Molecule Information

General Information of the Molecule (ID: Mol00487)

• Name: Mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) ,Homo sapiens
• Synonyms: Germinal center kinase-related protein kinase; GLK; MAPK/ERK kinase kinase kinase 3; MEK kinase kinase 3; MEKKK 3; RAB8IPL1
• Molecule Type: Protein
• Gene Name: MAP4K3
• Gene ID: 8491
• Location: chr2:39249266-39437301[-]
• Sequence:
  MNPGFDLSRRNPQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPGEDFAVVQQ
  EIIMMKDCKHPNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSELQIAYVSRET
  LQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIGTPYWMAP
  EVAAVERKGGYNQLCDLWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPPKLKDKM
  KWSNSFHHFVKMALTKNPKKRPTAEKLLQHPFVTQHLTRSLAIELLDKVNNPDHSTYHDF
  DDDDPEPLVAVPHRIHSTSRNVREEKTRSEITFGQVKFDPPLRKETEPHHELPDSDGFLD
  SSEEIYYTARSNLDLQLEYGQGHQGGYFLGANKSLLKSVEEELHQRGHVAHLEDDEGDDD
  ESKHSTLKAKIPPPLPPKPKSIFIPQEMHSTEDENQGTIKRCPMSGSPAKPSQVPPRPPP
  PRLPPHKPVALGNGMSSFQLNGERDGSLCQQQNEHRGTNLSRKEKKDVPKPISNGLPPTP
  KVHMGACFSKVFNGCPLKIHCASSWINPDTRDQYLIFGAEEGIYTLNLNELHETSMEQLF
  PRRCTWLYVMNNCLLSISGKASQLYSHNLPGLFDYARQMQKLPVAIPAHKLPDRILPRKF
  SVSAKIPETKWCQKCCVVRNPYTGHKYLCGALQTSIVLLEWVEPMQKFMLIKHIDFPIPC
  PLRMFEMLVVPEQEYPLVCVGVSRGRDFNQVVRFETVNPNSTSSWFTESDTPQTNVTHVT
  QLERDTILVCLDCCIKIVNLQGRLKSSRKLSSELTFDFQIESIVCLQDSVLAFWKHGMQG
  RSFRSNEVTQEISDSTRIFRLLGSDRVVVLESRPTDNPTANSNLYILAGHENSY
• Function: May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
• Uniprot ID: M4K3_HUMAN
• Ensembl ID: ENSG00000011566
• HGNC ID: HGNC:6865

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Levothyroxine

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Papillary thyroid carcinoma [1]

• Sensitive Disease: Papillary thyroid carcinoma [ICD-11: 2D10.1]
• Sensitive Drug: Levothyroxine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: JNk signaling pathway; Inhibition; hsa04010
• Cell Pathway Regulation: p38 signaling pathway; Inhibition; hsa04010
• In Vitro Model: TPC-1 cells; Thyroid; Homo sapiens (Human); CVCL_6298
• In Vitro Model: Nthy-ori3-1 cells; Thyroid; Homo sapiens (Human); CVCL_2659
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; EdU assay; Flow cytometry assay
• Mechanism Description: Over-expression of miR-206 decreases the Euthyrox-resistance by targeting MAP4k3 in papillary thyroid carcinoma.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Thyroid cancer [ICD-11: 2D10]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Thyroid
• The Specified Disease: Thyroid cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.79E-14; Fold-change: -5.29E-01; Z-score: -1.05E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.59E-13; Fold-change: -6.04E-01; Z-score: -1.39E+00

References

• Ref 1: Over-expression of miR-206 decreases the Euthyrox-resistance by targeting MAP4K3 in papillary thyroid carcinoma. Biomed Pharmacother. 2019 Jun;114:108605. doi: 10.1016/j.biopha.2019.108605. Epub 2019 Mar 21.