ACE2_BOVIN
ID ACE2_BOVIN Reviewed; 804 AA.
AC Q58DD0;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Angiotensin-converting enzyme 2;
DE EC=3.4.17.23 {ECO:0000250|UniProtKB:Q9BYF1};
DE AltName: Full=ACE-related carboxypeptidase;
DE EC=3.4.17.- {ECO:0000250|UniProtKB:Q9BYF1};
DE Contains:
DE RecName: Full=Processed angiotensin-converting enzyme 2;
DE Flags: Precursor;
GN Name=ACE2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
CC -!- FUNCTION: Essential counter-regulatory carboxypeptidase of the renin-
CC angiotensin hormone system that is a critical regulator of blood
CC volume, systemic vascular resistance, and thus cardiovascular
CC homeostasis. Converts angiotensin I to angiotensin 1-9, a nine-amino
CC acid peptide with anti-hypertrophic effects in cardiomyocytes, and
CC angiotensin II to angiotensin 1-7, which then acts as a beneficial
CC vasodilator and anti-proliferation agent, counterbalancing the actions
CC of the vasoconstrictor angiotensin II. Also removes the C-terminal
CC residue from three other vasoactive peptides, neurotensin, kinetensin,
CC and des-Arg bradykinin, but is not active on bradykinin. Also cleaves
CC other biological peptides, such as apelins, casomorphins and dynorphin
CC A. Plays an important role in amino acid transport by acting as binding
CC partner of amino acid transporter SLC6A19 in intestine, regulating
CC trafficking, expression on the cell surface, and its catalytic
CC activity. {ECO:0000250|UniProtKB:Q9BYF1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=angiotensin II + H2O = angiotensin-(1-7) + L-phenylalanine;
CC Xref=Rhea:RHEA:26554, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:58506, ChEBI:CHEBI:58922; EC=3.4.17.23;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:26555;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=angiotensin I + H2O = angiotensin-(1-9) + L-leucine;
CC Xref=Rhea:RHEA:63532, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147350, ChEBI:CHEBI:147351;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63533;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bradykinin(1-8) + H2O = bradykinin(1-7) + L-phenylalanine;
CC Xref=Rhea:RHEA:63536, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:133069, ChEBI:CHEBI:147352;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63537;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + neurotensin = L-leucine + neurotensin-(1-12);
CC Xref=Rhea:RHEA:63540, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147362, ChEBI:CHEBI:147363;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63541;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + kinetensin = kinetensin-(1-8) + L-leucine;
CC Xref=Rhea:RHEA:63544, ChEBI:CHEBI:15377, ChEBI:CHEBI:57427,
CC ChEBI:CHEBI:147364, ChEBI:CHEBI:147365;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63545;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dynorphin A-(1-13) + H2O = dynorphin A-(1-12) + L-lysine;
CC Xref=Rhea:RHEA:63556, ChEBI:CHEBI:15377, ChEBI:CHEBI:32551,
CC ChEBI:CHEBI:147381, ChEBI:CHEBI:147383;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63557;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apelin-13 + H2O = apelin-12 + L-phenylalanine;
CC Xref=Rhea:RHEA:63564, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147395, ChEBI:CHEBI:147396;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63565;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[Pyr1]apelin-13 + H2O = [Pyr1]apelin-12 + L-phenylalanine;
CC Xref=Rhea:RHEA:63604, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147415, ChEBI:CHEBI:147416;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63605;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apelin-17 + H2O = apelin-16 + L-phenylalanine;
CC Xref=Rhea:RHEA:63608, ChEBI:CHEBI:15377, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:147421, ChEBI:CHEBI:147422;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63609;
CC Evidence={ECO:0000250|UniProtKB:Q9BYF1};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996; Evidence={ECO:0000250};
CC Note=Binds 1 Cl(-) ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Homodimer. Interacts with the catalytically active form of
CC TMPRSS2 (By similarity). Interacts with SLC6A19; this interaction is
CC essential for expression and function of SLC6A19 in intestine (By
CC similarity). Interacts with ITGA5:ITGB1 (By similarity). Probably
CC interacts (via endocytic sorting signal motif) with AP2M1; the
CC interaction is inhibited by phosphorylation of Tyr-780 (By similarity).
CC Interacts (via PDZ-binding motif) with SLC9A3R1 (via PDZ domains); the
CC interaction may enhance ACE2 membrane residence (By similarity).
CC {ECO:0000250|UniProtKB:Q8R0I0, ECO:0000250|UniProtKB:Q9BYF1}.
CC -!- INTERACTION:
CC Q58DD0; P0DTC2: S; Xeno; NbExp=3; IntAct=EBI-26998567, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: [Processed angiotensin-converting enzyme 2]:
CC Secreted {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9BYF1};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q8R0I0}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:Q9BYF1}. Apical cell membrane
CC {ECO:0000250|UniProtKB:Q9BYF1}. Note=Detected in both cell membrane and
CC cytoplasm in neurons. {ECO:0000250|UniProtKB:Q8R0I0}.
CC -!- DOMAIN: The cytoplasmic tail contains several linear motifs such as
CC LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would
CC allow interaction with proteins that mediate endocytic trafficking and
CC autophagy. {ECO:0000250|UniProtKB:Q9BYF1}.
CC -!- PTM: Proteolytic cleavage by ADAM17 generates a secreted form. Also
CC cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated. Phosphorylation at Tyr-780 probably inhibits
CC interaction with AP2M1 and enables interactions with proteins
CC containing SH2 domains. {ECO:0000250|UniProtKB:Q9BYF1}.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR EMBL; BT021667; AAX46514.1; -; mRNA.
DR RefSeq; XP_005228486.1; XM_005228429.3.
DR AlphaFoldDB; Q58DD0; -.
DR SMR; Q58DD0; -.
DR IntAct; Q58DD0; 3.
DR STRING; 9913.ENSBTAP00000045721; -.
DR BindingDB; Q58DD0; -.
DR MEROPS; M02.006; -.
DR PaxDb; Q58DD0; -.
DR GeneID; 509235; -.
DR CTD; 59272; -.
DR eggNOG; KOG3690; Eukaryota.
DR HOGENOM; CLU_014364_3_0_1; -.
DR InParanoid; Q58DD0; -.
DR OrthoDB; 422699at2759; -.
DR TreeFam; TF312861; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IBA:GO_Central.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IEA:InterPro.
DR GO; GO:0001618; F:virus receptor activity; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd06461; M2_ACE; 1.
DR InterPro; IPR031588; Collectrin_dom.
DR InterPro; IPR001548; Peptidase_M2.
DR PANTHER; PTHR10514; PTHR10514; 1.
DR Pfam; PF16959; Collectrin; 1.
DR Pfam; PF01401; Peptidase_M2; 1.
DR PRINTS; PR00791; PEPDIPTASEA.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Cell membrane; Cell projection; Chloride; Cytoplasm;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Phosphoprotein; Protease; Reference proteome; Secreted;
KW Signal; Transmembrane; Transmembrane helix; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..804
FT /note="Angiotensin-converting enzyme 2"
FT /id="PRO_0000028568"
FT CHAIN 18..707
FT /note="Processed angiotensin-converting enzyme 2"
FT /id="PRO_0000292266"
FT TOPO_DOM 18..739
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 740..760
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 761..804
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 651..658
FT /note="Essential for cleavage by ADAM17"
FT /evidence="ECO:0000250"
FT REGION 696..715
FT /note="Essential for cleavage by TMPRSS11D and TMPRSS2"
FT /evidence="ECO:0000250"
FT REGION 771..804
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 777..785
FT /note="LIR"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 780..784
FT /note="SH2-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 780..783
FT /note="Endocytic sorting signal"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 791..794
FT /note="PTB"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 802..804
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT COMPBIAS 775..804
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 374
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 504
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 168
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 272
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 344..345
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 373
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 377
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 401
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 476
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 480
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 514
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOD_RES 780
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 90
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 298
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 431
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 659
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 689
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 343..360
FT /evidence="ECO:0000250"
FT DISULFID 529..541
FT /evidence="ECO:0000250"
SQ SEQUENCE 804 AA; 93067 MW; E81570A96872A963 CRC64;
MTGSFWLLLS LVAVTAAQST TEEQAKTFLE KFNHEAEDLS YQSSLASWNY NTNITDENVQ
KMNEARAKWS AFYEEQSRMA KTYSLEEIQN LTLKRQLKAL QHSGTSALSA EKSKRLNTIL
NKMSTIYSTG KVLDPNTQEC LALEPGLDDI MENSRDYNRR LWAWEGWRAE VGKQLRPLYE
EYVVLENEMA RANNYEDYGD YWRGDYEVTG AGDYDYSRDQ LMKDVERTFA EIKPLYEQLH
AYVRAKLMHT YPSYISPTGC LPAHLLGDMW GRFWTNLYSL TVPFEHKPSI DVTEKMENQS
WDAERIFKEA EKFFVSISLP YMTQGFWDNS MLTEPGDGRK VVCHPTAWDL GKGDFRIKMC
TKVTMDDFLT AHHEMGHIQY DMAYAAQPYL LRNGANEGFH EAVGEIMSLS AATPHYLKAL
GLLAPDFHED NETEINFLLK QALTIVGTLP FTYMLEKWRW MVFKGEIPKQ QWMEKWWEMK
REIVGVVEPL PHDETYCDPA CLFHVAEDYS FIRYYTRTIY QFQFHEALCK TAKHEGALFK
CDISNSTEAG QRLLQMLRLG KSEPWTLALE NIVGIKTMDV KPLLNYFEPL FTWLKEQNRN
SFVGWSTEWT PYSDQSIKVR ISLKSALGEN AYEWNDNEMY LFQSSVAYAM RKYFSEARNE
TVLFGEDNVW VSDKKPRISF KFFVTSPNNV SDIIPRTEVE NAIRLSRDRI NDVFQLDDNS
LEFLGIQPTL GPPYEPPVTI WLIIFGVVMG VVVIGIVVLI FTGIRNRRKK NQASSEENPY
GSVDLNKGEN NSGFQNIDDV QTSL
