| IED ID | IndEnz0002019335 |
| Enzyme Type ID | protease019335 |
| Protein Name |
Angiotensin-converting enzyme 2 EC 3.4.17.23 ACE-related carboxypeptidase EC 3.4.17.- Cleaved into: Processed angiotensin-converting enzyme 2 |
| Gene Name | Ace2 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MSSSSWLLLSLVAVTTAQSLTEENAKTFLNNFNQEAEDLSYQSSLASWNYNTNITEENAQKMSEAAAKWSAFYEEQSKTAQSFSLQEIQTPIIKRQLQALQQSGSSALSADKNKQLNTILNTMSTIYSTGKVCNPKNPQECLLLEPGLDEIMATSTDYNSRLWAWEGWRAEVGKQLRPLYEEYVVLKNEMARANNYNDYGDYWRGDYEAEGADGYNYNRNQLIEDVERTFAEIKPLYEHLHAYVRRKLMDTYPSYISPTGCLPAHLLGDMWGRFWTNLYPLTVPFAQKPNIDVTDAMMNQGWDAERIFQEAEKFFVSVGLPHMTQGFWANSMLTEPADGRKVVCHPTAWDLGHGDFRIKMCTKVTMDNFLTAHHEMGHIQYDMAYARQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLPSDFQEDSETEINFLLKQALTIVGTLPFTYMLEKWRWMVFRGEIPKEQWMKKWWEMKREIVGVVEPLPHDETYCDPASLFHVSNDYSFIRYYTRTIYQFQFQEALCQAAKYNGSLHKCDISNSTEAGQKLLKMLSLGNSEPWTKALENVVGARNMDVKPLLNYFQPLFDWLKEQNRNSFVGWNTEWSPYADQSIKVRISLKSALGANAYEWTNNEMFLFRSSVAYAMRKYFSIIKNQTVPFLEEDVRVSDLKPRVSFYFFVTSPQNVSDVIPRSEVEDAIRMSRGRINDVFGLNDNSLEFLGIHPTLEPPYQPPVTIWLIIFGVVMALVVVGIIILIVTGIKGRKKKNETKREENPYDSMDIGKGESNAGFQNSDDAQTSF |
| Enzyme Length | 805 |
| Uniprot Accession Number | Q8R0I0 |
| Absorption | |
| Active Site | ACT_SITE 375; /note=Proton acceptor; /evidence=ECO:0000250|UniProtKB:Q9BYF1; ACT_SITE 505; /note=Proton donor; /evidence=ECO:0000250|UniProtKB:Q9BYF1 |
| Activity Regulation | |
| Binding Site | BINDING 169; /note=Chloride; /evidence=ECO:0000250|UniProtKB:Q9BYF1; BINDING 273; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q9BYF1; BINDING 477; /note=Chloride; /evidence=ECO:0000250|UniProtKB:Q9BYF1; BINDING 481; /note=Chloride; /evidence=ECO:0000250|UniProtKB:Q9BYF1; BINDING 515; /note=Substrate; /evidence=ECO:0000250|UniProtKB:Q9BYF1 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine; Xref=Rhea:RHEA:26554, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:58506, ChEBI:CHEBI:58922; EC=3.4.17.23; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26555; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=angiotensin I + H2O = angiotensin-(1-9) + L-leucine; Xref=Rhea:RHEA:63532, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427, ChEBI:CHEBI:147350, ChEBI:CHEBI:147351; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63533; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=[des-Arg(9)]-bradykinin + H2O = [des-Phe(8), des-Arg(9)]-bradykinin + L-phenylalanine; Xref=Rhea:RHEA:63536, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:133069, ChEBI:CHEBI:147352; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63537; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=H2O + neurotensin = L-leucine + neurotensin-(1-12); Xref=Rhea:RHEA:63540, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427, ChEBI:CHEBI:147362, ChEBI:CHEBI:147363; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63541; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=H2O + kinetensin = kinetensin-(1-8) + L-leucine; Xref=Rhea:RHEA:63544, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427, ChEBI:CHEBI:147364, ChEBI:CHEBI:147365; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63545; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine; Xref=Rhea:RHEA:63556, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551, ChEBI:CHEBI:147381, ChEBI:CHEBI:147383; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63557; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=apelin-13 + H2O = apelin-12 + L-phenylalanine; Xref=Rhea:RHEA:63564, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:147395, ChEBI:CHEBI:147396; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63565; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=[Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine; Xref=Rhea:RHEA:63604, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:147415, ChEBI:CHEBI:147416; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63605; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; CATALYTIC ACTIVITY: Reaction=apelin-17 + H2O = apelin-16 + L-phenylalanine; Xref=Rhea:RHEA:63608, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:147421, ChEBI:CHEBI:147422; Evidence={ECO:0000250|UniProtKB:Q9BYF1};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63609; Evidence={ECO:0000250|UniProtKB:Q9BYF1}; |
| DNA Binding | |
| EC Number | 3.4.17.23; 3.4.17.- |
| Enzyme Function | FUNCTION: Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II. Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin. Also cleaves other biological peptides, such as apelins, casomorphins and dynorphin A (By similarity). By cleavage of angiotensin II, may be an important regulator of heart function (PubMed:12075344, PubMed:12967627). By cleavage of angiotensin II, may also have a protective role in acute lung injury (PubMed:16001071). Plays an important role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19, regulating its trafficking on the cell surface and its activity (PubMed:19185582, PubMed:18424768, PubMed:22677001). {ECO:0000250|UniProtKB:Q9BYF1, ECO:0000269|PubMed:12075344, ECO:0000269|PubMed:12967627, ECO:0000269|PubMed:16001071, ECO:0000269|PubMed:18424768, ECO:0000269|PubMed:19185582, ECO:0000269|PubMed:22677001}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Alternative sequence (1); Binding site (5); Chain (2); Compositional bias (1); Disulfide bond (3); Frameshift (1); Glycosylation (5); Metal binding (3); Modified residue (2); Motif (5); Region (4); Sequence conflict (3); Signal peptide (1); Topological domain (2); Transmembrane (1) |
| Keywords | 3D-structure;Alternative splicing;Carboxypeptidase;Cell membrane;Cell projection;Chloride;Cytoplasm;Disulfide bond;Glycoprotein;Hydrolase;Membrane;Metal-binding;Metalloprotease;Phosphoprotein;Protease;Reference proteome;Secreted;Signal;Transmembrane;Transmembrane helix;Zinc |
| Interact With | A0A6G6A1M4; A0A6M3G9R1; P0DTC2 |
| Induction | INDUCTION: Down-regulated in lung after acute injury. Exposure to cigarette smoke increases ACE2 expression up to 80% more in lungs (PubMed:32425701). {ECO:0000269|PubMed:16001071, ECO:0000269|PubMed:32425701}. |
| Subcellular Location | SUBCELLULAR LOCATION: [Processed angiotensin-converting enzyme 2]: Secreted {ECO:0000250}.; SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23535237}; Single-pass type I membrane protein {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:23535237}. Cell projection, cilium {ECO:0000250|UniProtKB:Q9BYF1}. Apical cell membrane {ECO:0000250|UniProtKB:Q9BYF1}. Note=Detected in both cell membrane and cytoplasm in neurons. {ECO:0000269|PubMed:23535237}. |
| Modified Residue | MOD_RES 781; /note=Phosphotyrosine; /evidence=ECO:0000250|UniProtKB:Q9BYF1; MOD_RES 783; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9BYF1 |
| Post Translational Modification | PTM: Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1 (By similarity). {ECO:0000250}.; PTM: Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains. {ECO:0000250|UniProtKB:Q9BYF1}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000255 |
