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Protein

Angiotensin-converting enzyme 2

Gene

ACE2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.4 Publications

Catalytic activityi

Angiotensin II + H2O = angiotensin-1-7 + L-phenylalanine.

Cofactori

Protein has several cofactor binding sites:

Enzyme regulationi

Activated by chloride and fluoride, but not bromide. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors linosipril, captopril and enalaprilat.4 Publications

Kineticsi

  1. KM=6.9 µM for angiotensin I1 Publication
  2. KM=2 µM for angiotensin II1 Publication
  3. KM=6.8 µM for apelin-131 Publication
  4. KM=5.5 µM for dynorphin-131 Publication

    pH dependencei

    Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei169 – 1691Chloride
    Binding sitei273 – 2731Substrate
    Binding sitei345 – 3451Substrate
    Binding sitei346 – 3461Substrate; via carbonyl oxygen
    Binding sitei371 – 3711Substrate
    Metal bindingi374 – 3741Zinc; catalytic
    Active sitei375 – 3751
    Metal bindingi378 – 3781Zinc; catalytic
    Metal bindingi402 – 4021Zinc; catalytic
    Binding sitei477 – 4771Chloride
    Binding sitei481 – 4811Chloride
    Active sitei505 – 5051
    Binding sitei515 – 5151Substrate

    GO - Molecular functioni

    • carboxypeptidase activity Source: UniProtKB
    • endopeptidase activity Source: UniProtKB
    • glycoprotein binding Source: BHF-UCL
    • peptide hormone binding Source: Ensembl
    • virus receptor activity Source: UniProtKB
    • zinc ion binding Source: BHF-UCL

    GO - Biological processi

    • angiotensin catabolic process in blood Source: BHF-UCL
    • angiotensin maturation Source: Reactome
    • angiotensin-mediated drinking behavior Source: BHF-UCL
    • cellular protein metabolic process Source: Reactome
    • maternal process involved in female pregnancy Source: Ensembl
    • positive regulation of gap junction assembly Source: BHF-UCL
    • positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
    • receptor biosynthetic process Source: BHF-UCL
    • receptor-mediated virion attachment to host cell Source: BHF-UCL
    • regulation of cardiac conduction Source: BHF-UCL
    • regulation of cell proliferation Source: BHF-UCL
    • regulation of cytokine production Source: BHF-UCL
    • regulation of inflammatory response Source: BHF-UCL
    • regulation of systemic arterial blood pressure by renin-angiotensin Source: BHF-UCL
    • regulation of vasoconstriction Source: BHF-UCL
    • regulation of vasodilation Source: BHF-UCL
    • viral entry into host cell Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Host-virus interaction

    Keywords - Ligandi

    Chloride, Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi3.4.15.1. 2681.
    3.4.17.23. 2681.
    ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.
    SABIO-RKQ9BYF1.

    Protein family/group databases

    MEROPSiM02.006.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Angiotensin-converting enzyme 2 (EC:3.4.17.23)
    Alternative name(s):
    ACE-related carboxypeptidase
    Angiotensin-converting enzyme homolog
    Short name:
    ACEH
    Metalloprotease MPROT15
    Cleaved into the following chain:
    Gene namesi
    Name:ACE2
    ORF Names:UNQ868/PRO1885
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome X

    Organism-specific databases

    HGNCiHGNC:13557. ACE2.

    Subcellular locationi

    Topology

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini18 – 740723ExtracellularSequence AnalysisAdd
    BLAST
    Transmembranei741 – 76121HelicalSequence AnalysisAdd
    BLAST
    Topological domaini762 – 80544CytoplasmicSequence AnalysisAdd
    BLAST

