ACE2_PONAB
ID ACE2_PONAB Reviewed; 805 AA.
AC Q5RFN1;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 90.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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-781 (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 -!- 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-781 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; CR857122; CAH89426.1; -; mRNA.
DR RefSeq; NP_001124604.1; NM_001131132.2.
DR AlphaFoldDB; Q5RFN1; -.
DR SMR; Q5RFN1; -.
DR STRING; 9601.ENSPPYP00000022536; -.
DR MEROPS; M02.006; -.
DR GeneID; 100171441; -.
DR KEGG; pon:100171441; -.
DR CTD; 59272; -.
DR eggNOG; KOG3690; Eukaryota.
DR InParanoid; Q5RFN1; -.
DR Proteomes; UP000001595; 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:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-KW.
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 2: Evidence at transcript 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..805
FT /note="Angiotensin-converting enzyme 2"
FT /id="PRO_0000028573"
FT CHAIN 18..708
FT /note="Processed angiotensin-converting enzyme 2"
FT /id="PRO_0000292271"
FT TOPO_DOM 18..740
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 741..761
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 762..805
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 652..659
FT /note="Essential for cleavage by ADAM17"
FT /evidence="ECO:0000250"
FT REGION 697..716
FT /note="Essential for cleavage by TMPRSS11D and TMPRSS2"
FT /evidence="ECO:0000250"
FT REGION 772..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 778..786
FT /note="LIR"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 781..785
FT /note="SH2-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 781..784
FT /note="Endocytic sorting signal"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 792..795
FT /note="PTB"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOTIF 803..805
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT COMPBIAS 785..805
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 375
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT ACT_SITE 505
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 169
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 273
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 345..346
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 477
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 481
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT BINDING 515
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOD_RES 781
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYF1"
FT MOD_RES 783
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 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 322
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 432
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 690
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 133..141
FT /evidence="ECO:0000250"
FT DISULFID 344..361
FT /evidence="ECO:0000250"
FT DISULFID 530..542
FT /evidence="ECO:0000250"
SQ SEQUENCE 805 AA; 92605 MW; 9F68CC1ACBC763F1 CRC64;
MSGSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ
NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL
NTMSTIYSTG KVCNPNNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY
EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDSYDYSRG QLIEDVEHTF EEIKPLYEHL
HAYVRAKLIN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ
AWDAQRIFKE AEKFFVSVGL PNMTQRFWEN SMLTDPGNVQ KVVCHPTAWD LGKGDFRILM
CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS
IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM
KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH
KCDISNSTEA GQKLLNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLDYFEP LFTWLKDQNK
NSFVGWSTDW SPYADQSIKV RISLKSALGN KAYEWNDNEI YLFRSSVAYA MRKYFLEVKN
QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN
SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVVL IFTGIRDRKK KNKARNEENP
YASIDISKGE NNPGFQNTDD VQTSF
