Angiotensin-converting enzyme

List of PDB id codes
1O86, 1O8A, 1UZE, 1UZF, 2C6F, 2C6N, 2IUL, 2IUX, 2OC2, 2XY9, 2XYD, 2YDM, 3BKK, 3BKL, 3L3N, 3NXQ, 4APH, 4APJ, 4BXK, 4BZR, 4BZS, 4C2N, 4C2O, 4C2P, 4C2Q, 4C2R, 4CA5, 4CA6

Identifiers

Symbols

ACE ; ACE1; CD143; DCP; DCP1; ICH; MVCD3

External IDs

OMIM: 106180 MGI: 87874 HomoloGene: 37351 ChEMBL: 1808 GeneCards: ACE Gene

EC number

3.4.15.1

Gene ontology
Molecular function	• actin binding • endopeptidase activity • carboxypeptidase activity • protein binding • drug binding • metallopeptidase activity • exopeptidase activity • tripeptidyl-peptidase activity • peptidyl-dipeptidase activity • zinc ion binding • chloride ion binding • mitogen-activated protein kinase kinase binding • bradykinin receptor binding • mitogen-activated protein kinase binding
Cellular component	• extracellular region • extracellular space • lysosome • endosome • plasma membrane • external side of plasma membrane • integral component of membrane • extracellular exosome
Biological process	• kidney development • blood vessel remodeling • angiotensin maturation • angiotensin catabolic process in blood • regulation of renal output by angiotensin • neutrophil mediated immunity • antigen processing and presentation of peptide antigen via MHC class I • regulation of systemic arterial blood pressure by renin-angiotensin • spermatogenesis • regulation of blood pressure • regulation of smooth muscle cell migration • regulation of vasoconstriction • mononuclear cell proliferation • regulation of vasodilation • hormone catabolic process • peptide catabolic process • cellular protein metabolic process • beta-amyloid metabolic process • arachidonic acid secretion • heart contraction • regulation of angiotensin metabolic process • hematopoietic stem cell differentiation • positive regulation of protein tyrosine kinase activity • cell proliferation in bone marrow • positive regulation of peptidyl-tyrosine autophosphorylation • regulation of hematopoietic stem cell proliferation • negative regulation of gap junction assembly • positive regulation of peptidyl-cysteine S-nitrosylation
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 17:
63.48 – 63.5 Mb

Chr 11:
105.97 – 105.99 Mb

PubMed search

Angiotensin-converting enzyme (EC 3.4.15.1), or "ACE" indirectly increases blood pressure by causing blood vessels to constrict. It does that by converting angiotensin I to angiotensin II, which constricts the vessels. For this reason, drugs known as ACE inhibitors are used to lower blood pressure.

ACE is also known by the following names: dipeptidyl carboxypeptidase I, peptidase P, dipeptide hydrolase, peptidyl dipeptidase, angiotensin converting enzyme, kininase II, angiotensin I-converting enzyme, carboxycathepsin, dipeptidyl carboxypeptidase, "hypertensin converting enzyme" peptidyl dipeptidase I, peptidyl-dipeptide hydrolase, peptidyldipeptide hydrolase, endothelial cell peptidyl dipeptidase, peptidyl dipeptidase-4, PDH, peptidyl dipeptide hydrolase, and DCP.

ACE, angiotensin I and angiotensin II are part of the renin-angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. ACE is secreted in the lungs and kidneys by cells in the endothelium (inner layer) of blood vessels.^[1]

Functions

Schematic diagram of the renin–angiotensin–aldosterone system

Anatomical diagram of the renin-angiotensin system, showing the role of ACE at the lungs.^[2]

It has two primary functions:

ACE catalyses the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor in a substrate concentration-dependent manner.^[3]
ACE degrades bradykinin, a potent vasodilator, and other vasoactive peptides.^[4]

These two actions make ACE inhibition a goal in the treatment of conditions such as high blood pressure, heart failure, diabetic nephropathy, and type 2 diabetes mellitus. Inhibition of ACE (by ACE inhibitors) results in the decreased formation of angiotensin II and decreased metabolism of bradykinin, leading to systematic dilation of the arteries and veins and a decrease in arterial blood pressure. In addition, inhibiting angiotensin II formation diminishes angiotensin II-mediated aldosterone secretion from the adrenal cortex, leading to a decrease in water and sodium reabsorption and a reduction in extracellular volume.^[5]

Kininase II is the same as angiotensin-converting enzyme. Thus, the same enzyme (ACE) that generates a vasoconstrictor (ANG II) also disposes of vasodilators (bradykinin).^[6]

Genetics and C and N domains function

The ACE gene, ACE, encodes two isozymes. The somatic isozyme is expressed in many tissues, mainly in the lung, including vascular endothelial cells, epithelial kidney cells, and testicular Leydig cells, whereas the germinal is expressed only in sperm. Brain tissue has ACE enzyme, which takes part in local RAAS and converts Aβ42 (which aggregates into plaques) to Aβ40 (which is thought to be less toxic) forms of beta amyloid. The latter is predominantly a function of N domain portion on the ACE enzyme. ACE inhibitors that cross the blood–brain barrier and have preferentially select N terminal activity may, therefore, cause accumulation of Aβ42 and progression of dementia.

