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Synonyms
angiotensin-converting enzyme 2, tmprss2, ace-2, angiotensin converting enzyme 2, hace2, angiotensin converting enzyme-2, sace2, ace 2, angiotensin converting enzyme ii, angiotensin-converting enzyme type 2,
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evolution
ACE2 is widely expressed in the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Remarkably, its structure is highly conserved. Comparison of human ACE2 with that of a civet (Paguma larvata), a bat (Rhinolophus sinicus), a bird (Nipponia nippon), a snake (Protobothrops mucrosquamatus), a frog (Xenopus laevis), and a fish (Callorhinchus milii) reveal amino acid sequence identity of 83%, 81%, 83%, 61%, 60%, and 59%, respectively
evolution
Spike protein of SARS-CoV-2 exhibits the highest binding to human (h)ACE2 of all the species tested, forming the highest number of hydrogen bonds with hACE2. Pangolin (Manis javanica) ACE2 shows the next highest binding affinity despite having a relatively low sequence homology, whereas the affinity of monkey ACE2 is much lower despite its high sequence similarity to hACE2. ACE2 species in the upper half of the predicted affinity range (Macaca fascicularis, Mesocricetus auratus, Canis luparis, Mustela putorius furot, Felis catus) are permissive to SARS-CoV-2 infection, supporting a correlation between binding affinity and infection susceptibility
physiological function
angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2 of certain species can be utilized by SARS-CoV-2. SARS-CoV-2 tends to utilize ACE2 of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2. SARS-CoV-2 has a high genetic relationship with a bat coronavirus (BatCoV RaTG13) with a 96% genomic nucleotide sequence identity. The close phylogenetic relationship to Bat RaTG13 provides evidence for a bat origin of SARS-CoV-2. Direct transmission of the virus from bats to humans is unlikely due to the lack of direct contact between bats and humans (in Wuhan, China). There are probably intermediate hosts transmitting SARS-CoV-2 to humans. Combined phylogenetic analysis and critical site marking is used to predict the utilizing capability of ACE2 from different animal species by SARS-CoV-2. It is confirmed that pangolin (Manis javanica), cat (Felis catus), cow (Bos taurus), buffalo (Bubalus bubalis), goat (Capra hircus), sheep (Ovis aries) and pigeon (Columba livia) ACE2 might be utilized by SARS-CoV-2, indicating potential interspecies transmission of the virus from bats to these animals and among these animals
physiological function
the receptor binding domain (RBD) of spike glycoprotein is responsible for entry of coronaviruses (SARS-CoV-2 and SARS-CoV) into host cells. The RBDs from the two viruses share 72% identity in amino acid sequences, and molecular simulation reveals highly similar ternary structures. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a distinct loop with flexible glycyl residues replacing rigid prolyl residues in SARS-CoV. Molecular modeling reveals that SARS-CoV-2 RBD has a stronger interaction with angiotensin converting enzyme 2 (ACE2). A unique phenylalanine F486 in the flexible loop likely plays a major role because its penetration into a deep hydrophobic pocket in ACE2. ACE2 is widely expressed with conserved primary structures throughout the animal kingdom from fish, amphibians, reptiles, birds, to mammals. Structural analysis suggests that ACE2 from these animals can potentially bind RBD of SARS-CoV-2, making them all possible natural hosts for the virus
physiological function
interaction between SARS-CoV-2 and ACE2. The binding free energy of SARS-CoV-2 spike protein to the civet ACE2 is -5.11 kcal/mol, i.e. a lower binding affinity than human ACE2. Compared with the human ACE2 molecule, the civet ACE2 has a substitution from phenylalanine to serine at position 40 in the first helix at the N-terminal lobe region. This mutation breaks the pi-pi stacking interactions between the N-terminal helices, resulting in the side-chain rearrangement and loose helix-packing structures
