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Q9BYF1 (ACE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Processed angiotensin-converting enzyme 2
Gene names
Name:ACE2
ORF Names:UNQ868/PRO1885
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length805 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.16 Ref.28

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit. Ref.15

Binds 1 chloride ion per subunit. Ref.15

Enzyme regulation

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. Ref.1 Ref.2 Ref.3 Ref.15

Subunit structure

Interacts with ITGB1. Interacts with SARS-CoV and HCoV-NL63 spike glycoprotein. Interacts with the catalytically active form of TMPRSS2. Ref.13 Ref.16 Ref.19 Ref.22 Ref.24 Ref.27

Subcellular location

Processed angiotensin-converting enzyme 2: Secreted Ref.3 Ref.27 Ref.28.

Cell membrane; Single-pass type I membrane protein Ref.3 Ref.27 Ref.28.

Tissue specificity

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. Ref.1 Ref.2 Ref.3 Ref.14 Ref.18 Ref.21

Induction

Up-regulated in failing heart. Ref.1 Ref.2 Ref.3 Ref.15 Ref.17 Ref.21

Post-translational modification

N-glycosylation on Asn-90 may limit SARS infectivity.

Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1. Ref.23 Ref.26 Ref.27 Ref.28

Sequence similarities

Belongs to the peptidase M2 family.

Biophysicochemical properties

Kinetic parameters:

KM=6.9 µM for angiotensin I Ref.15

KM=2 µM for angiotensin II

KM=6.8 µM for apelin-13

KM=5.5 µM for dynorphin-13

pH dependence:

Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   LigandChloride
Metal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processangiotensin catabolic process in blood

Inferred by curator Ref.2. Source: BHF-UCL

angiotensin maturation

Traceable author statement. Source: Reactome

angiotensin-mediated drinking behavior

Inferred from mutant phenotype PubMed 18258853. Source: BHF-UCL

cellular protein metabolic process

Traceable author statement. Source: Reactome

positive regulation of reactive oxygen species metabolic process

Inferred by curator PubMed 15380922. Source: BHF-UCL

receptor biosynthetic process

Inferred from mutant phenotype PubMed 18258853. Source: BHF-UCL

receptor-mediated virion attachment to host cell

Inferred from direct assay PubMed 18343844. Source: BHF-UCL

regulation of cell proliferation

Traceable author statement PubMed 17703127. Source: BHF-UCL

regulation of cytokine production

Inferred by curator PubMed 15380922. Source: BHF-UCL

regulation of inflammatory response

Inferred by curator PubMed 15380922. Source: BHF-UCL

regulation of systemic arterial blood pressure by renin-angiotensin

Inferred from mutant phenotype PubMed 18258853. Source: BHF-UCL

regulation of vasoconstriction

Inferred by curator PubMed 15380922. Source: BHF-UCL

regulation of vasodilation

Inferred by curator PubMed 15380922. Source: BHF-UCL

response to virus

Inferred from direct assay PubMed 18343844. Source: GOC

viral entry into host cell

Traceable author statement PubMed 15165741. Source: UniProtKB

   Cellular_componentcell surface

Inferred from direct assay Ref.28. Source: UniProtKB

extracellular region

Inferred from direct assay Ref.1. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 18258853. Source: BHF-UCL

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane raft

Traceable author statement PubMed 18279660. Source: BHF-UCL

plasma membrane

Inferred from direct assay Ref.27. Source: UniProtKB

   Molecular_functioncarboxypeptidase activity

Inferred from direct assay Ref.1. Source: UniProtKB

endopeptidase activity

Inferred from direct assay PubMed 15283675. Source: UniProtKB

glycoprotein binding

Inferred from physical interaction PubMed 18343844. Source: BHF-UCL

peptide hormone binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.27. Source: UniProtKB

virus receptor activity

Inferred from mutant phenotype Ref.28. Source: UniProtKB

zinc ion binding

Traceable author statement Ref.2. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BYF1-1)

