UniProt functional annotation for P12821

UniProt code: P12821.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
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: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Note=Binds 2 Zn(2+) ions per subunit.;
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.;
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 {ECO:0000269|PubMed:11076943, ECO:0000269|PubMed:12542396};
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}.
Induction: Up-regulated in failing heart. {ECO:0000269|PubMed:15151696, ECO:0000269|PubMed:15671045}.
Ptm: Phosphorylated by CK2 on Ser-1299; which allows membrane retention. {ECO:0000269|PubMed:12386153}.
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: 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.
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: 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.
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. {ECO:0000305}.
Sequence caution: Sequence=BAD92208.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.