Details of the Target

General Information of Target

Target ID LDTP09931
Target Name Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1)
Gene Name MAP4K1
Gene ID 11184
Synonyms
HPK1; Mitogen-activated protein kinase kinase kinase kinase 1; EC 2.7.11.1; Hematopoietic progenitor kinase; MAPK/ERK kinase kinase kinase 1; MEK kinase kinase 1; MEKKK 1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MADSKEGVLPLTAASTAPISFGFTRTSARRRLADSGDGAGPSPEEKDFLKTVEGRELQSV
KPQEAPKELVIPLIQNGHRRQPPARPPGPSTDTGALADGVVSQAVKELIAESKKSLEERE
NAGVDPTLAIPMIQKGCTPSGEGADSEPRAETVPEEANYEAVPVEAYGLAMLRGMGWKPG
EGIGRTFNQVVKPRVNSLRPKGLGLGANLTEAQALTPTGPSRMPRPDEEQEKDKEDQPQG
LVPGGAVVVLSGPHRGLYGKVEGLDPDNVRAMVRLAVGSRVVTVSEYYLRPVSQQEFDKN
TLDLRQQNGTASSRKTLWNQELYIQQDNSERKRKHLPDRQDGPAAKSEKAAPRSQHWLHR
DLRVRFVDNMYKGGQYYNTKMIIEDVLSPDTCVCRTDEGRVLEGLREDMLETLVPKAEGD
RVMVVLGPQTGRVGHLLSRDRARSRALVQLPRENQVVELHYDAICQYMGPSDTDDD
Target Type
Clinical trial
Target Bioclass
Enzyme
Family
Protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily
Function
Serine/threonine-protein kinase, which may play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway. May play a role in hematopoietic lineage decisions and growth regulation. Able to autophosphorylate. Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production.
TTD ID
T00749
Uniprot ID
Q92918
DrugMap ID
TTSHWUP
Ensemble ID
ENST00000396857.7
HGNC ID
HGNC:6863
ChEMBL ID
CHEMBL5749

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 6 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		CAmbiguous(92.44); C484(7.50)  LDD0209  [1]
CY-1
 Probe Info  		N.A.  LDD0246  [2]
4-Iodoacetamidophenylacetylene
 Probe Info  		C428(0.00); C698(0.00); C484(0.00); C494(0.00)  LDD0038  [3]
IA-alkyne
 Probe Info  		C698(0.00); C494(0.00); C674(0.00); C428(0.00)  LDD0036  [3]
Lodoacetamide azide
 Probe Info  		C698(0.00); C484(0.00); C494(0.00); C674(0.00)  LDD0037  [3]
KY-26
 Probe Info  		N.A.  LDD0301  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0625  F8 Ramos C484(1.07); C428(1.74)  LDD2187  [5]
 LDCM0572  Fragment10 Ramos C484(1.29); C428(1.24)  LDD2189  [5]
 LDCM0573  Fragment11 Ramos C484(5.73); C428(5.96)  LDD2190  [5]
 LDCM0574  Fragment12 Ramos C484(0.78); C428(0.87)  LDD2191  [5]
 LDCM0575  Fragment13 Ramos C484(0.86); C428(1.10)  LDD2192  [5]
 LDCM0576  Fragment14 Ramos C484(1.20); C428(1.15)  LDD2193  [5]
 LDCM0580  Fragment21 Ramos C484(0.55); C428(1.03)  LDD2195  [5]
 LDCM0582  Fragment23 Ramos C484(0.75); C428(1.07)  LDD2196  [5]
 LDCM0578  Fragment27 Ramos C484(0.71); C428(1.20)  LDD2197  [5]
 LDCM0586  Fragment28 Ramos C484(0.75); C428(0.72)  LDD2198  [5]
 LDCM0588  Fragment30 Ramos C484(1.03); C428(1.37)  LDD2199  [5]
 LDCM0589  Fragment31 Ramos C484(1.02); C428(1.22)  LDD2200  [5]
 LDCM0590  Fragment32 Ramos C484(1.52); C428(2.71)  LDD2201  [5]
 LDCM0468  Fragment33 Ramos C484(0.91); C428(1.12)  LDD2202  [5]
 LDCM0596  Fragment38 Ramos C484(0.70); C428(2.62)  LDD2203  [5]
 LDCM0566  Fragment4 Ramos C484(1.11); C428(1.13)  LDD2184  [5]
 LDCM0610  Fragment52 Ramos C484(0.64); C428(1.72)  LDD2204  [5]
 LDCM0614  Fragment56 Ramos C484(0.89); C428(1.91)  LDD2205  [5]
 LDCM0569  Fragment7 Ramos C484(1.02); C428(0.93)  LDD2186  [5]
 LDCM0571  Fragment9 Ramos C484(1.19); C428(1.63)  LDD2188  [5]
 LDCM0022  KB02 T cell C484(9.35)  LDD1703  [6]
 LDCM0023  KB03 Jurkat CAmbiguous(92.44); C484(7.50)  LDD0209  [1]
 LDCM0024  KB05 MONO-MAC-6 C494(2.41)  LDD3335  [7]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Tyrosine-protein kinase ABL1 (ABL1) Tyr protein kinase family P00519
Tyrosine-protein kinase Fyn (FYN) Tyr protein kinase family P06241
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCG1) . P19174
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Heat shock protein HSP 90-beta (HSP90AB1) Heat shock protein 90 family P08238
Immunoglobulin
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Signaling lymphocytic activation molecule (SLAMF1) . Q13291
Other
Click To Hide/Show 5 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Adapter molecule crk (CRK) CRK family P46108
Crk-like protein (CRKL) CRK family P46109
Growth factor receptor-bound protein 2 (GRB2) GRB2/sem-5/DRK family P62993
Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1) PI3K p85 subunit family P27986
SH2/SH3 adapter protein NCK1 (NCK1) . P16333

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Fostamatinib Small molecular drug DB12010
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Cfi-402411 Small molecular drug DXK49H
Phase 1
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Bgb-15025 Small molecular drug D8MS6C

References

1 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.
2 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
3 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
4 Direct Target Site Identification of a Sulfonyl-Triazole Covalent Kinase Probe by LC-MS Chemical Proteomics. Anal Chem. 2021 Sep 7;93(35):11946-11955. doi: 10.1021/acs.analchem.1c01591. Epub 2021 Aug 25.
5 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
6 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
7 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