Ace
entrez
11421
canonical
uniprot
P09470
canonical
ensembl
ENSMUSG00000020681
resolver
ensp
ENSMUSP00000001963
resolver
ensp
ENSMUSP00000001964
resolver
ensp
ENSMUSP00000119826
resolver
genesymbol
Ace
resolver
genesymbol_syn
Dcp1
resolver
uniprot
P22967
resolver
uniprot
Q3TU20
resolver
uniprot
Q6GTS2
resolver
uniprot_entry
ACE_MOUSE
resolver
uniprot_entry
Q3TU20_MOUSE
resolver
uniprot_sec
P22967
resolver
uniprot_sec
Q6GTS2
resolver
activity_regulation
ACTIVITY REGULATION: The dipeptidyl carboxypeptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat (PubMed:15665832, PubMed:35201898). The N-terminal catalytic domain, but not the C-terminal catalytic domain, is specifically inhibited by the phosphinic peptide RXP 407 (PubMed:11303049). {ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:15665832, ECO:0000269|PubMed:35201898}.; ACTIVITY REGULATION: [Isoform Testis-specific]: The putative GPIase activity is nearly insensitive to captopril. {ECO:0000269|PubMed:15665832}.
uniprot
proteins
amino_acid_sequence
MGAASGQRGRWPLSPPLLMLSLLVLLLQPSPAPALDPGLQPGNFSPDEAGAQLFAESYNSSAEVVMFQSTVASWAHDTNITEENARRQEEAALVSQEFAEVWGKKAKELYESIWQNFTDSKLRRIIGSIRTLGPANLPLAQRQQYNSLLSNMSRIYSTGKVCFPNKTATCWSLDPELTNILASSRSYAKLLFAWEGWHDAVGIPLKPLYQDFTAISNEAYRQDDFSDTGAFWRSWYESPSFEESLEHIYHQLEPLYLNLHAYVRRALHRRYGDKYVNLRGPIPAHLLGDMWAQSWENIYDMVVPFPDKPNLDVTSTMVQKGWNATHMFRVSEEFFTSLGLSPMPPEFWAESMLEKPTDGREVVCHASAWDFYNRKDFRIKQCTRVTMEQLATVHHEMGHVQYYLQYKDLHVSLRRGANPGFHEAIGDVLALSVSTPAHLHKIGLLDHVTNDIESDINYLLKMALEKIAFLPFGYLVDQWRWGVFSGRTPPSRYNFDWWYLRTKYQGICPPVARNETHFDAGAKFHIPNVTPYIRYFVSFVLQFQFHQALCKEAGHQGPLHQCDIYQSAQAGAKLKQVLQAGCSRPWQEVLKDLVGSDALDAKALLEYFQPVSQWLEEQNQRNGEVLGWPENQWRPPLPDNYPEGIDLETDEAKADRFVEEYDRTAQVLLNEYAEANWQYNTNITIEGSKILLEKSTEVSNHTLKYGTRAKTFDVSNFQNSSIKRIIKKLQNLDRAVLPPKELEEYNQILLDMETTYSLSNICYTNGTCMPLEPDLTNMMATSRKYEELLWAWKSWRDKVGRAILPFFPKYVEFSNKIAKLNGYTDAGDSWRSLYESDNLEQDLEKLYQELQPLYLNLHAYVRRSLHRHYGSEYINLDGPIPAHLLGNMWAQTWSNIYDLVAPFPSAPNIDATEAMIKQGWTPRRIFKEADNFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHPSAWDFYNGKDFRIKQCTSVNMEDLVIAHHEMGHIQYFMQYKDLPVTFREGANPGFHEAIGDIMALSVSTPKHLYSLNLLSTEGSGYEYDINFLMKMALDKIAFIPFSYLIDQWRWRVFDGSITKENYNQEWWSLRLKYQGLCPPVPRSQGDFDPGSKFHVPANVPYVRYFVSFIIQFQFHEALCRAAGHTGPLHKCDIYQSKEAGKLLADAMKLGYSKPWPEAMKLITGQPNMSASAMMNYFKPLTEWLVTENRRHGETLGWPEYNWAPNTARAEGSTAESNRVNFLGLYLEPQQARVGQWVLLFLGVALLVATVGLAHRLYNIRNHHSLRRPHRGPQFGSEVELRHS
uniprot
proteins
ec_number
3.4.15.1
uniprot
proteins
function
FUNCTION: 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 plasticity (PubMed:11723129, PubMed:12777443, PubMed:14757757, PubMed:16270063, PubMed:35201898, PubMed:7753170, PubMed:8642790, PubMed:9231832). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (PubMed:11303049). 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 angiotensin (PubMed:11303049, PubMed:14757757, PubMed:9231832). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (By similarity). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (By similarity). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (PubMed:35201898). 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 (PubMed:35201898). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (PubMed:35201898). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (PubMed:11303049). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (By similarity). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (By similarity). 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 (PubMed:11303049). {ECO:0000250|UniProtKB:P12821, ECO:0000269|PubMed:11303049, ECO:0000269|PubMed:11723129, ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:14757757, ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:35201898, ECO:0000269|PubMed:7753170, ECO:0000269|PubMed:8642790, ECO:0000269|PubMed:9231832}.; FUNCTION: [Angiotensin-converting enzyme, soluble form]: Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region. {ECO:0000250|UniProtKB:P12821}.; FUNCTION: [Isoform Testis-specific]: Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility (PubMed:1651914, PubMed:9482924). In contrast to somatic isoforms, only contains one catalytic domain (PubMed:16270063). Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates (PubMed:16270063). The identity of substrates that are needed for male fertility is unknown (PubMed:16270063). Isoform Testis-specific and isoform Somatic have distinct activities and cannot completely compensate for the loss of the other when expressed in somatic tissues or testis (PubMed:10831599, PubMed:11723129, PubMed:12777443, PubMed:16270063, PubMed:9664078). May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety (PubMed:15665832). The GPIase activity was reported to be essential for the egg-binding ability of the sperm (PubMed:15665832). This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect (PubMed:16270063). {ECO:0000269|PubMed:10831599, ECO:0000269|PubMed:11723129, ECO:0000269|PubMed:12777443, ECO:0000269|PubMed:15665832, ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:1651914, ECO:0000269|PubMed:9482924, ECO:0000269|PubMed:9664078}.
uniprot
proteins
mass_dalton
150918
uniprot
proteins
mutagenesis
MUTAGEN 395..399; /note="HEMGH->KEMGK: In ACE(7/7) mutant; knockin mice have normal blood pressure, renal function, and hematocrit. Knockin mice show normal plasma levels of angiotensin II but an elevation of plasma and urine peptide N-acetyl-SDKP (AcSDKP)."; /evidence="ECO:0000269|PubMed:14757757"; MUTAGEN 993; /note="H->K: Abolishes peptidase activity but no effect on GPIase activity; when associated with K-997."; /evidence="ECO:0000269|PubMed:15665832"; MUTAGEN 994; /note="E->D: Abolishes peptidase activity but no effect on GPIase activity."; /evidence="ECO:0000269|PubMed:15665832"; MUTAGEN 997; /note="H->K: Abolishes peptidase activity but no effect on GPIase activity; when associated with K-993."; /evidence="ECO:0000269|PubMed:15665832"; MUTAGEN P09470-2:413..417; /note="HEMGH->KEMGK: Abolished dipeptidyl carboxypeptidase activity. Knockin mice expressed in a knockout background display defects in male fertility. They however show normal blood pressure and kidney morphology."; /evidence="ECO:0000269|PubMed:16270063, ECO:0000269|PubMed:17135368
uniprot
proteins
post_translational_modification
PTM: [Angiotensin-converting enzyme, soluble form]: Produced following proteolytic cleavage by secretase enzymes that cleave the transmembrane form in the juxtamembrane stalk region upstream of the transmembrane region. Cleavage can take place at different sites of the juxtamembrane stalk region. {ECO:0000250|UniProtKB:P12821}.; PTM: Phosphorylated by CK2 on Ser-1305; which allows membrane retention (By similarity). Phosphorylated on tyrosine residues on its extracellular part, promoting cleavage by secretase enzymes and formation of the soluble form (Angiotensin-converting enzyme, soluble form) (By similarity). {ECO:0000250|UniProtKB:P12821, ECO:0000250|UniProtKB:P12822}.
uniprot
proteins
protein_family
Peptidase M2 family
uniprot
proteins
pubmed
10831599
uniprot
proteins
pubmed
11303049
uniprot
proteins
pubmed
11723129
uniprot
proteins
pubmed
12777443
uniprot
proteins
pubmed
14757757
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15665832
uniprot
proteins
pubmed
16154999
uniprot
proteins
pubmed
16270063
uniprot
proteins
pubmed
1651914
uniprot
proteins
pubmed
16944957
uniprot
proteins
pubmed
17114649
uniprot
proteins
pubmed
17135368
uniprot
proteins
pubmed
17634445
uniprot
proteins
pubmed
18443281
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2164636
uniprot
proteins
pubmed
23535237
uniprot
proteins
pubmed
2545691
uniprot
proteins
pubmed
2835538
uniprot
proteins
pubmed
2841312
uniprot
proteins
pubmed
35201898
uniprot
proteins
pubmed
7753170
uniprot
proteins
pubmed
8642790
uniprot
proteins
pubmed
9231832
uniprot
proteins
pubmed
9482924
uniprot
proteins
pubmed
9664078
uniprot
proteins
sequence_length
1312
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform Somatic]: Cell membrane {ECO:0000269|PubMed:23535237}; Single-pass type I membrane protein {ECO:0000255}. Cytoplasm {ECO:0000269|PubMed:23535237}. Note=Detected in both cell membrane and cytoplasm in neurons. {ECO:0000269|PubMed:23535237}.; SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]: Secreted {ECO:0000250|UniProtKB:P12821}.; SUBCELLULAR LOCATION: [Isoform Testis-specific]: Cell membrane {ECO:0000250|UniProtKB:P12821}; Single-pass type I membrane protein {ECO:0000255}. Secreted {ECO:0000250|UniProtKB:P12821}. Note=The testis-specific isoform can be cleaved before the transmembrane region, releasing a soluble form. {ECO:0000250|UniProtKB:P12821}.
uniprot
proteins
transmembrane_region
TRANSMEM 1265..1281; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins