ID   ACE2_HUMAN              Reviewed;         805 AA.
AC   Q9BYF1; C7ECU1; Q6UWP0; Q86WT0; Q9NRA7; Q9UFZ6;
DT   02-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT   02-AUG-2005, sequence version 2.
DT   12-AUG-2020, entry version 181.
DE   RecName: Full=Angiotensin-converting enzyme 2;
DE            EC=3.4.17.23 {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774};
DE   AltName: Full=Angiotensin-converting enzyme homolog {ECO:0000303|PubMed:10924499};
DE            Short=ACEH {ECO:0000303|PubMed:10924499};
DE   AltName: Full=Angiotensin-converting enzyme-related carboxypeptidase {ECO:0000303|PubMed:10969042};
DE            Short=ACE-related carboxypeptidase;
DE            EC=3.4.17.- {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774, ECO:0000269|PubMed:27217402, ECO:0000269|PubMed:28293165};
DE   AltName: Full=Metalloprotease MPROT15 {ECO:0000303|Ref.6};
DE   Contains:
DE     RecName: Full=Processed angiotensin-converting enzyme 2 {ECO:0000303|PubMed:24227843};
DE   Flags: Precursor;
GN   Name=ACE2 {ECO:0000312|HGNC:HGNC:13557}; ORFNames=UNQ868/PRO1885;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION,
RP   ACTIVITY REGULATION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RC   TISSUE=Heart;
RX   PubMed=10969042; DOI=10.1161/01.res.87.5.e1;
RA   Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N.,
RA   Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.;
RT   "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2)
RT   converts angiotensin I to angiotensin 1-9.";
RL   Circ. Res. 87:E1-E9(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION,
RP   FUNCTION, ACTIVITY REGULATION, AND CATALYTIC ACTIVITY.
RC   TISSUE=Lymphoma;
RX   PubMed=10924499; DOI=10.1074/jbc.m002615200;
RA   Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.;
RT   "A human homolog of angiotensin-converting enzyme. Cloning and functional
RT   expression as a captopril-insensitive carboxypeptidase.";
RL   J. Biol. Chem. 275:33238-33243(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ACTIVITY REGULATION, SUBCELLULAR
RP   LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Testis;
RX   PubMed=15231706; DOI=10.1210/en.2004-0443;
RA   Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K.L., Yarski M.A.,
RA   Smith A.I., Lew R.A.;
RT   "The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is
RT   selectively expressed by adult Leydig cells of the testis.";
RL   Endocrinology 145:4703-4711(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-638.
RC   TISSUE=Lung, and Testis;
RX   PubMed=15937940; DOI=10.1002/ajmg.a.30779;
RA   Itoyama S., Keicho N., Hijikata M., Quy T., Phi N.C., Long H.T., Ha L.D.,
RA   Ban V.V., Matsushita I., Yanai H., Kirikae F., Kirikae T., Kuratsuji T.,
RA   Sasazuki T.;
RT   "Identification of an alternative 5'-untranslated exon and new
RT   polymorphisms of angiotensin-converting enzyme 2 gene: lack of association
RT   with SARS in the Vietnamese population.";
RL   Am. J. Med. Genet. A 136:52-57(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Suzuki Y., Watanabe M., Sugano S.;
RT   "Cloning, expression analysis and chromosomal localization of a novel ACE
RT   like enzyme.";
RL   Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Southan C., Burgess N.;
RT   "MPROT15 polypeptide and MPROT15 polynucleotide.";
RL   Patent number CA2248987, 13-NOV-1999.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Li K.K.B., Yip C.W., Hon C.C., Lam C.Y., Leung F.C.C.;
RT   "Comparative susceptibility to SARS-CoV mediated by ACE2 protein of 15
RT   different species.";
RL   Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-26.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [11]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and Testis;
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   [12]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-805 (ISOFORM 1).
RC   TISSUE=Testis;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [13]
RP   PROTEIN SEQUENCE OF 679-689, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP   INTERACTION WITH ITGB1.
RX   PubMed=15276642; DOI=10.1016/j.bbadis.2004.05.005;
RA   Lin Q., Keller R.S., Weaver B., Zisman L.S.;
RT   "Interaction of ACE2 and integrin beta1 in failing human heart.";
RL   Biochim. Biophys. Acta 1689:175-178(2004).
RN   [14]
RP   TISSUE SPECIFICITY.
RX   PubMed=12459472; DOI=10.1016/s0014-5793(02)03640-2;
RA   Harmer D., Gilbert M., Borman R., Clark K.L.;
RT   "Quantitative mRNA expression profiling of ACE 2, a novel homologue of
RT   angiotensin converting enzyme.";
RL   FEBS Lett. 532:107-110(2002).
RN   [15]
RP   ACTIVITY REGULATION.
RX   PubMed=12358520; DOI=10.1021/ja0277226;
RA   Dales N.A., Gould A.E., Brown J.A., Calderwood E.F., Guan B., Minor C.A.,
RA   Gavin J.M., Hales P., Kaushik V.K., Stewart M., Tummino P.J., Vickers C.S.,
RA   Ocain T.D., Patane M.A.;
RT   "Substrate-based design of the first class of angiotensin-converting
RT   enzyme-related carboxypeptidase (ACE2) inhibitors.";
RL   J. Am. Chem. Soc. 124:11852-11853(2002).
RN   [16]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE
RP   SPECIFICITY, ACTIVITY REGULATION, AND COFACTOR.
RX   PubMed=11815627; DOI=10.1074/jbc.m200581200;
RA   Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K.,
RA   Parsons T., Baronas E., Hsieh F., Acton S., Patane M.A., Nichols A.,
RA   Tummino P.;
RT   "Hydrolysis of biological peptides by human angiotensin-converting enzyme-
RT   related carboxypeptidase.";
RL   J. Biol. Chem. 277:14838-14843(2002).
RN   [17]
RP   FUNCTION, CATALYTIC ACTIVITY, AND INDUCTION.
RX   PubMed=14504186; DOI=10.1161/01.cir.0000094734.67990.99;
RA   Zisman L.S., Keller R.S., Weaver B., Lin Q., Speth R., Bristow M.R.,
RA   Canver C.C.;
RT   "Increased angiotensin-(1-7)-forming activity in failing human heart
RT   ventricles: evidence for upregulation of the angiotensin-converting enzyme
RT   Homologue ACE2.";
RL   Circulation 108:1707-1712(2003).
RN   [18]
RP   FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION), GLYCOSYLATION, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=14647384; DOI=10.1038/nature02145;
RA   Li W., Moore M.J., Vasilieva N., Sui J., Wong S.-K., Berne M.A.,
RA   Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H.,
RA   Farzan M.;
RT   "Angiotensin-converting enzyme 2 is a functional receptor for the SARS
RT   coronavirus.";
RL   Nature 426:450-454(2003).
RN   [19]
RP   INDUCTION.
RX   PubMed=15151696; DOI=10.1186/1741-7015-2-19;
RA   Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.;
RT   "ACE2 gene expression is up-regulated in the human failing heart.";
RL   BMC Med. 2:19-19(2004).
RN   [20]
RP   TISSUE SPECIFICITY.
RX   PubMed=15141377; DOI=10.1002/path.1570;
RA   Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H.;
RT   "Tissue distribution of ACE2 protein, the functional receptor for SARS
RT   coronavirus. A first step in understanding SARS pathogenesis.";
RL   J. Pathol. 203:631-637(2004).
RN   [21]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SARS-COV SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION).
RX   PubMed=15452268; DOI=10.1128/jvi.78.20.11429-11433.2004;
RA   Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M.,
RA   Sullivan J.L., Farzan M., Choe H.;
RT   "Efficient replication of severe acute respiratory syndrome coronavirus in
RT   mouse cells is limited by murine angiotensin-converting enzyme 2.";
RL   J. Virol. 78:11429-11433(2004).
RN   [22]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90.
RC   TISSUE=Bile;
RX   PubMed=15084671; DOI=10.1074/mcp.m400015-mcp200;
RA   Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J.,
RA   Argani P., Goggins M.G., Maitra A., Pandey A.;
RT   "A proteomic analysis of human bile.";
RL   Mol. Cell. Proteomics 3:715-728(2004).
RN   [23]
RP   TISSUE SPECIFICITY, AND 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   [24]
RP   FUNCTION (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION), AND MUTAGENESIS.
RX   PubMed=15791205; DOI=10.1038/sj.emboj.7600640;
RA   Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K.,
RA   Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A.,
RA   Guan Y., Choe H., Farzan M.;
RT   "Receptor and viral determinants of SARS-coronavirus adaptation to human
RT   ACE2.";
RL   EMBO J. 24:1634-1643(2005).
RN   [25]
RP   PROTEOLYTIC CLEAVAGE, AND SUBCELLULAR LOCATION.
RX   PubMed=15983030; DOI=10.1074/jbc.m505111200;
RA   Lambert D.W., Yarski M., Warner F.J., Thornhill P., Parkin E.T.,
RA   Smith A.I., Hooper N.M., Turner A.J.;
RT   "Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated
RT   ectodomain shedding of the severe-acute respiratory syndrome-coronavirus
RT   (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).";
RL   J. Biol. Chem. 280:30113-30119(2005).
RN   [26]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HCOV-NL63 SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION).
RX   PubMed=15897467; DOI=10.1073/pnas.0409465102;
RA   Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Poehlmann S.;
RT   "Human coronavirus NL63 employs the severe acute respiratory syndrome
RT   coronavirus receptor for cellular entry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:7988-7993(2005).
RN   [27]
RP   FUNCTION, ACTIVE SITE, AND MUTAGENESIS OF ARG-273; HIS-345 AND HIS-505.
RX   PubMed=16008552; DOI=10.1111/j.1742-4658.2005.04756.x;
RA   Guy J.L., Jackson R.M., Jensen H.A., Hooper N.M., Turner A.J.;
RT   "Identification of critical active-site residues in angiotensin-converting
RT   enzyme-2 (ACE2) by site-directed mutagenesis.";
RL   FEBS J. 272:3512-3520(2005).
RN   [28]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP   REGULATION, AND MUTAGENESIS OF ARG-169; TRP-271; LYS-481 AND ARG-514.
RX   PubMed=19021774; DOI=10.1111/j.1742-4658.2008.06733.x;
RA   Rushworth C.A., Guy J.L., Turner A.J.;
RT   "Residues affecting the chloride regulation and substrate selectivity of
RT   the angiotensin-converting enzymes (ACE and ACE2) identified by site-
RT   directed mutagenesis.";
RL   FEBS J. 275:6033-6042(2008).
RN   [29]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=18424768; DOI=10.1096/fj.08-107300;
RA   Kowalczuk S., Broeer A., Tietze N., Vanslambrouck J.M., Rasko J.E.,
RA   Broeer S.;
RT   "A protein complex in the brush-border membrane explains a Hartnup disorder
RT   allele.";
RL   FASEB J. 22:2880-2887(2008).
RN   [30]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-546.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [31]
RP   FUNCTION, AND MUTAGENESIS OF ARG-273.
RX   PubMed=19185582; DOI=10.1053/j.gastro.2008.10.055;
RA   Camargo S.M., Singer D., Makrides V., Huggel K., Pos K.M., Wagner C.A.,
RA   Kuba K., Danilczyk U., Skovby F., Kleta R., Penninger J.M., Verrey F.;
RT   "Tissue-specific amino acid transporter partners ACE2 and collectrin
RT   differentially interact with hartnup mutations.";
RL   Gastroenterology 136:872-882(2009).
RN   [32]
RP   PROTEOLYTIC CLEAVAGE.
RX   PubMed=21563828; DOI=10.1021/bi200525y;
RA   Lai Z.W., Hanchapola I., Steer D.L., Smith A.I.;
RT   "Angiotensin-converting enzyme 2 ectodomain shedding cleavage-site
RT   identification: determinants and constraints.";
RL   Biochemistry 50:5182-5194(2011).
RN   [33]
RP   SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, AND INTERACTION WITH TMPRSS2.
RX   PubMed=21068237; DOI=10.1128/jvi.02062-10;
RA   Shulla A., Heald-Sargent T., Subramanya G., Zhao J., Perlman S.,
RA   Gallagher T.;
RT   "A transmembrane serine protease is linked to the severe acute respiratory
RT   syndrome coronavirus receptor and activates virus entry.";
RL   J. Virol. 85:873-882(2011).
RN   [34]
RP   FUNCTION (MICROBIAL INFECTION), SUBCELLULAR LOCATION, AND PROTEOLYTIC
RP   CLEAVAGE.
RX   PubMed=24227843; DOI=10.1128/jvi.02202-13;
RA   Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O.,
RA   Poehlmann S.;
RT   "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by
RT   TMPRSS2 augments entry driven by the severe acute respiratory syndrome
RT   coronavirus spike protein.";
RL   J. Virol. 88:1293-1307(2014).
RN   [35]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, 3D-STRUCTURE
RP   MODELING, AND ACTIVE SITE.
RX   PubMed=27217402; DOI=10.1161/hypertensionaha.115.06892;
RA   Wang W., McKinnie S.M., Farhan M., Paul M., McDonald T., McLean B.,
RA   Llorens-Cortes C., Hazra S., Murray A.G., Vederas J.C., Oudit G.Y.;
RT   "Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-
RT   Apelin-13 and Apelin-17: Physiological Effects in the Cardiovascular
RT   System.";
RL   Hypertension 68:365-377(2016).
RN   [36]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=28293165; DOI=10.3389/fnins.2017.00092;
RA   Yang P., Kuc R.E., Brame A.L., Dyson A., Singer M., Glen R.C., Cheriyan J.,
RA   Wilkinson I.B., Davenport A.P., Maguire J.J.;
RT   "[Pyr1]Apelin-13(1-12) Is a Biologically Active ACE2 Metabolite of the
RT   Endogenous Cardiovascular Peptide [Pyr1]Apelin-13.";
RL   Front. Neurosci. 11:92-92(2017).
RN   [37]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=32142651; DOI=10.1016/j.cell.2020.02.052;
RA   Hoffmann M., Kleine-Weber H., Schroeder S., Krueger N., Herrler T.,
RA   Erichsen S., Schiergens T.S., Herrler G., Wu N.H., Nitsche A.,
RA   Mueller M.A., Drosten C., Poehlmann S.;
RT   "SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a
RT   clinically proven protease inhibitor.";
RL   Cell 181:1-10(2020).
RN   [38]
RP   INTERACTION WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION).
RX   PubMed=32075877; DOI=10.1126/science.abb2507;
RA   Wrapp D., Wang N., Corbett K.S., Goldsmith J.A., Hsieh C.L., Abiona O.,
RA   Graham B.S., McLellan J.S.;
RT   "Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.";
RL   Science 367:1260-1263(2020).
RN   [39]
RP   FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH SARS-COV-2 SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION).
