Human Gene ACE (ENST00000290866.10)
  Description: Homo sapiens angiotensin I converting enzyme (ACE), transcript variant 5, mRNA. (from RefSeq NM_001382701)
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].
Gencode Transcript: ENST00000290866.10
Gencode Gene: ENSG00000159640.17
Transcript (Including UTRs)
   Position: hg38 chr17:63,477,061-63,498,373 Size: 21,313 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg38 chr17:63,477,095-63,497,366 Size: 20,272 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:63,477,061-63,498,373)mRNA (may differ from genome)Protein (1306 aa)
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ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  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";

-  MalaCards Disease Associations
  MalaCards Gene Search: ACE
Diseases sorted by gene-association score: renal tubular dysgenesis* (643), myocardial infarction* (615), microvascular complications of diabetes 3* (605), hemorrhage, intracerebral* (332), renal dysplasia* (179), renal tubular dysgenesis, ace-related* (100), cardiovascular disease risk factor )* (45), anuria (33), nephrosclerosis (33), hypertensive heart disease (32), congestive heart failure (28), diastolic heart failure (26), renovascular hypertension (25), pulmonary edema (24), coronary restenosis (23), malignant hypertension (22), acute myocardial infarction (22), hypertensive retinopathy (22), coronary artery disease (20), cerebrovascular disease (19), hypersensitivity reaction type iv disease (19), acute mountain sickness (19), stroke, ischemic (18), systolic heart failure (18), neurosarcoidosis (18), vascular disease (18), moderate and severe traumatic brain injury (18), aortic coarctation (18), mesangioproliferative glomerulopathy (18), hepatoportal sclerosis (18), pediatric hypertension (17), peripheral artery disease (17), renal artery disease (17), heart disease (17), sarcoidosis 1 (16), skin sarcoidosis (16), alcoholic cardiomyopathy (15), kidney disease (15), angioedema (15), generalized atherosclerosis (15), uveoparotid fever (15), renal hypertension (14), diabetic neuropathy (14), pneumoconiosis due to talc (14), kaolin pneumoconiosis (14), mitral valve disease (14), end stage renal failure (13), systemic scleroderma (13), hyporeninemic hypoaldosteronism (13), hypertension, diastolic (13), autosomal dominant polycystic kidney disease (13), kanzaki disease (13), marek disease (12), peripheral vascular disease (12), oligohydramnios (12), ischemia (11), ischemic heart disease (11), angina pectoris (11), posterior urethral valves (11), intermittent claudication (11), interstitial nephritis (10), coronary stenosis (10), hypoaldosteronism (10), hypokalemia (10), nonarteritic anterior ischemic optic neuropathy (10), cerebral sarcoidosis (10), hyperaldosteronism (10), diabetes mellitus, insulin-dependent (10), loeffler syndrome (9), ischemic optic neuropathy (9), subacute cutaneous lupus erythematosus (9), hereditary angioedema (9), familial vesicoureteral reflux (9), granulomatous dermatitis (9), dilated cardiomyopathy (9), adult respiratory distress syndrome (9), cerebral atherosclerosis (9), vasculogenic impotence (9), rheumatic heart disease (8), renal artery obstruction (8), chronic kidney failure (8), microvascular complications of diabetes 5 (8), iga glomerulonephritis (8), mcardle disease (8), arterial calcification of infancy (8), fibromuscular dysplasia (8), atrial fibrillation (8), atrial septal defect 4 (8), acute anterolateral myocardial infarction (8), hypertensive encephalopathy (8), aortic atherosclerosis (8), syndrome of inappropriate antidiuretic hormone (7), aortic valve disease 1 (7), pseudohyperkalemia, familial, 2, due to red cell leak (7), anthracosilicosis (7), carotid artery disease (7), hepatorenal syndrome (7), urinary system disease (7), pulmonary sarcoidosis (7), obstructive sleep apnea (7), sleep apnea (7), idiopathic edema (7), vesicoureteral reflux (7), mitral valve insufficiency (7), tropical calcific pancreatitis (7), angiokeratoma of fordyce (7), silicosis (7), arteritic anterior ischemic optic neuropathy (7), ischemic colitis (7), hypertensive nephropathy (6), pure autonomic failure (6), limb ischemia (6), glucose metabolism disease (6), patella, chondromalacia of (6), cardiac arrest (6), carotid stenosis (6), hypertension, essential (6), fiedler's myocarditis (6), migraine with aura (6), membranous nephropathy (6), acquired metabolic disease (6), heart conduction disease (6), vascular dementia (6), pyelonephritis (6), optic nerve sheath meningioma (6), intermediate coronary syndrome (6), orthostatic proteinuria (6), neuroretinitis (5), aortic valve insufficiency (5), extrinsic cardiomyopathy (5), diabetes mellitus, noninsulin-dependent (5), sexual disorder (5), granulomatous hepatitis (5), subdural empyema (4), optic nerve neoplasm (4), multiple cranial nerve palsy (4), focal segmental glomerulosclerosis (4), follicular mucinosis (4), ureteral disease (4), artery disease (4), malignant essential hypertension (4), granulomatous angiitis (4), pulmonary hypertension (4), aortic valve disease 2 (4), cardiomyopathy (3), respiratory failure (3), lipid metabolism disorder (3), arteriosclerosis (3), connective tissue disease (2), mood disorder (2), intrinsic cardiomyopathy (2), hypersensitivity reaction disease (1), immune system disease (1), respiratory system disease (1), cardiomyopathy, familial hypertrophic (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 38.50 RPKM in Small Intestine - Terminal Ileum
Total median expression: 93.26 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -6.8034-0.200 Picture PostScript Text
3' UTR -401.801007-0.399 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR001548 - Peptidase_M2

