3.4.17.23 analysis receptor binding domain-ACE2 binding assay based on time-resolved FRET, which reliably monitors the interaction in a physiologically relevant and cellular context. The modular assay can monitor the impact of different cellular components, such as heparan sulfate, lipids, and membrane proteins on the receptor binding domain-ACE2 interaction and it can be extended to the full-length spike protein. The assay is high throughput compatible and can detect small-molecule competitive and allosteric modulators of the receptor binding domain-ACE2 interaction 764432 3.4.17.23 D206G deleterious missense variant 762786 3.4.17.23 D355N variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 D38V variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 D509Yr variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 E23K the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 E329G variant shows a strong binding affinity with SARS-CoV-2 spike protein variants with very strong E329G-V483A, E329G-G476S, strong E329G-A419S, E329G-A348T and moderate E329G-S383C,E329G-F486L interaction 765112 3.4.17.23 E37K non-synonymous single nucleotide polymorphism 765112 3.4.17.23 E484K mutation forms high-affinity complexes (~40% more than wild-type) 763365 3.4.17.23 E484K/N501Y variant possesses both enhanced affinity and antibody resistance 763365 3.4.17.23 F72V variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 G211R deleterious missense variant 762786 3.4.17.23 G211R missense variant, mutation affect protein structure and stability 762786 3.4.17.23 G326E variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 G352V variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 G726R non-synonymous single nucleotide polymorphism 765112 3.4.17.23 H345A no activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl 668550 3.4.17.23 H345L no activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl 668550 3.4.17.23 H34R variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 H378R deleterious missense variant 762786 3.4.17.23 H378R non-synonymous single nucleotide polymorphism 765112 3.4.17.23 H378R the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 H505A 1.5% of wild-type activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl as substrate 668550 3.4.17.23 H505L no activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl 668550 3.4.17.23 I21V the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 I468V deleterious missense variant 762786 3.4.17.23 K26R missense variant, mutation affect protein structure and stability 762786 3.4.17.23 K26R the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 K31R variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 K341R deleterious missense variant 762786 3.4.17.23 K417T/E484K/N501Y variant possesses both enhanced affinity and antibody resistance 763365 3.4.17.23 K481Q angiotensin I cleavage activity is 21% of wild-type activity, angiotensin II cleavage activity is 71.8% of wild-type activity 692319 3.4.17.23 K68E variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 L584A the point mutation in the ACE2 ectodomain markedly attenuates shedding. The resultant ACE2-L584A mutant trafficks to the cell membrane and facilitates SARS-CoV entry into target cells 707074 3.4.17.23 L595V non-synonymous single nucleotide polymorphism 765112 3.4.17.23 L731F deleterious missense variant 762786 3.4.17.23 L79I mutation increases binding of SARS-CoV-2 spike protein 765703 3.4.17.23 M62V variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 additional information ACE2 overexpression leads to markedly increased myocyte volume, assessed in primary rabbit myocytes 708684 3.4.17.23 additional information construction of a soluble truncated mutant enzyme lacking the transmembrane and cytosolic domains 657967, 659147 3.4.17.23 additional information construction of cytoplasmic tail deletion mutants by introduction of a stop codon at position amino acid 763. Construction of chimeric proteins containing portions of human ACE2 and portions of human CD4 or human beta-defensin-2, both showing loss of domain shedding 707074 3.4.17.23 additional information construction of several transgenic linages with differential virological and immunological outcome of severe acute respiratory syndrome coronavirus infection in susceptible and resistant transgenic mice expressing human ACE2, overview. Transgenic lineages AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively, are both permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appears to be more intense in AC70 than in AC22 mice, especially in the brain, differential SARS-CoV-induced morbidity and mortality between AC70 and AC22 mice, overview 709743 3.4.17.23 additional information generation of triple-transgenic-model mice with brain ACE2 overexpression on a chronically hypertensive, AngII-increased background. The transgenic mice show dramatically decreased baseline spontaneous baroreflex sensitivity