ACE2

Protein identityUniProt · HPA

UniProt accession

Q9BYF1

Gene

ACE2

Ensembl

ENSG00000130234

Chromosome

X

Canonical length

805 aa

Protein class

Enzymes, Metabolic proteins, Predicted membrane proteins, Predicted secreted proteins, Transporters

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

Canonical amino-acid sequenceUniProt

805 residues, UniProt reviewed canonical sequence.

>Q9BYF1|ACE2
     1  MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ
    61  NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL
   121  NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY
   181  EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL
   241  HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ
   301  AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM
   361  CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS
   421  IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM
   481  KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH
   541  KCDISNSTEA GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK
   601  NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA MRQYFLKVKN
   661  QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN
   721  SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVIL IFTGIRDRKK KNKARSGENP
   781  YASIDISKGE NNPGFQNTDD VQTSF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACE2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

231 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACE2.

Disease | AutoantibodyPubMed

Conditions in which antibodies against ACE2 are reported. Each links to that disease's full target list.

• COVID-19 18
• Scleroderma, Systemic 3

ReferencesPubMed · IEDB

Publications for ACE2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.25

gnomAD pLI

1

gnomAD missense Z

1.25

DepMap mean gene effect

0.14

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiotensin maturation
• angiotensin-mediated drinking behavior
• blood vessel diameter maintenance
• entry receptor-mediated virion attachment to host cell
• maternal process involved in female pregnancy
• membrane fusion
• negative regulation of ERK1 and ERK2 cascade
• negative regulation of smooth muscle cell proliferation
• negative regulation of transcription by RNA polymerase II
• positive regulation of amino acid transport
• positive regulation of cardiac muscle contraction
• positive regulation of gap junction assembly
• positive regulation of L-proline import across plasma membrane
• positive regulation of reactive oxygen species metabolic process
• receptor-mediated endocytosis of virus by host cell
• receptor-mediated virion attachment to host cell
• regulation of cardiac conduction
• regulation of cell population proliferation
• regulation of cytokine production
• regulation of inflammatory response
• regulation of systemic arterial blood pressure by renin-angiotensin
• regulation of vasoconstriction
• symbiont entry into host cell
• tryptophan transport
• viral life cycle

Molecular functions

• carboxypeptidase activity
• endopeptidase activity
• identical protein binding
• metallocarboxypeptidase activity
• metallopeptidase activity
• peptidyl-dipeptidase activity
• transporter activator activity
• virus receptor activity
• zinc ion binding

Cellular components

• apical plasma membrane
• brush border membrane
• cell surface
• cilium
• endocytic vesicle membrane
• endoplasmic reticulum lumen
• extracellular exosome
• extracellular region
• extracellular space
• membrane
• membrane raft
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M2, peptidyl-dipeptidase A
• Collectrin domain
• Angiotensin-converting enzyme
• Renal amino acid transporter

KeywordsUniProt

• Carboxypeptidase
• Cell membrane
• Cell projection
• Chloride
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Hydrolase
• Isopeptide bond
• Membrane
• Metal-binding
• Metalloprotease
• Phosphoprotein
• Protease
• Receptor
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ACE2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SLC6A19
• ITGA5
• TMPRSS2
• ITGB1
• AP2M1
• GRM2
• HSPA5
• NHERF1
• PDZK1
• SHANK1
• SNX27
• VIM