RX   PubMed=32155444; DOI=10.1016/j.cell.2020.02.058;
RA   Walls A.C., Park Y.J., Tortorici M.A., Wall A., McGuire A.T., Veesler D.;
RT   "Structure, function, and antigenicity of the SARS-CoV-2 spike
RT   glycoprotein.";
RL   Cell 180:1-12(2020).
RN   [40]
RP   TISSUE SPECIFICITY, AND INDUCTION BY ISR.
RX   DOI=10.1016/j.cell.2020.04.035;
RA   Ziegler C.G.K., Allon S.J., Nyquist S.K., Mbano I.M., Miao V.N.,
RA   Tzouanas C.N., Cao Y., Yousif A.S., Bals J., Hauser B.M., Feldman J.,
RA   Muus C., Wadsworth M.H., Kazer S.W., Hughes T.K., Doran B., Gatter G.J.,
RA   Vukovic M., Taliaferro F., Mead B.E., Guo Z., Wang J.P., Gras D.,
RA   Plaisant M., Ansari M., Angelidis I., Adler H., Sucre J.M.S., Taylor C.J.,
RA   Lin B., Waghray A., Mitsialis V., Dwyer D.F., Buchheit K.M., Boyce J.A.,
RA   Barrett N.A., Laidlaw T.M., Carroll S.L., Colonna L., Tkachev V.,
RA   Peterson C.W., Yu A., Zheng H.B., Gideon H.P., Winchell C.G., Lin P.L.,
RA   Bingle C.D., Snapper S.B., Kropski J.A., Theis F.J., Schiller H.B.,
RA   Zaragosi L.E., Barbry P., Leslie A., Kiem H.P., Flynn J.L., Fortune S.M.,
RA   Berger B., Finberg R.W., Kean L.S., Garber M., Schmidt A.G., Lingwood D.,
RA   Shalek A.K., Ordovas-Montanes J.;
RT   "SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway
RT   epithelial cells and is detected in specific cell subsets across tissues.";
RL   Cell 0:0-0(2020).
RN   [41]
RP   TISSUE SPECIFICITY, AND INDUCTION BY CIGARETTE SMOKE.
RX   PubMed=32425701; DOI=10.1016/j.devcel.2020.05.012;
RA   Smith J.C., Sausville E.L., Girish V., Yuan M.L., Vasudevan A., John K.M.,
RA   Sheltzer J.M.;
RT   "Cigarette smoke exposure and inflammatory signaling increase the
RT   expression of the SARS-CoV-2 receptor ACE2 in the respiratory tract.";
RL   Dev. Cell 0:0-0(2020).
RN   [42]
RP   FUNCTION (MICROBIAL INFECTION).
RX   PubMed=32221306; DOI=10.1038/s41467-020-15562-9;
RA   Ou X., Liu Y., Lei X., Li P., Mi D., Ren L., Guo L., Guo R., Chen T.,
RA   Hu J., Xiang Z., Mu Z., Chen X., Chen J., Hu K., Jin Q., Wang J., Qian Z.;
RT   "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and
RT   its immune cross-reactivity with SARS-CoV.";
RL   Nat. Commun. 11:1620-1620(2020).
RN   [43]
RP   TISSUE SPECIFICITY.
RX   PubMed=32327758; DOI=10.1038/s41591-020-0868-6;
RG   HCA Lung Biological Network;
RA   Sungnak W., Huang N., Becavin C., Berg M., Queen R., Litvinukova M.,
RA   Talavera-Lopez C., Maatz H., Reichart D., Sampaziotis F., Worlock K.B.,
RA   Yoshida M., Barnes J.L.;
RT   "SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells
RT   together with innate immune genes.";
RL   Nat. Med. 0:0-0(2020).
RN   [44]
RP   TISSUE SPECIFICITY.
RX   PubMed=32358202; DOI=10.1126/science.abc1669;
RA   Lamers M.M., Beumer J., van der Vaart J., Knoops K., Puschhof J.,
RA   Breugem T.I., Ravelli R.B.G., Paul van Schayck J., Mykytyn A.Z.,
RA   Duimel H.Q., van Donselaar E., Riesebosch S., Kuijpers H.J.H.,
RA   Schippers D., van de Wetering W.J., de Graaf M., Koopmans M., Cuppen E.,
RA   Peters P.J., Haagmans B.L., Clevers H.;
RT   "SARS-CoV-2 productively infects human gut enterocytes.";
RL   Science 0:0-0(2020).
RN   [45] {ECO:0000244|PDB:1R42, ECO:0000244|PDB:1R4L}
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-615 IN COMPLEXES WITH ZINC;
RP   CHLORIDE AND MLN-4760 INHIBITOR, DOMAIN, REACTION MECHANISM, ACTIVE SITE,
RP   DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-53; ASN-90; ASN-103; ASN-322;
RP   ASN-432 AND ASN-546.
RX   PubMed=14754895; DOI=10.1074/jbc.m311191200;
RA   Towler P., Staker B., Prasad S.G., Menon S., Tang J., Parsons T., Ryan D.,
RA   Fisher M., Williams D., Dales N.A., Patane M.A., Pantoliano M.W.;
RT   "ACE2 X-ray structures reveal a large hinge-bending motion important for
RT   inhibitor binding and catalysis.";
RL   J. Biol. Chem. 279:17996-18007(2004).
RN   [46] {ECO:0000244|PDB:2AJF}
RP   X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 19-615 IN COMPLEX WITH ZINC, AND
RP   GLYCOSYLATION AT ASN-53; ASN-90; ASN-322 AND ASN-546.
RX   PubMed=16166518; DOI=10.1126/science.1116480;
RA   Li F., Li W., Farzan M., Harrison S.C.;
RT   "Structure of SARS coronavirus spike receptor-binding domain complexed with
RT   receptor.";
RL   Science 309:1864-1868(2005).
RN   [47] {ECO:0000244|PDB:6ACG, ECO:0000244|PDB:6ACJ, ECO:0000244|PDB:6ACK}
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 19-615.
RX   PubMed=30102747; DOI=10.1371/journal.ppat.1007236;
RA   Song W., Gui M., Wang X., Xiang Y.;
RT   "Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex
RT   with its host cell receptor ACE2.";
RL   PLoS Pathog. 14:e1007236-e1007236(2018).
RN   [48] {ECO:0000244|PDB:6CS2}
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.40 ANGSTROMS) OF 19-615.
RX   PubMed=30356097; DOI=10.1038/s41598-018-34171-7;
RA   Kirchdoerfer R.N., Wang N., Pallesen J., Wrapp D., Turner H.L.,
RA   Cottrell C.A., Corbett K.S., Graham B.S., McLellan J.S., Ward A.B.;
RT   "Stabilized coronavirus spikes are resistant to conformational changes
RT   induced by receptor recognition or proteolysis.";
RL   Sci. Rep. 8:15701-15701(2018).
RN   [49] {ECO:0000244|PDB:6M0J}
RP   X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 19-615 IN COMPLEX WITH SARS-COV-2
RP   SPIKE GLYCOPROTEIN.
RX   PubMed=32225176; DOI=10.1038/s41586-020-2180-5;
RA   Lan J., Ge J., Yu J., Shan S., Zhou H., Fan S., Zhang Q., Shi X., Wang Q.,
RA   Zhang L., Wang X.;
RT   "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the
RT   ACE2 receptor.";
RL   Nature 0:0-0(2020).
RN   [50] {ECO:0000244|PDB:6VW1}
RP   X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 19-615 AND IN COMPLEX WITH
RP   SARS-COV-2 SPIKE GLYCOPROTEIN, INTERACTION WITH SARS-COV-2 SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION), INTERACTION WITH SARS-COV SPIKE
RP   GLYCOPROTEIN (MICROBIAL INFECTION), AND FUNCTION (MICROBIAL INFECTION).
