ACE_RAT
ID ACE_RAT Reviewed; 1313 AA.
AC P47820; Q7TMC6; Q8CFN1; Q9EQM9;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Angiotensin-converting enzyme {ECO:0000303|PubMed:8292044};
DE Short=ACE {ECO:0000303|PubMed:8292044};
DE EC=3.4.15.1 {ECO:0000250|UniProtKB:P12821};
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:8292044}; Synonyms=Dcp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC), AND VARIANT LYS-207.
RC TISSUE=Lung;
RX PubMed=8292044; DOI=10.1006/bbrc.1994.1053;
RA Koike G., Krieger J.E., Jacob H.J., Mukoyama M., Pratt R.E., Dzau V.J.;
RT "Angiotensin converting enzyme and genetic hypertension: cloning of rat
RT cDNAs and characterization of the enzyme.";
RL Biochem. Biophys. Res. Commun. 198:380-386(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC).
RC STRAIN=Fischer 344/N, and Lewis/N; TISSUE=Lung;
RA Jafarian-Tehrani M., Listwak S., Barrientos R.M., Michaud A., Corvol P.,
RA Sternberg E.M.;
RT "Characterization of a missense mutation in the angiotensin I-converting
RT enzyme cDNA in exudative inflammation resistant F344/N rats.";
RL Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=12963491; DOI=10.1016/s0006-2952(03)00457-x;
RA Tian X.-L., Paul M.;
RT "Species-specific splicing and expression of angiotensin converting
RT enzyme.";
RL Biochem. Pharmacol. 66:1037-1044(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SOMATIC).
RC TISSUE=Lung;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-1313 (ISOFORM SOMATIC), AND VARIANT
RP LYS-207.
RC TISSUE=Kidney;
RA Tsetsarkin K.A., Dymshits G.M., Markel A.L., Redina O.E.;
RT "Analysis of the angiotensin converting enzyme (Ace) cDNA sequence and mRNA
RT level of expression in WAG and ISIAH rats.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=20487892; DOI=10.1016/0197-0186(82)90081-x;
RA Benuck M., Berg M.J., Marks N.;
RT "Separate metabolic pathways for Leu-enkephalin and Met-enkephalin-Arg(6)-
RT Phe(7) degradation by rat striatal synaptosomal membranes.";
RL Neurochem. Int. 4:389-396(1982).
RN [7]
RP FUNCTION.
RX PubMed=12500972; DOI=10.1074/jbc.m212030200;
RA Rioli V., Gozzo F.C., Heimann A.S., Linardi A., Krieger J.E., Shida C.S.,
RA Almeida P.C., Hyslop S., Eberlin M.N., Ferro E.S.;
RT "Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and
RT angiotensin-converting enzyme.";
RL J. Biol. Chem. 278:8547-8555(2003).
RN [8]
RP 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 [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 (By
CC similarity). Composed of two similar catalytic domains, each possessing
CC a functional active site, with different selectivity for substrates (By
CC similarity). Plays a major role in the angiotensin-renin system that
CC 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 (By similarity). Also able
CC to inactivate bradykinin, a potent vasodilator, and therefore enhance
CC the blood pressure response (By similarity). Acts as a regulator of
CC synaptic transmission by mediating cleavage of neuropeptide hormones,
CC such as substance P, neurotensin or enkephalins (By similarity).
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:20487892). Acts as a regulator of
CC synaptic plasticity in the nucleus accumbens of the brain by mediating
CC cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid
CC receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-
CC Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-
CC term synaptic potentiation of glutamate release (By similarity). Also
CC acts as a regulator of hematopoietic stem cell differentiation by
CC mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP)
CC (PubMed:12500972, PubMed:18077343). Acts as a regulator of cannabinoid
CC signaling pathway by mediating degradation of hemopressin, an
CC antagonist peptide of the cannabinoid receptor CNR1 (PubMed:12500972,
CC PubMed:18077343). 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 (By similarity). 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:12500972,
CC ECO:0000269|PubMed:18077343, ECO:0000269|PubMed:20487892}.
