Table 1 Known and predicted SLiMs in SARS-CoV-2 host-entry interactions.

Previously identified motifs are marked with (✓). Regular expressions follow POSIX definitions (23). The symbols ‘x’ and ‘.’ mark any residues in the definition of main residues and regular expressions.

RegionProtein
(UniProt
accession)
MotifELM class*Main
residues
Regular
expression
StartEndSequenceBinding
domain
Interaction
partner§
Interaction
type
ExtracellularSARS-CoV-2
spike
protein
(P0DTC2)
RGDLIG_RGDRGDRGD403405RGDPF00362 and
PF01839
RGD-binding
integrins, most
probably α5β1
and αvβ3
Host:virus
Multibasic
cleavage
sites (✓)
RRxR682687RRAR|SVPF00082 or
IPR001254
Furin-like PCs/
TMPRSS2
Host:virus
KxxKR811817KPSKR|SF
CendR (✓)LIG_NRP_
CendR_1
RxxR[RK].{0,2}[R]$682685RRARPF00754Neuropilin-1Host:virus
Integrin αv
(similar for
other α
chains)
(P06756)
Multibasic
cleavage
sites (✓)
xKR888892TKR|DLPF00082Furin-like PCsHost
Integrin β3
(similar for
other β
chains)
(P05106)
MIDAS (✓)DxSxSD.[TS].S145149DLSYSThe acidic part
of RGD-like
ligands
Host
Furin
(P09958)
RGDLIG_RGDRGDRGD498500RGDPF00362 and
PF01839
Possibly
RGD-binding
integrin dimers
Host
MIDASDxSxSD.[TS].S543547DISNS-Unknown
partner with
acidic residue
via metal ion
coordination
Host
Multibasic
cleavage
site (✓)
R697716RTEVEKAIRM
SRSRINDAFR
IPR001254TMPRSS2Host
IntracellularACE2
(Q9BYF1)
I-BAR
binding
LIG_IBAR_
NPY_1
NPYNPY779781NPYIPR027681I-BAR domain–
containing proteins
like IRSp53 or IRTKS
Host
Endocytic
sorting
signal
TRG_
ENDOCYTIC_2
YPxΦY[^P].[LMVIF]781784YASIPF00928Adapter protein
complex μ2 subunit
SH2
binding
YxxΦD((Y)[DE][^KRHG]
[DESTAPILVMFYW]
[^KR])|((Y)
[NQSTAILVMFY]
[^KRHG][ILV][^KR])
781785YASIDPF00017SH2 domain of SFKs
LIR
autophagy
LIG_LIR_
Gen_1
ExxYxxΦxΦ[EDST].{0,2}[WFY]
[^RKP][^PG]
[ILMV].{0,4}[LIVFM]
778786ENPYASIDIPF02991Related proteins LC3,
Atg8, GABARAP. There
may be some variation
in LIR motif specificity
apoPTBLIG_PTB_
Apo_2
Nxx[FY](.[^P].NP.[FY])|(.
[ILVMFY].N..[FY].)
789796GENNPGFQPF08416PTB-containing protein
with a preference for
NxxF core motifs
PBMLIG_PDZ_
Class_1
TxF$[ST].[ACVILF]$800805DVQTSFPF00595PDZ-containing proteins
with TxF$ preferences
such as NHERF3 and
SHANK1
Integrin β3
(P05106)
apoPTB (✓)LIG_PTB_
Apo_2
Nxx[FY](.[^P].NP.[FY])|(.
[ILVMFY].N..[FY].)
767774TANNPLYKPF00373
PF00630
Talins (high affinity)
Dok1 (low affinity)
Filamin-A (binding to
both apoPTB motifs
simultaneously)
Host
779786TFTNITYRPF00373
PF00630
Kindlin
Filamin-A (binding to
both apoPTB motifs
simultaneously)
PTB (✓)LIG_PTB_
Phospho_1
Nxx(Y)(.[^P].NP.(Y))|(.
[ILVMFY].N..(Y))
767773TANNPLYPF08416
PF00640
PF02174
Talins (low affinity)
Dok1 (high affinity)
Shc (binding to both PTB
motifs simultaneously)
779785TFTNITYPF00640Shc (binding to both
apoPTB motifs
simultaneously)
LIR
autophagy
LIG_LIR_
Gen_1
ExxYxxΦxΦ[EDST].{0,2}[WFY]
[^RKP][^PG]
[ILMV].{0,4}[LIVFM]
777783TSTFTNIPF02991Atg8 protein familyHost
Integrin β1
(P05556)
ApoPTB
(✓)
LIG_PTB_
Apo_2
Nxx[FY](.[^P].NP.[FY])|
(.[ILVMFY].N..[FY].)
777784TGENPIYKPF00373,
PF10480
PF00630
Talins (high affinity)
Dok1 (low affinity)
ICAP-1
Filamin-A (binding to
both apoPTB motifs
simultaneously)
Host
789796TVVNPKYEPF00373
PF00630
Kindlin
Filamin-A (binding to
both apoPTB motifs
simultaneously)
PTB (✓)LIG_PTB_
Phospho_1
Nxx(Y)(.[^P].NP.(Y))|(.
[ILVMFY].N..(Y))
777783TGENPIYPF10480
PF00640
PF02174
Talins (low affinity)
Dok1 (high affinity)
ICAP-1
Shc (binding to both PTB
motifs simultaneously)
789795TVVNPKYPF00640Shc (binding to both PTB
motifs simultaneously)

*Motif identifier as in the ELM resource.

†“|” denotes cleavage points for protease-recognition motifs.

‡Defined through use of Pfam (103) or InterPro (104), where applicable.

§PC, proprotein convertases.

║Not a SLiM but a structural motif.