RX   PubMed=32225175; DOI=10.1038/s41586-020-2179-y;
RA   Shang J., Ye G., Shi K., Wan Y., Luo C., Aihara H., Geng Q., Auerbach A.,
RA   Li F.;
RT   "Structural basis of receptor recognition by SARS-CoV-2.";
RL   Nature 0:0-0(2020).
RN   [51] {ECO:0000244|PDB:6M17, ECO:0000244|PDB:6M18, ECO:0000244|PDB:6M1D}
RP   STRUCTURE BY ELECTRON MICROSCOPY (2.90 ANGSTROMS) OF 18-805, INTERACTION
RP   WITH SARS-COV-2 SPIKE GLYCOPROTEIN (MICROBIAL INFECTION), INTERACTION WITH
RP   SLC6A19, SUBUNIT, AND PROTEOLYTIC CLEAVAGE.
RX   PubMed=32132184; DOI=10.1126/science.abb2762;
RA   Yan R., Zhang Y., Li Y., Xia L., Guo Y., Zhou Q.;
RT   "Structural basis for the recognition of the SARS-CoV-2 by full-length
RT   human ACE2.";
RL   Science 0:0-0(2020).
CC   -!- FUNCTION: Essential counter-regulatory carboxypeptidase of the renin-
CC       angiotensin hormone system that is a critical regulator of blood
CC       volume, systemic vascular resistance, and thus cardiovascular
CC       homeostasis (PubMed:27217402). Converts angiotensin I to angiotensin 1-
CC       9, a nine-amino acid peptide with anti-hypertrophic effects in
CC       cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts
CC       as a beneficial vasodilator and anti-proliferation agent,
CC       counterbalancing the actions of the vasoconstrictor angiotensin II
CC       (PubMed:10969042, PubMed:10924499, PubMed:11815627, PubMed:19021774,
CC       PubMed:14504186). Also removes the C-terminal residue from three other
CC       vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin,
CC       but is not active on bradykinin (PubMed:10969042, PubMed:11815627).
CC       Also cleaves other biological peptides, such as apelins (apelin-13,
CC       [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-
CC       7, neocasomorphin) and dynorphin A with high efficiency
CC       (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2
CC       C-terminus is homologous to collectrin and is responsible for the
CC       trafficking of the neutral amino acid transporter SL6A19 to the plasma
CC       membrane of gut epithelial cells via direct interaction, regulating its
CC       expression on the cell surface and its catalytic activity
CC       (PubMed:18424768, PubMed:19185582). {ECO:0000269|PubMed:10924499,
CC       ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:11815627,
CC       ECO:0000269|PubMed:14504186, ECO:0000269|PubMed:18424768,
CC       ECO:0000269|PubMed:19021774, ECO:0000269|PubMed:19185582,
CC       ECO:0000269|PubMed:27217402}.
CC   -!- FUNCTION: (Microbial infection) Acts as a receptor for human
CC       coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus
CC       NL63/HCoV-NL63. {ECO:0000269|PubMed:14647384,
CC       ECO:0000269|PubMed:15452268, ECO:0000269|PubMed:15791205,
CC       ECO:0000269|PubMed:15897467, ECO:0000269|PubMed:24227843,
CC       ECO:0000269|PubMed:32142651, ECO:0000269|PubMed:32155444,
CC       ECO:0000269|PubMed:32221306, ECO:0000269|PubMed:32225175}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine;
CC         Xref=Rhea:RHEA:26554, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC         ChEBI:CHEBI:58506, ChEBI:CHEBI:58922; EC=3.4.17.23;
CC         Evidence={ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:11815627,
CC         ECO:0000269|PubMed:19021774, ECO:0000305|PubMed:14504186};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26555;
CC         Evidence={ECO:0000269|PubMed:14504186};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=angiotensin I + H2O = angiotensin-(1-9) + L-leucine;
CC         Xref=Rhea:RHEA:63532, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC         ChEBI:CHEBI:147350, ChEBI:CHEBI:147351;
CC         Evidence={ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042,
CC         ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:19021774};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63533;
CC         Evidence={ECO:0000305|PubMed:10924499, ECO:0000305|PubMed:10969042,
CC         ECO:0000305|PubMed:11815627, ECO:0000305|PubMed:19021774};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[des-Arg(9)]-bradykinin + H2O = [des-Phe(8), des-Arg(9)]-
CC         bradykinin + L-phenylalanine; Xref=Rhea:RHEA:63536,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:58095, ChEBI:CHEBI:133069,
CC         ChEBI:CHEBI:147352; Evidence={ECO:0000269|PubMed:10969042,
CC         ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63537;
CC         Evidence={ECO:0000305|PubMed:10969042, ECO:0000305|PubMed:11815627};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + neurotensin = L-leucine + neurotensin-(1-12);
CC         Xref=Rhea:RHEA:63540, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC         ChEBI:CHEBI:147362, ChEBI:CHEBI:147363;
CC         Evidence={ECO:0000269|PubMed:10969042};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63541;
CC         Evidence={ECO:0000305|PubMed:10969042};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + neurotensin-(1-8) = L-arginine + neurotensin-(1-7);
CC         Xref=Rhea:RHEA:63572, ChEBI:CHEBI:15377, ChEBI:CHEBI:32682,
CC         ChEBI:CHEBI:147393, ChEBI:CHEBI:147394;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63573;
CC         Evidence={ECO:0000305|PubMed:11815627};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + kinetensin = kinetensin-(1-8) + L-leucine;
CC         Xref=Rhea:RHEA:63544, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC         ChEBI:CHEBI:147364, ChEBI:CHEBI:147365;
CC         Evidence={ECO:0000269|PubMed:10969042};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63545;
CC         Evidence={ECO:0000305|PubMed:10969042};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine;
CC         Xref=Rhea:RHEA:63556, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC         ChEBI:CHEBI:147381, ChEBI:CHEBI:147383;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63557;
CC         Evidence={ECO:0000305|PubMed:11815627};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=apelin-13 + H2O = apelin-12 + L-phenylalanine;
CC         Xref=Rhea:RHEA:63564, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC         ChEBI:CHEBI:147395, ChEBI:CHEBI:147396;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63565;
CC         Evidence={ECO:0000305|PubMed:11815627};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=[Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine;
CC         Xref=Rhea:RHEA:63604, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC         ChEBI:CHEBI:147415, ChEBI:CHEBI:147416;
CC         Evidence={ECO:0000269|PubMed:27217402, ECO:0000269|PubMed:28293165};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63605;
CC         Evidence={ECO:0000269|PubMed:27217402};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=apelin-17 + H2O = apelin-16 + L-phenylalanine;
CC         Xref=Rhea:RHEA:63608, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC         ChEBI:CHEBI:147421, ChEBI:CHEBI:147422;
CC         Evidence={ECO:0000269|PubMed:27217402};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63609;
CC         Evidence={ECO:0000269|PubMed:27217402};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-casomorphin-7 + H2O = beta-casomorphin-6 + L-isoleucine;
CC         Xref=Rhea:RHEA:63568, ChEBI:CHEBI:15377, ChEBI:CHEBI:58045,
CC         ChEBI:CHEBI:147390, ChEBI:CHEBI:147391;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63569;
CC         Evidence={ECO:0000305|PubMed:11815627};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + neocasomorphin = L-isoleucine + neocasomorphin-(1-5);
CC         Xref=Rhea:RHEA:63600, ChEBI:CHEBI:15377, ChEBI:CHEBI:58045,
CC         ChEBI:CHEBI:147417, ChEBI:CHEBI:147418;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63601;
CC         Evidence={ECO:0000305|PubMed:11815627};
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:11815627};
CC   -!- COFACTOR:
CC       Name=chloride; Xref=ChEBI:CHEBI:17996;
CC         Evidence={ECO:0000269|PubMed:11815627};
CC       Note=Binds 1 Cl(-) ion per subunit. {ECO:0000269|PubMed:11815627};
CC   -!- ACTIVITY REGULATION: Regulated by chloride and fluoride, but not
CC       bromide (PubMed:11815627). Chloride increases angiotensin I and
CC       decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-
CC       4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by
CC       the ACE inhibitors lisinopril, captopril and enalaprilat
CC       (PubMed:10969042, PubMed:10924499). Highly potent and selective in
CC       vitro ACE2 inhibitors were identified (PubMed:12358520).
