Ace (rat, UniProt P47820) - manual literature synthesis
Manual
Ace (rat, UniProt P47820) - manual literature synthesis
No deep-research provider was run for this gene. This file is a manual synthesis
written by the reviewer from the cached publications in publications/ and the
UniProt record Ace-uniprot.txt. Every claim carries its provenance.
Identity and structure
- Rat Ace encodes somatic angiotensin I-converting enzyme (ACE, kininase II,
EC 3.4.15.1), a 1,313-residue type I membrane ectoenzyme
PMID:8292044.
- The somatic enzyme has two homologous zinc metallopeptidase (peptidase M2)
domains, each with its own active site
[UniProtKB:P47820 "Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates"];
[UniProtKB:P47820 "Belongs to the peptidase M2 family."].
- Topology: signal peptide 1-35, extracellular 36-1265, single TM helix
1266-1282, short cytoplasmic tail [UniProtKB:P47820 FT TOPO_DOM/TRANSMEM].
- A soluble (plasma) form is generated by juxtamembrane shedding
[UniProtKB:P47820 "Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region."].
- A testis-specific isoform (germinal ACE, ACE-T), produced from an alternative
intragenic promoter, contains only the C-domain and is needed for male fertility
[UniProtKB:P47820 "Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility."].
In rat it is on the sperm midpiece and is completely shed when sperm enter the
epididymis PMID:12444051.
- Cofactors: zinc (two per somatic subunit) and chloride activation
[UniProtKB:P47820 "Note=Binds 2 Zn(2+) ions per subunit."];
[UniProtKB:P47820 "The dipeptidyl carboxypeptidase activity is strongly activated by chloride."].
Molecular function
- Peptidyl-dipeptidase (dipeptidyl carboxypeptidase): releases C-terminal
dipeptides from oligopeptides
[UniProtKB:P47820 "Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins"].
- Rat enzyme, direct biochemistry:
- Rat CSF peptidyl dipeptidase converts Ang I to Ang II and degrades bradykinin
sequentially PMID:2172462.
- Rat striatal synaptic membranes: ACE converts Met-enkephalin-Arg6-Phe7 to
Met-enkephalin PMID:20487892.
- ACE is the dominant kininase in rat plasma
PMID:11299220.
- Rat intestinal brush-border ACE hydrolyses C-terminal prolyl peptides and acts
as a digestive peptidase PMID:2827504.
- Hemopressin and related hemoglobin peptides interact with ACE
PMID:12500972.
- Tissue ACE in rat organs hydrolyses Hip-His-Leu and the N-domain-selective
substrate Abz-SDK(Dnp)P PMID:16148611.
- Substrates by similarity to human/mouse ACE (UniProt): substance P,
neurotensin, AcSDKP (N-domain), amyloid-beta (N-domain), GnRH, cholecystokinin
[UniProtKB:P47820 "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 region"].
Physiology (rat)
- Blood pressure: Ace lies at the Bp1 hypertension QTL of SHRSP
PMID:1655275,
although no functional coding difference was found between SHRSP and WKY
PMID:8292044.
Antisense knock-down of Ace lowered blood pressure in SHR
PMID:10506486.
Ace is the most likely chromosome-10 modifier of malignant hypertension and
end-organ damage in Ren2 transgenic rats; serum Ace activity and protein track
the QTL PMID:19307186.
The authors propose that reduced Ace, through AcSDKP accumulation, mitigates
damage PMID:19307186.
- Ang-(1-7) is a further ACE substrate in rat vasculature
PMID:10642323.
- Expression is regulated developmentally and by many stimuli (thyroid hormone,
glucocorticoids, aldosterone, shear stress, glucose, hypoxia, ACE inhibitors);
these are regulatory inputs to Ace, not processes Ace performs
PMID:7977726, PMID:1659346, PMID:11447075, PMID:9048650, PMID:17626897, PMID:14527966, PMID:9495881.
- Many rat GO annotations derive from ACE-inhibitor pharmacology (captopril,
enalapril, perindopril, ramipril) with downstream readouts (apoptosis, LPS
response, neurogenesis, feeding, angiogenesis, organ regeneration, fetal growth).
These document indirect consequences of Ang II/kinin balance rather than
processes executed by ACE.
Localization