General Information of Target

Target ID LDTP13582
Target Name E3 ubiquitin-protein ligase CBL-C (CBLC)
Gene Name CBLC
Gene ID 23624
Synonyms
CBL3; RNF57; E3 ubiquitin-protein ligase CBL-C; EC 2.3.2.27; RING finger protein 57; RING-type E3 ubiquitin transferase CBL-C; SH3-binding protein CBL-3; SH3-binding protein CBL-C; Signal transduction protein CBL-C
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MQEAPAALPTEPGPSPVPAFLGKLWALVGDPGTDHLIRWSPSGTSFLVSDQSRFAKEVLP
QYFKHSNMASFVRQLNMYGFRKVVSIEQGGLLRPERDHVEFQHPSFVRGREQLLERVRRK
VPALRGDDGRWRPEDLGRLLGEVQALRGVQESTEARLRELRQQNEILWREVVTLRQSHGQ
QHRVIGKLIQCLFGPLQAGPSNAGGKRKLSLMLDEGSSCPTPAKFNTCPLPGALLQDPYF
IQSPLPETNLGLSPHRARGPIISDIPEDSPSPEGTRLSPSSDGRREKGLALLKEEPASPG
GDGEAGLALAPNECDFCVTAPPPLPVAVVQAILEGKGSFSPEGPRNAQQPEPGDPREIPD
RGPLGLESGDRSPESLLPPMLLQPPQESVEPAGPLDVLGPSLQGREWTLMDLDMELSLMQ
PLVPERGEPELAVKGLNSPSPGKDPTLGAPLLLDVQAALGGPALGLPGALTIYSTPESRT
ASYLGPEASPSP
Target Bioclass
Enzyme
Function
Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Functionally coupled with the E2 ubiquitin-protein ligases UB2D1, UB2D2 and UB2D3. Regulator of EGFR mediated signal transduction; upon EGF activation, ubiquitinates EGFR. Isoform 1, but not isoform 2, inhibits EGF stimulated MAPK1 activation. Promotes ubiquitination of SRC phosphorylated at 'Tyr-419'. In collaboration with CD2AP may act as regulatory checkpoint for Ret signaling by modulating the rate of RET degradation after ligand activation; CD2AP converts it from an inhibitor to a promoter of RET degradation; the function limits the potency of GDNF on neuronal survival.
Uniprot ID
Q9ULV8
Ensemble ID
ENST00000341505.4
HGNC ID
HGNC:15961

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AU565 SNV: p.S43L DBIA    Probe Info 
CCK81 Deletion: p.G72VfsTer207 DBIA    Probe Info 
HT SNV: p.T268A .
LS123 SNV: p.Y277Ter DBIA    Probe Info 
MDST8 SNV: p.T152I .
MELHO SNV: p.Y261F .
NCIH1155 SNV: p.R455I DBIA    Probe Info 
TOV21G SNV: p.R10Ter .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 3 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C354(1.87)  LDD3320  [1]
NAIA_5
 Probe Info 
C32(20.00)  LDD2227  [2]
IA-alkyne
 Probe Info 
N.A.  LDD0162  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0276  AC17 HEK-293T C189(1.07)  LDD0874  [4]
 LDCM0277  AC18 HEK-293T C189(1.00)  LDD0875  [4]
 LDCM0278  AC19 HEK-293T C189(1.13)  LDD0876  [4]
 LDCM0280  AC20 HEK-293T C189(1.02)  LDD0878  [4]
 LDCM0281  AC21 HEK-293T C189(1.12)  LDD0879  [4]
 LDCM0282  AC22 HEK-293T C189(0.99)  LDD0880  [4]
 LDCM0283  AC23 HEK-293T C189(1.09)  LDD0881  [4]
 LDCM0284  AC24 HEK-293T C189(0.99)  LDD0882  [4]
 LDCM0320  AC57 HEK-293T C189(1.02)  LDD0918  [4]
 LDCM0321  AC58 HEK-293T C189(0.96)  LDD0919  [4]
 LDCM0322  AC59 HEK-293T C189(0.98)  LDD0920  [4]
 LDCM0324  AC60 HEK-293T C189(0.64)  LDD0922  [4]
 LDCM0325  AC61 HEK-293T C189(0.98)  LDD0923  [4]
 LDCM0326  AC62 HEK-293T C189(0.96)  LDD0924  [4]
 LDCM0327  AC63 HEK-293T C189(1.13)  LDD0925  [4]
 LDCM0328  AC64 HEK-293T C189(1.03)  LDD0926  [4]