    GO - Cellular componenti

    • cell surface Source: UniProtKB
    • cytoplasm Source: UniProtKB-SubCell
    • extracellular exosome Source: UniProtKB
    • extracellular region Source: UniProtKB
    • extracellular space Source: BHF-UCL
    • integral component of membrane Source: UniProtKB-KW
    • membrane raft Source: BHF-UCL
    • plasma membrane Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi24 – 263QAK → KAE: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi31 – 311K → D: Abolishes interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi37 – 371E → A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi38 – 381D → A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi41 – 411Y → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi68 – 681K → D: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi82 – 843MYP → NFS: Inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi110 – 1101E → P: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi135 – 1362PD → SM: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi160 – 1601E → R: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi192 – 1921R → D: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi219 – 2191R → D: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi239 – 2391H → Q: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi309 – 3091K → D: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi312 – 3121E → A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi324 – 3241T → A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi338 – 3403NVQ → DDR: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi350 – 3501D → A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi353 – 3531K → H, A or D: Abolishes interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi355 – 3551D → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi357 – 3571R → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi359 – 3591L → K or A: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi383 – 3831M → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi389 – 3891P → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi393 – 3931R → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi425 – 4273SPD → PSN: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi465 – 4673KGE → QDK: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi559 – 5591R → S: Slightly inhibits interaction with SARS-CoV spike glycoprotein. 1 Publication
    Mutagenesisi603 – 6031F → T: No effect on interaction with SARS-CoV spike glycoprotein. 1 Publication

    Organism-specific databases

    PharmGKBiPA425.

    Chemistry

    DrugBankiDB00722. Lisinopril.
    DB00691. Moexipril.

    Polymorphism and mutation databases

    BioMutaiACE2.
    DMDMi71658783.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Chaini18 – 805788Angiotensin-converting enzyme 2PRO_0000028570Add
    BLAST
    Chaini18 – 708691Processed angiotensin-converting enzyme 2PRO_0000292268Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi53 – 531N-linked (GlcNAc...)1 Publication
    Glycosylationi90 – 901N-linked (GlcNAc...)2 Publications
    Glycosylationi103 – 1031N-linked (GlcNAc...)1 Publication
    Disulfide bondi133 ↔ 1411 Publication
    Glycosylationi322 – 3221N-linked (GlcNAc...)1 Publication
    Disulfide bondi344 ↔ 3611 Publication
    Glycosylationi432 – 4321N-linked (GlcNAc...)1 Publication
    Disulfide bondi530 ↔ 5421 Publication
    Glycosylationi546 – 5461N-linked (GlcNAc...)2 Publications
    Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence Analysis

    Post-translational modificationi

    N-glycosylation on Asn-90 may limit SARS infectivity.5 Publications
    Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1.4 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiQ9BYF1.
    PRIDEiQ9BYF1.

    PTM databases

    PhosphoSiteiQ9BYF1.

    Miscellaneous databases

    PMAP-CutDBQ9BYF1.

    Expressioni

    Tissue specificityi

    Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells. Expressed in lung alveolar epithelial cells, enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level). Expressed in heart, kidney, testis, and gastrointestinal system.6 Publications

    Inductioni

    Up-regulated in failing heart.2 Publications

    Gene expression databases

    BgeeiQ9BYF1.
    CleanExiHS_ACE2.
    GenevisibleiQ9BYF1. HS.

    Organism-specific databases

    HPAiCAB026174.
    HPA000288.

    Interactioni

    Subunit structurei

    Interacts with ITGB1. Interacts with SARS-CoV and HCoV-NL63 spike glycoprotein. Interacts with the catalytically active form of TMPRSS2.7 Publications

    Protein-protein interaction databases

    BioGridi121864. 4 interactions.
    DIPiDIP-44689N.
    IntActiQ9BYF1. 1 interaction.
    MINTiMINT-4538816.
    STRINGi9606.ENSP00000252519.

