX PubMed=7902354; DOI=10.1016/s0021-9258(19)74453-6;
RA Sen I., Kasturi S., Abdul-Jabbar M., Sen G.C.;
RT "Mutations in two specific residues of testicular angiotensin-converting
RT enzyme change its catalytic properties.";
RL J. Biol. Chem. 268:25748-25754(1993).
RN [13]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=8171037; DOI=10.1073/pnas.91.9.4072;
RA Fournie-Zaluski M.C., Gonzalez W., Turcaud S., Pham I., Roques B.P.,
RA Michel J.B.;
RT "Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase
RT by the orally active inhibitor mixanpril: a potential therapeutic approach
RT in hypertension.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:4072-4076(1994).
RN [14]
RP SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE FORM),
RP PHOSPHORYLATION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=15252021; DOI=10.1074/jbc.m407176200;
RA Santhamma K.R., Sadhukhan R., Kinter M., Chattopadhyay S., McCue B.,
RA Sen I.;
RT "Role of tyrosine phosphorylation in the regulation of cleavage secretion
RT of angiotensin-converting enzyme.";
RL J. Biol. Chem. 279:40227-40236(2004).
RN [15]
RP SUBCELLULAR LOCATION (ANGIOTENSIN-CONVERTING ENZYME, SOLUBLE FORM),
RP INTERACTION WITH CALMODULIN, PHOSPHORYLATION AT SER-1303, PROTEOLYTIC
RP CLEAVAGE, AND MUTAGENESIS OF SER-1303.
RX PubMed=16096279; DOI=10.1074/jbc.m501718200;
RA Chattopadhyay S., Santhamma K.R., Sengupta S., McCue B., Kinter M.,
RA Sen G.C., Sen I.;
RT "Calmodulin binds to the cytoplasmic domain of angiotensin-converting
RT enzyme and regulates its phosphorylation and cleavage secretion.";
RL J. Biol. Chem. 280:33847-33855(2005).
RN [16]
RP FUNCTION (ISOFORM TESTIS-SPECIFIC).
RX PubMed=16270062; DOI=10.1038/nm1105-1139;
RA Leisle L., Parkin E.T., Turner A.J., Hooper N.M.;
RT "Angiotensin-converting enzyme as a GPIase: a critical reevaluation.";
RL Nat. Med. 11:1139-1140(2005).
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:7902354, PubMed:8171037). Composed of two similar catalytic
CC domains, each possessing a functional active site, with different
CC selectivity for substrates (By similarity). Plays a major role in the
CC angiotensin-renin system that regulates blood pressure and sodium
CC retention by the kidney by converting angiotensin I to angiotensin II,
CC resulting in an increase of the vasoconstrictor activity of angiotensin
CC (PubMed:7902354). Also able to inactivate bradykinin, a potent
CC vasodilator, and therefore enhance the blood pressure response (By
CC similarity). Acts as a regulator of synaptic transmission by mediating
CC cleavage of neuropeptide hormones, such as substance P, neurotensin or
CC enkephalins (By similarity). Catalyzes degradation of different
CC enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-
CC enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (By
CC similarity). Acts as a regulator of synaptic plasticity in the nucleus
CC accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe,
CC a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin
CC (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases
CC activation of OPRM1, leading to long-term synaptic potentiation of
CC glutamate release (By similarity). Also acts as a regulator of
CC hematopoietic stem cell differentiation by mediating degradation of
CC hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (By similarity). Acts as
CC a regulator of cannabinoid signaling pathway by mediating degradation
CC of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1
CC (By similarity). Involved in amyloid-beta metabolism by catalyzing
CC degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42
CC peptides, thereby preventing plaque formation (By similarity).
CC Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8
CC and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and
CC degradation) hormones (PubMed:2554881). Degradation of hemoregulatory
CC peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by
CC the N-terminal catalytic domain, while angiotensin I and
CC cholecystokinin cleavage is mediated by the C-terminal catalytic region
CC (By similarity). {ECO:0000250|UniProtKB:P09470,
CC ECO:0000250|UniProtKB:P12821, ECO:0000269|PubMed:2554881,
CC ECO:0000269|PubMed:7902354, ECO:0000269|PubMed:8171037}.
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 (By similarity).
CC In contrast to somatic isoforms, only contains one catalytic domain (By
CC similarity). Acts as a dipeptidyl carboxypeptidase that removes
CC dipeptides from the C-terminus of substrates (PubMed:7902354). The
CC identity of substrates that are needed for male fertility is unknown
CC (By similarity). May also have a glycosidase activity which releases
CC GPI-anchored proteins from the membrane by cleaving the mannose linkage
CC in the GPI moiety (By similarity). The GPIase activity was reported to
CC be essential for the egg-binding ability of the sperm (By similarity).
CC This activity is however unclear and has been challenged by other
CC groups, suggesting that it may be indirect (PubMed:16270062).