Pfam Domains:
PF01401 - Angiotensin-converting enzyme

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1O86
- X-ray MuPIT

1O8A
- X-ray MuPIT

1UZE
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
1UZF - X-ray MuPIT 2C6F - X-ray MuPIT 2C6N - X-ray MuPIT
2IUL - X-ray MuPIT 2IUX - X-ray MuPIT 2OC2 - X-ray MuPIT
2XY9 - X-ray MuPIT 2XYD - X-ray MuPIT 2YDM - X-ray MuPIT
3BKK - X-ray MuPIT 3BKL - X-ray MuPIT 3L3N - X-ray MuPIT
3NXQ - X-ray MuPIT


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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl   
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003779 actin binding
GO:0004175 endopeptidase activity
GO:0004180 carboxypeptidase activity
GO:0005515 protein binding
GO:0008144 drug binding
GO:0008233 peptidase activity
GO:0008237 metallopeptidase activity
GO:0008238 exopeptidase activity
GO:0008240 tripeptidyl-peptidase activity
GO:0008241 peptidyl-dipeptidase activity
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0031404 chloride ion binding
GO:0031434 mitogen-activated protein kinase kinase binding
GO:0031711 bradykinin receptor binding
GO:0046872 metal ion binding
GO:0051019 mitogen-activated protein kinase binding
GO:0070573 metallodipeptidase activity

Biological Process:
GO:0001822 kidney development
GO:0001974 blood vessel remodeling
GO:0002003 angiotensin maturation
GO:0002019 regulation of renal output by angiotensin
GO:0002446 neutrophil mediated immunity
GO:0002474 antigen processing and presentation of peptide antigen via MHC class I
GO:0003081 regulation of systemic arterial blood pressure by renin-angiotensin
GO:0006508 proteolysis
GO:0007283 spermatogenesis
GO:0008217 regulation of blood pressure
GO:0014910 regulation of smooth muscle cell migration
GO:0019229 regulation of vasoconstriction
GO:0032943 mononuclear cell proliferation
GO:0042447 hormone catabolic process
GO:0043171 peptide catabolic process
GO:0050435 beta-amyloid metabolic process
GO:0050482 arachidonic acid secretion
GO:0060047 heart contraction
GO:0060177 regulation of angiotensin metabolic process
GO:0060218 hematopoietic stem cell differentiation
GO:0061098 positive regulation of protein tyrosine kinase activity
GO:0071838 cell proliferation in bone marrow
GO:0097746 regulation of blood vessel diameter
GO:1900086 positive regulation of peptidyl-tyrosine autophosphorylation
GO:1902033 regulation of hematopoietic stem cell proliferation
GO:1903597 negative regulation of gap junction assembly
GO:2000170 positive regulation of peptidyl-cysteine S-nitrosylation