| Structure 3D | Electron microscopy (1) |
| Cross Reference PDB | 7FDK; |
| Mapped Pubmed ID | 11217851; 12466851; 15356152; 15561968; 16007097; 16141072; 16505206; 16615898; 16723697; 16738017; 16804085; 16878172; 16946085; 17198697; 17340620; 17499227; 17579661; 17600118; 18164957; 18192335; 18235039; 18263657; 18310259; 18356559; 18376006; 18403726; 18441099; 18448662; 18554416; 18650320; 18660448; 18956256; 19004932; 19015603; 19124678; 19334288; 19478081; 19521566; 19650157; 19759332; 19808375; 19880118; 19926873; 19948988; 20186149; 20357030; 20562862; 20671240; 20679547; 20798044; 21188549; 21208466; 21252069; 21267068; 21285291; 21481527; 21677750; 21814048; 21818366; 21880865; 21946695; 21968754; 22036945; 22246130; 22288735; 22289845; 22330342; 22460555; 22474255; 22508831; 22518292; 22580272; 22616805; 22665126; 22693641; 22790597; 22837003; 22933108; 22947377; 23043153; 23127535; 23160880; 23328447; 23392115; 23608725; 23671869; 23761674; 23951161; 24048198; 24067190; 24161906; 24177423; 24193738; 24379178; 24400109; 24414175; 24446061; 24454948; 24464749; 24477684; 24581232; 24695436; 24728465; 24756097; 24760518; 24799609; 24800825; 24911884; 25175177; 25249154; 25291359; 25301841; 25391767; 25448263; 25484288; 25489058; 25519733; 25650385; 25721616; 25867182; 25890286; 25968123; 25968580; 26029927; 26078188; 26144375; 26224885; 26245758; 26389599; 26441236; 26498282; 26767952; 26813885; 26883384; 27018342; 27019629; 27053009; 27070147; 27379538; 27592222; 27601681; 27612496; 27649628; 27806985; 27917469; 27927599; 28101297; 28142259; 28249676; 28273875; 28721275; 28808068; 28842425; 28845018; 28935640; 28935757; 29128354; 29138810; 29196099; 29211853; 29225087; 29266779; 29363860; 29559844; 29570986; 29679094; 29706566; 29761600; 29884907; 29990483; 30207087; 30604460; 30628484; 31393582; 31440756; 31484552; 31519791; 31564162; 31610731; 31645418; 31775868; 31786979; 31805278; 31853045; 31861139; 31987854; 32015507; 32275855; 32322207; 32338605; 32368013; 32379417; 32380511; 32404477; 32413319; 32418199; 32441816; 32472097; 32485164; 32511354; 32513532; 32525008; 32558150; 32564694; 32607866; 32669323; 32725927; 32750141; 32755395; 32820248; 32837584; 32966801; 32967005; 32971570; 32991738; 33008593; 33057007; 33078906; 33097186; 33106680; 33168188; 33275517; 33284956; 33372179; 33422505; 33488611; 33558541; 33566370; 33626084; 33636719; 33658332; 33725024; 33727353; 33811970; 33932339; 33963249; 33991451; 34018203; 34158856; 34290590; 34305888; 34907257; 34932561; |
| Motif | MOTIF 778..786; /note=LIR; /evidence=ECO:0000250|UniProtKB:Q9BYF1; MOTIF 781..785; /note=SH2-binding; /evidence=ECO:0000250|UniProtKB:Q9BYF1; MOTIF 781..784; /note=Endocytic sorting signal; /evidence=ECO:0000250|UniProtKB:Q9BYF1; MOTIF 792..795; /note=PTB; /evidence=ECO:0000250|UniProtKB:Q9BYF1; MOTIF 803..805; /note=PDZ-binding; /evidence=ECO:0000250|UniProtKB:Q9BYF1 |
| Gene Encoded By | |
| Mass | 92,368 |
| Kinetics | |
| Metal Binding | METAL 374; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:Q9BYF1; METAL 378; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:Q9BYF1; METAL 402; /note=Zinc; catalytic; /evidence=ECO:0000250|UniProtKB:Q9BYF1 |
| Rhea ID | RHEA:26554; RHEA:26555; RHEA:63532; RHEA:63533; RHEA:63536; RHEA:63537; RHEA:63540; RHEA:63541; RHEA:63544; RHEA:63545; RHEA:63556; RHEA:63557; RHEA:63564; RHEA:63565; RHEA:63604; RHEA:63605; RHEA:63608; RHEA:63609 |
| Cross Reference Brenda | 3.4.17.23; |