General Information of the Protein
Protein ID
PT01164
Protein Name
Mitogen-activated protein kinase kinase kinase 7
Secondarily
Protein Name
Transforming growth factor-beta-activated kinase 1
Gene Name
MAP3K7
Secondarily
Gene Name
TAK1
Sequence
MSTASAASSSSSSSAGEMIEAPSQVLNFEEIDYKEIEVEEVVGRGAFGVVCKAKWRAKDVAIKQIESESERKAFIVELRQLSRVNHPNIVKLYGACLNPVCLVMEYAEGGSLYNVLHGAEPLPYYTAAHAMSWCLQCSQGVAYLHSMQPKALIHRDLKPPNLLLVAGGTVLKICDFGTACDIQTHMTNNKGSAAWMAPEVFEGSNYSEKCDVFSWGIILWEVITRRKPFDEIGGPAFRIMWAVHNGTRPPLIKNLPKPIESLMTRCWSKDPSQRPSMEEIVKIMTHLMRYFPGADEPLQYPCQYSDEGQSNSATSTGSFMDIASTNTSNKSDTNMEQVPATNDTIKRLESKLLKNQAKQQSESGRLSLGASRGSSVESLPPTSEGKRMSADMSEIEARIAATTAYSKPKRGHRKTASFGNILDVPEIVISGNGQPRRRSIQDLTVTGTEPGQVSSRSSSPSVRMITTSGPTSEKPTRSHPWTPDDSTDTNGSDNSIPMAYLTLDHQLQPLAPCPNSKESMAVFEQHCKMAQEYMKVQTEIALLLQRKQELVAELDQDEKDQQNTSRLVQEHKKLLDENKSLSTYYQQCKKQLEVIRSQQQKRQGTS
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
TKL protein kinase group
>
TKL protein kinase MLK family
>
TKL protein kinase TAK1 subfamily
Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Plays an important role in the cascades of cellular responses evoked by changes in the environment (PubMed:10094049, PubMed:11460167, PubMed:12589052, PubMed:16845370, PubMed:16893890, PubMed:21512573, PubMed:8663074, PubMed:9079627). Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR) (PubMed:9079627, PubMed:16893890). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7 (PubMed:8663074, PubMed:11460167). These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs); both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1) (PubMed:8663074, PubMed:11460167, PubMed:12589052). Independently of MAP2Ks and p38 MAPKs, acts as a key activator of NF-kappa-B by promoting activation of the I-kappa-B-kinase (IKK) core complex (PubMed:8663074, PubMed:12589052). Mechanistically, recruited to polyubiquitin chains of RIPK2 and IKBKG/NEMO via TAB2/MAP3K7IP2 and TAB3/MAP3K7IP3, and catalyzes phosphorylation and activation of IKBKB/IKKB component of the IKK complex, leading to NF-kappa-B activation (PubMed:10094049, PubMed:11460167). In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B (PubMed:16893890). Promotes TRIM5 capsid-specific restriction activity (PubMed:21512573). Phosphorylates RIPK1 at 'Ser-321' which positively regulates RIPK1 interaction with RIPK3 to promote necroptosis but negatively regulates RIPK1 kinase activity and its interaction with FADD to mediate apoptosis (By similarity).