and brain ACE2 activity compared with nontransgenic mice, whereas peripheral ACE2 activity/expression remains unaffected 708683 3.4.17.23 additional information M2-mutant CHO cells, mutated in tumor necrosis factor alpha-converting enzyme, TACE, show reduced shedding of the ectodomain of ACE2 and increased release of the larger soluble enzyme form, compared to the smaller one, overview. Tandem mutation in the juxtamembrane region also causes a decreaee in the small soluble enzyme form 707055 3.4.17.23 additional information overexpression of ACE 2 might have a protective effect by inhibiting cell growth and vascular endothelial growth factor a production in vitro 710171 3.4.17.23 additional information overexpression of ACE2 favorably affects the pathological process of left ventricular remodeling after myocardial infarction by inhibiting ACE activity, reducing AngII levels and upregulating Ang(1-7) expression 708649 3.4.17.23 additional information overexpression of ACE2, by usage of a recombinant adeno-associated virus 6 delivery system, in myocardium of stroke-prone spontaneously hypertensive rats mediates onset of experimental severe cardiac fibrosis 708684 3.4.17.23 N33I variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 N501Y mutation forms high-affinity complexes (~40% more than wild-type) 763365 3.4.17.23 N51S variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 N580A the mutation in the ectodomain has no effect on sACE2 release 707074 3.4.17.23 N64K the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 N720D missense variant, mutation affect protein structure and stability 762786 3.4.17.23 N720D non-synonymous single nucleotide polymorphism 765112 3.4.17.23 P263S non-synonymous single nucleotide polymorphism 765112 3.4.17.23 P284S non-synonymous single nucleotide polymorphism 765112 3.4.17.23 P583A the mutation in the ectodomain has no effect on sACE2 release 707074 3.4.17.23 Q102P the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 Q35K variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 Q37K variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 Q388L variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 Q42L mutation increases binding of SARS-CoV-2 spike protein 765703 3.4.17.23 R169Q angiotensin I cleavage activity is 5.2% of wild-type activity, angiotensin II cleavage activity is 1.1% of wild-type activity. The mutant enzyme does not show any activity with angiotensin I in the absence of chloride ions 692319 3.4.17.23 R169Q as active as wild-type enzyme with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl as substrate 668550 3.4.17.23 R169QK481QR514Q angiotensin I cleavage activity is 53.2% of wild-type activity, angiotensin II cleavage activity is 203.4% of wild-type activity 692319 3.4.17.23 R219C deleterious missense variant 762786 3.4.17.23 R219H deleterious missense variant 762786 3.4.17.23 R273K no activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl 668550 3.4.17.23 R273Q no activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl 668550 3.4.17.23 R514Q about 10% of wild-type activity with (7-methoxycoumarin-4-yl)acetyl-APK-2,4-dinitrophenyl as substrate 668550 3.4.17.23 R514Q angiotensin I cleavage activity is 52% of wild-type activity, angiotensin II cleavage activity is 179.3% of wild-type activity, enhancement of angiotensin II cleavage is a result of a 2.5-fold increase in Vmax compared with the wild-type 692319 3.4.17.23 R582A the mutation in the ectodomain has no effect on sACE2 release 707074 3.4.17.23 R697G deleterious missense variant 762786 3.4.17.23 R768W non-synonymous single nucleotide polymorphism 765112 3.4.17.23 S19P deleterious missense variant 762786 3.4.17.23 S19P the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 S477N mutation forms high-affinity complexes (~40% more than wild-type) 763365 3.4.17.23 S477N/E484K variant possesses both enhanced affinity and antibody resistance 763365 3.4.17.23 S547C deleterious missense variant 762786 3.4.17.23 S563L non-synonymous single nucleotide polymorphism 765112 3.4.17.23 S692P deleterious missense variant 762786 3.4.17.23 T27A the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 T92I the variant in the binding region increases disease susceptibility towards SARS-CoV-2 762786 3.4.17.23 V581A the mutation in the ectodomain has no effect on sACE2 release 707074 3.4.17.23 V604A the mutation in the ectodomain has no effect on sACE2 release 707074 3.4.17.23 W271A angiotensin I cleavage activity is 5.3% of wild-type activity, angiotensin II cleavage activity is 0.9% of wild-type activity. Lacks any significant chloride sensitivity with the substrate angiotensin I 692319 3.4.17.23 W459C non-synonymous single nucleotide polymorphism 765112 3.4.17.23 Y252N non-synonymous single nucleotide polymorphism 765112 3.4.17.23 Y50F variant exhibits lower binding to SARS-CoV-2 S protein 762786 3.4.17.23 Y83H variant exhibits lower binding to SARS-CoV-2 S protein 762786