ACE - Angiotensin-converting enzyme - human protein (Function)
 
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ACE »  Angiotensin-converting enzyme   [ EC 3.4.15.1EC 3.2.1.- ]  (ACE)
 
Protein also known as:  Dipeptidyl carboxypeptidase I; CD antigen CD143. Cleaved into:  Angiotensin-converting enzyme, soluble form.
Gene name:  ACE
Family name: Peptidase M2
Entry whose protein(s) existence is based on evidence at protein level
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1 298 4
GENE REF ISO

Function

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Overview 
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also 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.  
  • CuratedUniProtKB
GO molecular function 
Isoform  Somatic-1   Actin bindingdefinition[GO:0003779]  
1
  • IDAUniProtKB
Bradykinin receptor bindingdefinition[GO:0031711]  
1
  • IPIBHF-UCL
Carboxypeptidase activitydefinition[GO:0004180]  
  • IEAUniProtKB KW
Chloride ion bindingdefinition[GO:0031404]  
1
  • IDABHF-UCL
Drug bindingdefinition[GO:0008144]  
1
  • IDABHF-UCL
Endopeptidase activitydefinition[GO:0004175]  
1
  • IDAUniProtKB
Metallopeptidase activitydefinition[GO:0008237]  
4
  • IDAUniProtKB
  • ISSOrtholog Curator
Peptidyl-dipeptidase activitydefinition[GO:0008241]  
5
  • IDAUniProtKB
Isoform  Somatic-1   Protein bindingdefinition[GO:0005515]  
1
  • IPIUniProtKB
Zinc ion bindingdefinition[GO:0008270]  
1
  • IDABHF-UCL
GO biological process 
Angiotensin catabolic process in blooddefinition[GO:0002005]  
1
  • ICUniProtKB
Arachidonic acid secretiondefinition[GO:0050482]  
1
  • IDABHF-UCL
Blood vessel remodelingdefinition[GO:0001974]  
1
  • ICBHF-UCL
Hematopoietic stem cell differentiationdefinition[GO:0060218]  
1
  • ICBHF-UCL
Hormone catabolic processdefinition[GO:0042447]  
2
  • ISSBHF-UCL
Kidney developmentdefinition[GO:0001822]  
1
  • IMPBHF-UCL
Mononuclear cell proliferationdefinition[GO:0032943]  
1
  • ICBHF-UCL
Peptide catabolic processdefinition[GO:0043171]  
1
  • IDABHF-UCL
Regulation of blood pressuredefinition[GO:0008217]  
1
  • ISSBHF-UCL
  • ISSOrtholog Curator
Regulation of renal output by angiotensindefinition[GO:0002019]  
1
  • ICBHF-UCL
Regulation of smooth muscle cell migrationdefinition[GO:0014910]  
  • ISSOrtholog Curator
Regulation of systemic arterial blood pressure by renin-angiotensindefinition[GO:0003081]  
1
  • ICUniProtKB
Regulation of vasoconstrictiondefinition[GO:0019229]  
1
  • ICUniProtKB
Regulation of vasodilationdefinition[GO:0042312]  
1
  • ICBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.4.15.1: Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.  
  • CuratedUniProtKB
It requires the following cofactors
Binds 2 zinc ions per subunit.  
  • CuratedUniProtKB
Binds 3 chloride ions per subunit.  
  • CuratedUniProtKB
Isoform  Testis-specific   Only binds 1 zinc ion per subunit.  
  • CuratedUniProtKB
It is regulated in the following manner
Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Chagas disease (American trypanosomiasis)  hsa05142+1636  
Hypertrophic cardiomyopathy (HCM)  hsa05410+1636  
Renin-angiotensin system  hsa04614+1636  
According to Reactome, this protein belongs to the following pathway:
Metabolism of proteins  REACT_17015  
 
More information is available from:
Note 
Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction.  
  • CuratedUniProtKB
The glycosidase activity probably uses different active site residues than the metalloprotease activity.  
  • CuratedUniProtKB
 

Biophysicochemical properties

Kinetic parameters
KM 2.51 mM for Hip-His-Leu

Keywords

Molecular function 
Carboxypeptidase  definition   [KW-0121]
Hydrolase  definition   [KW-0378]
Metalloprotease  definition   [KW-0482]
Protease  definition   [KW-0645]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Enzyme and pathway databases
SABIO-RK: P12821
Other
GeneWiki: Angiotensin-converting_enzyme
GenomeRNAi: 1636
PRO: PR:P12821
Chemistry
GuidetoPHARMACOLOGY: 1613