    Structurei

    Secondary structure

    1
    805
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi23 – 5230Combined sources
    Helixi56 – 7722Combined sources
    Turni78 – 825Combined sources
    Helixi85 – 873Combined sources
    Helixi91 – 10010Combined sources
    Helixi104 – 1074Combined sources
    Helixi110 – 12920Combined sources
    Beta strandi131 – 1344Combined sources
    Beta strandi137 – 1437Combined sources
    Turni144 – 1463Combined sources
    Helixi148 – 1547Combined sources
    Helixi158 – 17114Combined sources
    Helixi173 – 19321Combined sources
    Beta strandi196 – 1983Combined sources
    Helixi199 – 2046Combined sources
    Turni205 – 2073Combined sources
    Turni213 – 2153Combined sources
    Helixi220 – 25132Combined sources
    Turni253 – 2553Combined sources
    Beta strandi258 – 2603Combined sources
    Helixi264 – 2663Combined sources
    Beta strandi267 – 2715Combined sources
    Helixi276 – 2783Combined sources
    Helixi279 – 2824Combined sources
    Turni284 – 2874Combined sources
    Turni294 – 2974Combined sources
    Helixi298 – 3003Combined sources
    Helixi304 – 31613Combined sources
    Turni317 – 3193Combined sources
    Helixi327 – 3304Combined sources
    Beta strandi338 – 3403Combined sources
    Beta strandi347 – 3526Combined sources
    Beta strandi355 – 3595Combined sources
    Helixi366 – 38419Combined sources
    Turni385 – 3873Combined sources
    Helixi390 – 3923Combined sources
    Helixi400 – 41314Combined sources
    Helixi415 – 4206Combined sources
    Turni422 – 4265Combined sources
    Helixi432 – 44615Combined sources
    Helixi449 – 46517Combined sources
    Beta strandi466 – 4683Combined sources
    Helixi470 – 4723Combined sources
    Helixi473 – 48311Combined sources
    Beta strandi486 – 4883Combined sources
    Helixi499 – 5024Combined sources
    Helixi504 – 5074Combined sources
    Helixi514 – 53118Combined sources
    Turni532 – 5343Combined sources
    Helixi539 – 5413Combined sources
    Helixi548 – 55811Combined sources
    Turni559 – 5624Combined sources
    Helixi566 – 5749Combined sources
    Beta strandi575 – 5784Combined sources
    Helixi582 – 59817Combined sources
    Beta strandi600 – 6023Combined sources
    Beta strandi607 – 6093Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1R42X-ray2.20A1-615[»]
    1R4LX-ray3.00A1-615[»]
    1XJPmodel-B19-615[»]
    2AJFX-ray2.90A/B19-615[»]
    3D0GX-ray2.80A/B56-615[»]
    3D0HX-ray3.10A/B56-615[»]
    3D0IX-ray2.90A/B56-615[»]
    3KBHX-ray3.31A/B/C/D19-615[»]
    3SCIX-ray2.90A/B19-615[»]
    3SCJX-ray3.00A/B19-615[»]
    3SCKX-ray3.00A/B83-615[»]
    3SCLX-ray3.00A/B83-615[»]
    ProteinModelPortaliQ9BYF1.
    SMRiQ9BYF1. Positions 19-615.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9BYF1.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni30 – 4112Interaction with SARS-CoV spike glycoproteinAdd
    BLAST
    Regioni82 – 843Interaction with SARS-CoV spike glycoprotein
    Regioni353 – 3575Interaction with SARS-CoV spike glycoprotein
    Regioni652 – 6598Essential for cleavage by ADAM17
    Regioni697 – 71620Essential for cleavage by TMPRSS11D and TMPRSS2Add
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase M2 family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG71044.
    GeneTreeiENSGT00520000055576.
    HOGENOMiHOG000292210.
    HOVERGENiHBG000265.
    InParanoidiQ9BYF1.
    KOiK09708.
    OMAiCNPNNPQ.
    OrthoDBiEOG76HQ13.
    PhylomeDBiQ9BYF1.
    TreeFamiTF312861.

    Family and domain databases

    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 1 hit.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q9BYF1-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY
    60 70 80 90 100
    NTNITEENVQ NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL
    110 120 130 140 150
    QQNGSSVLSE DKSKRLNTIL NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE
    160 170 180 190 200
    IMANSLDYNE RLWAWESWRS EVGKQLRPLY EEYVVLKNEM ARANHYEDYG
    210 220 230 240 250
    DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL HAYVRAKLMN
    260 270 280 290 300
    AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ
    310 320 330 340 350
    AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD
    360 370 380 390 400
    LGKGDFRILM CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF
    410 420 430 440 450
    HEAVGEIMSL SAATPKHLKS IGLLSPDFQE DNETEINFLL KQALTIVGTL
    460 470 480 490 500
    PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM KREIVGVVEP VPHDETYCDP
    510 520 530 540 550
    ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH KCDISNSTEA
    560 570 580 590 600
    GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK
    610 620 630 640 650
    NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA
    660 670 680 690 700
    MRQYFLKVKN QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV
    710 720 730 740 750
    EKAIRMSRSR INDAFRLNDN SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM
    760 770 780 790 800
    GVIVVGIVIL IFTGIRDRKK KNKARSGENP YASIDISKGE NNPGFQNTDD

