Details of the Target

General Information of Target

Target ID LDTP10787
Target Name Tribbles homolog 3 (TRIB3)
Gene Name TRIB3
Gene ID 57761
Synonyms
C20orf97; NIPK; SKIP3; TRB3; Tribbles homolog 3; TRB-3; Neuronal cell death-inducible putative kinase; SINK; p65-interacting inhibitor of NF-kappa-B
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MSWGTELWDQFDNLEKHTQWGIDILEKYIKFVKERTEIELSYAKQLRNLSKKYQPKKNSK
EEEEYKYTSCKAFISNLNEMNDYAGQHEVISENMASQIIVDLARYVQELKQERKSNFHDG
RKAQQHIETCWKQLESSKRRFERDCKEADRAQQYFEKMDADINVTKADVEKARQQAQIRH
QMAEDSKADYSSILQKFNHEQHEYYHTHIPNIFQKIQEMEERRIVRMGESMKTYAEVDRQ
VIPIIGKCLDGIVKAAESIDQKNDSQLVIEAYKSGFEPPGDIEFEDYTQPMKRTVSDNSL
SNSRGEGKPDLKFGGKSKGKLWPFIKKNKLMSLLTSPHQPPPPPPASASPSAVPNGPQSP
KQQKEPLSHRFNEFMTSKPKIHCFRSLKRGLSLKLGATPEDFSNLPPEQRRKKLQQKVDE
LNKEIQKEMDQRDAITKMKDVYLKNPQMGDPASLDHKLAEVSQNIEKLRVETQKFEAWLA
EVEGRLPARSEQARRQSGLYDSQNPPTVNNCAQDRESPDGSYTEEQSQESEMKVLATDFD
DEFDDEEPLPAIGTCKALYTFEGQNEGTISVVEGETLYVIEEDKGDGWTRIRRNEDEEGY
VPTSYVEVCLDKNAKDS
Target Bioclass
Enzyme
Family
Protein kinase superfamily, CAMK Ser/Thr protein kinase family, Tribbles subfamily
Subcellular location
Nucleus
Function
Inactive protein kinase which acts as a regulator of the integrated stress response (ISR), a process for adaptation to various stress. Inhibits the transcriptional activity of DDIT3/CHOP and is involved in DDIT3/CHOP-dependent cell death during ER stress. May play a role in programmed neuronal cell death but does not appear to affect non-neuronal cells. Acts as a negative feedback regulator of the ATF4-dependent transcription during the ISR: while TRIB3 expression is promoted by ATF4, TRIB3 protein interacts with ATF4 and inhibits ATF4 transcription activity. Disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. May bind directly to and mask the 'Thr-308' phosphorylation site in AKT1. Interacts with the NF-kappa-B transactivator p65 RELA and inhibits its phosphorylation and thus its transcriptional activation activity. Interacts with MAPK kinases and regulates activation of MAP kinases. Can inhibit APOBEC3A editing of nuclear DNA.
Uniprot ID
Q96RU7
Ensemble ID
ENST00000217233.9
HGNC ID
HGNC:16228

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
BTD
 Probe Info  		C186(1.31)  LDD2135  [1]
Johansson_61
 Probe Info  		_(4.35)  LDD1485  [2]
AHL-Pu-1
 Probe Info  		C46(2.07); C222(3.99)  LDD0171  [3]
DBIA
 Probe Info  		C222(29.30)  LDD0209  [4]
TFBX
 Probe Info  		N.A.  LDD0148  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0026  4SU-RNA+native RNA DM93 C46(2.07); C222(3.99)  LDD0171  [3]
 LDCM0216  AC100 HCT 116 C88(0.88); C96(0.88)  LDD0533  [6]
 LDCM0217  AC101 HCT 116 C88(0.82); C96(0.82)  LDD0534  [6]
 LDCM0218  AC102 HCT 116 C88(0.97); C96(0.97)  LDD0535  [6]
 LDCM0219  AC103 HCT 116 C88(1.06); C96(1.06)  LDD0536  [6]
 LDCM0220  AC104 HCT 116 C88(0.73); C96(0.73)  LDD0537  [6]