 LDCM0329  AC65 HEK-293T C189(1.19)  LDD0927  [4]
 LDCM0330  AC66 HEK-293T C189(1.08)  LDD0928  [4]
 LDCM0331  AC67 HEK-293T C189(1.01)  LDD0929  [4]
 LDCM0332  AC68 HEK-293T C189(1.09)  LDD0930  [4]
 LDCM0333  AC69 HEK-293T C189(1.30)  LDD0931  [4]
 LDCM0335  AC70 HEK-293T C189(0.95)  LDD0933  [4]
 LDCM0336  AC71 HEK-293T C189(0.89)  LDD0934  [4]
 LDCM0337  AC72 HEK-293T C189(1.60)  LDD0935  [4]
 LDCM0338  AC73 HEK-293T C189(1.38)  LDD0936  [4]
 LDCM0339  AC74 HEK-293T C189(1.43)  LDD0937  [4]
 LDCM0340  AC75 HEK-293T C189(1.32)  LDD0938  [4]
 LDCM0341  AC76 HEK-293T C189(1.19)  LDD0939  [4]
 LDCM0342  AC77 HEK-293T C189(1.03)  LDD0940  [4]
 LDCM0343  AC78 HEK-293T C189(1.06)  LDD0941  [4]
 LDCM0344  AC79 HEK-293T C189(1.46)  LDD0942  [4]
 LDCM0346  AC80 HEK-293T C189(1.22)  LDD0944  [4]
 LDCM0347  AC81 HEK-293T C189(0.96)  LDD0945  [4]
 LDCM0348  AC82 HEK-293T C189(1.32)  LDD0946  [4]
 LDCM0632  CL-Sc Hep-G2 C32(20.00)  LDD2227  [2]
 LDCM0367  CL1 HEK-293T C189(0.43)  LDD0965  [4]
 LDCM0368  CL10 HEK-293T C189(0.96)  LDD0966  [4]
 LDCM0374  CL105 HEK-293T C189(0.87)  LDD0972  [4]
 LDCM0375  CL106 HEK-293T C189(0.91)  LDD0973  [4]
 LDCM0376  CL107 HEK-293T C189(1.04)  LDD0974  [4]
 LDCM0377  CL108 HEK-293T C189(0.97)  LDD0975  [4]
 LDCM0378  CL109 HEK-293T C189(0.89)  LDD0976  [4]
 LDCM0379  CL11 HEK-293T C189(1.15)  LDD0977  [4]
 LDCM0380  CL110 HEK-293T C189(0.88)  LDD0978  [4]
 LDCM0381  CL111 HEK-293T C189(0.86)  LDD0979  [4]
 LDCM0390  CL12 HEK-293T C189(0.81)  LDD0988  [4]
 LDCM0396  CL125 HEK-293T C189(0.92)  LDD0994  [4]
 LDCM0397  CL126 HEK-293T C189(0.89)  LDD0995  [4]
 LDCM0398  CL127 HEK-293T C189(0.99)  LDD0996  [4]
 LDCM0399  CL128 HEK-293T C189(0.93)  LDD0997  [4]
 LDCM0400  CL13 HEK-293T C189(0.64)  LDD0998  [4]
 LDCM0401  CL14 HEK-293T C189(0.69)  LDD0999  [4]
 LDCM0402  CL15 HEK-293T C189(0.59)  LDD1000  [4]
 LDCM0403  CL16 HEK-293T C189(0.74)  LDD1001  [4]
 LDCM0404  CL17 HEK-293T C189(0.65)  LDD1002  [4]
 LDCM0405  CL18 HEK-293T C189(0.89)  LDD1003  [4]
 LDCM0406  CL19 HEK-293T C189(0.87)  LDD1004  [4]
 LDCM0407  CL2 HEK-293T C189(0.55)  LDD1005  [4]
 LDCM0408  CL20 HEK-293T C189(0.92)  LDD1006  [4]
 LDCM0409  CL21 HEK-293T C189(0.70)  LDD1007  [4]
 LDCM0410  CL22 HEK-293T C189(0.98)  LDD1008  [4]
 LDCM0411  CL23 HEK-293T C189(0.81)  LDD1009  [4]
 LDCM0412  CL24 HEK-293T C189(0.93)  LDD1010  [4]
 LDCM0413  CL25 HEK-293T C189(0.82)  LDD1011  [4]
 LDCM0414  CL26 HEK-293T C189(0.90)  LDD1012  [4]
 LDCM0415  CL27 HEK-293T C189(0.97)  LDD1013  [4]
 LDCM0416  CL28 HEK-293T C189(0.88)  LDD1014  [4]
 LDCM0417  CL29 HEK-293T C189(0.88)  LDD1015  [4]
 LDCM0418  CL3 HEK-293T C189(0.86)  LDD1016  [4]
 LDCM0419  CL30 HEK-293T C189(1.01)  LDD1017  [4]
 LDCM0429  CL4 HEK-293T C189(0.77)  LDD1027  [4]
 LDCM0436  CL46 HEK-293T C189(1.11)  LDD1034  [4]
 LDCM0437  CL47 HEK-293T C189(1.09)  LDD1035  [4]
 LDCM0438  CL48 HEK-293T C189(1.25)  LDD1036  [4]
 LDCM0439  CL49 HEK-293T C189(1.04)  LDD1037  [4]
 LDCM0440  CL5 HEK-293T C189(0.74)  LDD1038  [4]
 LDCM0441  CL50 HEK-293T C189(1.05)  LDD1039  [4]
