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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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.  
1
  • UniProtKB
GO molecular function 
Isoform  Somatic-1   Actin bindingdefinition[GO:0003779]  
1
  • UniProtKB
Bradykinin receptor bindingdefinition[GO:0031711]  
1
  • BHF-UCL
Carboxypeptidase activitydefinition[GO:0004180]  
1
  • UniProtKB KW
Chloride ion bindingdefinition[GO:0031404]  
1
  • BHF-UCL
Drug bindingdefinition[GO:0008144]  
1
  • BHF-UCL
Endopeptidase activitydefinition[GO:0004175]  
2
  • BHF-UCL
  • UniProtKB
Exopeptidase activitydefinition[GO:0008238]  
1
  • BHF-UCL
Metallopeptidase activitydefinition[GO:0008237]  
5
  • UniProtKB
  • Ortholog Curator
Mitogen-activated protein kinase bindingdefinition[GO:0051019]  
1
  • BHF-UCL
Mitogen-activated protein kinase kinase bindingdefinition[GO:0031434]  
1
  • BHF-UCL
Peptidyl-dipeptidase activitydefinition[GO:0008241]  
11
  • BHF-UCL
  • UniProtKB
Isoform  Somatic-1   Protein bindingdefinition[GO:0005515]  
1
  • UniProtKB
Tripeptidyl-peptidase activitydefinition[GO:0008240]  
1
  • BHF-UCL
Zinc ion bindingdefinition[GO:0008270]  
1
  • BHF-UCL
GO biological process 
Angiotensin catabolic process in blooddefinition[GO:0002005]  
1
  • UniProtKB
Antigen processing and presentation of peptide antigen via MHC class Idefinition[GO:0002474]  
1
  • BHF-UCL
Arachidonic acid secretiondefinition[GO:0050482]  
1
  • BHF-UCL
Beta-amyloid metabolic processdefinition[GO:0050435]  
2
  • BHF-UCL
Blood vessel remodelingdefinition[GO:0001974]  
1
  • BHF-UCL
Cell proliferation in bone marrowdefinition[GO:0071838]  
1
  • Ortholog Curator
Heart contractiondefinition[GO:0060047]  
1
  • Ortholog Curator
Hematopoietic stem cell differentiationdefinition[GO:0060218]  
1
  • BHF-UCL
Hormone catabolic processdefinition[GO:0042447]  
2
  • BHF-UCL
Kidney developmentdefinition[GO:0001822]  
1
  • BHF-UCL
Mononuclear cell proliferationdefinition[GO:0032943]  
1
  • BHF-UCL
Negative regulation of gap junction assemblydefinition[GO:1903597]  
1
  • Ortholog Curator
Neutrophil mediated immunitydefinition[GO:0002446]  
1
  • Ortholog Curator
Peptide catabolic processdefinition[GO:0043171]  
2
  • BHF-UCL
Positive regulation of peptidyl-cysteine S-nitrosylationdefinition[GO:2000170]  
1
  • Ortholog Curator
Positive regulation of peptidyl-tyrosine autophosphorylationdefinition[GO:1900086]  
1
  • Ortholog Curator
Positive regulation of protein tyrosine kinase activitydefinition[GO:0061098]  
1
  • Ortholog Curator
Regulation of angiotensin metabolic processdefinition[GO:0060177]  
1
  • BHF-UCL
Regulation of blood pressuredefinition[GO:0008217]  
2
  • BHF-UCL
  • Ortholog Curator
Regulation of hematopoietic stem cell proliferationdefinition[GO:1902033]  
2
  • BHF-UCL
  • Ortholog Curator
Regulation of renal output by angiotensindefinition[GO:0002019]  
1
  • BHF-UCL
Regulation of smooth muscle cell migrationdefinition[GO:0014910]  
1
  • Ortholog Curator
Regulation of systemic arterial blood pressure by renin-angiotensindefinition[GO:0003081]  
2
  • UniProtKB
  • BHF-UCL
Regulation of vasoconstrictiondefinition[GO:0019229]  
1
  • UniProtKB
Regulation of vasodilationdefinition[GO:0042312]  
1
  • BHF-UCL
Spermatogenesisdefinition[GO:0007283]  
1
  • Ortholog Curator
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.  
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  • UniProtKB
It requires the following cofactors
 Zn(2+) : Binds 2 Zn(2+) ions per subunit.  
1
  • UniProtKB
 chloride : Binds 3 chloride ions per subunit.  
1
  • UniProtKB
Isoform  Testis-specific    Zn(2+) : Only binds 1 Zn(2+) ion per subunit.  
1
  • UniProtKB
It is regulated in the following manner
Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat.  
1
  • UniProtKB
 
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 Angiotensinogen to Angiotensins  REACT_147707  
 
More information is available from:
Note 
Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction.  
1
  • UniProtKB
The glycosidase activity probably uses different active site residues than the metalloprotease activity.  
1
  • UniProtKB
 

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