 LDCM0221  AC105 HCT 116 C88(0.89); C96(0.89)  LDD0538  [6]
 LDCM0222  AC106 HCT 116 C88(0.98); C96(0.98)  LDD0539  [6]
 LDCM0223  AC107 HCT 116 C88(1.08); C96(1.08)  LDD0540  [6]
 LDCM0224  AC108 HCT 116 C88(1.00); C96(1.00)  LDD0541  [6]
 LDCM0225  AC109 HCT 116 C88(1.09); C96(1.09)  LDD0542  [6]
 LDCM0226  AC11 HEK-293T C222(0.85)  LDD1509  [7]
 LDCM0227  AC110 HCT 116 C88(0.87); C96(0.87)  LDD0544  [6]
 LDCM0228  AC111 HCT 116 C88(1.00); C96(1.00)  LDD0545  [6]
 LDCM0229  AC112 HCT 116 C88(1.00); C96(1.00)  LDD0546  [6]
 LDCM0237  AC12 HEK-293T C222(0.99)  LDD1510  [7]
 LDCM0259  AC14 HEK-293T C222(0.96)  LDD1512  [7]
 LDCM0270  AC15 HEK-293T C222(0.85)  LDD1513  [7]
 LDCM0278  AC19 HEK-293T C222(1.51)  LDD1517  [7]
 LDCM0280  AC20 HEK-293T C222(1.03)  LDD1519  [7]
 LDCM0282  AC22 HEK-293T C222(0.98)  LDD1521  [7]
 LDCM0283  AC23 HEK-293T C222(0.72)  LDD1522  [7]
 LDCM0287  AC27 HEK-293T C222(1.28)  LDD1526  [7]
 LDCM0288  AC28 HEK-293T C222(1.16)  LDD1527  [7]
 LDCM0290  AC3 HEK-293T C222(1.07)  LDD1529  [7]
 LDCM0291  AC30 HEK-293T C222(1.13)  LDD1530  [7]
 LDCM0292  AC31 HEK-293T C222(0.66)  LDD1531  [7]
 LDCM0296  AC35 HEK-293T C222(0.99)  LDD1535  [7]
 LDCM0297  AC36 HEK-293T C222(0.98)  LDD1536  [7]
 LDCM0299  AC38 HEK-293T C222(1.23)  LDD1538  [7]
 LDCM0300  AC39 HEK-293T C222(0.56)  LDD1539  [7]
 LDCM0301  AC4 HEK-293T C222(0.81)  LDD1540  [7]
 LDCM0305  AC43 HEK-293T C222(1.02)  LDD1544  [7]
 LDCM0306  AC44 HEK-293T C222(1.12)  LDD1545  [7]
 LDCM0308  AC46 HEK-293T C222(0.98)  LDD1547  [7]
 LDCM0309  AC47 HEK-293T C222(0.64)  LDD1548  [7]
 LDCM0314  AC51 HEK-293T C222(0.96)  LDD1553  [7]
 LDCM0315  AC52 HEK-293T C222(1.22)  LDD1554  [7]
 LDCM0317  AC54 HEK-293T C222(1.08)  LDD1556  [7]
 LDCM0318  AC55 HEK-293T C222(0.59)  LDD1557  [7]
 LDCM0322  AC59 HEK-293T C222(1.36)  LDD1561  [7]
 LDCM0323  AC6 HEK-293T C222(1.04)  LDD1562  [7]
 LDCM0324  AC60 HEK-293T C222(1.08)  LDD1563  [7]
 LDCM0326  AC62 HEK-293T C222(0.99)  LDD1565  [7]
 LDCM0327  AC63 HEK-293T C222(0.90)  LDD1566  [7]
 LDCM0332  AC68 HCT 116 C88(1.00); C96(1.00)  LDD0649  [6]
 LDCM0333  AC69 HCT 116 C88(0.97); C96(0.97)  LDD0650  [6]
 LDCM0334  AC7 HEK-293T C222(0.60)  LDD1568  [7]
 LDCM0335  AC70 HCT 116 C88(0.93); C96(0.93)  LDD0652  [6]
 LDCM0336  AC71 HCT 116 C88(1.09); C96(1.09)  LDD0653  [6]
 LDCM0337  AC72 HCT 116 C88(0.91); C96(0.91)  LDD0654  [6]
 LDCM0338  AC73 HCT 116 C88(0.85); C96(0.85)  LDD0655  [6]
 LDCM0339  AC74 HCT 116 C88(0.96); C96(0.96)  LDD0656  [6]
 LDCM0340  AC75 HCT 116 C88(1.01); C96(1.01)  LDD0657  [6]
 LDCM0341  AC76 HCT 116 C88(1.32); C96(1.32)  LDD0658  [6]
 LDCM0342  AC77 HCT 116 C88(0.93); C96(0.93)  LDD0659  [6]
 LDCM0343  AC78 HCT 116 C88(1.09); C96(1.09)  LDD0660  [6]
 LDCM0344  AC79 HCT 116 C88(1.11); C96(1.11)  LDD0661  [6]
 LDCM0346  AC80 HCT 116 C88(1.21); C96(1.21)  LDD0663  [6]