    VQTSF
    Length:805
    Mass (Da):92,463
    Last modified:August 2, 2005 - v2
    Checksum:i8EE6EB0A931550E8
    GO
    Isoform 2 (identifier: Q9BYF1-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         555-555: F → L
         556-805: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:555
    Mass (Da):63,912
    Checksum:i3A3842AB792E2DBC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti18 – 181Q → H in CAB53682 (PubMed:17974005).Curated
    Sequence conflicti508 – 5081N → D in AAQ89076 (PubMed:12975309).Curated
    Sequence conflicti631 – 6311K → R in BAB40370 (Ref. 5) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti26 – 261K → R.1 Publication
    Corresponds to variant rs4646116 [ dbSNP | Ensembl ].
    VAR_023082
    Natural varianti638 – 6381N → S.1 Publication
    Corresponds to variant rs183135788 [ dbSNP | Ensembl ].
    VAR_023083

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei555 – 5551F → L in isoform 2. 1 PublicationVSP_014901
    Alternative sequencei556 – 805250Missing in isoform 2. 1 PublicationVSP_014902Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF291820 mRNA. Translation: AAF99721.1.
    AF241254 mRNA. Translation: AAF78220.1.
    AY623811 mRNA. Translation: AAT45083.1.
    AB193259 mRNA. Translation: BAD99266.1.
    AB193260 mRNA. Translation: BAD99267.1.
    AB046569 mRNA. Translation: BAB40370.1.
    E39033 mRNA. No translation available.
    GQ262784 mRNA. Translation: ACT66268.1.
    AY358714 mRNA. Translation: AAQ89076.1.
    AY217547 Genomic DNA. Translation: AAO25651.1.
    CH471074 Genomic DNA. Translation: EAW98892.1.
    BC039902 mRNA. Translation: AAH39902.1.
    BC048094 mRNA. Translation: AAH48094.2.
    AL110224 mRNA. Translation: CAB53682.1.
    CCDSiCCDS14169.1. [Q9BYF1-1]
    PIRiT14762.
    RefSeqiNP_068576.1. NM_021804.2. [Q9BYF1-1]
    UniGeneiHs.178098.

    Genome annotation databases

    EnsembliENST00000252519; ENSP00000252519; ENSG00000130234. [Q9BYF1-1]
    ENST00000427411; ENSP00000389326; ENSG00000130234. [Q9BYF1-1]
    GeneIDi59272.
    KEGGihsa:59272.
    UCSCiuc004cxa.1. human. [Q9BYF1-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF291820 mRNA. Translation: AAF99721.1.
    AF241254 mRNA. Translation: AAF78220.1.
    AY623811 mRNA. Translation: AAT45083.1.
    AB193259 mRNA. Translation: BAD99266.1.
    AB193260 mRNA. Translation: BAD99267.1.
    AB046569 mRNA. Translation: BAB40370.1.
    E39033 mRNA. No translation available.
    GQ262784 mRNA. Translation: ACT66268.1.
    AY358714 mRNA. Translation: AAQ89076.1.
    AY217547 Genomic DNA. Translation: AAO25651.1.
    CH471074 Genomic DNA. Translation: EAW98892.1.
    BC039902 mRNA. Translation: AAH39902.1.
    BC048094 mRNA. Translation: AAH48094.2.
    AL110224 mRNA. Translation: CAB53682.1.
    CCDSiCCDS14169.1. [Q9BYF1-1]
    PIRiT14762.
    RefSeqiNP_068576.1. NM_021804.2. [Q9BYF1-1]
    UniGeneiHs.178098.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1R42X-ray2.20A1-615[»]
    1R4LX-ray3.00A1-615[»]
    1XJPmodel-B19-615[»]
    2AJFX-ray2.90A/B19-615[»]
    3D0GX-ray2.80A/B56-615[»]
    3D0HX-ray3.10A/B56-615[»]
    3D0IX-ray2.90A/B56-615[»]
    3KBHX-ray3.31A/B/C/D19-615[»]
    3SCIX-ray2.90A/B19-615[»]
    3SCJX-ray3.00A/B19-615[»]
    3SCKX-ray3.00A/B83-615[»]
    3SCLX-ray3.00A/B83-615[»]
    ProteinModelPortaliQ9BYF1.
    SMRiQ9BYF1. Positions 19-615.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi121864. 4 interactions.
    DIPiDIP-44689N.
    IntActiQ9BYF1. 1 interaction.
    MINTiMINT-4538816.
    STRINGi9606.ENSP00000252519.