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005768 endosome
GO:0005886 plasma membrane
GO:0009897 external side of plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AK296566 - Homo sapiens cDNA FLJ60635 complete cds, highly similar to Angiotensin-converting enzyme, somatic isoform precursor (EC 3.4.15.1).
AK309514 - Homo sapiens cDNA, FLJ99555.
JQ927553 - Homo sapiens isolate 11E1492 angiotensin I converting enzyme peptidyl-dipeptidase A 1 transcript variant (ACE) mRNA, complete cds, alternatively spliced.
AK300516 - Homo sapiens cDNA FLJ58944 complete cds, highly similar to Angiotensin-converting enzyme, somatic isoform precursor (EC 3.4.15.1).
AB208971 - Homo sapiens mRNA for angiotensin I converting enzyme isoform 1 precursor variant protein.
J04144 - Human angiotensin I-converting enzyme mRNA, complete cds.
HW061214 - JP 2012529430-A/89: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
JB252022 - Sequence 89 from Patent EP2440214.
LP764921 - Sequence 89 from Patent EP3276004.
S81361 - angiotensin I-converting enzyme [human, gastric HGT-1 cell line, mRNA Partial, 405 nt].
HW061213 - JP 2012529430-A/88: METHODS FOR TREATING CHRONIC KIDNEY DISEASE.
JB252021 - Sequence 88 from Patent EP2440214.
LP764920 - Sequence 88 from Patent EP3276004.
BC036375 - Homo sapiens angiotensin I converting enzyme (peptidyl-dipeptidase A) 1, mRNA (cDNA clone MGC:26566 IMAGE:4826875), complete cds.
X16295 - Human mRNA for angiotensin I converting enzyme (ACE).
AK302019 - Homo sapiens cDNA FLJ53482 complete cds, moderately similar to Angiotensin-converting enzyme, somatic isoform precursor (EC 3.4.15.1).
AK301988 - Homo sapiens cDNA FLJ61451 complete cds, highly similar to Angiotensin-converting enzyme, testis-specific isoform precursor (EC 3.4.15.1).
M26657 - Human testicular angiotensin converting enzyme mRNA, complete cds.
M29981 - Human aberrantly spliced angiotensin converting enzyme mRNA, complete cds.
M26658 - Human testicular angiotensin converting enzyme mRNA (5' variant), complete cds.
JD277476 - Sequence 258500 from Patent EP1572962.
JD338596 - Sequence 319620 from Patent EP1572962.
JD422743 - Sequence 403767 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04614 - Renin-angiotensin system
hsa05142 - Chagas disease
hsa05410 - Hypertrophic cardiomyopathy (HCM)

BioCarta from NCI Cancer Genome Anatomy Project
h_ace2Pathway - Angiotensin-converting enzyme 2 regulates heart function

Reactome (by CSHL, EBI, and GO)

Protein P12821 (Reactome details) participates in the following event(s):

R-HSA-2022398 ACE hydrolyzes Angiotensin-(1-9) to Angiotensin-(1-7)
R-HSA-2022405 ACE hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2065355 Secreted ACE hydrolyzes Angiotensin-(1-10) to Angiotensin-(1-8)
R-HSA-2022377 Metabolism of Angiotensinogen to Angiotensins
R-HSA-2980736 Peptide hormone metabolism
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: ACE_HUMAN, B0LPF0, B4DXI3, DCP, DCP1, E7EU16, ENST00000290866.1, ENST00000290866.2, ENST00000290866.3, ENST00000290866.4, ENST00000290866.5, ENST00000290866.6, ENST00000290866.7, ENST00000290866.8, ENST00000290866.9, NM_001382701, P12821, P22966, Q53YX9, Q59GY8, Q7M4L4, uc002jau.1, uc002jau.2, uc002jau.3, uc002jau.4, uc002jau.5
UCSC ID: ENST00000290866.10
RefSeq Accession: NM_000789
Protein: P12821 (aka ACE_HUMAN)
CCDS: CCDS11637.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.