 LDCM0442  CL51 HEK-293T C189(0.86)  LDD1040  [4]
 LDCM0443  CL52 HEK-293T C189(1.11)  LDD1041  [4]
 LDCM0444  CL53 HEK-293T C189(0.85)  LDD1042  [4]
 LDCM0445  CL54 HEK-293T C189(0.79)  LDD1043  [4]
 LDCM0446  CL55 HEK-293T C189(1.29)  LDD1044  [4]
 LDCM0447  CL56 HEK-293T C189(0.72)  LDD1045  [4]
 LDCM0448  CL57 HEK-293T C189(1.28)  LDD1046  [4]
 LDCM0449  CL58 HEK-293T C189(1.38)  LDD1047  [4]
 LDCM0450  CL59 HEK-293T C189(1.05)  LDD1048  [4]
 LDCM0451  CL6 HEK-293T C189(0.66)  LDD1049  [4]
 LDCM0452  CL60 HEK-293T C189(1.29)  LDD1050  [4]
 LDCM0453  CL61 HEK-293T C189(0.81)  LDD1051  [4]
 LDCM0454  CL62 HEK-293T C189(1.00)  LDD1052  [4]
 LDCM0455  CL63 HEK-293T C189(1.06)  LDD1053  [4]
 LDCM0456  CL64 HEK-293T C189(1.03)  LDD1054  [4]
 LDCM0457  CL65 HEK-293T C189(1.10)  LDD1055  [4]
 LDCM0458  CL66 HEK-293T C189(1.21)  LDD1056  [4]
 LDCM0459  CL67 HEK-293T C189(1.32)  LDD1057  [4]
 LDCM0460  CL68 HEK-293T C189(1.09)  LDD1058  [4]
 LDCM0461  CL69 HEK-293T C189(1.03)  LDD1059  [4]
 LDCM0462  CL7 HEK-293T C189(0.92)  LDD1060  [4]
 LDCM0463  CL70 HEK-293T C189(1.21)  LDD1061  [4]
 LDCM0464  CL71 HEK-293T C189(1.14)  LDD1062  [4]
 LDCM0465  CL72 HEK-293T C189(1.15)  LDD1063  [4]
 LDCM0466  CL73 HEK-293T C189(1.06)  LDD1064  [4]
 LDCM0467  CL74 HEK-293T C189(1.33)  LDD1065  [4]
 LDCM0469  CL76 HEK-293T C189(1.42)  LDD1067  [4]
 LDCM0470  CL77 HEK-293T C189(1.33)  LDD1068  [4]
 LDCM0471  CL78 HEK-293T C189(1.22)  LDD1069  [4]
 LDCM0472  CL79 HEK-293T C189(1.43)  LDD1070  [4]
 LDCM0473  CL8 HEK-293T C189(1.34)  LDD1071  [4]
 LDCM0474  CL80 HEK-293T C189(0.87)  LDD1072  [4]
 LDCM0475  CL81 HEK-293T C189(1.26)  LDD1073  [4]
 LDCM0476  CL82 HEK-293T C189(1.62)  LDD1074  [4]
 LDCM0477  CL83 HEK-293T C189(1.66)  LDD1075  [4]
 LDCM0478  CL84 HEK-293T C189(1.13)  LDD1076  [4]
 LDCM0479  CL85 HEK-293T C189(1.08)  LDD1077  [4]
 LDCM0480  CL86 HEK-293T C189(0.84)  LDD1078  [4]
 LDCM0481  CL87 HEK-293T C189(1.49)  LDD1079  [4]
 LDCM0482  CL88 HEK-293T C189(1.56)  LDD1080  [4]
 LDCM0483  CL89 HEK-293T C189(1.34)  LDD1081  [4]
 LDCM0484  CL9 HEK-293T C189(1.22)  LDD1082  [4]
 LDCM0485  CL90 HEK-293T C189(1.03)  LDD1083  [4]
 LDCM0468  Fragment33 HEK-293T C189(1.07)  LDD1066  [4]
 LDCM0022  KB02 A431 C354(1.80)  LDD2258  [1]
 LDCM0023  KB03 A431 C354(2.32)  LDD2675  [1]
 LDCM0024  KB05 RVH421 C354(1.87)  LDD3320  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tyrosine-protein kinase Yes (YES1) Tyr protein kinase family P07947
Ubiquitin-conjugating enzyme E2 K (UBE2K) Ubiquitin-conjugating enzyme family P61086
Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Ataxin-1 (ATXN1) ATXN1 family P54253
TAR DNA-binding protein 43 (TARDBP) . Q13148

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264
3 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
4 Reimagining high-throughput profiling of reactive cysteines for cell-based screening of large electrophile libraries. Nat Biotechnol. 2021 May;39(5):630-641. doi: 10.1038/s41587-020-00778-3. Epub 2021 Jan 4.