Table 2.
Selected host proteins in infection
| Primary process | Gene/complex/family | Protein name | PPI? | Abundance? | Phosphorylation? | Act.? | Function in infection (known and/or hypothesized) | Cell location | Selected SARS-CoV-2 proteomics references |
|---|---|---|---|---|---|---|---|---|---|
| Host cell entry | ACE2 | Angiotensin-converting enzyme 2 | S | +/− | Virus receptor | PM | (41, 46, 47, 48, 49, 57, 61, 74, 86) | ||
| TMPRSS2 | Transmembrane protease serine 2 | S | Cleaves S (“priming”), especially at S2' site | PM | (41, 48, 49, 61) | ||||
| CTSB | Cathepsin B | S? | Cleaves S, alternative to TMPRSS2 | EN | (41, 46, 78, 112) | ||||
| CTSL | Cathepsin L | S | Cleaves S, alternative to TMPRSS2 | EN | (41, 46, 49, 61, 112) | ||||
| Endosomal release | PIKFYVE | 1-phosphatidylinositol 3-phosphate 5-kinase | Endosome maturation, with TPC2 | EN | (101) | ||||
| Protein expression | NUP98 | Nuclear pore complex protein Nup98 | Orf6 | + | Prevent host nuclear mRNA export | NM | (56, 101) | ||
| LARP1 | La-related protein 1 | N | - | Prioritize virus protein expression | CP, NU | (56, 101, 112) | |||
| UPF1 | Regulator of nonsense transcripts 1 | N | Binding by N represses NMD? | CP, NU | (56, 112) | ||||
| EIF4H | Eukaryotic translation initiation factor 4H | Nsp9 | Cap-dependent mRNA translation | PN | (56) | ||||
| EIF4E2 | Eukaryotic translation initiation factor 4E type 2 | Nsp2 | Represses cap-dependent translation | CP | (56, 112) | ||||
| Sec61 complex | SEC61 channel-forming translocon complex | Nsp8 | Protein entry into endoplasmic reticulum | CP, ERM | (56, 57) | ||||
| BRD4 | Bromodomain-containing protein 4 | E | + | Interference with antiviral response? | NU | (48, 56) | |||
| Protein processing | FURIN | Furin | S | Cleaves S (“priming”), especially at S1/S2 site | Golgi | ||||
| Protein degradation | CUL2 | Cullin 2 | Orf10 | + | Increase degradation of restriction factors? | CP, NU | (56, 59) | ||
| Cell signaling | CDK | Cyclin-dependent kinase | − | Cell cycle arrest, S/G2 | NU, MT, CP | (101) | |||
| MAPK | Mitogen-activated protein kinase | + | + | Viral replication+, stress response | NU, CP, MT | (59, 101, 102, 122) | |||
| AKT | RAC-alpha serine/threonine-protein kinase | + | + | −/+ | Viral replication+, cell proliferation & apoptosis regulation | NU, CP (PM) | (59, 101) | ||
| Cell structure | PHB complex | Prohibitin complex | nsp2 | Signaling interference, mitochondrial antiviral signaling, apoptosis− | MT, NU, CP, PM | (56, 112, 129) | |||
| CK2 complex | Casein kinase II | N | + | Cytoskeleton changes, filopodia+ | CP, NU | (56, 101, 102) | |||
| Stress, immunity | HSPA5 | Endoplasmic reticulum chaperone BiP | Unfolded protein response, virus receptor? | CP, PM | (61) | ||||
| NKRF | NF-kappaB–repressing factor | (nsp10) | IL-8 induction | NO, NU, CP | (78) | ||||
| CFB | Complement factor B | −/+ | + | Alternative complement pathway factor | Secreted | (120, 121, 122) | |||
| CFD | Complement factor D | Activates complement-dependent killing | Secreted | (120, 123) | |||||
| CFI | Complement factor I | + | + | Prevented from modulating complement | Secreted | (120, 123) | |||
| CFH | Complement factor H | +/− | + | Prevented from modulating complement | Secreted | (120, 122, 123) |
Abbreviations: Cell location—CP, cytoplasm; EN, endosome; ER, endoplasmic reticulum; ERM, ER membrane; LY, lysosome; MT, mitochondria; NM, nuclear membrane; NO, nucleolus; NU, nucleus; PM, plasma membrane; PN, perinuclear; other—HS, heparan sulfate; MAVS, mitochondrial antiviral signaling; NMD, nonsense mediated decay.
See supplemental Table S1 for more information on these proteins, complexes, and families. NKFR = nsp10 PPI may not be direct.