CC       {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042,
CC       ECO:0000269|PubMed:11815627, ECO:0000269|PubMed:12358520,
CC       ECO:0000269|PubMed:15231706, ECO:0000269|PubMed:19021774}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=6.9 uM for angiotensin I {ECO:0000269|PubMed:11815627};
CC         KM=2.0 uM for angiotensin II {ECO:0000269|PubMed:11815627};
CC         KM=6.8 uM for apelin-13 {ECO:0000269|PubMed:11815627};
CC         KM=290 uM for [des-Arg(9)]-bradykinin {ECO:0000269|PubMed:11815627};
CC         KM=130 uM for Lys-[des-Arg(9)]-bradykinin
CC         {ECO:0000269|PubMed:11815627};
CC         KM=31 uM for beta-casomorphin {ECO:0000269|PubMed:11815627};
CC         KM=5.5 uM for dynorphin A-(1-13) {ECO:0000269|PubMed:11815627};
CC         KM=300 uM for neurotensin-(1-8) {ECO:0000269|PubMed:11815627};
CC         KM=58.6 uM for angiotensin II {ECO:0000269|PubMed:19021774};
CC         KM=12 uM for [Pyr1]apelin-13 {ECO:0000269|PubMed:27217402};
CC         KM=19 uM for apelin-17 {ECO:0000269|PubMed:27217402};
CC         Vmax=28.7 nmol/min/mg enzyme with angiotensin II as substrate
CC         {ECO:0000269|PubMed:19021774};
CC         Note=kcat is 0.034 sec(-1) with angiotensin I as substrate. kcat is
CC         3.5 sec(-1) with angiotensin II as substrate. kcat is 13 sec(-1) with
CC         apelin-13 as substrate. kcat is 62 sec(-1) with [des-Arg(9)]-
CC         bradykinin as substrate. kcat is 26 sec(-1) with Lys-[des-Arg(9)]-
CC         bradykinin as substrate. kcat is 6.8 sec(-1) with beta-casomorphin as
CC         substrate. kcat is 16 sec(-1) with dynorphin A-(1-13) as substrate.
CC         kcat is 57 sec(-1) with neurotensin-(1-8) as substrate
CC         (PubMed:11815627). kcat is 19.1 sec(-1) with [Pyr1]apelin-13 as
CC         substrate. kcat is 7.7 sec(-1) with apelin-17 as substrate
CC         (PubMed:27217402). {ECO:0000269|PubMed:11815627,
CC         ECO:0000269|PubMed:27217402};
CC       pH dependence:
CC         Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.
CC         {ECO:0000269|PubMed:11815627};
CC   -!- SUBUNIT: Homodimer (PubMed:32132184). Interacts with ITGB1
CC       (PubMed:15276642). Interacts with the catalytically active form of
CC       TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is
CC       essential for expression and function of SLC6A19 in intestine (By
CC       similarity). {ECO:0000250|UniProtKB:Q8R0I0,
CC       ECO:0000269|PubMed:15276642, ECO:0000269|PubMed:21068237,
CC       ECO:0000269|PubMed:32132184}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus/SARS-CoV
CC       spike protein. {ECO:0000269|PubMed:14647384,
CC       ECO:0000269|PubMed:15452268, ECO:0000269|PubMed:15791205,
CC       ECO:0000269|PubMed:32225175}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SARS coronavirus-2/SARS-
CC       CoV-2 spike protein. {ECO:0000269|PubMed:32075877,
CC       ECO:0000269|PubMed:32132184, ECO:0000269|PubMed:32155444,
CC       ECO:0000269|PubMed:32225175}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with human coronavirus
CC       NL63/HCoV-NL63 spike glycoprotein. {ECO:0000269|PubMed:15897467}.
CC   -!- INTERACTION:
CC       Q9BYF1; PRO_0000032457 [P01019]: AGT; NbExp=2; IntAct=EBI-7730807, EBI-25493366;
CC       Q9BYF1; P05556: ITGB1; NbExp=4; IntAct=EBI-7730807, EBI-703066;
CC       Q9BYF1; PRO_0000006688 [P01042]: KNG1; NbExp=2; IntAct=EBI-7730807, EBI-6623273;
CC       Q9BYF1; PRO_0000019524 [P30990]: NTS; NbExp=2; IntAct=EBI-7730807, EBI-6655817;
CC       Q9BYF1; Q695T7: SLC6A19; NbExp=3; IntAct=EBI-7730807, EBI-25475705;
CC       Q9BYF1; O15393: TMPRSS2; NbExp=3; IntAct=EBI-7730807, EBI-12549863;
CC       Q9BYF1; P0DTC2: S; Xeno; NbExp=23; IntAct=EBI-7730807, EBI-25474821;
CC       Q9BYF1; P59594: S; Xeno; NbExp=29; IntAct=EBI-7730807, EBI-15582614;
CC       Q9BYF1; PRO_0000037209 [P59594]: S; Xeno; NbExp=3; IntAct=EBI-7730807, EBI-25475261;
CC       Q9BYF1; Q5GDB5: S; Xeno; NbExp=2; IntAct=EBI-7730807, EBI-25566398;
CC       Q9BYF1; Q6Q1S2: S; Xeno; NbExp=3; IntAct=EBI-7730807, EBI-15814420;
CC       Q9BYF1-1; P59594: S; Xeno; NbExp=2; IntAct=EBI-15814450, EBI-15582614;
CC       Q9BYF1-1; Q6Q1S2: S; Xeno; NbExp=3; IntAct=EBI-15814450, EBI-15814420;
CC   -!- SUBCELLULAR LOCATION: [Processed angiotensin-converting enzyme 2]:
CC       Secreted {ECO:0000269|PubMed:15983030}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18424768};
CC       Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC       {ECO:0000250|UniProtKB:Q8R0I0}. Note=Detected in both cell membrane and
CC       cytoplasm in neurons. {ECO:0000250|UniProtKB:Q8R0I0}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9BYF1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9BYF1-2; Sequence=VSP_014901, VSP_014902;
CC   -!- TISSUE SPECIFICITY: Expressed in endothelial cells from small and large
CC       arteries, and in arterial smooth muscle cells (at protein level)
CC       (PubMed:15141377). Expressed in lung alveolar epithelial cells,
CC       enterocytes of the small intestine, Leydig cells and Sertoli cells (at
CC       protein level) (PubMed:15141377). Expressed in the renal proximal
CC       tubule and the small intestine (at protein level) (PubMed:18424768).
CC       Expressed in heart, kidney, testis, and gastrointestinal system
CC       (PubMed:10969042, PubMed:10924499, PubMed:15231706, PubMed:12459472,
CC       PubMed:15671045). In lung, expressed at high levels in secretory club
CC       and goblet cells as well as in alveolar type 2 cells (PubMed:32425701).
CC       Coexpressed with TMPRSS2 within lung alveolar type 2 cells, ileal
CC       absorptive enterocytes, intestinal epithelial cells, cornea,
CC       gallbladder and nasal goblet secretory cells (Ref.40, PubMed:32327758,
CC       PubMed:32358202). {ECO:0000269|PubMed:10924499,
CC       ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:12459472,
CC       ECO:0000269|PubMed:15141377, ECO:0000269|PubMed:15231706,
CC       ECO:0000269|PubMed:15671045, ECO:0000269|PubMed:18424768,
CC       ECO:0000269|PubMed:32327758, ECO:0000269|PubMed:32358202,
CC       ECO:0000269|PubMed:32425701, ECO:0000269|Ref.40}.
CC   -!- INDUCTION: Up-regulated in failing heart (PubMed:14504186,
CC       PubMed:15151696, PubMed:15671045). Expression is induced by IFNA and
CC       IFNG (Ref.40, PubMed:32425701). Exposure to cigarette smoke strongly
CC       increases expression in lungs (PubMed:32425701).
CC       {ECO:0000269|PubMed:14504186, ECO:0000269|PubMed:15151696,
CC       ECO:0000269|PubMed:15671045, ECO:0000269|PubMed:32425701,
CC       ECO:0000269|Ref.40}.
CC   -!- INDUCTION: (Microbial infection) In airway epithelial cells, expression
CC       is increased upon influenza A virus infection (Ref.40).
CC       {ECO:0000269|Ref.40}.
CC   -!- DOMAIN: The extracellular region of the ACE2 enzyme is composed of two
CC       domains. The first is a zinc metallopeptidase domain (residues 19-611).
CC       The second domain is located at the C-terminus (residues 612-740) and
CC       is 48% identical to human collectrin. {ECO:0000269|PubMed:14754895}.
CC   -!- PTM: N-glycosylation on Asn-90 may limit SARS infectivity.
CC       {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:14647384,
CC       ECO:0000269|PubMed:14754895, ECO:0000269|PubMed:15084671,
CC       ECO:0000269|PubMed:19159218}.
CC   -!- PTM: Proteolytic cleavage by ADAM17 generates a secreted form
CC       (PubMed:15983030). Also cleaved by serine proteases: TMPRSS2, TMPRSS11D
CC       and HPN/TMPRSS1. {ECO:0000269|PubMed:15983030,
CC       ECO:0000269|PubMed:21068237, ECO:0000269|PubMed:21563828,
CC       ECO:0000269|PubMed:24227843, ECO:0000269|PubMed:32132184}.
CC   -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/ace2/";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=A way in - Issue 223 of
CC       March 2020;
CC       URL="https://web.expasy.org/spotlight/back_issues/223/";
DR   EMBL; AF291820; AAF99721.1; -; mRNA.
DR   EMBL; AF241254; AAF78220.1; -; mRNA.
DR   EMBL; AY623811; AAT45083.1; -; mRNA.
DR   EMBL; AB193259; BAD99266.1; -; mRNA.
DR   EMBL; AB193260; BAD99267.1; -; mRNA.
DR   EMBL; AB046569; BAB40370.1; -; mRNA.
DR   EMBL; E39033; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; GQ262784; ACT66268.1; -; mRNA.
DR   EMBL; AY358714; AAQ89076.1; -; mRNA.
DR   EMBL; AY217547; AAO25651.1; -; Genomic_DNA.
DR   EMBL; CH471074; EAW98892.1; -; Genomic_DNA.
DR   EMBL; BC039902; AAH39902.1; -; mRNA.
DR   EMBL; BC048094; AAH48094.2; -; mRNA.
DR   EMBL; AL110224; CAB53682.1; -; mRNA.
DR   CCDS; CCDS14169.1; -. [Q9BYF1-1]
DR   PIR; T14762; T14762.
DR   RefSeq; NP_068576.1; NM_021804.2. [Q9BYF1-1]
DR   PDB; 1R42; X-ray; 2.20 A; A=1-615.
DR   PDB; 1R4L; X-ray; 3.00 A; A=1-615.
DR   PDB; 1XJP; Model; -; B=19-615.
DR   PDB; 2AJF; X-ray; 2.90 A; A/B=19-615.
DR   PDB; 3D0G; X-ray; 2.80 A; A/B=56-615.
DR   PDB; 3D0H; X-ray; 3.10 A; A/B=56-615.
DR   PDB; 3D0I; X-ray; 2.90 A; A/B=56-615.
DR   PDB; 3KBH; X-ray; 3.31 A; A/B/C/D=19-615.
DR   PDB; 3SCI; X-ray; 2.90 A; A/B=19-615.
DR   PDB; 3SCJ; X-ray; 3.00 A; A/B=19-615.
DR   PDB; 3SCK; X-ray; 3.00 A; A/B=83-615.
DR   PDB; 3SCL; X-ray; 3.00 A; A/B=83-615.
DR   PDB; 6ACG; EM; 5.40 A; D=19-615.
DR   PDB; 6ACJ; EM; 4.20 A; D=19-615.
DR   PDB; 6ACK; EM; 4.50 A; D=19-615.
DR   PDB; 6CS2; EM; 4.40 A; D=19-615.
DR   PDB; 6LZG; X-ray; 2.50 A; A=19-614.
DR   PDB; 6M0J; X-ray; 2.45 A; A=19-615.
DR   PDB; 6M17; EM; 2.90 A; B/D=18-805.
DR   PDB; 6M18; EM; 2.90 A; B/D=18-805.
DR   PDB; 6M1D; EM; 4.50 A; B/D=18-805.
DR   PDB; 6VW1; X-ray; 2.68 A; A/B=19-615.
DR   PDBsum; 1R42; -.
DR   PDBsum; 1R4L; -.
DR   PDBsum; 1XJP; -.
DR   PDBsum; 2AJF; -.
DR   PDBsum; 3D0G; -.
DR   PDBsum; 3D0H; -.
DR   PDBsum; 3D0I; -.
DR   PDBsum; 3KBH; -.
DR   PDBsum; 3SCI; -.
DR   PDBsum; 3SCJ; -.
DR   PDBsum; 3SCK; -.
DR   PDBsum; 3SCL; -.
DR   PDBsum; 6ACG; -.
DR   PDBsum; 6ACJ; -.
DR   PDBsum; 6ACK; -.
DR   PDBsum; 6CS2; -.
DR   PDBsum; 6LZG; -.
DR   PDBsum; 6M0J; -.
DR   PDBsum; 6M17; -.
DR   PDBsum; 6M18; -.
DR   PDBsum; 6M1D; -.
DR   PDBsum; 6VW1; -.
DR   SMR; Q9BYF1; -.
DR   BioGRID; 121864; 12.
DR   ComplexPortal; CPX-5683; SARS-CoV-2 Spike - human ACE2 receptor complex.
DR   ComplexPortal; CPX-5684; SARS-CoV-2 Spike - human ACE2-SLC6A19 complex.
DR   ComplexPortal; CPX-5695; SARS-CoV Spike - human ACE2 receptor complex.
DR   DIP; DIP-44689N; -.
DR   IntAct; Q9BYF1; 20.
DR   MINT; Q9BYF1; -.
DR   STRING; 9606.ENSP00000389326; -.
DR   BindingDB; Q9BYF1; -.
DR   ChEMBL; CHEMBL3736; -.
DR   DrugBank; DB00608; Chloroquine.