 LDCM0347  AC81 HCT 116 C88(1.23); C96(1.23)  LDD0664  [6]
 LDCM0348  AC82 HCT 116 C88(1.06); C96(1.06)  LDD0665  [6]
 LDCM0365  AC98 HCT 116 C88(0.84); C96(0.84)  LDD0682  [6]
 LDCM0366  AC99 HCT 116 C88(0.80); C96(0.80)  LDD0683  [6]
 LDCM0368  CL10 HEK-293T C222(0.85)  LDD1572  [7]
 LDCM0379  CL11 HEK-293T C222(0.80)  LDD1583  [7]
 LDCM0404  CL17 HCT 116 C88(0.97); C96(0.97)  LDD0721  [6]
 LDCM0405  CL18 HCT 116 C88(0.92); C96(0.92)  LDD0722  [6]
 LDCM0406  CL19 HCT 116 C88(1.02); C96(1.02)  LDD0723  [6]
 LDCM0408  CL20 HCT 116 C88(1.04); C96(1.04)  LDD0725  [6]
 LDCM0409  CL21 HCT 116 C88(0.96); C96(0.96)  LDD0726  [6]
 LDCM0410  CL22 HCT 116 C88(0.82); C96(0.82)  LDD0727  [6]
 LDCM0411  CL23 HCT 116 C88(0.90); C96(0.90)  LDD0728  [6]
 LDCM0412  CL24 HCT 116 C88(1.03); C96(1.03)  LDD0729  [6]
 LDCM0413  CL25 HCT 116 C88(0.82); C96(0.82)  LDD0730  [6]
 LDCM0414  CL26 HCT 116 C88(1.06); C96(1.06)  LDD0731  [6]
 LDCM0415  CL27 HCT 116 C88(1.04); C96(1.04)  LDD0732  [6]
 LDCM0416  CL28 HCT 116 C88(0.76); C96(0.76)  LDD0733  [6]
 LDCM0417  CL29 HCT 116 C88(1.00); C96(1.00)  LDD0734  [6]
 LDCM0419  CL30 HCT 116 C88(1.06); C96(1.06)  LDD0736  [6]
 LDCM0420  CL31 HCT 116 C88(1.22); C96(1.22)  LDD0737  [6]
 LDCM0421  CL32 HEK-293T C222(1.01)  LDD1625  [7]
 LDCM0423  CL34 HEK-293T C222(1.01)  LDD1627  [7]
 LDCM0424  CL35 HEK-293T C222(0.93)  LDD1628  [7]
 LDCM0433  CL43 HEK-293T C222(0.82)  LDD1637  [7]
 LDCM0434  CL44 HEK-293T C222(1.00)  LDD1638  [7]
 LDCM0436  CL46 HEK-293T C222(1.04)  LDD1640  [7]
 LDCM0437  CL47 HEK-293T C222(0.59)  LDD1641  [7]
 LDCM0446  CL55 HEK-293T C222(0.81)  LDD1649  [7]
 LDCM0447  CL56 HEK-293T C222(1.00)  LDD1650  [7]
 LDCM0449  CL58 HEK-293T C222(1.13)  LDD1652  [7]
 LDCM0450  CL59 HEK-293T C222(0.82)  LDD1653  [7]
 LDCM0453  CL61 HCT 116 C88(0.56); C96(0.56)  LDD0770  [6]
 LDCM0454  CL62 HCT 116 C88(0.56); C96(0.56)  LDD0771  [6]
 LDCM0455  CL63 HCT 116 C88(0.57); C96(0.57)  LDD0772  [6]
 LDCM0456  CL64 HCT 116 C88(0.65); C96(0.65)  LDD0773  [6]
 LDCM0457  CL65 HCT 116 C88(0.76); C96(0.76)  LDD0774  [6]
 LDCM0458  CL66 HCT 116 C88(0.53); C96(0.53)  LDD0775  [6]
 LDCM0459  CL67 HCT 116 C88(1.09); C96(1.09)  LDD0776  [6]
 LDCM0460  CL68 HCT 116 C88(0.84); C96(0.84)  LDD0777  [6]
 LDCM0461  CL69 HCT 116 C88(0.55); C96(0.55)  LDD0778  [6]
 LDCM0462  CL7 HEK-293T C222(1.09)  LDD1665  [7]
 LDCM0463  CL70 HCT 116 C88(0.78); C96(0.78)  LDD0780  [6]
 LDCM0464  CL71 HCT 116 C88(0.77); C96(0.77)  LDD0781  [6]
 LDCM0465  CL72 HCT 116 C88(0.93); C96(0.93)  LDD0782  [6]
 LDCM0466  CL73 HCT 116 C88(0.61); C96(0.61)  LDD0783  [6]
 LDCM0467  CL74 HCT 116 C88(0.81); C96(0.81)  LDD0784  [6]
 LDCM0469  CL76 HCT 116 C88(0.97); C96(0.97)  LDD0786  [6]
 LDCM0470  CL77 HCT 116 C88(0.79); C96(0.79)  LDD0787  [6]
 LDCM0471  CL78 HCT 116 C88(0.80); C96(0.80)  LDD0788  [6]
