Description: Homo sapiens angiotensin I converting enzyme (peptidyl-dipeptidase A) 1 (ACE), transcript variant 1, mRNA. RefSeq Summary (NM_000789): This gene encodes an enzyme involved in in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. ACE also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored proteins in testes. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2020]. Transcript (Including UTRs) Position: hg19 chr17:61,554,422-61,575,741 Size: 21,320 Total Exon Count: 25 Strand: + Coding Region Position: hg19 chr17:61,554,456-61,574,727 Size: 20,272 Coding Exon Count: 25
ID:ACE_HUMAN DESCRIPTION: RecName: Full=Angiotensin-converting enzyme; Short=ACE; EC=3.2.1.-; EC=3.4.15.1; AltName: Full=Dipeptidyl carboxypeptidase I; AltName: Full=Kininase II; AltName: CD_antigen=CD143; Contains: RecName: Full=Angiotensin-converting enzyme, soluble form; Flags: Precursor; FUNCTION: 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. CATALYTIC ACTIVITY: 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. COFACTOR: Binds 2 zinc ions per subunit. Isoform Testis-specific only binds 1 zinc ion per subunit. COFACTOR: Binds 3 chloride ions per subunit. ENZYME REGULATION: Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=2.51 mM for Hip-His-Leu; SUBCELLULAR LOCATION: Angiotensin-converting enzyme, soluble form: Secreted. SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in lung, kidney, heart, gastrointestinal system and prostate. Isoform Testis-specific is expressed in spermatocytes and adult testis. INDUCTION: Up-regulated in failing heart. PTM: Phosphorylated by CK2 on Ser-1299; which allows membrane retention. DISEASE: Genetic variations in ACE may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. DISEASE: Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). DISEASE: Genetic variations in ACE are associated with susceptibility to microvascular complications of diabetes type 3 (MVCD3) [MIM:612624]. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new- onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. DISEASE: Defects in ACE are a cause of susceptibility to intracerebral hemorrhage (ICH) [MIM:614519]. A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke. MISCELLANEOUS: Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction. MISCELLANEOUS: The glycosidase activity probably uses different active site residues than the metalloprotease activity. SIMILARITY: Belongs to the peptidase M2 family. SEQUENCE CAUTION: Sequence=BAD92208.1; Type=Erroneous initiation; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACE"; WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and polymorphism database; URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=ACE";
ACE activity Kong, X. D. et al. 2004, [ACE gene polymorphisms associated with serum ACE activity in the Henan Hans of China], Yi chuan xue bao. 2004 Nov;31(11):1196-202.
[PubMed 15651670]
This findings suggested that serum ACE levels were partially determined by genetic predisposition (the polymorphism of ACE gene). Haplotype B may be related to the quantitative trait loci of high-level activity,whereas high-resolution genetic mapping linked with ACE was still necessary to characterize definitely the functional variants.
ACEI-related cough Yau-Jiunn Lee 2001, Angiotensin-converting enzyme gene insertion/deletion, not bradykinin B2 receptor -58T/C gene polymorphism, associated with angiotensin-converting enzyme inhibitor-related cough in Chinese female patients with non-insulin-dependent diabetes mellitus., Metabolism: clinical and experimental. 2001 Nov;50(11):1346-50.
[PubMed 11699055]
In conclusion, our results indicate that Chinese diabetic female subjects are susceptible to ACEI-related cough, and this susceptibility may be genetically predetermined.
affective disorder Arinami T et al. 1996, An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders., Biological psychiatry. 1996 Dec;40(11):1122-7.
[PubMed 8931914]
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P12821
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.