Angiotensin-converting enzyme

Angiotensin-converting enzyme

Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity15615692,20826823,2558109,4322742,7523412,7683654. Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates10913258,1320019,1851160,19773553,7683654,7876104. Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin11432860,1851160,19773553,23056909,4322742. Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response15615692,2558109,4322742,6055465,6270633,7683654. Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins15615692,6208535,6270633,656131. Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu)2982830,6270633,656131. Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP)26403559,7876104,8257427,8609242. Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR118077343. Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation11604391,16154999,19773553. Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones10336644,2983326,7683654,9371719. Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region10336644,19773553,7876104

Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region

Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility1651327,1668266. In contrast to somatic isoforms, only contains one catalytic domain1651327,1668266. Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates1668266,24297181. The identity of substrates that are needed for male fertility is unknown (By similarity). May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety. The GPIase activity was reported to be essential for the egg-binding ability of the sperm (By similarity). This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect (By similarity)

Quoted from UniProt’s FUNCTION annotation for P12821 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Vesicles

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cell membrane · Cytoplasm · Secreted

Expression by cell type

Single cell type RNA, the 2 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Enterocytes90.1 nCPM
• Late spermatids55.1 nCPM

Expression by tissue

The tissues this gene is enriched in, by consensus RNA. A tissue absent from this list is one the Atlas does not call specific for this gene, which is not the same as absent from it.

• intestine249.7 nTPM
• testis96.4 nTPM