Angiotensin-converting enzyme 2
Details
- Name
- Angiotensin-converting enzyme 2
- Synonyms
- 3.4.17.23
- ACE-related carboxypeptidase
- ACEH
- Angiotensin-converting enzyme homolog
- Angiotensin-converting enzyme-related carboxypeptidase
- Metalloprotease MPROT15
- Gene Name
- ACE2
- UniProtKB Entry
- Q9BYF1Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0001955|Angiotensin-converting enzyme 2 MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQ NMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTIL NTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLY EEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHL HAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQ AWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILM CTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKS IGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEM KREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLH KCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNK NSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKN QMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDN SLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENP YASIDISKGENNPGFQNTDDVQTSF
- Number of residues
- 805
- Molecular Weight
- 92462.4
- Theoretical pI
- 5.23
- GO Classification
- Functionsidentical protein binding / metallopeptidase activity / peptidyl-dipeptidase activityProcessesblood vessel diameter maintenance / entry receptor-mediated virion attachment to host cell / maternal process involved in female pregnancy / membrane fusion / negative regulation of ERK1 and ERK2 cascade / negative regulation of signaling receptor activity / negative regulation of smooth muscle cell proliferation / positive regulation of amino acid transport / positive regulation of L-proline import across plasma membrane / receptor-mediated endocytosis of virus by host cell / regulation of cell population proliferation / regulation of transmembrane transporter activity / symbiont entry into host cell / viral life cycleComponentsapical plasma membrane / brush border membrane / cilium / endocytic vesicle membrane / endoplasmic reticulum lumen / membrane
- General 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 (PubMed:27217402). 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 (PubMed:10924499, PubMed:10969042, PubMed:11815627, PubMed:14504186, PubMed:19021774). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity (PubMed:18424768, PubMed:19185582)
- Specific Function
- carboxypeptidase activity
- Pfam Domain Function
- Signal Regions
- 1-17
- Transmembrane Regions
- 741-761
- Cellular Location
- Secreted
- Gene sequence
>lcl|BSEQ0010689|Angiotensin-converting enzyme 2 (ACE2) ATGTCAAGCTCTTCCTGGCTCCTTCTCAGCCTTGTTGCTGTAACTGCTGCTCAGTCCACC ATTGAGGAACAGGCCAAGACATTTTTGGACAAGTTTAACCACGAAGCCGAAGACCTGTTC TATCAAAGTTCACTTGCTTCTTGGAATTATAACACCAATATTACTGAAGAGAATGTCCAA AACATGAATAATGCTGGGGACAAATGGTCTGCCTTTTTAAAGGAACAGTCCACACTTGCC CAAATGTATCCACTACAAGAAATTCAGAATCTCACAGTCAAGCTTCAGCTGCAGGCTCTT CAGCAAAATGGGTCTTCAGTGCTCTCAGAAGACAAGAGCAAACGGTTGAACACAATTCTA AATACAATGAGCACCATCTACAGTACTGGAAAAGTTTGTAACCCAGATAATCCACAAGAA TGCTTATTACTTGAACCAGGTTTGAATGAAATAATGGCAAACAGTTTAGACTACAATGAG AGGCTCTGGGCTTGGGAAAGCTGGAGATCTGAGGTCGGCAAGCAGCTGAGGCCATTATAT GAAGAGTATGTGGTCTTGAAAAATGAGATGGCAAGAGCAAATCATTATGAGGACTATGGG GATTATTGGAGAGGAGACTATGAAGTAAATGGGGTAGATGGCTATGACTACAGCCGCGGC CAGTTGATTGAAGATGTGGAACATACCTTTGAAGAGATTAAACCATTATATGAACATCTT CATGCCTATGTGAGGGCAAAGTTGATGAATGCCTATCCTTCCTATATCAGTCCAATTGGA TGCCTCCCTGCTCATTTGCTTGGTGATATGTGGGGTAGATTTTGGACAAATCTGTACTCT TTGACAGTTCCCTTTGGACAGAAACCAAACATAGATGTTACTGATGCAATGGTGGACCAG GCCTGGGATGCACAGAGAATATTCAAGGAGGCCGAGAAGTTCTTTGTATCTGTTGGTCTT CCTAATATGACTCAAGGATTCTGGGAAAATTCCATGCTAACGGACCCAGGAAATGTTCAG AAAGCAGTCTGCCATCCCACAGCTTGGGACCTGGGGAAGGGCGACTTCAGGATCCTTATG TGCACAAAGGTGACAATGGACGACTTCCTGACAGCTCATCATGAGATGGGGCATATCCAG TATGATATGGCATATGCTGCACAACCTTTTCTGCTAAGAAATGGAGCTAATGAAGGATTC CATGAAGCTGTTGGGGAAATCATGTCACTTTCTGCAGCCACACCTAAGCATTTAAAATCC ATTGGTCTTCTGTCACCCGATTTTCAAGAAGACAATGAAACAGAAATAAACTTCCTGCTC AAACAAGCACTCACGATTGTTGGGACTCTGCCATTTACTTACATGTTAGAGAAGTGGAGG TGGATGGTCTTTAAAGGGGAAATTCCCAAAGACCAGTGGATGAAAAAGTGGTGGGAGATG AAGCGAGAGATAGTTGGGGTGGTGGAACCTGTGCCCCATGATGAAACATACTGTGACCCC GCATCTCTGTTCCATGTTTCTAATGATTACTCATTCATTCGATATTACACAAGGACCCTT TACCAATTCCAGTTTCAAGAAGCACTTTGTCAAGCAGCTAAACATGAAGGCCCTCTGCAC AAATGTGACATCTCAAACTCTACAGAAGCTGGACAGAAACTGTTCAATATGCTGAGGCTT GGAAAATCAGAACCCTGGACCCTAGCATTGGAAAATGTTGTAGGAGCAAAGAACATGAAT GTAAGGCCACTGCTCAACTACTTTGAGCCCTTATTTACCTGGCTGAAAGACCAGAACAAG AATTCTTTTGTGGGATGGAGTACCGACTGGAGTCCATATGCAGACCAAAGCATCAAAGTG AGGATAAGCCTAAAATCAGCTCTTGGAGATAAAGCATATGAATGGAACGACAATGAAATG TACCTGTTCCGATCATCTGTTGCATATGCTATGAGGCAGTACTTTTTAAAAGTAAAAAAT CAGATGATTCTTTTTGGGGAGGAGGATGTGCGAGTGGCTAATTTGAAACCAAGAATCTCC TTTAATTTCTTTGTCACTGCACCTAAAAATGTGTCTGATATCATTCCTAGAACTGAAGTT GAAAAGGCCATCAGGATGTCCCGGAGCCGTATCAATGATGCTTTCCGTCTGAATGACAAC AGCCTAGAGTTTCTGGGGATACAGCCAACACTTGGACCTCCTAACCAGCCCCCTGTTTCC ATATGGCTGATTGTTTTTGGAGTTGTGATGGGAGTGATAGTGGTTGGCATTGTCATCCTG ATCTTCACTGGGATCAGAGATCGGAAGAAGAAAAATAAAGCAAGAAGTGGAGAAAATCCT TATGCCTCCATCGATATTAGCAAAGGAGAAAATAATCCAGGATTCCAAAACACTGATGAT GTTCAGACCTCCTTTTAG