 LDCM0472  CL79 HCT 116 C88(0.92); C96(0.92)  LDD0789  [6]
 LDCM0473  CL8 HEK-293T C222(1.40)  LDD1676  [7]
 LDCM0474  CL80 HCT 116 C88(0.80); C96(0.80)  LDD0791  [6]
 LDCM0475  CL81 HCT 116 C88(0.76); C96(0.76)  LDD0792  [6]
 LDCM0476  CL82 HCT 116 C88(0.91); C96(0.91)  LDD0793  [6]
 LDCM0477  CL83 HCT 116 C88(0.70); C96(0.70)  LDD0794  [6]
 LDCM0478  CL84 HCT 116 C88(0.67); C96(0.67)  LDD0795  [6]
 LDCM0479  CL85 HCT 116 C88(0.98); C96(0.98)  LDD0796  [6]
 LDCM0480  CL86 HCT 116 C88(1.07); C96(1.07)  LDD0797  [6]
 LDCM0481  CL87 HCT 116 C88(0.82); C96(0.82)  LDD0798  [6]
 LDCM0482  CL88 HCT 116 C88(1.10); C96(1.10)  LDD0799  [6]
 LDCM0483  CL89 HCT 116 C88(1.23); C96(1.23)  LDD0800  [6]
 LDCM0485  CL90 HCT 116 C88(1.18); C96(1.18)  LDD0802  [6]
 LDCM0486  CL91 HEK-293T C222(0.91)  LDD1689  [7]
 LDCM0487  CL92 HEK-293T C222(1.08)  LDD1690  [7]
 LDCM0489  CL94 HEK-293T C222(0.76)  LDD1692  [7]
 LDCM0490  CL95 HEK-293T C222(0.79)  LDD1693  [7]
 LDCM0468  Fragment33 HCT 116 C88(0.68); C96(0.68)  LDD0785  [6]
 LDCM0569  Fragment7 Jurkat _(4.35)  LDD1485  [2]
 LDCM0022  KB02 769-P C222(5.51)  LDD2246  [8]
 LDCM0023  KB03 Jurkat C222(29.30)  LDD0209  [4]
 LDCM0024  KB05 MEWO C222(3.19)  LDD3319  [8]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C186(1.31)  LDD2135  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 10 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
5'-AMP-activated protein kinase subunit beta-2 (PRKAB2) 5'-AMP-activated protein kinase beta subunit family O43741
Maspardin (SPG21) AB hydrolase superfamily Q9NZD8
Protein arginine N-methyltransferase 5 (PRMT5) Protein arginine N-methyltransferase family O14744
DNA dC->dU-editing enzyme APOBEC-3C (APOBEC3C) Cytidine and deoxycytidylate deaminase family Q9NRW3
Probable E3 ubiquitin-protein ligase DTX2 (DTX2) Deltex family Q86UW9
Histone acetyltransferase type B catalytic subunit (HAT1) HAT1 family O14929
Protein-arginine deiminase type-4 (PADI4) Protein arginine deiminase family Q9UM07
Exosome complex component RRP46 (EXOSC5) RNase PH family Q9NQT4
Sulfite oxidase, mitochondrial (SUOX) . P51687
Ubiquitin domain-containing protein 2 (UBTD2) . Q8WUN7
Transporter and channel
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
MyoD family inhibitor (MDFI) MDFI family Q99750
Sodium channel modifier 1 (SCNM1) . Q9BWG6
Transcription factor
Click To Hide/Show 9 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Homeobox protein Hox-B5 (HOXB5) Antp homeobox family P09067
Homeobox protein Hox-C8 (HOXC8) Antp homeobox family P31273
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) BZIP family P18848
Zinc finger protein 417 (ZNF417) Krueppel C2H2-type zinc-finger protein family Q8TAU3
Zinc finger protein 587 (ZNF587) Krueppel C2H2-type zinc-finger protein family Q96SQ5
Iroquois-class homeodomain protein IRX-6 (IRX6) TALE/IRO homeobox family P78412