    Chemistry

    BindingDBiQ9BYF1.
    ChEMBLiCHEMBL2096989.
    DrugBankiDB00722. Lisinopril.
    DB00691. Moexipril.
    GuidetoPHARMACOLOGYi1614.

    Protein family/group databases

    MEROPSiM02.006.

    PTM databases

    PhosphoSiteiQ9BYF1.

    Polymorphism and mutation databases

    BioMutaiACE2.
    DMDMi71658783.

    Proteomic databases

    PaxDbiQ9BYF1.
    PRIDEiQ9BYF1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000252519; ENSP00000252519; ENSG00000130234. [Q9BYF1-1]
    ENST00000427411; ENSP00000389326; ENSG00000130234. [Q9BYF1-1]
    GeneIDi59272.
    KEGGihsa:59272.
    UCSCiuc004cxa.1. human. [Q9BYF1-1]

    Organism-specific databases

    CTDi59272.
    GeneCardsiGC0XM015579.
    HGNCiHGNC:13557. ACE2.
    HPAiCAB026174.
    HPA000288.
    MIMi300335. gene.
    neXtProtiNX_Q9BYF1.
    PharmGKBiPA425.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiNOG71044.
    GeneTreeiENSGT00520000055576.
    HOGENOMiHOG000292210.
    HOVERGENiHBG000265.
    InParanoidiQ9BYF1.
    KOiK09708.
    OMAiCNPNNPQ.
    OrthoDBiEOG76HQ13.
    PhylomeDBiQ9BYF1.
    TreeFamiTF312861.

    Enzyme and pathway databases

    BRENDAi3.4.15.1. 2681.
    3.4.17.23. 2681.
    ReactomeiREACT_147707. Metabolism of Angiotensinogen to Angiotensins.
    SABIO-RKQ9BYF1.

    Miscellaneous databases

    ChiTaRSiACE2. human.
    EvolutionaryTraceiQ9BYF1.
    GeneWikiiAngiotensin-converting_enzyme_2.
    GenomeRNAii59272.
    NextBioi65154.
    PMAP-CutDBQ9BYF1.
    PROiQ9BYF1.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ9BYF1.
    CleanExiHS_ACE2.
    GenevisibleiQ9BYF1. HS.

