Table 1 Degron motifs and cancer-associated dysfunction.
Gene
name
Protein
name
E3 ligase or subunit-
recognizing degron
InstanceStarting
position
Motif*SourceAssociated mechanism in cancer
TP53p53MDM2FSDLWKLL19F[^P]{3}W[^P]{2,3}
[VIL]
DEG_MDM2_1Increased degradation
by increased E3
ligase activity
CDKN1Bp27KIP1SKP2-CKS1SVEQTPKK183..[DE].(T)P.KDEG_SCF_SKP2-
CKS1_1
Increased degradation
by increased E3
ligase activity
CTNNB1β-cateninβ-TrCP1DSGIHS32D(S)G.{2,3}([ST])DEG_SCF_TRCP1_1Missense mutations
in degron
MYCMYCFBXW7LLPTPPLS55[LIVMP].{0,2}(T)P..
([ST])
DEG_SCF_FBW7_1Translocation, mutation of the
posttranslational modification site
needed for E3 ligase binding,
increased gene expression,
and stabilization by MCV-mediated
inhibition of FBWX7
ERGERGSPOPASSSS42[AVP].[ST][ST][ST](61)Gene deletion by chromosomal
translocation
HIF1AHIF-1αVHLLAPAAGDTIISLDF400[IL]A(P).{6,8}
[FLIVM].[FLIVM]
DEG_ODPH_VHL_1Stabilization by E3 ligase
inactivation
NOTCH1NOTCH1FBXW7PFLTPSPE2508[LIVMP].{0,2}(T)P..EDEG_SCF_FBW7_2Truncating mutations in C-terminal
PEST region
TP63p63ITCHPPPY540PP.Y(342)Reduced gene
expression
NFE2L2NRF2KEAP1DEETGE77[DNS].[DES][TNS]
GE
DEG_Kelch_Keap1_1Missense mutations in both
degrons, NRF2 deletion induces
tumor formation
NFE2L2NRF2KEAP1QDIDLGV26QD.DLGVDEG_Kelch_Keap1_2
ETV1ETV1COP1DEQFVPDY67[STDE]{1,3}.{0,2}
[TSDE].{2,3}
VP[STDE]G{0,1}
[FLIMVYPA]
DEG_COP1Translocation deleting
the N-terminal degron
CSF1RCSF-1RCBLLLQPNNYQFC963[DN].(Y)[ST]..P(157)Mutations abolishing posttranslational
modification site needed for E3
ligase binding
METc-Met
(HGFR)
CBLDYR1002D(Y)R(157)Mutations in posttranslational
modification site needed for E3 ligase
binding/exon skipping/translocation
deleting the degron
SH2BAPSCBLRAVENQYSFY623RA[VI].NQ(Y)[ST](157)
AURKBAurora
kinase B
CDH1QKENS3.KEN.DEG_APCC_KENBOX_2
CCNA1Cyclin A1CDC20/CDH1FDIYMD135[ILVMF].[ILMVP]
[FHY].[DE]
LIG_APCC_ABBA_1
CCNB1Cyclin B1CDC20/CDH1PRTALGDIG41.R..L..[LIVM].DEG_APCC_DBOX_1
PTTG1SecurinCDC20DKENG8.KEN.DEG_APCC_KENBOX_2

*Definition of regular expressions describing linear motif sequence conservation: [LIV], [] refers to group of amino acids, in this case, Leu, Ile, and Val are all allowed; [^P], anything but Pro is allowed; a period (.) denotes any kind of residue; (T), modified residue (that is, phosphorylated Thr); .{0.2}, variable length position, in this case, 0, 1, and 2 positions of any kind of amino acid.

†Known motifs are represented as standard regular expressions and were taken from the ELM database (48) or from the references cited.

‡Does not meet standard motif definition.