Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTBMJUOC)

• DOT Name: Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4)
• Synonyms: EC 2.7.11.1; HPK/GCK-like kinase HGK; MAPK/ERK kinase kinase kinase 4; MEK kinase kinase 4; MEKKK 4; Nck-interacting kinase
• Gene Name: MAP4K4
• UniProt ID: M4K4_HUMAN
• PDB ID: 4OBO; 4OBP; 4OBQ; 4RVT; 4U3Y; 4U3Z; 4U40; 4U41; 4U42; 4U43; 4U44; 4U45; 4ZK5; 4ZP5; 5DI1; 5J95; 5W5Q
• EC Number: 2.7.11.1
• Pfam ID: PF00780 ; PF00069
• Sequence:
  MANDSPAKSLVDIDLSSLRDPAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTE
  DEEEEIKLEINMLKKYSHHRNIATYYGAFIKKSPPGHDDQLWLVMEFCGAGSITDLVKNT
  KGNTLKEDWIAYISREILRGLAHLHIHHVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDR
  TVGRRNTFIGTPYWMAPEVIACDENPDATYDYRSDLWSCGITAIEMAEGAPPLCDMHPMR
  ALFLIPRNPPPRLKSKKWSKKFFSFIEGCLVKNYMQRPSTEQLLKHPFIRDQPNERQVRI
  QLKDHIDRTRKKRGEKDETEYEYSGSEEEEEEVPEQEGEPSSIVNVPGESTLRRDFLRLQ
  QENKERSEALRRQQLLQEQQLREQEEYKRQLLAERQKRIEQQKEQRRRLEEQQRREREAR
  RQQEREQRRREQEEKRRLEELERRRKEEEERRRAEEEKRRVEREQEYIRRQLEEEQRHLE
  VLQQQLLQEQAMLLECRWREMEEHRQAERLQRQLQQEQAYLLSLQHDHRRPHPQHSQQPP
  PPQQERSKPSFHAPEPKAHYEPADRAREVEDRFRKTNHSSPEAQSKQTGRVLEPPVPSRS
  ESFSNGNSESVHPALQRPAEPQVPVRTTSRSPVLSRRDSPLQGSGQQNSQAGQRNSTSIE
  PRLLWERVEKLVPRPGSGSSSGSSNSGSQPGSHPGSQSGSGERFRVRSSSKSEGSPSQRL
  ENAVKKPEDKKEVFRPLKPADLTALAKELRAVEDVRPPHKVTDYSSSSEESGTTDEEDDD
  VEQEGADESTSGPEDTRAASSLNLSNGETESVKTMIVHDDVESEPAMTPSKEGTLIVRQT
  QSASSTLQKHKSSSSFTPFIDPRLLQISPSSGTTVTSVVGFSCDGMRPEAIRQDPTRKGS
  VVNVNPTNTRPQSDTPEIRKYKKRFNSEILCAALWGVNLLVGTESGLMLLDRSGQGKVYP
  LINRRRFQQMDVLEGLNVLVTISGKKDKLRVYYLSWLRNKILHNDPEVEKKQGWTTVGDL
  EGCVHYKVVKYERIKFLVIALKSSVEVYAWAPKPYHKFMAFKSFGELVHKPLLVDLTVEE
  GQRLKVIYGSCAGFHAVDVDSGSVYDIYLPTHIQCSIKPHAIIILPNTDGMELLVCYEDE
  GVYVNTYGRITKDVVLQWGEMPTSVAYIRSNQTMGWGEKAIEIRSVETGHLDGVFMHKRA
  QRLKFLCERNDKVFFASVRSGGSSQVYFMTLGRTSLLSW
• Function: Serine/threonine kinase that may play a role in the response to environmental stress and cytokines such as TNF-alpha. Appears to act upstream of the JUN N-terminal pathway. Phosphorylates SMAD1 on Thr-322.
• Tissue Specificity: Widely expressed. Isoform 5 is abundant in the brain. Isoform 4 is predominant in the liver, skeletal muscle and placenta.
• KEGG Pathway: MAPK sig.ling pathway (hsa04010)
• Reactome Pathway: Oxidative Stress Induced Senescence (R-HSA-2559580)

Molecular Interaction Atlas (MIA) of This DOT

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[1]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[18]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[18]
Sulfate	DMW0ZBF	Investigative	Sulfate affects the methylation of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[26]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[11]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[12]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[13]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[14]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[9]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[15]
Sertraline	DM0FB1J	Approved	Sertraline decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[16]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[19]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[20]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[21]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[22]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[23]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[24]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl decreases the expression of Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4).	[25]

References

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