CC {ECO:0000250|UniProtKB:P09470, ECO:0000250|UniProtKB:P12821,
CC ECO:0000269|PubMed:16270062, ECO:0000269|PubMed:7902354}.
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:7902354};
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:7902354};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561;
CC Evidence={ECO:0000269|PubMed:7902354};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71456;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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: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:7902354};
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 strongly activated by chloride (By similarity). Specifically inhibited
CC by lisinopril (PubMed:7902354). Inhibited by mixanpril, an orally-
CC active drug used for the treatment of hypertension (PubMed:8171037).
CC {ECO:0000250|UniProtKB:P12821, ECO:0000269|PubMed:7902354,
CC ECO:0000269|PubMed:8171037}.
CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: Strongly inhibited by
CC lisinopril and captopril. {ECO:0000250|UniProtKB:P12821}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.6 mM for Hip-His-Leu {ECO:0000269|PubMed:7902354};
CC KM=0.09 mM for angiotensin I {ECO:0000269|PubMed:7902354};
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 (PubMed:16096279).
CC {ECO:0000250|UniProtKB:P12821, ECO:0000269|PubMed:16096279}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P12821};
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:15252021, ECO:0000269|PubMed:16096279}.
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;
CC IsoId=P12822-1; Sequence=Displayed;
CC Name=Testis-specific; Synonyms=ACE-T;
CC IsoId=P12822-2, P22968-1;
CC Sequence=VSP_037644, VSP_037645;
CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Testis-specific isoform
CC is expressed in spermatocytes, adult testis.
CC {ECO:0000269|PubMed:2550457}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:1654880}.
CC -!- PTM: Phosphorylated by CK2 on Ser-1303; 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) (PubMed:15252021). {ECO:0000250|UniProtKB:P12821,
CC ECO:0000269|PubMed:15252021}.
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:15252021, PubMed:16096279). Cleavage can take place at
CC different sites of the juxtamembrane stalk region (By similarity).
CC {ECO:0000250|UniProtKB:P12821, ECO:0000269|PubMed:15252021,
CC ECO:0000269|PubMed:16096279}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR EMBL; X62551; CAA44428.1; -; mRNA.
DR EMBL; J05041; AAA31153.1; -; mRNA.
DR EMBL; M58579; AAA31151.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M58580; AAA31152.1; -; Genomic_DNA.
DR PIR; A34402; A34402.
DR PIR; S35484; S35484.
DR RefSeq; NP_001075864.1; NM_001082395.1. [P12822-1]
DR RefSeq; NP_001164540.1; NM_001171069.1. [P12822-2]
DR AlphaFoldDB; P12822; -.
DR SMR; P12822; -.
DR BindingDB; P12822; -.
DR ChEMBL; CHEMBL4074; -.
DR DrugCentral; P12822; -.
DR MEROPS; M02.001; -.
DR MEROPS; M02.004; -.
DR PRIDE; P12822; -.
DR GeneID; 100009274; -.
DR KEGG; ocu:100009274; -.
DR CTD; 1636; -.
DR eggNOG; KOG3690; Eukaryota.
DR InParanoid; P12822; -.
DR OrthoDB; 422699at2759; -.
DR BRENDA; 3.4.15.1; 1749.
DR SABIO-RK; P12822; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0031404; F:chloride ion binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070573; F:metallodipeptidase activity; ISS:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; ISS:UniProtKB.
DR GO; GO:0002003; P:angiotensin maturation; ISS:UniProtKB.
DR GO; GO:0010815; P:bradykinin catabolic process; ISS:UniProtKB.
DR GO; GO:0042447; P:hormone catabolic process; ISS:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; ISS:UniProtKB.
DR GO; GO:0008217; P:regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0010814; P:substance P catabolic process; ISS:UniProtKB.
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..33
FT /evidence="ECO:0000269|PubMed:1654880,
FT ECO:0000269|PubMed:6291514, ECO:0000269|PubMed:6314908"
FT CHAIN 34..1310
FT /note="Angiotensin-converting enzyme"
FT /id="PRO_0000028551"
FT CHAIN 34..1236
FT /note="Angiotensin-converting enzyme, soluble form"
FT /evidence="ECO:0000305|PubMed:8294466"
FT /id="PRO_0000028552"
FT TOPO_DOM 34..1260
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1261..1281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1282..1310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 35..634
FT /note="Peptidase M2 1"
FT REGION 635..1236
FT /note="Peptidase M2 2"
FT REGION 1219..1260
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 524
FT /note="Proton donor 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 993
FT /note="Proton acceptor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 1122
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 422
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 533
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 795
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 833
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 992
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 996
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 1020
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 1094
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1098
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1131
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT SITE 1236..1237
FT /note="Cleavage"
FT /evidence="ECO:0000269|PubMed:16096279,
FT ECO:0000269|PubMed:8294466"
FT MOD_RES 1303
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16096279"
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 151
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 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 681
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 718
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 946
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 162..170
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 761..767
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 961..979
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 1147..1159
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT VAR_SEQ 1..573
FT /note="Missing (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:2550457"
FT /id="VSP_037644"
FT VAR_SEQ 574..645
FT /note="RAVLQAGCSRPWQEVLKDMVASDALDAQPLLDYFQPVTQWLQEQNERNGEVL
FT GWPEYQWRPPLPNNYPEGID -> MGQGWAAPGLPSLLLLLLCCGHSLLVPSRVAARRV
FT TVNQGTTSQATTTSKATTSIRATTHQTTAHQTTQSPN (in isoform Testis-
FT specific)"
FT /evidence="ECO:0000303|PubMed:2550457"
FT /id="VSP_037645"
FT MUTAGEN 727
FT /note="K->E: No effect on activity. 20-fold reduction in
FT catalytic efficiency; when associated with F-809."
