MGP Database

MGP000798

UniProt Annotations

Entry Information

Gene Name	angiotensin I converting enzyme
Protein Entry	ACE_HUMAN
UniProt ID	P12821
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=4; Name=Somatic-1; IsoId=P12821-1; Sequence=Displayed; Name=Somatic-2; Synonyms=Soluble; IsoId=P12821-2; Sequence=VSP_029932, VSP_029933; Note=Incomplete sequence.; Name=Testis-specific; Synonyms=ACE-T; IsoId=P12821-3, P22966-1; Sequence=VSP_035120, VSP_035121; Note=Variant in position: 32:S->P (in dbSNP:rs4317). Variant in position: 49:S->G (in dbSNP:rs4318).; Name=4; IsoId=P12821-4; Sequence=VSP_054836, VSP_054837; Note=No experimental confirmation available.;
Biophysicochemical Properties	Kinetic parameters: KM=2.51 mM for Hip-His-Leu {ECO:0000269\|PubMed:11076943, ECO:0000269\|PubMed:12542396};
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	Isoform Testis-specific: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.;
Cofactor	Name=chloride; Xref=ChEBI:CHEBI:17996; Note=Binds 3 chloride ions per subunit.;
Cofactor	Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
Disease	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. {ECO:0000269\|PubMed:15277638}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease	Ischemic stroke (ISCHSTR) [MIM:601367]: 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. {ECO:0000269\|PubMed:15534175}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease	Microvascular complications of diabetes 3 (MVCD3) [MIM:612624]: 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. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease	Renal tubular dysgenesis (RTD) [MIM:267430]: 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). {ECO:0000269\|PubMed:16116425}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Enzyme Regulation	Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat.
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.
Induction	Up-regulated in failing heart. {ECO:0000269\|PubMed:15151696, ECO:0000269\|PubMed:15671045}.
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.
Ptm	Phosphorylated by CK2 on Ser-1299; which allows membrane retention. {ECO:0000269\|PubMed:12386153}.
Sequence Caution	Sequence=BAD92208.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
Similarity	Belongs to the peptidase M2 family. {ECO:0000305}.
Subcellular Location	Angiotensin-converting enzyme, soluble form: Secreted.
Subcellular Location	Cell membrane; Single-pass type I membrane protein. Cytoplasm {ECO:0000250}. Note=Detected in both cell membrane and cytoplasm in neurons. {ECO:0000250}.
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. {ECO:0000269\|PubMed:10924499, ECO:0000269\|PubMed:10969042, ECO:0000269\|PubMed:12459472, ECO:0000269\|PubMed:15671045}.
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";