Pathology

Elevated levels of ACE are found in sarcoidosis, and are used in diagnosing and monitoring this disease. Elevated levels of ACE are also found in leprosy, hyperthyroidism, acute hepatitis, primary biliary cirrhosis, diabetes mellitus, multiple myeloma, osteoarthritis, amyloidosis, Gaucher disease, pneumoconiosis, histoplasmosis, miliary tuberculosis.
Serum levels are decreased in renal disease, obstructive pulmonary disease, and hypothyroidism.

Influence on athletic performance

ACE gene is a I/D polymorphism leading to the presence(I) or absence (D) the carriers of the ACE insertion allele of an alu repeat in intron 16 of the gene.^[7] With the insertion, observed higher maximum oxygen uptake (VO2max), increase in training, and increased muscle when paired with individuals carrying the deletion allele.
Individuals with the insertion are associated with long distance and endurance events. This is seen in studies that suggest that it is due to lower levels of angiotensin II. The deletion of the Alu increases angiotensin II that in turn increases the vasoconstriction of blood vessels. This is observed in short distance events and seen mostly in swimmers.^[8]

References

↑ Kierszenbaum, Abraham L. (2007). Histology and cell biology: an introduction to pathology. Mosby Elsevier. ISBN 0-323-04527-8.
↑ Page 866-867 (Integration of Salt and Water Balance) and 1059 (The Adrenal Gland) in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. p. 1300. ISBN 1-4160-2328-3.
↑ Zhang R, Xu X, Chen T, Li L, Rao P (May 2000). "An assay for angiotensin-converting enzyme using capillary zone electrophoresis". Anal. Biochem. 280 (2): 286–90. doi:10.1006/abio.2000.4535. PMID 10790312.
↑ Imig JD (March 2004). "ACE Inhibition and Bradykinin-Mediated Renal Vascular Responses: EDHF Involvement". Hypertension 43 (3): 533–5. doi:10.1161/01.HYP.0000118054.86193.ce. PMID 14757781.
↑ Klabunde RE. "ACE-inhibitors". Cardiovascular Pharmacology Concepts. cvpharmacology.com. Retrieved 2009-03-26.
↑ Boron and Boulpaed Medical Physiology 2nd edition Updated
↑ Wang P, Fedoruk MN, Rupert JL (2008). "Keeping pace with ACE: are ACE inhibitors and angiotensin II type 1 receptor antagonists potential doping agents?". Sports Med 38 (12): 1065–79. doi:10.2165/00007256-200838120-00008. PMID 19026021.
↑ Costa AM, Silva AJ, Garrido ND, Louro H, de Oliveira RJ, Breitenfeld L (August 2009). "Association between ACE D allele and elite short distance swimming". Eur. J. Appl. Physiol. 106 (6): 785–90. doi:10.1007/s00421-009-1080-z. PMID 19458960.

External links

Proteopedia Angiotensin-converting_enzyme - the Angiotensin-Converting Enzyme Structure in Interactive 3D
Angiotensin Converting Enzyme at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery

1o86: CRYSTAL STRUCTURE OF HUMAN ANGIOTENSIN CONVERTING ENZYME IN COMPLEX WITH LISINOPRIL.

1o8a: CRYSTAL STRUCTURE OF HUMAN ANGIOTENSIN CONVERTING ENZYME (NATIVE).

1uze: COMPLEX OF THE ANTI-HYPERTENSIVE DRUG ENALAPRILAT AND THE HUMAN TESTICULAR ANGIOTENSIN I-CONVERTING ENZYME

1uzf: COMPLEX OF THE ANTI-HYPERTENSIVE DRUG CAPTOPRIL AN THE HUMAN TESTICULAR ANGIOTENSIN I-CONVERTING ENZYME

2c6f: STRUCTURE OF HUMAN SOMATIC ANGIONTENSIN-I CONVERTING ENZYME N DOMAIN

2c6n: STRUCTURE OF HUMAN SOMATIC ANGIONTENSIN-I CONVERTING ENZYME N DOMAIN WITH LISINOPRIL

2iul: HUMAN TACE G13 MUTANT

2iux: HUMAN TACE MUTANT G1234

2oc2: Structure of testis ACE with RXPA380

Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50

51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100

101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150

151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200

201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249

251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299

301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

Hydrolase: proteases (EC 3.4)

3.4.11-19: Exopeptidase

3.4.11	Aminopeptidase Alanine Arginyl Aspartyl Cystinyl Leucyl Glutamyl Methionyl 1 2 O

3.4.13	Dipeptidase 1 2 3

3.4.14	Dipeptidyl peptidase Cathepsin C Dipeptidyl peptidase-4 Tripeptidyl peptidase Tripeptidyl peptidase I Tripeptidyl peptidase II

3.4.15	Angiotensin-converting enzyme

3.4.16	Serine type carboxypeptidases: Cathepsin A DD-transpeptidase

3.4.17	Metalloexopeptidases Carboxypeptidase A A2 B C E Glutamate II

Other/ungrouped	Metalloexopeptidase

3.4.21-25: Endopeptidase

Other/ungrouped: Amyloid precursor protein secretase

3.4.99: Unknown

Staphylokinase

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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