DR   DrugBank; DB01611; Hydroxychloroquine.
DR   DrugBank; DB15643; N-(2-Aminoethyl)-1-aziridineethanamine.
DR   DrugBank; DB05203; SPP1148.
DR   GuidetoPHARMACOLOGY; 1614; -.
DR   MEROPS; M02.006; -.
DR   TCDB; 2.A.22.6.3; the neurotransmitter:sodium symporter (nss) family.
DR   GlyConnect; 1012; 4 N-Linked glycans (3 sites).
DR   GlyConnect; 2841; 134 N-Linked glycans (7 sites), 6 O-Linked glycans (56 sites).
DR   GlyGen; Q9BYF1; 7 sites.
DR   iPTMnet; Q9BYF1; -.
DR   PhosphoSitePlus; Q9BYF1; -.
DR   BioMuta; ACE2; -.
DR   DMDM; 71658783; -.
DR   jPOST; Q9BYF1; -.
DR   MassIVE; Q9BYF1; -.
DR   PaxDb; Q9BYF1; -.
DR   PeptideAtlas; Q9BYF1; -.
DR   PRIDE; Q9BYF1; -.
DR   ProteomicsDB; 79634; -. [Q9BYF1-1]
DR   ProteomicsDB; 79635; -. [Q9BYF1-2]
DR   Antibodypedia; 344; 915 antibodies.
DR   Ensembl; ENST00000252519; ENSP00000252519; ENSG00000130234. [Q9BYF1-1]
DR   Ensembl; ENST00000427411; ENSP00000389326; ENSG00000130234. [Q9BYF1-1]
DR   GeneID; 59272; -.
DR   KEGG; hsa:59272; -.
DR   UCSC; uc004cxa.2; human. [Q9BYF1-1]
DR   CTD; 59272; -.
DR   DisGeNET; 59272; -.
DR   EuPathDB; HostDB:ENSG00000130234.10; -.
DR   GeneCards; ACE2; -.
DR   HGNC; HGNC:13557; ACE2.
DR   HPA; ENSG00000130234; Tissue enriched (intestine).
DR   MIM; 300335; gene.
DR   neXtProt; NX_Q9BYF1; -.
DR   OpenTargets; ENSG00000130234; -.
DR   PharmGKB; PA425; -.
DR   eggNOG; KOG3690; Eukaryota.
DR   GeneTree; ENSGT00940000158077; -.
DR   HOGENOM; CLU_014364_3_0_1; -.
DR   InParanoid; Q9BYF1; -.
DR   KO; K09708; -.
DR   OMA; RWWEMKR; -.
DR   OrthoDB; 422699at2759; -.
DR   PhylomeDB; Q9BYF1; -.
DR   TreeFam; TF312861; -.
DR   BRENDA; 3.4.15.1; 2681.
DR   BRENDA; 3.4.17.23; 2681.
DR   PathwayCommons; Q9BYF1; -.
DR   Reactome; R-HSA-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR   SABIO-RK; Q9BYF1; -.
DR   SIGNOR; Q9BYF1; -.
DR   BioGRID-ORCS; 59272; 2 hits in 501 CRISPR screens.
DR   ChiTaRS; ACE2; human.
DR   EvolutionaryTrace; Q9BYF1; -.
DR   GeneWiki; Angiotensin-converting_enzyme_2; -.
DR   GenomeRNAi; 59272; -.
DR   Pharos; Q9BYF1; Tchem.
DR   PRO; PR:Q9BYF1; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9BYF1; protein.
DR   Bgee; ENSG00000130234; Expressed in jejunal mucosa and 142 other tissues.
DR   Genevisible; Q9BYF1; HS.
DR   GO; GO:0031526; C:brush border membrane; IEA:Ensembl.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0045121; C:membrane raft; TAS:BHF-UCL.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0004180; F:carboxypeptidase activity; IDA:UniProtKB.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0004181; F:metallocarboxypeptidase activity; EXP:Reactome.
DR   GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:UniProtKB.
DR   GO; GO:0001618; F:virus receptor activity; IDA:BHF-UCL.
DR   GO; GO:0008270; F:zinc ion binding; TAS:BHF-UCL.
DR   GO; GO:0002003; P:angiotensin maturation; TAS:Reactome.
DR   GO; GO:0003051; P:angiotensin-mediated drinking behavior; IMP:BHF-UCL.
DR   GO; GO:0051957; P:positive regulation of amino acid transport; IMP:UniProtKB.
DR   GO; GO:0060452; P:positive regulation of cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:1903598; P:positive regulation of gap junction assembly; IMP:BHF-UCL.
DR   GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IC:BHF-UCL.
DR   GO; GO:0032800; P:receptor biosynthetic process; IMP:BHF-UCL.
DR   GO; GO:0046813; P:receptor-mediated virion attachment to host cell; IDA:BHF-UCL.
DR   GO; GO:0097746; P:regulation of blood vessel diameter; IC:BHF-UCL.
DR   GO; GO:1903779; P:regulation of cardiac conduction; IMP:BHF-UCL.
DR   GO; GO:0042127; P:regulation of cell population proliferation; TAS:BHF-UCL.
DR   GO; GO:0001817; P:regulation of cytokine production; IC:BHF-UCL.
DR   GO; GO:0050727; P:regulation of inflammatory response; IC:BHF-UCL.
DR   GO; GO:0003081; P:regulation of systemic arterial blood pressure by renin-angiotensin; IMP:BHF-UCL.
DR   GO; GO:0019229; P:regulation of vasoconstriction; IC:BHF-UCL.
DR   GO; GO:0015827; P:tryptophan transport; IEA:Ensembl.
DR   GO; GO:0046718; P:viral entry into host cell; TAS:UniProtKB.
DR   CDD; cd06461; M2_ACE; 1.
DR   InterPro; IPR031588; Collectrin_dom.
DR   InterPro; IPR001548; Peptidase_M2.
DR   PANTHER; PTHR10514; PTHR10514; 1.
DR   Pfam; PF16959; Collectrin; 1.
DR   Pfam; PF01401; Peptidase_M2; 1.