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Uniprot ID
Primary ID:
O43318

Secondarily ID:
B2RE27
E1P523
O43317
O43319
Q5TDN2
Q5TDN3
Q5TDT7
Q9NTR3
Q9NZ70
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Ensembl ID
ENSG00000135341
HGNC ID
HGNC:6859
Subcellular Location
Cytoplasm
Cell membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000068 , A-549
Compound ID Compound Name Compound Formula
CP0177256
US9505765, 194
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C16H13FN4O2
 1
1
IC50 = 43 nM
   TI
   LI
   LO
   TS
CP0415490
US9505765, 39
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C14H18N4O2
 1
1
IC50 = 43 nM
   TI
   LI
   LO
   TS
CP0415491
US9505765, 192
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C14H18N4O2
 1
1
IC50 = 78 nM
   TI
   LI
   LO
   TS
CP0283664
US9505765, 38
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C13H16N4O2
 1
1
IC50 = 85 nM
   TI
   LI
   LO
   TS
CP0203286
US9505765, 179
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C15H20N4O2
 1
1
IC50 = 87 nM
   TI
   LI
   LO
   TS
CP0089169
US9505765, 191
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C11H9F3N4O2
 1
1
IC50 = 150 nM
   TI
   LI
   LO
   TS
CP0223286
US9505765, 188
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C12H14N4O2
 1
1
IC50 = 170 nM
   TI
   LI
   LO
   TS
CP0203287
US9505765, 181
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C16H20N4O2
 1
1
IC50 = 180 nM
   TI
   LI
   LO
   TS
CP0301215
US9505765, 189
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C12H14N4O2
 1
1
IC50 = 180 nM
   TI
   LI
   LO
   TS
CP0321891
US9505765, 199
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C15H16F2N4O2
 1
1
IC50 = 180 nM
   TI
   LI
   LO
   TS
CP0320934
US9505765, 184
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C15H20N4O2
 1
1
IC50 = 190 nM
   TI
   LI
   LO
   TS
CP0873419
(E)-3-(4-sec-butoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)acrylamide
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C13H16N4O2
 1
1
IC50 = 190 nM
   TI
   LI
   LO
   TS
CP0211772
US9505765, 177
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C15H19N3O3
 1
1
IC50 = 620 nM
   TI
   LI
   LO
   TS
CP0301214
US9505765, 180
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C17H22N4O2
 1
1
IC50 = 630 nM
   TI
   LI
   LO
   TS
CP0203289
US9505765, 196
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C13H15ClN4O2
 1
1
IC50 = 750 nM
   TI
   LI
   LO
   TS
CP0301216
US9505765, 201
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C17H15N3O3
 1
1
IC50 = 800 nM
   TI
   LI
   LO
   TS
CP0364892
US9505765, 186
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C13H14N4O2
 1
1
IC50 = 850 nM
   TI
   LI
   LO
   TS
CP0089101
US9505765, 195
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C13H16N4O2
 1
1
IC50 = 920 nM
   TI
   LI
   LO
   TS
CP0203285
US9505765, 175
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C15H19N3O2
 1
1
IC50 = 990 nM
   TI
   LI
   LO
   TS
CP0089168
US9505765, 190
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C15H12N4O2
 1
1
IC50 = 1000 nM
   TI
   LI
   LO
   TS
CP0203288
US9505765, 193
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C13H16N4O3
 1
1
IC50 = 1200 nM
   TI
   LI
   LO
   TS
CP0364888
US9505765, 93
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C16H12N4O
 1
1
IC50 = 2200 nM
   TI
   LI
   LO
   TS
CP0806452
(S,E)-N-(2-hydroxypropyl)-3-(4-isobutoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)acrylamide
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C16H22N4O3
 1
1
IC50 = 3400 nM
   TI
   LI
   LO
   TS
CP0321890
US9505765, 198
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C14H18N4O2
 1
1
IC50 = 8400 nM
   TI
   LI
   LO
   TS
CP0218703
US9505765, 23
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C12H14ClN3O2
 1
1
IC50 = 12000 nM
   TI
   LI
   LO
   TS
CP0807129
(R,E)-N-(2-hydroxypropyl)-3-(4-isobutoxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)acrylamide
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C16H22N4O3
 1
1
IC50 = 12000 nM
   TI
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   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0026383
(5Z)-7-Oxozeaenol
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C19H22O7
 4
1 IC50 = 5.6 nM
2 IC50 = 9 nM
3 IC50 = 11 nM
4 IC50 = 80 nM
CP0018477
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide
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C21H16ClF3N4O3
 1
1 Kd = 690 nM
Clinical Information about the Protein
Target 1 ( TGF-beta-activated kinase 1 (MAP3K7) )
Target Type Literature-reported Target