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medicine
angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2 of certain species can be utilized by SARS-CoV-2. SARS-CoV-2 tends to utilize ACE2 of various mammals, except murines, and some birds, such as pigeon. This prediction may help to screen the intermediate hosts of SARS-CoV-2. SARS-CoV-2 has a high genetic relationship with a bat coronavirus (BatCoV RaTG13) with a 96% genomic nucleotide sequence identity. The close phylogenetic relationship to Bat RaTG13 provides evidence for a bat origin of SARS-CoV-2. Direct transmission of the virus from bats to humans is unlikely due to the lack of direct contact between bats and humans (in Wuhan, China). There are probably intermediate hosts transmitting SARS-CoV-2 to humans. Combined phylogenetic analysis and critical site marking is used to predict the utilizing capability of ACE2 from different animal species by SARS-CoV-2. It is confirmed that pangolin (Manis javanica), cat (Felis catus), cow (Bos taurus), buffalo (Bubalus bubalis), goat (Capra hircus), sheep (Ovis aries) and pigeon (Columba livia) ACE2 might be utilized by SARS-CoV-2, indicating potential interspecies transmission of the virus from bats to these animals and among these animals
medicine
among 226000 SARSCoV-2 sequences, 1573 missense mutations are found in the spike gene, and 226 of them were within the receptor-binding domain region that directly interacts with human ACE2. Modeling shows that most of the 74 missense mutations in the receptor-binding domain region of the interaction interface have little impact on spike binding to ACE2, whereas several within the spike receptor-binding domain increase the binding affinity toward human ACE2 thus making the virus likely more contagious
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Chen, Y.; Guo, Y.; Pan, Y.; Zhao, Z.
Structure analysis of the receptor binding of 2019-nCoV
Biochem. Biophys. Res. Commun.
525
135-140
2020
Nipponia nippon (A0A091UR55), Rhinolophus sinicus (E2DHI7), Paguma larvata (Q56NL1), Homo sapiens (Q9BYF1), Callorhinchus milii (XP_007889845.1), Xenopus laevis (XP_018104311.1), Protobothrops mucrosquamatus (XP_029140508.1)
brenda
Qiu, Y.; Zhao, Y.B.; Wang, Q.; Li, J.Y.; Zhou, Z.J.; Liao, C.H.; Ge, X.Y.
Predicting the angiotensin converting enzyme 2 (ACE2) utilizing capability as the receptor of SARS-CoV-2
Microbes Infect.
22
221-225
2020
Columba livia (A0A2I0MLI2), Sus scrofa (K7GLM4), Felis catus (Q56H28), Paguma larvata (Q56NL1), Mus musculus (Q8R0I0), Homo sapiens (Q9BYF1), Homo sapiens, Rhinolophus sinicus (U5WHY8), Capra hircus (W6CG84), Bos taurus (XP_005228485.1), Bubalus bubalis (XP_006041602.1), Ovis aries (XP_011961657.1), Manis javanica (XP_017505752.1)
brenda
Piplani, S.; Singh, P.K.; Winkler, D.A.; Petrovsky, N.
In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
Sci. Rep.
11
13063
2021
Mesocricetus auratus (A0A1U7QTA1), Macaca fascicularis (A0A2K5X283), Equus caballus (F6V9L3), Canis lupus familiaris (J9P7Y2), Canis lupus familiaris, Bos taurus (Q2HJI5), Mustela putorius furo (Q2WG88), Mustela putorius furo, Felis catus (Q56H28), Paguma larvata (Q56NL1), Mus musculus (Q8R0I0), Homo sapiens (Q9BYF1), Homo sapiens, Rhinolophus sinicus (U5WHY8), Ophiophagus hannah (V8NIH2), Panthera tigris (XP_007090142), Manis javanica (XP_017505752.1)
brenda
Chen, P.; Wang, J.; Xu, X.; Li, Y.; Zhu, Y.; Li, X.; Li, M.; Hao, P.
Molecular dynamic simulation analysis of SARS-CoV-2 spike mutations and evaluation of ACE2 from pets and wild animals for infection risk
Comput. Biol. Chem.
96
107613
2022
Manis javanica, Paguma larvata (Q56NL1), Mus musculus (Q8R0I0), Homo sapiens (Q9BYF1)
brenda