DR   PRINTS; PR00791; PEPDIPTASEA.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Carboxypeptidase; Cell membrane;
KW   Chloride; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Host cell receptor for virus entry; Host-virus interaction;
KW   Hydrolase; Membrane; Metal-binding; Metalloprotease; Polymorphism;
KW   Protease; Receptor; Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix; Zinc.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..805
FT                   /note="Angiotensin-converting enzyme 2"
FT                   /id="PRO_0000028570"
FT   CHAIN           18..708
FT                   /note="Processed angiotensin-converting enzyme 2"
FT                   /id="PRO_0000292268"
FT   TOPO_DOM        18..740
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        741..761
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        762..805
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          30..41
FT                   /note="Interaction with SARS-CoV spike glycoprotein"
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   REGION          82..84
FT                   /note="Interaction with SARS-CoV spike glycoprotein"
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   REGION          345..346
FT                   /note="Substrate binding"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   REGION          353..357
FT                   /note="Interaction with SARS-CoV spike glycoprotein"
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   REGION          652..659
FT                   /note="Essential for cleavage by ADAM17"
FT                   /evidence="ECO:0000269|PubMed:24227843"
FT   REGION          697..716
FT                   /note="Essential for cleavage by TMPRSS11D and TMPRSS2"
FT                   /evidence="ECO:0000269|PubMed:24227843"
FT   ACT_SITE        375
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000305|PubMed:14754895,
FT                   ECO:0000305|PubMed:27217402"
FT   ACT_SITE        505
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   METAL           374
FT                   /note="Zinc; catalytic"
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   METAL           378
FT                   /note="Zinc; catalytic"
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   METAL           402
FT                   /note="Zinc; catalytic"
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   BINDING         169
FT                   /note="Chloride"
FT                   /evidence="ECO:0000269|PubMed:14754895,
FT                   ECO:0000305|PubMed:19021774"
FT   BINDING         273
FT                   /note="Substrate"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   BINDING         477
FT                   /note="Chloride"
FT                   /evidence="ECO:0000269|PubMed:14754895,
FT                   ECO:0000305|PubMed:19021774"
FT   BINDING         481
FT                   /note="Chloride"
FT                   /evidence="ECO:0000269|PubMed:14754895,
FT                   ECO:0000305|PubMed:19021774"
FT   BINDING         515
FT                   /note="Substrate"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   CARBOHYD        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   CARBOHYD        90
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14754895,
FT                   ECO:0000269|PubMed:15084671"
FT   CARBOHYD        103
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   CARBOHYD        322
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000305|PubMed:14754895"
FT   CARBOHYD        432
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   CARBOHYD        546
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:14754895,
FT                   ECO:0000269|PubMed:19159218"
FT   CARBOHYD        690
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        133..141
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   DISULFID        344..361
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   DISULFID        530..542
FT                   /evidence="ECO:0000269|PubMed:14754895"
FT   VAR_SEQ         555
FT                   /note="F -> L (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12975309"
FT                   /id="VSP_014901"
FT   VAR_SEQ         556..805
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:12975309"
FT                   /id="VSP_014902"
FT   VARIANT         26
FT                   /note="K -> R (in dbSNP:rs4646116)"
FT                   /evidence="ECO:0000269|Ref.9"
FT                   /id="VAR_023082"
FT   VARIANT         638
FT                   /note="N -> S (in dbSNP:rs183135788)"
FT                   /evidence="ECO:0000269|PubMed:15937940"
FT                   /id="VAR_023083"
FT   MUTAGEN         24..26
FT                   /note="QAK->KAE: Slightly inhibits interaction with SARS-
FT                   CoV spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         31
FT                   /note="K->D: Abolishes interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         37
FT                   /note="E->A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         38
FT                   /note="D->A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         41
FT                   /note="Y->A: Strongly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         68
FT                   /note="K->D: Slightly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         82..84
FT                   /note="MYP->NFS: Inhibits interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         110
FT                   /note="E->P: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         135..136
FT                   /note="PD->SM: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         160
FT                   /note="E->R: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         169
FT                   /note="R->Q: About 95% loss of angiotensin I cleavage."
FT                   /evidence="ECO:0000269|PubMed:19021774"
FT   MUTAGEN         192
FT                   /note="R->D: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         219
FT                   /note="R->D: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         239
FT                   /note="H->Q: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         271
FT                   /note="W->Q: About 95% loss of angiotensin I cleavage."
FT                   /evidence="ECO:0000269|PubMed:19021774"
FT   MUTAGEN         273
FT                   /note="R->Q: Complete loss of enzyme activity. Does not
FT                   affect amino acid transport activity of SLC6A19."
FT                   /evidence="ECO:0000269|PubMed:16008552,
FT                   ECO:0000269|PubMed:19185582"
FT   MUTAGEN         309
FT                   /note="K->D: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         312
FT                   /note="E->A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         324
FT                   /note="T->A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         338..340
FT                   /note="NVQ->DDR: No effect on interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         345
FT                   /note="H->A: Complete loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:16008552"
FT   MUTAGEN         350
FT                   /note="D->A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         353
FT                   /note="K->H,A,D: Abolishes interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         355
FT                   /note="D->A: Strongly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         357
FT                   /note="R->A: Strongly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         359
FT                   /note="L->K,A: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         383
FT                   /note="M->A: Slightly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         389
FT                   /note="P->A: Slightly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         393
FT                   /note="R->A: Slightly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         425..427
FT                   /note="SPD->PSN: Slightly inhibits interaction with SARS-
FT                   CoV spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         465..467
FT                   /note="KGE->QDK: No effect on interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         481
FT                   /note="K->Q: About 80% loss of angiotensin I cleavage."
FT                   /evidence="ECO:0000269|PubMed:19021774"
FT   MUTAGEN         505
FT                   /note="H->A: Complete loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:16008552"
FT   MUTAGEN         514
FT                   /note="R->Q: About 50% loss of angiotensin I cleavage but
FT                   two-fold greater activity with angiotensin II."
FT                   /evidence="ECO:0000269|PubMed:19021774"
FT   MUTAGEN         559
FT                   /note="R->S: Slightly inhibits interaction with SARS-CoV
FT                   spike glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   MUTAGEN         603
FT                   /note="F->T: No effect on interaction with SARS-CoV spike
FT                   glycoprotein."
FT                   /evidence="ECO:0000269|PubMed:15791205"
FT   CONFLICT        18
FT                   /note="Q -> H (in Ref. 12; CAB53682)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        508
FT                   /note="N -> D (in Ref. 8; AAQ89076)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        631
FT                   /note="K -> R (in Ref. 5; BAB40370)"
FT                   /evidence="ECO:0000305"
FT   HELIX           23..52
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           56..77
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            78..82
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           85..87
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   HELIX           91..100
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           104..107
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           110..129
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          131..134
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          137..143
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            144..146
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           148..154
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           158..171
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           173..193
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          196..198
FT                   /evidence="ECO:0000244|PDB:1R4L"
FT   HELIX           199..204
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            205..207
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            213..215
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           220..251
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            253..255
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          258..260
FT                   /evidence="ECO:0000244|PDB:3SCJ"
FT   HELIX           264..266
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          267..271
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           276..278
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           279..282
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            284..287
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            294..297
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           298..300
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           304..316
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            317..319
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           327..330
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            337..339
FT                   /evidence="ECO:0000244|PDB:6M0J"
FT   STRAND          347..352
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          355..359
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           366..384
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            385..387
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           390..392
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          396..399
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           400..413
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           415..420
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            422..426
FT                   /evidence="ECO:0000244|PDB:1R4L"
FT   HELIX           432..446
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           449..465
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          466..468
FT                   /evidence="ECO:0000244|PDB:1R4L"
FT   HELIX           470..472
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           473..483
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          486..488
FT                   /evidence="ECO:0000244|PDB:3D0G"
FT   HELIX           499..502
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           504..507
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           514..531
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            532..534
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           539..541
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           548..558
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            559..562
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           566..574
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          575..578
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   HELIX           582..598
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          600..602
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   STRAND          607..609
FT                   /evidence="ECO:0000244|PDB:1R42"
FT   TURN            612..615
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          618..622
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           624..627
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          629..631
FT                   /evidence="ECO:0000244|PDB:6M18"
FT   HELIX           637..657
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           667..669
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          670..673
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          677..686
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          690..694
FT                   /evidence="ECO:0000244|PDB:6M18"
FT   HELIX           697..706
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           708..715
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   STRAND          719..724
FT                   /evidence="ECO:0000244|PDB:6M17"
FT   HELIX           741..766
FT                   /evidence="ECO:0000244|PDB:6M17"
SQ   SEQUENCE   805 AA;  92463 MW;  8EE6EB0A931550E8 CRC64;
     MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ
     NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL
     NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY
     EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL
     HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ
     AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM
     CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS
     IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM
     KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH
     KCDISNSTEA GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK
     NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA MRQYFLKVKN
     QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN
     SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVIL IFTGIRDRKK KNKARSGENP
     YASIDISKGE NNPGFQNTDD VQTSF
//