FT /evidence="ECO:0000269|PubMed:7902354"
FT MUTAGEN 809
FT /note="Y->F: No effect on activity. 20-fold reduction in
FT catalytic efficiency; when associated with E-727."
FT /evidence="ECO:0000269|PubMed:7902354"
FT MUTAGEN 1303
FT /note="S->A: Abolished phosphorylation without affecting
FT calmodulin-binding."
FT /evidence="ECO:0000269|PubMed:16096279"
FT MUTAGEN 1303
FT /note="S->D: Mimics phosphorylation; does not affect
FT calmodulin-binding."
FT /evidence="ECO:0000269|PubMed:16096279"
FT CONFLICT 48
FT /note="E -> N (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1310 AA; 150406 MW; 04777FAB17981DEA CRC64;
MGAAPGRRGP RLLRPPPPLL LLLLLLRPPP AALTLDPGLL PGDFAADEAG ARLFASSYNS
SAEQVLFRST AASWAHDTNI TAENARRQEE EALLSQEFAE AWGKKAKELY DPVWQNFTDP
ELRRIIGAVR TLGPANLPLA KRQQYNSLLS NMSQIYSTGK VCFPNKTASC WSLDPDLNNI
LASSRSYAML LFAWEGWHNA VGIPLKPLYQ EFTALSNEAY RQDGFSDTGA YWRSWYDSPT
FEEDLERIYH QLEPLYLNLH AYVRRVLHRR YGDRYINLRG PIPAHLLGNM WAQSWESIYD
MVVPFPDKPN LDVTSTMVQK GWNATHMFRV AEEFFTSLGL LPMPPEFWAE SMLEKPEDGR
EVVCHASAWD FYNRKDFRIK QCTQVTMDQL STVHHEMGHV QYYLQYKDQP VSLRRANPGF
HEAIGDVLAL SVSTPAHLHK IGLLDHVTND TESDINYLLK MALEKIAFLP FGYLVDQWRW
GVFSGRTPSS RYNFDWWYLR TKYQGICPPV VRNETHFDAG AKFHIPSVTP YIRYFVSFVL
QFQFHQALCM EAGHQGPLHQ CDIYQSTRAG AKLRAVLQAG CSRPWQEVLK DMVASDALDA
QPLLDYFQPV TQWLQEQNER NGEVLGWPEY QWRPPLPNNY PEGIDLVTDE AEASRFVEEY
DRSFQAVWNE YAEANWNYNT NITTEASKIL LQKNMQIANH TLTYGNWARR FDVSNFQNAT
SKRIIKKVQD LQRAVLPVKE LEEYNQILLD METIYSVANV CRVDGSCLQL EPDLTNLMAT
SRKYDELLWV WTSWRDKVGR AILPYFPKYV EFTNKAARLN GYVDAGDSWR SMYETPTLEQ
DLERLFQELQ PLYLNLHAYV GRALHRHYGA QHINLEGPIP AHLLGNMWAQ TWSNIYDLVA
PFPSASTMDA TEAMIKQGWT PRRMFEEADK FFISLGLLPV PPEFWNKSML EKPTDGREVV
CHASAWDFYN GKDFRIKQCT TVNMEDLVVV HHEMGHIQYF MQYKDLPVAL REGANPGFHE
AIGDVLALSV STPKHLHSIN LLSSEGGGYE HDINFLMKMA LDKIAFIPFS YLVDEWRWRV
FDGSITKENY NQEWWSLRLK YQGLCPPAPR SQGDFDPGAK FHIPSSVPYI RYFVSFIIQF
QFHEALCKAA GHTGPLHTCD IYQSKEAGKR LADAMKLGYS KPWPEAMKVI TGQPNMSASA
MMNYFKPLMD WLLTENGRHG EKLGWPQYTW TPNSARSEGS LPDSGRVNFL GMNLDAQQAR
VGQWVLLFLG VALLLASLGL TQRLFSIRYQ SLRQPHHGPQ FGSEVELRHS