    Family and domain databases

    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 1 hit.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9."
      Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N., Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.
      Circ. Res. 87:E1-E9(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, ENZYME REGULATION.
      Tissue: Heart.
    2. "A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase."
      Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.
      J. Biol. Chem. 275:33238-33243(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION, FUNCTION, ENZYME REGULATION.
      Tissue: Lymphoma.
    3. "The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis."
      Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K.L., Yarski M.A., Smith A.I., Lew R.A.
      Endocrinology 145:4703-4711(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION.
      Tissue: Testis.
    4. "Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population."
      Itoyama S., Keicho N., Hijikata M., Quy T., Phi N.C., Long H.T., Ha L.D., Ban V.V., Matsushita I., Yanai H., Kirikae F., Kirikae T., Kuratsuji T., Sasazuki T.
      Am. J. Med. Genet. A 136:52-57(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-638.
      Tissue: Lung and Testis.
    5. "Cloning, expression analysis and chromosomal localization of a novel ACE like enzyme."
      Suzuki Y., Watanabe M., Sugano S.
      Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    6. "MPROT15 polypeptide and MPROT15 polynucleotide."
      Southan C., Burgess N.
      Patent number JP11318472, 24-NOV-1999
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    7. "Comparative susceptibility to SARS-CoV mediated by ACE2 protein of 15 different species."
      Li K.K.B., Yip C.W., Hon C.C., Lam C.Y., Leung F.C.C.
      Submitted (JUN-2009) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    9. SeattleSNPs variation discovery resource
      Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-26.
    10. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    11. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Brain and Testis.
    12. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-805 (ISOFORM 1).
      Tissue: Testis.
    13. "Interaction of ACE2 and integrin beta1 in failing human heart."
      Lin Q., Keller R.S., Weaver B., Zisman L.S.
      Biochim. Biophys. Acta 1689:175-178(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 679-689, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH ITGB1.
    14. "Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme."
      Harmer D., Gilbert M., Borman R., Clark K.L.
      FEBS Lett. 532:107-110(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    15. "Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase."
      Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K., Parsons T., Baronas E., Hsieh F., Acton S., Patane M.A., Nichols A., Tummino P.
      J. Biol. Chem. 277:14838-14843(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.
    16. "Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus."
      Li W., Moore M.J., Vasilieva N., Sui J., Wong S.-K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M.
      Nature 426:450-454(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN, GLYCOSYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
    17. "ACE2 gene expression is up-regulated in the human failing heart."
      Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.
      BMC Med. 2:19-19(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    18. "Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis."
      Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H.
      J. Pathol. 203:631-637(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    19. "Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2."
      Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M., Sullivan J.L., Farzan M., Choe H.
      J. Virol. 78:11429-11433(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN.
    20. Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90.
      Tissue: Bile.
    21. Cited for: TISSUE SPECIFICITY, INDUCTION.
    22. Cited for: INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN, MUTAGENESIS.
    23. "Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)."
      Lambert D.W., Yarski M., Warner F.J., Thornhill P., Parkin E.T., Smith A.I., Hooper N.M., Turner A.J.
      J. Biol. Chem. 280:30113-30119(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC CLEAVAGE.
    24. "Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry."
      Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Poehlmann S.
      Proc. Natl. Acad. Sci. U.S.A. 102:7988-7993(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HCOV-NL63 SPIKE GLYCOPROTEIN.
    25. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-546.
      Tissue: Liver.
    26. "Angiotensin-converting enzyme 2 ectodomain shedding cleavage-site identification: determinants and constraints."
      Lai Z.W., Hanchapola I., Steer D.L., Smith A.I.
      Biochemistry 50:5182-5194(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC CLEAVAGE.
    27. "A transmembrane serine protease is linked to the severe acute respiratory syndrome coronavirus receptor and activates virus entry."
      Shulla A., Heald-Sargent T., Subramanya G., Zhao J., Perlman S., Gallagher T.
      J. Virol. 85:873-882(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE, INTERACTION WITH TMPRSS2.
    28. "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
      Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
      J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC CLEAVAGE.
    29. "ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis."
      Towler P., Staker B., Prasad S.G., Menon S., Tang J., Parsons T., Ryan D., Fisher M., Williams D., Dales N.A., Patane M.A., Pantoliano M.W.
      J. Biol. Chem. 279:17996-18007(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 19-615, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 19-615 IN COMPLEX WITH MLN-4760, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53; ASN-90; ASN-103; ASN-322; ASN-432 AND ASN-546.

    Entry informationi

    Entry nameiACE2_HUMAN
    AccessioniPrimary (citable) accession number: Q9BYF1
    Secondary accession number(s): C7ECU1
    , Q6UWP0, Q86WT0, Q9NRA7, Q9UFZ6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 2, 2005
    Last sequence update: August 2, 2005
    Last modified: June 24, 2015
    This is version 139 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome X
      Human chromosome X: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Peptidase families
      Classification of peptidase families and list of entries
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.