Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTGFNPD)

• DTT Name: HUMAN angiotensin-converting enzyme (ACE)
• Synonyms: Kininase II; Dipeptidyl carboxypeptidase I; DCP1; DCP; CD143 antigen; CD143; ACE
• Gene Name: SLC33A1
• BioChemical Class: Glycosylase
• UniProt ID: ACE_HUMAN
• TTD ID: T98311
• EC Number: EC 3.2.1.-
• Sequence:
  MGAASGRRGPGLLLPLPLLLLLPPQPALALDPGLQPGNFSADEAGAQLFAQSYNSSAEQV
  LFQSVAASWAHDTNITAENARRQEEAALLSQEFAEAWGQKAKELYEPIWQNFTDPQLRRI
  IGAVRTLGSANLPLAKRQQYNALLSNMSRIYSTAKVCLPNKTATCWSLDPDLTNILASSR
  SYAMLLFAWEGWHNAAGIPLKPLYEDFTALSNEAYKQDGFTDTGAYWRSWYNSPTFEDDL
  EHLYQQLEPLYLNLHAFVRRALHRRYGDRYINLRGPIPAHLLGDMWAQSWENIYDMVVPF
  PDKPNLDVTSTMLQQGWNATHMFRVAEEFFTSLELSPMPPEFWEGSMLEKPADGREVVCH
  ASAWDFYNRKDFRIKQCTRVTMDQLSTVHHEMGHIQYYLQYKDLPVSLRRGANPGFHEAI
  GDVLALSVSTPEHLHKIGLLDRVTNDTESDINYLLKMALEKIAFLPFGYLVDQWRWGVFS
  GRTPPSRYNFDWWYLRTKYQGICPPVTRNETHFDAGAKFHVPNVTPYIRYFVSFVLQFQF
  HEALCKEAGYEGPLHQCDIYRSTKAGAKLRKVLQAGSSRPWQEVLKDMVGLDALDAQPLL
  KYFQPVTQWLQEQNQQNGEVLGWPEYQWHPPLPDNYPEGIDLVTDEAEASKFVEEYDRTS
  QVVWNEYAEANWNYNTNITTETSKILLQKNMQIANHTLKYGTQARKFDVNQLQNTTIKRI
  IKKVQDLERAALPAQELEEYNKILLDMETTYSVATVCHPNGSCLQLEPDLTNVMATSRKY
  EDLLWAWEGWRDKAGRAILQFYPKYVELINQAARLNGYVDAGDSWRSMYETPSLEQDLER
  LFQELQPLYLNLHAYVRRALHRHYGAQHINLEGPIPAHLLGNMWAQTWSNIYDLVVPFPS
  APSMDTTEAMLKQGWTPRRMFKEADDFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHAS
  AWDFYNGKDFRIKQCTTVNLEDLVVAHHEMGHIQYFMQYKDLPVALREGANPGFHEAIGD
  VLALSVSTPKHLHSLNLLSSEGGSDEHDINFLMKMALDKIAFIPFSYLVDQWRWRVFDGS
  ITKENYNQEWWSLRLKYQGLCPPVPRTQGDFDPGAKFHIPSSVPYIRYFVSFIIQFQFHE
  ALCQAAGHTGPLHKCDIYQSKEAGQRLATAMKLGFSRPWPEAMQLITGQPNMSASAMLSY
  FKPLLDWLRTENELHGEKLGWPQYNWTPNSARSEGPLPDSGRVSFLGLDLDAQQARVGQW
  LLLFLGIALLVATLGLSQRLFSIRHRSLHRHSHGPQFGSEVELRHS
• Function: Able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin.
• KEGG Pathway:
  Renin-angiotensin system (hsa04614)
  Renin secretion (hsa04924)
  Chagas disease (hsa05142)
  Coronavirus disease - COVID-19 (hsa05171)
  Hypertrophic cardiomyopathy (hsa05410)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway: Metabolism of Angiotensinogen to Angiotensins (R-HSA-2022377)
• BioCyc Pathway: MetaCyc:HS08412-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Captopril	DM458UM	Chronic heart failure	BD1Z	Approved	[2]
Lisinopril	DMUOK4C	Chronic heart failure	BD1Z	Approved	[1]
Ramipril	DM2R68E	Acute heart failure	BD10-BD13	Approved	[2]

References

• [1] Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Am Heart Assoc. 2020 Apr 7;9(7):e016219.
• [2] Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB. Curr Cardiol Rep. 2020 Apr 14;22(5):31.