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Reviewed, UniProtKB/Swiss-Prot Q9BYF1 (ACE2_HUMAN)

Last modified September 23, 2008. Version 61. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Angiotensin-converting enzyme 2
    EC=3.4.17.-
Alternative name(s):
    ACE-related carboxypeptidase
    Angiotensin-converting enzyme homolog
      Short name=ACEH
Cleaved into the following 1 chains:
    1- Recommended name:
            Processed angiotensin-converting enzyme 2
Gene names
Name: ACE2
ORF Names: UNQ868/PRO1885
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

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

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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.

Cofactor

Binds 1 zinc ion per subunit.

Binds 1 chloride ion per subunit.

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.

Subunit structure

Interacts with ITGB1. Interacts with SARS-CoV and HCoV-NL63 spike glycoprotein.

Subcellular location

Processed angiotensin-converting enzyme 2: Secreted.

Cell membrane; Single-pass type I membrane protein.

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.

Induction

Up-regulated in failing heart.

Post-translational modification

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

Sequence similarities

Belongs to the peptidase M2 family.

Biophysicochemical properties

Kinetic parameters:

KM=6.9 µM for angiotensin I

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.

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Ontologies

Keywords

   Biological processHost-virus interaction
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
Transmembrane
   LigandChloride
Metal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMGlycoprotein
   Technical term3D-structure
Direct protein sequencing

Gene Ontology (GO)

   Biological processangiotensin catabolic process in blood Ref.2

Inferred by curator. Source: UniProtKB

angiotensin-mediated drinking behavior

Inferred from mutant phenotype. Source: UniProtKB

oxygen and reactive oxygen species metabolic process

Inferred by curator. Source: UniProtKB

receptor biosynthetic process

Inferred from mutant phenotype. Source: UniProtKB

regulation of cell proliferation

Traceable author statement. Source: UniProtKB

regulation of cytokine production

Inferred by curator. Source: UniProtKB

regulation of inflammatory response

Inferred by curator. Source: UniProtKB

regulation of vasoconstriction

Inferred by curator. Source: UniProtKB

regulation of vasodilation

Inferred by curator. Source: UniProtKB

virion attachment, binding of host cell surface receptor

Inferred from direct assay. Source: UniProtKB

   Cellular componentcell surface

Inferred from direct assay. Source: UniProtKB

extracellular space

Inferred from direct assay. Source: UniProtKB

membrane raft

Traceable author statement. Source: UniProtKB

   Molecular functioncarboxypeptidase activity Ref.1 Ref.2

Inferred from direct assay. Source: UniProtKB

glycoprotein binding

Inferred from physical interaction. Source: UniProtKB

viral receptor activity

Inferred from direct assay. Source: UniProtKB

zinc ion binding Ref.2

Traceable author statement. Source: UniProtKB

Complete GO annotation...

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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.
Notes: No experimental confirmation available.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 805788Angiotensin-converting enzyme 2
Chain18 – ?Processed angiotensin-converting enzyme 2

Regions

Topological domain18 – 740723Extracellular Potential
Transmembrane741 – 76121 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

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...)
Glycosylation1031N-linked (GlcNAc...)
Glycosylation3221N-linked (GlcNAc...) Probable
Glycosylation4321N-linked (GlcNAc...)
Glycosylation5461N-linked (GlcNAc...)
Glycosylation6901N-linked (GlcNAc...) Potential
Disulfide bond133 ↔ 141
Disulfide bond344 ↔ 361
Disulfide bond530 ↔ 542

Natural variations

Alternative sequence5551F → L in isoform 2.
Alternative sequence556 – 805250Missing in isoform 2.
Natural variant261K → R: dbSNP rs4646116.
Natural variant6381N → S

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.9
Sequence conflict5081N → D in AAQ89076. Ref.6
Sequence conflict6311K → R in BAB40370. Ref.5

Secondary structure

1 ......................................................................................... 805
Helix Strand Turn

Details...