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. In contrast to
CC somatic isoforms, only contains one catalytic domain. Acts as a
CC dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus
CC of substrates (By similarity). The identity of substrates that are
CC needed for male fertility is unknown. May also have a glycosidase
CC activity which releases GPI-anchored proteins from the membrane by
CC cleaving the mannose linkage in the GPI moiety. The GPIase activity was
CC reported to be essential for the egg-binding ability of the sperm. This
CC activity is however unclear and has been challenged by other groups,
CC suggesting that it may be indirect (By similarity).
CC {ECO:0000250|UniProtKB:P09470, ECO:0000250|UniProtKB:P12821}.
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:0000250|UniProtKB:P12821};
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:0000250|UniProtKB:P12821};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63561;
CC Evidence={ECO:0000250|UniProtKB:P12821};
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:0000269|PubMed:20487892};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70676;
CC Evidence={ECO:0000269|PubMed:20487892};
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:0000250|UniProtKB:P12821};
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. The dipeptidyl carboxypeptidase
CC activity is specifically inhibited by lisinopril, captopril and
CC enalaprilat. {ECO:0000250|UniProtKB:P12821}.
CC -!- ACTIVITY REGULATION: [Isoform Testis-specific]: Strongly inhibited by
CC lisinopril and captopril. {ECO:0000250|UniProtKB:P12821}.
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: 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: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;
CC IsoId=P47820-1; Sequence=Displayed;
CC Name=Testis-specific; Synonyms=ACE-T;
CC IsoId=P47820-2, Q8CFN1-1;
CC Sequence=VSP_037642, VSP_037643;
CC -!- TISSUE SPECIFICITY: Expressed in brain, kidney, lung, skeletal muscle
CC and heart. {ECO:0000269|PubMed:12963491}.
CC -!- TISSUE SPECIFICITY: [Isoform Testis-specific]: Testis-specific isoform
CC is expressed in spermatocytes, adult testis.
CC {ECO:0000269|PubMed:12963491}.
CC -!- INDUCTION: Up-regulated after myocardial infarction.
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. Cleavage can take place at different sites of the juxtamembrane
CC stalk region. {ECO:0000250|UniProtKB:P12821}.
CC -!- PTM: Phosphorylated by CK2 on Ser-1306; 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 -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR EMBL; U03708; AAA82110.1; -; mRNA.
DR EMBL; U03734; AAA82111.1; -; mRNA.
DR EMBL; AF201331; AAG35596.1; -; mRNA.
DR EMBL; AF201332; AAG35597.1; -; mRNA.
DR EMBL; AF539425; AAN17280.1; -; mRNA.
DR EMBL; BC085760; AAH85760.1; -; mRNA.
DR EMBL; AF532783; AAP80808.1; -; mRNA.
DR EMBL; AF532784; AAP80809.1; -; mRNA.
DR PIR; JC2038; JC2038.
DR RefSeq; NP_036676.1; NM_012544.1.
DR AlphaFoldDB; P47820; -.
DR SMR; P47820; -.
DR STRING; 10116.ENSRNOP00000010627; -.
DR BindingDB; P47820; -.
DR ChEMBL; CHEMBL2625; -.
DR DrugCentral; P47820; -.
DR GuidetoPHARMACOLOGY; 1613; -.
DR MEROPS; M02.001; -.
DR MEROPS; M02.004; -.
DR GlyGen; P47820; 14 sites, 5 N-linked glycans (1 site).
DR iPTMnet; P47820; -.
DR PhosphoSitePlus; P47820; -.
DR jPOST; P47820; -.
DR PaxDb; P47820; -.
DR PRIDE; P47820; -.
DR ABCD; P47820; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000010627; ENSRNOP00000010627; ENSRNOG00000062101. [P47820-1]
DR GeneID; 24310; -.
DR KEGG; rno:24310; -.
DR UCSC; RGD:2493; rat. [P47820-1]
DR CTD; 1636; -.
DR RGD; 2493; Ace.
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000162051; -.
DR InParanoid; P47820; -.
DR OrthoDB; 422699at2759; -.
DR PhylomeDB; P47820; -.
DR TreeFam; TF312861; -.
DR BRENDA; 3.4.15.1; 5301.
DR Reactome; R-RNO-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR PRO; PR:P47820; -.
DR Proteomes; UP000002494; Chromosome 10.
DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0070062; C:extracellular exosome; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
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:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0097225; C:sperm midpiece; IDA:RGD.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0031711; F:bradykinin receptor binding; ISO:RGD.
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:RGD.
DR GO; GO:0008238; F:exopeptidase activity; ISO:RGD.
DR GO; GO:1901363; F:heterocyclic compound binding; IDA:RGD.
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; IMP:RGD.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0050435; P:amyloid-beta metabolic process; ISO:RGD.
DR GO; GO:0060978; P:angiogenesis involved in coronary vascular morphogenesis; IMP:RGD.
DR GO; GO:0002003; P:angiotensin maturation; ISS:UniProtKB.
DR GO; GO:0031100; P:animal organ regeneration; IMP:RGD.
DR GO; GO:0050482; P:arachidonic acid secretion; ISO:RGD.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0071838; P:cell proliferation in bone marrow; ISO:RGD.
DR GO; GO:1904045; P:cellular response to aldosterone; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IEP:RGD.
DR GO; GO:0042755; P:eating behavior; IMP:RGD.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0060047; P:heart contraction; ISO:RGD.
DR GO; GO:0042447; P:hormone catabolic process; ISS:UniProtKB.
DR GO; GO:0042445; P:hormone metabolic process; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEP:RGD.
DR GO; GO:0048286; P:lung alveolus development; IMP:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0008584; P:male gonad development; IEP:RGD.
DR GO; GO:0090281; P:negative regulation of calcium ion import; IMP:RGD.
DR GO; GO:1903597; P:negative regulation of gap junction assembly; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0046325; P:negative regulation of glucose import; IMP:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0035814; P:negative regulation of renal sodium excretion; IMP:RGD.
DR GO; GO:0002446; P:neutrophil mediated immunity; ISO:RGD.
DR GO; GO:0043171; P:peptide catabolic process; IDA:RGD.
DR GO; GO:0006518; P:peptide metabolic process; IMP:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0045777; P:positive regulation of blood pressure; IMP:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IMP:RGD.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IMP:RGD.
DR GO; GO:2000170; P:positive regulation of peptidyl-cysteine S-nitrosylation; ISO:RGD.
DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; IMP:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0010608; P:post-transcriptional regulation of gene expression; ISO:RGD.
DR GO; GO:0060177; P:regulation of angiotensin metabolic process; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; IDA:BHF-UCL.
DR GO; GO:1902033; P:regulation of hematopoietic stem cell proliferation; ISO:RGD.
DR GO; GO:0014910; P:regulation of smooth muscle cell migration; IDA: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; ISO:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0034616; P:response to laminar fluid shear stress; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0097066; P:response to thyroid hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IMP:RGD.
DR GO; GO:0007283; P:spermatogenesis; ISO:RGD.
DR GO; GO:0010814; P:substance P catabolic process; ISS:UniProtKB.
DR GO; GO:0042310; P:vasoconstriction; IMP:RGD.
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; 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..35
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT CHAIN 36..1313
FT /note="Angiotensin-converting enzyme"
FT /id="PRO_0000028557"
FT CHAIN 36..1238
FT /note="Angiotensin-converting enzyme, soluble form"
FT /id="PRO_0000028558"
FT TOPO_DOM 36..1265
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1266..1282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1283..1313
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 36..636
FT /note="Peptidase M2 1"
FT REGION 637..1238
FT /note="Peptidase M2 2"
FT REGION 1221..1262
FT /note="Juxtamembrane stalk"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT ACT_SITE 397
FT /note="Proton acceptor 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 526
FT /note="Proton donor 1"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 995
FT /note="Proton acceptor 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT ACT_SITE 1124
FT /note="Proton donor 2"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 237
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 396
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 400
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 424
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 535
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 797
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 835
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 994
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 998
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 1022
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 1096
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1100
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT BINDING 1133
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT MOD_RES 1306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 60
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 80
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 152
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 683
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 701
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 720
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 766
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 948
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 163..171
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 763..769
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 963..981
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT DISULFID 1149..1161
FT /evidence="ECO:0000250|UniProtKB:P12821"
FT VAR_SEQ 1..581
FT /note="Missing (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:12963491"
FT /id="VSP_037642"
FT VAR_SEQ 582..646
FT /note="GCSRPWQEVLKDLVGSDALDASALMEYFQPVSQWLQEQNQRNGEVLGWPEYQ
FT WRPPLPDNYPEGI -> MGQGWATPGLPRFLFLLLCCGHLLPVLSQVAADHVTANQGIT
FT NQATTRSQTTHQSTISQTIQTSNGTPGRGQGHEGARSQGPAGGNSNKTTPCGKEGEACL
FT FSSSPPT (in isoform Testis-specific)"
FT /evidence="ECO:0000303|PubMed:12963491"
FT /id="VSP_037643"
FT VARIANT 207
FT /note="R -> K"
FT /evidence="ECO:0000269|PubMed:8292044, ECO:0000269|Ref.5"
FT CONFLICT 341
FT /note="L -> F (in Ref. 2; AAG35596)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1313 AA; 150908 MW; 8CB5D0015F129591 CRC64;
MGAASGQRGR WPLSPPLLML SLLLLLLLPP SPAPALDPGL QPGNFSADEA GAQLFADSYN
SSAEVVMFQS TAASWAHDTN ITEENARLQE EAALINQEFA EVWGKKAKEL YESIWQNFTD
QKLRRIIGSV QTLGPANLPL TQRLQYNSLL SNMSRIYSTG KVCFPNKTAT CWSLDPELTN
ILASSRNYAK VLFAWEGWHD AVGIPLRPLY QDFTALSNEA YRQDGFSDTG AYWRSWYESP
SFEESLEHLY HQVEPLYLNL HAFVRRALHR RYGDKYINLR GPIPAHLLGD MWAQSWENIY
DMVVPFPDKP NLDVTSTMVQ KGWNATHMFR VAEEFFTSLG LSPMPPEFWA ESMLEKPADG
REVVCHASAW DFYNRKDFRI KQCTRVTMDQ LSTVHHEMGH VQYYLQYKDL HVSLRRGANP
GFHEAIGDVL ALSVSTPAHL HKIGLLDRVA NDIESDINYL LKMALEKIAF LPFGYLVDQW
RWGVFSGRTP PSRYNYDWWY LRTKYQGICP PVARNETHFD AGAKFHIPSV TPYIRYFVSF
VLQFQFHQAL CKEAGHQGPL HQCDIYQSTK AGAKLQQVLQ AGCSRPWQEV LKDLVGSDAL
DASALMEYFQ PVSQWLQEQN QRNGEVLGWP EYQWRPPLPD NYPEGIDLET DEAKANRFVE
EYDRTAKVLW NEYAEANWHY NTNITIEGSK ILLQKNKEVS NHTLKYGTWA KTFDVSNFQN
STIKRIIKKV QNVDRAVLPP NELEEYNQIL LDMETTYSVA NVCYTNGTCL SLEPDLTNIM
ATSRKYEELL WVWKSWRDKV GRAILPFFPK YVDFSNKIAK LNGYSDAGDS WRSSYESDDL
EQDLEKLYQE LQPLYLNLHA YVRRSLHRHY GSEYINLDGP IPAHLLGNMW AQTWSNIYDL
VAPFPSAPSI DATEAMIKQG WTPRRIFKEA DNFFTSLGLL PVPPEFWNKS MLEKPTDGRE
VVCHASAWDF YNGKDFRIKQ CTSVNMEELV IAHHEMGHIQ YFMQYKDLPV TFREGANPGF
HEAIGDVLAL SVSTPKHLHS LNLLSSEGSG YEHDINFLMK MALDKIAFIP FSYLIDQWRW
RVFDGSITKE NYNQEWWSLR LKYQGLCPPV PRSQGDFDPG SKFHVPANVP YIRYFISFII
QFQFHEALCR AAGHTGPLYK CDIYQSKEAG KLLADAMKLG YSKQWPEAMK IITGQPNMSA
SAIMNYFKPL TEWLVTENRR HGETLGWPEY TWTPNTARAE GSLPESSRVN FLGMYLEPQQ
ARVGQWVLLF LGVALLVATV GLAHRLYNIH NHHSLRRPHR GPQFGSEVEL RHS