Homeobox protein PKNOX2 (PKNOX2) TALE/MEIS homeobox family Q96KN3
B-cell lymphoma 6 protein (BCL6) . P41182
Transcription factor 19 (TCF19) . Q9Y242
Other
Click To Hide/Show 32 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
A-kinase anchor protein 8-like (AKAP8L) AKAP95 family Q9ULX6
Chromatin assembly factor 1 subunit A (CHAF1A) CHAF1A family Q13111
Cancer/testis antigen 1 (CTAG1A; CTAG1B) CTAG/PCC1 family P78358
Stabilizer of axonemal microtubules 1 (SAXO1) FAM154 family Q8IYX7
Protein FAM161A (FAM161A) FAM161 family Q3B820
Protein FAM90A1 (FAM90A1) FAM90 family Q86YD7
EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) Fibulin family O95967
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Protein INCA1 (INCA1) INCA family Q0VD86
Keratin, type I cytoskeletal 26 (KRT26) Intermediate filament family Q7Z3Y9
Phakinin (BFSP2) Intermediate filament family Q13515
Protein Mis18-beta (OIP5) Mis18 family O43482
Mitotic interactor and substrate of PLK1 (MISP) MISP family Q8IVT2
Partitioning defective 6 homolog beta (PARD6B) PAR6 family Q9BYG5
X-linked retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) RPGRIP1 family Q96KN7
Tektin-3 (TEKT3) Tektin family Q9BXF9
Tektin-4 (TEKT4) Tektin family Q8WW24
U1 small nuclear ribonucleoprotein C (SNRPC) U1 small nuclear ribonucleoprotein C family P09234
Synaptic plasticity regulator PANTS (C22orf39) UPF0545 family Q6P5X5
rRNA-processing protein UTP23 homolog (UTP23) UTP23/FCF1 family Q9BRU9
Armadillo repeat-containing protein 7 (ARMC7) . Q9H6L4
BAG family molecular chaperone regulator 3 (BAG3) . O95817
Chromobox protein homolog 8 (CBX8) . Q9HC52
Developmental pluripotency-associated protein 3 (DPPA3) . Q6W0C5
Heterogeneous nuclear ribonucleoprotein F (HNRNPF) . P52597
INO80 complex subunit B (INO80B) . Q9C086
Kelch-like protein 38 (KLHL38) . Q2WGJ6
KN motif and ankyrin repeat domain-containing protein 2 (KANK2) . Q63ZY3
Leukocyte receptor cluster member 1 (LENG1) . Q96BZ8
Protein phosphatase 1 regulatory subunit 26 (PPP1R26) . Q5T8A7
Sprouty-related, EVH1 domain-containing protein 1 (SPRED1) . Q7Z699
Sterile alpha motif domain-containing protein 11 (SAMD11) . Q96NU1

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 Proteome-wide covalent ligand discovery in native biological systems. Nature. 2016 Jun 23;534(7608):570-4. doi: 10.1038/nature18002. Epub 2016 Jun 15.
3 Chemoproteomic capture of RNA binding activity in living cells. Nat Commun. 2023 Oct 7;14(1):6282. doi: 10.1038/s41467-023-41844-z.
Mass spectrometry data entry: PXD044625
4 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
5 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
6 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.
7 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402
8 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