- Chromosome Location
- X
- Locus
- Xp22.2
- External Identifiers
- General References
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- Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ: A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000 Oct 27;275(43):33238-43. [Article]
- Douglas GC, O'Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI, Lew RA: The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology. 2004 Oct;145(10):4703-11. Epub 2004 Jul 1. [Article]
- Itoyama S, Keicho N, Hijikata M, Quy T, Phi NC, Long HT, Ha LD, Ban VV, Matsushita I, Yanai H, Kirikae F, Kirikae T, Kuratsuji T, Sasazuki T: Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population. Am J Med Genet A. 2005 Jul 1;136(1):52-7. [Article]
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- Lin Q, Keller RS, Weaver B, Zisman LS: Interaction of ACE2 and integrin beta1 in failing human heart. Biochim Biophys Acta. 2004 Aug 4;1689(3):175-8. [Article]
- Harmer D, Gilbert M, Borman R, Clark KL: Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002 Dec 4;532(1-2):107-10. [Article]
- Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, Godbout K, Parsons T, Baronas E, Hsieh F, Acton S, Patane M, Nichols A, Tummino P: Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002 Apr 26;277(17):14838-43. Epub 2002 Jan 28. [Article]
- Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, Farzan M: Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. [Article]
- Goulter AB, Goddard MJ, Allen JC, Clark KL: ACE2 gene expression is up-regulated in the human failing heart. BMC Med. 2004 May 19;2:19. [Article]
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- Li W, Greenough TC, Moore MJ, Vasilieva N, Somasundaran M, Sullivan JL, Farzan M, Choe H: Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. J Virol. 2004 Oct;78(20):11429-33. [Article]
- Kristiansen TZ, Bunkenborg J, Gronborg M, Molina H, Thuluvath PJ, Argani P, Goggins MG, Maitra A, Pandey A: A proteomic analysis of human bile. Mol Cell Proteomics. 2004 Jul;3(7):715-28. Epub 2004 Apr 14. [Article]
- Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, Tikellis C, Grant SL, Lew RA, Smith AI, Cooper ME, Johnston CI: Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005 Feb;26(4):369-75; discussion 322-4. Epub 2005 Jan 25. [Article]
- Li W, Zhang C, Sui J, Kuhn JH, Moore MJ, Luo S, Wong SK, Huang IC, Xu K, Vasilieva N, Murakami A, He Y, Marasco WA, Guan Y, Choe H, Farzan M: Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005 Apr 20;24(8):1634-43. Epub 2005 Mar 24. [Article]
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- Lai ZW, Hanchapola I, Steer DL, Smith AI: Angiotensin-converting enzyme 2 ectodomain shedding cleavage-site identification: determinants and constraints. Biochemistry. 2011 Jun 14;50(23):5182-94. doi: 10.1021/bi200525y. Epub 2011 May 20. [Article]
- Shulla A, Heald-Sargent T, Subramanya G, Zhao J, Perlman S, Gallagher T: A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry. J Virol. 2011 Jan;85(2):873-82. doi: 10.1128/JVI.02062-10. Epub 2010 Nov 10. [Article]
- Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S: TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014 Jan;88(2):1293-307. doi: 10.1128/JVI.02202-13. Epub 2013 Nov 13. [Article]
- Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA, Pantoliano MW: ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem. 2004 Apr 23;279(17):17996-8007. Epub 2004 Jan 30. [Article]
Associated Data
- Bio-Entities
Bio-Entity Type Angiotensin-converting enzyme 2 (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details SPP1148 investigational unknown target Details N-(2-Aminoethyl)-1-aziridineethanamine experimental unknown target inhibitor Details Chloroquine approved, investigational, vet_approved unknown target modulator Details Hydroxychloroquine approved unknown target modulator Details Bromhexine approved yes target binder Details Bromhexine approved unknown enzyme binder Details ORE-1001 investigational yes target inhibitor Details