| General Information |
| MoonProt ID | 413 |
| First appeared in release | 3.0 |
| Name(s) | Angiotensin-converting enzyme 2
Gene: ACE2
Alternative name(s):
Angiotensin-converting enzyme homolog Short name: ACEH
Angiotensin-converting enzyme-related carboxypeptidase Short name: ACE-related carboxypeptidase
Metalloprotease MPROT15 |
| UniProt ID | Q9BYF1 (ACE2_HUMAN) |
| GO terms | GO:0046718 viral entry into host cell
GO:0046813 receptor-mediated virion attachment to host cell
GO:0009986 cell surface
GO:0005886 plasma membrane
GO:0001618 virus receptor activity
GO:0005515 protein binding
GO:0051957 positive regulation of amino acid transport
GO:0005576 extracellular region
GO:0004180 carboxypeptidase activity
GO:0008233 peptidase activity
GO:0016787 hydrolase activity
GO:0046872 metal ion binding
GO:0006508 proteolysis
GO:0016032 viral process
GO:0008237 metallopeptidase activity
GO:0005737 cytoplasm
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0008241 peptidyl-dipeptidase activity
GO:0004175 endopeptidase activity
GO:0070062 extracellular exosome |
| Organisms for which functions have been demonstrated | Homo sapiens (Human) |
| Sequence length | 805 amino acids |
| FASTA sequence | >sp|Q9BYF1|ACE2_HUMAN Angiotensin-converting enzyme 2 OS=Homo sapiens OX=9606 GN=ACE2 PE=1 SV=2
MSSSSWLLLSLVAVTAAQSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQSTLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDNPQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYEDYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYISPIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVSVGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMGHIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEINFLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETYCDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNMLRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQSIKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKPRISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQPPVSIWLIVFGVVMGVIVVGIVILIFTGIRDRKKKNKARSGENPYASIDISKGENNPGFQNTDDVQTSF |
| Structure Information |
| PDB ID | 1R42, 1R4L, 1XJP, 2AJF, 3D0G, 3D0H, 3D0I, 3KBH, 3SCI, 3SCJ, 3SCK, 3SCL, 6ACG, 6ACJ, 6ACK, 6CS2, 6LZG, 6M0J, 6M17, 6M18, 6M1D, 6VW1 |
| Quaternary structure | Homodimer (PubMed: 32132184) |
| SCOP | Class d: Alpha and beta proteins (a+b).
Fold d.92: Zincin-like.
Superfamily d.92.1: Metalloproteases ("zincins"), catalytic domain.
Family d.92.1.5: Neurolysin-like.
Combines M2, M3 and M32 families of metalloproteases.
The N-terminal half of the structure is multihelical; the C-terminal half contains the thermolysin-like catalytic domain. |
| CATH | 1 Matching CATH Superfamily.
Superfamily: 3.30.70.1840 Spike protein, C-terminal core receptor binding subdomain.
2 Matching CATH Domains.
Domain: 2ajfE01 PDB code 2ajf, chain E, domain 01 Superfamily: 3.30.70.1840.
Domain: 2ajfF01 PDB code 2ajf, chain F, domain 01 Superfamily: 3.30.70.1840. |
| TM Helix Prediction | 1 ( 741 - 763) transmembrane protein |
| DisProt Annotation | Disorder content: 4.6%
Term: Disorder, Fragment 769-805
Term: Regulation of phosphorylation, Fragment 779-783 |
| Predicted Disorder Regions | predicted disorder between 45-50 and 760-800 |
| Connections to Disease |
| OMIM ID | 300335 ANGIOTENSIN I-CONVERTING ENZYME 2; ACE2 |
| Function 1 |
| Function description | Carboxypeptidase enzyme |
| References for function | Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. Journal of Biological Chemistry. 2004 Apr 23;279(17):17996-8007.
Gheblawi, M., Wang, K., Viveiros, A., Nguyen, Q., Zhong, J., Turner, A., Raizada, M., Grant, M., & Oudit, G. (2020). Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circulation Research, 126, 1456-1474. 10.1161/CIRCRESAHA.120.317015 |
| E.C. number | 3.4.17.23 |
| Location of functional site(s) | His374, His378, His401, Glu406
Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, Ryan D, Fisher M, Williams D, Dales NA, Patane MA. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. Journal of Biological Chemistry. 2004 Apr 23;279(17):17996-8007. |
| Cellular location of function | Transmembrane protein in the plasma membrane |
| Comments | "ACE2 acts as a simple carboxypeptidase able to hydrolyze Ang I, forming Ang 1–9 and Ang II to Ang 1–7". "Cleaves and inactivates bioactive apelin peptides apelin-13 and apelin-36 through a negative feedback mechanism in the heart and vasculature" (Gheblawi et al. 2020). |
| Function 2 |
| Function description | chaperone for BoAT in amino acid transport |
| References for function | Camargo SM, Singer D, Makrides V, Huggel K, Pos KM, Wagner CA, Kuba K, Danilczyk U, Skovby F, Kleta R, Penninger JM. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology. 2009 Mar 1;136(3):872-82.
Gheblawi, M., Wang, K., Viveiros, A., Nguyen, Q., Zhong, J., Turner, A., Raizada, M., Grant, M., & Oudit, G. (2020). Angiotensin-Converting Enzyme 2: SARS-CoV-2 Receptor and Regulator of the Renin-Angiotensin System: Celebrating the 20th Anniversary of the Discovery of ACE2. Circulation Research, 126, 1456-1474. 10.1161/CIRCRESAHA.120.317015 |
| E.C. number | |
| Location of functional site(s) | Collectrin-like Domain of ACE2 Mediating Homo Dimerization
|
| Cellular location of function | plasma membrane |
| Comments | "ACE2 is necessary for the expression of the Hartnup transporter in the intestine, and the differential functional association of mutant B(0)AT1 transporters with ACE2 in the intestine regulates the phenotypic heterogeneity of human Hartnup disorder" (Gheblawi et al. 2020). |