ID   ACE_THETS               Reviewed;         616 AA.
AC   Q6Q4G4;
DT   30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   24-JAN-2024, entry version 58.
DE   RecName: Full=Angiotensin-converting enzyme;
DE            EC=3.4.15.1;
DE   AltName: Full=Dipeptidyl carboxypeptidase I;
DE   AltName: Full=Kininase II;
DE   AltName: Full=TtACE;
DE   Flags: Precursor;
GN   Name=ACE;
OS   Theromyzon tessulatum (Duck leech).
OC   Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Annelida; Clitellata;
OC   Hirudinea; Rhynchobdellida; Glossiphoniidae; Theromyzon.
OX   NCBI_TaxID=13286;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, ACTIVITY REGULATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=15175004; DOI=10.1042/bj20040522;
RA   Riviere G., Michaud A., Deloffre L., Vandenbulcke F., Levoye A., Breton C.,
RA   Corvol P., Salzet M., Vieau D.;
RT   "Characterization of the first non-insect invertebrate functional
RT   angiotensin-converting enzyme (ACE): leech TtACE resembles the N-domain of
RT   mammalian ACE.";
RL   Biochem. J. 382:565-573(2004).
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:15175004};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- COFACTOR:
CC       Name=chloride; Xref=ChEBI:CHEBI:17996; Evidence={ECO:0000250};
CC       Note=Chloride. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activated by chloride. Inhibited by captopril and
CC       lisinopril, and to a lesser extent by delaprilat.
CC       {ECO:0000269|PubMed:15175004}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Epithelial cells of the midgut.
CC       {ECO:0000269|PubMed:15175004}.
CC   -!- DEVELOPMENTAL STAGE: Expressed at stages 1 and 2.
CC   -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR   EMBL; AY560004; AAS57725.1; -; mRNA.
DR   AlphaFoldDB; Q6Q4G4; -.
DR   SMR; Q6Q4G4; -.
DR   MEROPS; M02.005; -.
DR   GlyCosmos; Q6Q4G4; 6 sites, No reported glycans.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:InterPro.
DR   GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008241; F:peptidyl-dipeptidase activity; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd06461; M2_ACE; 1.
DR   Gene3D; 1.10.1370.30; -; 2.
DR   InterPro; IPR001548; Peptidase_M2.
DR   PANTHER; PTHR10514; ANGIOTENSIN-CONVERTING ENZYME; 1.
DR   PANTHER; PTHR10514:SF27; ANGIOTENSIN-CONVERTING ENZYME; 1.
DR   Pfam; PF01401; Peptidase_M2; 1.
DR   PRINTS; PR00791; PEPDIPTASEA.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   PROSITE; PS52011; PEPTIDASE_M2; 1.
PE   2: Evidence at transcript level;
KW   Carboxypeptidase; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW   Metalloprotease; Protease; Secreted; Signal; Zinc.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   CHAIN           24..616
FT                   /note="Angiotensin-converting enzyme"
FT                   /id="PRO_0000028566"
FT   DOMAIN          27..610
FT                   /note="Peptidase M2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   ACT_SITE        377
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   ACT_SITE        506
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         180
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         218
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         376
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         380
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         404
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         478
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         482
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   BINDING         515
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   CARBOHYD        61
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        96
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        428
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        535
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        573
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        142..152
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   DISULFID        345..363
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
FT   DISULFID        531..543
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01355"
SQ   SEQUENCE   616 AA;  71481 MW;  70171D38354349FC CRC64;
     MNLINFSYLN LLFGAGLFSV LESATILNTE SDAKKWLTTY NDEAGKYIYD ATEAEWNYNT
     NLTDHNLGIS IKKSNDLATF TEQKAIEANK KFVWKNFTDP LLKREFSKIT DIGTASLSDE
     DFQKMSGLNS DLTKIYSTAK VCNKPNDPSG KCYPLDPDLS DIISKSNDLE ELTWAWKGWR
     DASGKHMPDK YDEFVQLLNK AANINGYEDN GDYWRSWYES PTFRKDCEDL WQEIKPFYEQ
     LHAYVRRKLQ KKYPQIAFPK EGHIPAHLLG NMWAQSWENI EYLLRPAPDL PSMDITEELV
     KQNYTALKLF QLSDTFFKSL GLIQMPQPFW EKSMIEKPAD RDVVCHASAW DFYNRKDFRI
     KQCTVVDMHW FMTTHHEMGH IEYYLHYKDQ PISFRSGANP GFHEAIADIA SLSVATPEYM
     QSVSLLPNFT DDPNGDLNFL MNQALTKVAF LPFGYLIDQW RWDVFSGDTP RPKYNSKWWH
     NRCKYQGVYP PVIRSEQDFD AGSKFHVPNN TPYIRYFVAH IIQFQFHEAL CKAANNSRPL
     HRCNIANSKE AGKKLAELMK SGSSIPWPKV LENLTGSEKM SAKSLMAYYK PLIDWPEKRK
     PRAENWMGGK MSSWIV
//