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.
Isoform 2 (identifier: Q9BYF1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     555-555: F → L
     556-805: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 805788Angiotensin-converting enzyme 2
PRO_0000028570
Chain18 – 708691Processed angiotensin-converting enzyme 2
PRO_0000292268

Regions

Topological domain18 – 740723Extracellular Potential
Transmembrane741 – 76121Helical; Potential
Topological domain762 – 80544Cytoplasmic Potential
Region30 – 4112Interaction with SARS-CoV spike glycoprotein
Region82 – 843Interaction with SARS-CoV spike glycoprotein
Region353 – 3575Interaction with SARS-CoV spike glycoprotein
Region652 – 6598Essential for cleavage by ADAM17
Region697 – 71620Essential for cleavage by TMPRSS11D and TMPRSS2

Sites

Active site3751
Active site5051
Metal binding3741Zinc; catalytic
Metal binding3781Zinc; catalytic
Metal binding4021Zinc; catalytic
Binding site1691Chloride
Binding site2731Substrate
Binding site3451Substrate
Binding site3461Substrate; via carbonyl oxygen
Binding site3711Substrate
Binding site4771Chloride
Binding site4811Chloride
Binding site5151Substrate

Amino acid modifications

Glycosylation531N-linked (GlcNAc...) Probable
Glycosylation901N-linked (GlcNAc...) Ref.20 Ref.29
Glycosylation1031N-linked (GlcNAc...) Ref.29
Glycosylation3221N-linked (GlcNAc...) Probable
Glycosylation4321N-linked (GlcNAc...) Ref.29
Glycosylation5461N-linked (GlcNAc...) Ref.25 Ref.29
Glycosylation6901N-linked (GlcNAc...) Potential
Disulfide bond133 ↔ 141 Ref.29
Disulfide bond344 ↔ 361 Ref.29
Disulfide bond530 ↔ 542 Ref.29

Natural variations

Alternative sequence5551F → L in isoform 2.
VSP_014901
Alternative sequence556 – 805250Missing in isoform 2.
VSP_014902
Natural variant261K → R. Ref.9
Corresponds to variant rs4646116 [ dbSNP | Ensembl ].
VAR_023082
Natural variant6381N → S. Ref.4
Corresponds to variant rs183135788 [ dbSNP | Ensembl ].
VAR_023083

Experimental info

Mutagenesis24 – 263QAK → KAE: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis311K → D: Abolishes interaction with SARS-CoV spike glycoprotein.
Mutagenesis371E → A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis381D → A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis411Y → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis681K → D: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis82 – 843MYP → NFS: Inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis1101E → P: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis135 – 1362PD → SM: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis1601E → R: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis1921R → D: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis2191R → D: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis2391H → Q: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3091K → D: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3121E → A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3241T → A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis338 – 3403NVQ → DDR: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3501D → A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3531K → H, A or D: Abolishes interaction with SARS-CoV spike glycoprotein.
Mutagenesis3551D → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis3571R → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis3591L → K or A: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis3831M → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis3891P → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis3931R → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis425 – 4273SPD → PSN: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis465 – 4673KGE → QDK: No effect on interaction with SARS-CoV spike glycoprotein.
Mutagenesis5591R → S: Slightly inhibits interaction with SARS-CoV spike glycoprotein.
Mutagenesis6031F → T: No effect on interaction with SARS-CoV spike glycoprotein.
Sequence conflict181Q → H in CAB53682. Ref.12
Sequence conflict5081N → D in AAQ89076. Ref.8
Sequence conflict6311K → R in BAB40370. Ref.5

Secondary structure

..................................................................................................... 805
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified August 2, 2005. Version 2.
Checksum: 8EE6EB0A931550E8

FASTA80592,463
        10         20         30         40         50         60 
MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ 

        70         80         90        100        110        120 
NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL 

       130        140        150        160        170        180 
NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY 

       190        200        210        220        230        240 
EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL 

       250        260        270        280        290        300 
HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ 

       310        320        330        340        350        360 
AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM 

       370        380        390        400        410        420 
CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS 

       430        440        450        460        470        480 
IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM 

       490        500        510        520        530        540 
KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH 

       550        560        570        580        590        600 
KCDISNSTEA GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK 

       610        620        630        640        650        660 
NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA MRQYFLKVKN 

       670        680        690        700        710        720 
QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN 

       730        740        750        760        770        780 
SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVIL IFTGIRDRKK KNKARSGENP 

       790        800 
YASIDISKGE NNPGFQNTDD VQTSF 

« Hide

Isoform 2 [UniParc].

Checksum: 3A3842AB792E2DBC
Show »

FASTA55563,912

References

« Hide 'large scale' references
[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]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
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]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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]"A proteomic analysis of human bile."
Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A.
Mol. Cell. Proteomics 3:715-728(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90.
Tissue: Bile.
[21]"Myocardial infarction increases ACE2 expression in rat and humans."
Burrell L.M., Risvanis J., Kubota E., Dean R.G., MacDonald P.S., Lu S., Tikellis C., Grant S.L., Lew R.A., Smith A.I., Cooper M.E., Johnston C.I.
Eur. Heart J. 26:369-375(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[22]"Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2."
Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K., Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A., Guan Y., Choe H., Farzan M.
EMBO J. 24:1634-1643(2005) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS14169.1. [Q9BYF1-1]
PIRT14762.
RefSeqNP_068576.1. NM_021804.2. [Q9BYF1-1]
UniGeneHs.178098.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9BYF1.
SMRQ9BYF1. Positions 19-615.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121864. 3 interactions.
DIPDIP-44689N.
IntActQ9BYF1. 1 interaction.
MINTMINT-4538816.
STRING9606.ENSP00000252519.

Chemistry

BindingDBQ9BYF1.
ChEMBLCHEMBL2096989.
DrugBankDB00691. Moexipril.
GuidetoPHARMACOLOGY1614.

Protein family/group databases

MEROPSM02.006.

PTM databases

PhosphoSiteQ9BYF1.

Polymorphism databases

DMDM71658783.

Proteomic databases

PaxDbQ9BYF1.
PRIDEQ9BYF1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000252519; ENSP00000252519; ENSG00000130234. [Q9BYF1-1]
ENST00000427411; ENSP00000389326; ENSG00000130234. [Q9BYF1-1]
GeneID59272.
KEGGhsa:59272.
UCSCuc004cxa.1. human. [Q9BYF1-1]

Organism-specific databases

CTD59272.
GeneCardsGC0XM015489.
HGNCHGNC:13557. ACE2.
HPACAB026174.
HPA000288.
MIM300335. gene.
neXtProtNX_Q9BYF1.
PharmGKBPA425.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71044.
HOGENOMHOG000292210.
HOVERGENHBG000265.
InParanoidQ9BYF1.
KOK09708.
OMARDGANEG.
OrthoDBEOG76HQ13.
PhylomeDBQ9BYF1.
TreeFamTF312861.

Enzyme and pathway databases

BRENDA3.4.15.1. 2681.
ReactomeREACT_17015. Metabolism of proteins.
SABIO-RKQ9BYF1.

Gene expression databases

BgeeQ9BYF1.
CleanExHS_ACE2.
GenevestigatorQ9BYF1.

Family and domain databases

InterProIPR001548. Peptidase_M2.
[Graphical view]
PANTHERPTHR10514. PTHR10514. 1 hit.
PfamPF01401. Peptidase_M2. 1 hit.
[Graphical view]
PRINTSPR00791. PEPDIPTASEA.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSACE2. human.
EvolutionaryTraceQ9BYF1.
GeneWikiAngiotensin-converting_enzyme_2.
GenomeRNAi59272.
NextBio65154.
PMAP-CutDBQ9BYF1.
PROQ9BYF1.
SOURCESearch...

Entry information

Entry nameACE2_HUMAN
AccessionPrimary (citable) accession number: Q9BYF1
Secondary accession number(s): C7ECU1 expand/collapse secondary AC list , Q6UWP0, Q86WT0, Q9NRA7, Q9UFZ6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 2, 2005
Last sequence update: August 2, 2005
Last modified: July 9, 2014
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM