Protein: Angiotensin-converting enzyme (ACE) (EC 3.4.15.1) (Dipeptidyl carboxypeptidase I) (Kininase II) [Cleaved into: Angiotensin-converting enzyme, soluble form] (F1RRW5)
Organism: Sus scrofa (Pig)
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 (By similarity). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (By similarity). 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 (By similarity). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response. 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) (By similarity). 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) (By similarity). 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 (By similarity).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P12821}; Single-pass type I membrane protein {ECO:0000255}. Cytoplasm {ECO:0000250|UniProtKB:P09470}. Note=Detected in both cell membrane and cytoplasm in neurons. {ECO:0000250|UniProtKB:P09470}.; SUBCELLULAR LOCATION: [Angiotensin-converting enzyme, soluble form]: Secreted {ECO:0000250|UniProtKB:P12821}.
Interaction partners:
- Angiotensinogen
- Kininogen 1.
- renin
- Angiotensin-converting enzyme
- Type-1 angiotensin II receptor
- Urea transporter 1
- Aminopeptidase N
- Dipeptidyl peptidase 4
- Mineralocorticoid receptor
- Neprilysin
Sequence:
MGAASGCRWPWPPLLPLLLMLLLPPPPLPVALALDSALQPGNFTADEAGAEDFAQSFNSSSEQVLFQSTAASWAHDTNITEENARRQEEAALISQEFSEVWGQKAKALYDPIWQNFTSRTLRRIIGVVRTLGSANLSPAKRQQYNSLLSNMTRIYSTAKVCFPNKTATCWSLDPELTNILATSRSYTLLLYAWEGWHNAAGIPLKPLYQDFTALSNEAYKQDGFSDTGAYWRSLYDSPTFTEDLERLYHQLEPLYLNLHAYVRRALHRQYGDRFINLRGPIPAHLLGNMWAQSWNNIYDMVVPFPGKPSLDVTSAMVQKGWNVTHMFRVAEEFFTSLGLLPMPPEFWAESMLEKPSDGREVVCHASAWDFYNRKDFRIKQCTQVTMDQLSTVHHEMGHVQYYLQYKDQHVSLRRGANPGFHEAIGDVLALSVSTPAHLHKIGLLDHVTSDWESDINYLLKMALEKIAFLPFGYLVDQWRWGVFSGRTPPLYNYDWWYLRTKYQGVCPPVVRNETHFDAGAKYHVPNVTPYIRYFVSFILQFQFHQALCKEAGHQGPLHQCDIYQSTRAGAKLRAVLQAGSSRPWQEVLKDMVGSGALDAQPLLDYFQPVTQWLEEQNQRSGDILGWPEYQWRPPMPDNYPEGIDLVSDEAEASKFVEEYDRRSQVVLNEYAEANWDYNTNITAEGSKRVLEKSTQMANHTVKYGIWARKFDVANIQNFTLKRMIKKIQDLERAALPFKELEEYNQILLDMETAYSVASVCHANSTCLQLEPDLTNLMATSRSYEELLWAWKGWRDKVGRAILPYFPKYVELTNKAARLNGYEDGGDAWRAAYEMPFLEQELEQLFQELQPLYLNLHAYVRRALHHHYGPEHINLEGPIPAHLLGNMWAQTWSNIYDLVVPFPSASKMDASEAMINQGWTPQRMFKEADNFFTSLGLLPVPPEFWNKSMLEKPTDGREVVCHASAWDFFNGKDFRIKQCTTVNMEDLVVAHHEMGHIQYFMQYKDLPVTFREGANPGFHEAIGDVLALSVSTPKHLRSINLLKSEDDGYEEDINFLMKMALDKVAFVPFSYLVDQWRWRVFDRSITKENYNQEWWSLRLKYQGLCPPVARSQGDFDPGAKFHIPSSVPYIRYFVSFIIQFQFHEALCQAAGHKGPLHKCDIYQSKEAGRRLADAMKLGLSKPWPEAMQLITGQPNVSASAMMTYFKPLLDWLVTENGRHGEKLGWPQYNWTPNSARLEGSFAGTGRVNFLGLNLEEQQARVGQWVLLFLGVTLLVATMGLTQRLFSIRHQILRRTHRGPQFGSEVELRHS