ACE2_PAGLA
ID ACE2_PAGLA Reviewed; 805 AA.
AC Q56NL1;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, 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 Paguma larvata (Masked palm civet).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Viverridae; Paradoxurinae;
OC Paguma.
OX NCBI_TaxID=9675;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH SARS-COV S PROTEIN.
RX PubMed=15791205; DOI=10.1038/sj.emboj.7600640;
RA Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K.,
RA Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A.,
RA Guan Y., Choe H., Farzan M.;
RT "Receptor and viral determinants of SARS-coronavirus adaptation to human
RT ACE2.";
RL EMBO J. 24:1634-1643(2005).
RN [2] {ECO:0007744|PDB:3SCK, ECO:0007744|PDB:3SCL}
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 19-613 IN COMPLEXES WITH ZINC AND
RP SARS CORONAVIRUS SPIKE GLYCOPROTEIN, COFACTOR, AND DISULFIDE BONDS.
RX PubMed=22291007; DOI=10.1074/jbc.m111.325803;
RA Wu K., Peng G., Wilken M., Geraghty R.J., Li F.;
RT "Mechanisms of host receptor adaptation by severe acute respiratory
RT syndrome coronavirus.";
RL J. Biol. Chem. 287:8904-8911(2012).
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 -!- FUNCTION: (Microbial infection) Acts as a receptor for human
CC coronavirus SARS. {ECO:0000269|PubMed:15791205}.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000305|PubMed:22291007};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:22291007};
CC -!- COFACTOR:
CC Name=chloride; Xref=ChEBI:CHEBI:17996;
CC Note=Binds 1 Cl(-) ion per subunit.;
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 -!- SUBUNIT: (Microbial infection) Interacts with SARS-CoV S protein.
CC {ECO:0000269|PubMed:15791205}.
CC -!- INTERACTION:
CC Q56NL1; P59594: S; Xeno; NbExp=4; IntAct=EBI-25498790, EBI-15582614;
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; AY881174; AAX63775.1; -; mRNA.
DR PDB; 3D0G; X-ray; 2.80 A; A/B=19-55.
DR PDB; 3D0H; X-ray; 3.10 A; A/B=19-55.
DR PDB; 3D0I; X-ray; 2.90 A; A/B=19-55.
DR PDB; 3SCK; X-ray; 3.00 A; A/B=19-82.
DR PDB; 3SCL; X-ray; 3.00 A; A/B=19-82.
DR PDBsum; 3D0G; -.
DR PDBsum; 3D0H; -.
DR PDBsum; 3D0I; -.
DR PDBsum; 3SCK; -.
DR PDBsum; 3SCL; -.
DR AlphaFoldDB; Q56NL1; -.
DR SMR; Q56NL1; -.
DR IntAct; Q56NL1; 2.
DR MEROPS; M02.006; -.
DR BRENDA; 3.4.17.23; 16967.
DR EvolutionaryTrace; Q56NL1; -.
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 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cell membrane; Cell projection; Chloride;
KW Cytoplasm; Disulfide bond; Glycoprotein; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Phosphoprotein; Protease; Secreted; Signal;
KW 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_0000028572"
FT CHAIN 18..708
FT /note="Processed angiotensin-converting enzyme 2"
FT /id="PRO_0000292270"
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 30..41
FT /note="Interaction with SARS S protein"
FT REGION 82..84
FT /note="Interaction with SARS S protein"
FT /evidence="ECO:0000250"
FT REGION 90..93
FT /note="Interaction with SARS S protein"
FT REGION 353..357
FT /note="Interaction with SARS S protein"
FT /evidence="ECO:0000250"
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 771..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 776..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:0000269|PubMed:22291007"
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:0000269|PubMed:22291007"
FT BINDING 378
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:22291007"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:22291007"
FT BINDING 477
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000269|PubMed:22291007"
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 216
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 546
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 660
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:0000269|PubMed:22291007"
FT DISULFID 344..361
FT /evidence="ECO:0000269|PubMed:22291007"
FT DISULFID 530..542
FT /evidence="ECO:0000269|PubMed:22291007"
FT HELIX 21..52
FT /evidence="ECO:0007829|PDB:3D0G"
SQ SEQUENCE 805 AA; 92611 MW; CF6406851F73E378 CRC64;
MSGSFWLLLS FAALTAAQST TEELAKTFLE TFNYEAQELS YQSSVASWNY NTNITDENAK
NMNEAGAKWS AYYEEQSKLA QTYPLAEIQD AKIKRQLQAL QQSGSSVLSA DKSQRLNTIL
NAMSTIYSTG KACNPNNPQE CLLLEPGLDN IMENSKDYNE RLWAWEGWRA EVGKQLRPLY
EEYVALKNEM ARANNYEDYG DYWRGDYEEE WTGGYNYSRN QLIQDVEDTF EQIKPLYQHL
HAYVRAKLMD TYPSRISRTG CLPAHLLGDM WGRFWTNLYP LTVPFGQKPN IDVTDAMVNQ
NWDARRIFKE AEKFFVSVGL PNMTQGFWEN SMLTEPGDGR KVVCHPTAWD LGKGDFRIKM
CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPNHLKT
IGLLSPAFSE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGAIPK EQWMQKWWEM
KRNIVGVVEP VPHDETYCDP ASLFHVANDY SFIRYYTRTI YQFQFQEALC QIAKHEGPLH
KCDISNSTEA GKKLLEMLSL GRSEPWTLAL ERVVGAKNMN VTPLLNYFEP LFTWLKEQNR
NSFVGWDTDW RPYSDQSIKV RISLKSALGE KAYEWNDNEM YLFRSSIAYA MREYFSKVKN
QTIPFVEDNV WVSDLKPRIS FNFFVTFSNN VSDVIPRSEV EDAIRMSRSR INDAFRLDDN
SLEFLGIEPT LSPPYRPPVT IWLIVFGVVM GAIVVGIVLL IVSGIRNRRK NDQAGSEENP
YASVDLNKGE NNPGFQHADD VQTSF
