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angiotensin converting enzyme 2 (ACE2)

Function: 1) carboxypeptidase 2) converts angiotensin 1 to angiotensin 1-9 3) converts angiotensin 2 to angiotensin 1-7 4) hydrolyzes apelin-13 & dynorphin-13 with high efficiency 5) regulator of heart function 6) interacts with ITGB1, HCOV-SARS, HCOV-NL63 S protein 7) processing by ADAM17 may lead to a secreted protein 8) binds 1 Zn+2 & 1 Cl- per subunit 9) may hydrolyze bradykinin Inhibition: - inhibited by MLN-4760, cFP-Leu, EDTA - NOT inhibited by benzylsuccinate, a carboxypeptidase A inhibitor or ACE inhibitors Kinetic parameters: - KM=6.9 uM for angiotensin 1 - KM=2 uM for angiotensin 2 - KM=6.8 uM for apelin-13 - KM=5.5 uM for dynorphin-13 - pH dependence: - Optimum pH is 6.5 in the presence of 1 M NaCl - active from pH 6-9 Compartment: 1) membrane protein 2) processing by ADAM17 may lead to a secreted protein Expression: 1) endothelial cells* from a) small & large arteries b) arterial smooth muscle cells 2) lung alveolar epithelial cells (pneumocytes)* 3) myofiber membrane of the diaphragm muscle [6] 4) enterocytes of the small intestine* 5) Leydig cells 6) Sertoli cells 7) heart*, up-regulated in failing heart 8) kidney* 9) testis* 10) gastrointestinal system * high levels of expression * expression upregulated by the farnesyl X receptor (FXR) [7] Pathology: - functional receptor for human coronaviruses, SARS & NL63 including SARS CoV2 [5] - SARS CoV spike glyxoprotein receptor is ACE2 - cell entry of SARS CoV2 also requires proteolysis of spike glycoprotein by cell surface serine protease TMPRSS2 expressed on type II pneumocytes - N-glycosylation on Asn-90 may limit SARS infectivity [2]

Related

angiotensin I angiotensin II (Giapreza) angiotensin-converting enzyme (ACE) in serum/plasma/blood SARS-CoV

General

angiotensin converting enzyme (ACE) carboxypeptidase

Properties

SIZE: entity length = 805 aa MW = 92 kD COMPARTMENT: cellular membrane MOTIF: signal sequence {1-17} SARS-CoV {30-41} N-glycosylation site {N53} SARS-CoV {82-84} N-glycosylation site {N90} N-glycosylation site {N103} cysteine residue {C133} MODIFICATION: cysteine residue {C141} cysteine residue {C141} MODIFICATION: cysteine residue {C133} binding site SITE: 169-169 FOR-BINDING-OF: Cl- binding site SITE: 273-273 FOR-BINDING-OF: Substrate N-glycosylation site {N322} cysteine residue {C344} MODIFICATION: cysteine residue {C361} binding site SITE: 345-345 FOR-BINDING-OF: Substrate binding site SITE: 346-346 FOR-BINDING-OF: Substrate SARS-CoV {353-357} cysteine residue {C361} MODIFICATION: cysteine residue {C344} binding site SITE: 371-371 FOR-BINDING-OF: Substrate Zn+2-binding site SITE: 374-374 glutamate residue {E375} Zn+2-binding site SITE: 378-378 Zn+2-binding site SITE: 402-402 N-glycosylation site {N432} binding site SITE: 477-477 FOR-BINDING-OF: Chloride binding site SITE: 481-481 FOR-BINDING-OF: Chloride histidine residue {H505} binding site SITE: 515-515 FOR-BINDING-OF: Substrate cysteine residue {C530} MODIFICATION: cysteine residue {C542} cysteine residue {C542} MODIFICATION: cysteine residue {C530} N-glycosylation site {N546} N-glycosylation site {N690} transmembrane domain {741-761} MISC-INFO: KM [ANGIOTENSIN_1] 6.9 UM KM [ANGIOTENSIN_2] 2 UM KM [APELIN_13] 6.8 UM KM [DYNORPHIN_13] 5.5 UM

Database Correlations

OMIM 300335 UniProt Q9BYF1 Pfam PF01401 Entrez Gene 59272 Kegg hsa:5927

References

  1. OMIM :accession 300335
  2. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, Berne MA et al Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003 Nov 27;426(6965):450-4. PMID: 14647384
  3. SeattleSNPs http://pga.gs.washington.edu/data/ace2/
  4. UniProt :accession Q9BYF1
  5. Hoffmann M, Kleine-Weber H, Schroeder S SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Mar 4. pii: S0092-8674(20)30229-4. PMID: 32142651
  6. Shi Z, de Vries HJ, Vlaar APJ et al Diaphragm Pathology in Critically Ill Patients With COVID-19 and Postmortem Findings From 3 Medical Centers. JAMA Intern Med. Published online November 16, 2020. PMID: 33196760 PMCID: PMC7670391 Free PMC article https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2773060
  7. Brevini T, Maes M, Webb GJ et al FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2. Nature 2022. Dec 5. PMID: 36470304 https://www.nature.com/articles/s41586-022-05594-0