Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQBCEJ)

• DTT Name: MAPK/ERK kinase kinase 1 (MAP3K1)
• Synonyms: Mitogenactivated protein kinase kinase kinase 1; Mitogen-activated protein kinase kinase kinase 1; MEKK1; MEKK 1; MEKK; MEK kinase 1; MAPKKK1
• Gene Name: MAP3K1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: M3K1_HUMAN
• TTD ID: T06031
• EC Number: EC 2.7.11.25
• Sequence:
  MAAAAGNRASSSGFPGARATSPEAGGGGGALKASSAPAAAAGLLREAGSGGRERADWRRR
  QLRKVRSVELDQLPEQPLFLAASPPASSTSPSPEPADAAGSGTGFQPVAVPPPHGAASRG
  GAHLTESVAAPDSGASSPAAAEPGEKRAPAAEPSPAAAPAGREMENKETLKGLHKMDDRP
  EERMIREKLKATCMPAWKHEWLERRNRRGPVVVKPIPVKGDGSEMNHLAAESPGEVQASA
  ASPASKGRRSPSPGNSPSGRTVKSESPGVRRKRVSPVPFQSGRITPPRRAPSPDGFSPYS
  PEETNRRVNKVMRARLYLLQQIGPNSFLIGGDSPDNKYRVFIGPQNCSCARGTFCIHLLF
  VMLRVFQLEPSDPMLWRKTLKNFEVESLFQKYHSRRSSRIKAPSRNTIQKFVSRMSNSHT
  LSSSSTSTSSSENSIKDEEEQMCPICLLGMLDEESLTVCEDGCRNKLHHHCMSIWAEECR
  RNREPLICPLCRSKWRSHDFYSHELSSPVDSPSSLRAAQQQTVQQQPLAGSRRNQESNFN
  LTHYGTQQIPPAYKDLAEPWIQVFGMELVGCLFSRNWNVREMALRRLSHDVSGALLLANG
  ESTGNSGGSSGSSPSGGATSGSSQTSISGDVVEACCSVLSMVCADPVYKVYVAALKTLRA
  MLVYTPCHSLAERIKLQRLLQPVVDTILVKCADANSRTSQLSISTLLELCKGQAGELAVG
  REILKAGSIGIGGVDYVLNCILGNQTESNNWQELLGRLCLIDRLLLEFPAEFYPHIVSTD
  VSQAEPVEIRYKKLLSLLTFALQSIDNSHSMVGKLSRRIYLSSARMVTTVPHVFSKLLEM
  LSVSSSTHFTRMRRRLMAIADEVEIAEAIQLGVEDTLDGQQDSFLQASVPNNYLETTENS
  SPECTVHLEKTGKGLCATKLSASSEDISERLASISVGPSSSTTTTTTTTEQPKPMVQTKG
  RPHSQCLNSSPLSHHSQLMFPALSTPSSSTPSVPAGTATDVSKHRLQGFIPCRIPSASPQ
  TQRKFSLQFHRNCPENKDSDKLSPVFTQSRPLPSSNIHRPKPSRPTPGNTSKQGDPSKNS
  MTLDLNSSSKCDDSFGCSSNSSNAVIPSDETVFTPVEEKCRLDVNTELNSSIEDLLEASM
  PSSDTTVTFKSEVAVLSPEKAENDDTYKDDVNHNQKCKEKMEAEEEEALAIAMAMSASQD
  ALPIVPQLQVENGEDIIIIQQDTPETLPGHTKAKQPYREDTEWLKGQQIGLGAFSSCYQA
  QDVGTGTLMAVKQVTYVRNTSSEQEEVVEALREEIRMMSHLNHPNIIRMLGATCEKSNYN
  LFIEWMAGGSVAHLLSKYGAFKESVVINYTEQLLRGLSYLHENQIIHRDVKGANLLIDST
  GQRLRIADFGAAARLASKGTGAGEFQGQLLGTIAFMAPEVLRGQQYGRSCDVWSVGCAII
  EMACAKPPWNAEKHSNHLALIFKIASATTAPSIPSHLSPGLRDVALRCLELQPQDRPPSR
  ELLKHPVFRTTW
• Function: Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. May phosphorylate the MAPK8/JNK1 kinase. Activates CHUK and IKBKB, the central protein kinases of the NF-kappa-B pathway. Component of a protein kinase signal transduction cascade.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Ubiquitin mediated proteolysis (hsa04120)
  RIG-I-like receptor signaling pathway (hsa04622)
  Neurotrophin signaling pathway (hsa04722)
  GnRH signaling pathway (hsa04912)
  Hepatitis B (hsa05161)
  HTLV-I infection (hsa05166)
• Reactome Pathway:
  FCERI mediated MAPK activation (R-HSA-2871796)
  TRAF6 mediated NF-kB activation (R-HSA-933542)
  TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation (R-HSA-975138)
  MyD88 cascade initiated on plasma membrane (R-HSA-975871)
  MyD88 (R-HSA-166058)

Molecular Interaction Atlas (MIA) of This DTT

4 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[1]
LLZ16406	DMOGZLU	Discovery agent	N.A.	Investigative	[1]
Ro092210	DM2DXHO	Discovery agent	N.A.	Investigative	[1]
U0126	DM31OGF	Discovery agent	N.A.	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Psoriasis	EA90	Skin	6.07E-03	-0.28	-0.52

References

• [1] Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci. 2002 Jan;23(1):40-5.