Molecule Information

General Information of the Molecule (ID: Mol00662)

• Name: Microtubule-associated protein tau (MAPT) ,Homo sapiens
• Synonyms: Neurofibrillary tangle protein; Paired helical filament-tau; PHF-tau; MAPTL; MTBT1; TAU
• Molecule Type: Protein
• Gene Name: MAPT
• Gene ID: 4137
• Location: chr17:45894527-46028334[+]
• Sequence:
  MAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPG
  SETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAG
  HVTQEPESGKVVQEGFLREPGPPGLSHQLMSGMPGAPLLPEGPREATRQPSGTGPEDTEG
  GRHAPELLKHQLLGDLHQEGPPLKGAGGKERPGSKEEVDEDRDVDESSPQDSPPSKASPA
  QDGRPPQTAAREATSIPGFPAEGAIPLPVDFLSKVSTEIPASEPDGPSVGRAKGQDAPLE
  FTFHVEITPNVQKEQAHSEEHLGRAAFPGAPGEGPEARGPSLGEDTKEADLPEPSEKQPA
  AAPRGKPVSRVPQLKARMVSKSKDGTGSDDKKAKTSTRSSAKTLKNRPCLSPKHPTPGSS
  DPLIQPSSPAVCPEPPSSPKYVSSVTSRTGSSGAKEMKLKGADGKTKIATPRGAAPPGQK
  GQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREP
  KKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLD
  LSNVQSKCGSKDNIKHVPGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEK
  LDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDT
  SPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL
• Function: Promotes microtubule assembly and stability, and might be involved in the establishment and maintenance of neuronal polarity. The C-terminus binds axonal microtubules while the N-terminus binds neural plasma membrane components, suggesting that tau functions as a linker protein between both. Axonal polarity is predetermined by TAU/MAPT localization (in the neuronal cell) in the domain of the cell body defined by the centrosome. The short isoforms allow plasticity of the cytoskeleton whereas the longer isoforms may preferentially play a role in its stabilization.
• Uniprot ID: TAU_HUMAN
• Ensembl ID: ENSG00000186868
• HGNC ID: HGNC:6893

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

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: p53 signaling pathway; Activation; hsa04115
• In Vitro Model: Calu3 cells; Lung; Homo sapiens (Human); CVCL_0609
• In Vitro Model: H1975 cells; Lung; Homo sapiens (Human); CVCL_1511
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: H4006 cells; Lung; Homo sapiens (Human); N.A.
• In Vitro Model: 293FT cells; Kidney; Homo sapiens (Human); CVCL_6911
• In Vitro Model: HCC95 cells; Lung; Homo sapiens (Human); CVCL_5137
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis; Luciferase assay
• Experiment for Drug Resistance: CellTiter-Glo assay
• Mechanism Description: miR186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer The chemosensitizing effects of miR186 are partially due to the induction of the p53 mediated apoptotic pathway via MAPT down-regulation.

Disease Class: Gastric cancer [2]

• Sensitive Disease: Gastric cancer [ICD-11: 2B72.1]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: MGC-803 cells; Gastric; Homo sapiens (Human); CVCL_5334
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: GES-1 cells; Gastric; Homo sapiens (Human); CVCL_EQ22
• In Vitro Model: MkN-45 cells; Gastric; Homo sapiens (Human); CVCL_0434
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: MAPT is a microtubule-associated protein which promotes the assembly of tubulin into microtubules to stabilize microtubule structure. Reduced expression of MAPT has been also associated with a better response to paclitaxel in gastric cancer patients, reduced expression of miR-34c-5p, provides a possible mechanism of paclitaxel resistance in gastric cancer, overexpression of miR-34c-5p reduces MAPT expression and restores paclitaxel sensitivity.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.68E-01; Fold-change: -2.70E-01; Z-score: -3.09E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.02E-07; Fold-change: 1.02E-01; Z-score: 8.92E-01

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.52E-04; Fold-change: -1.76E-01; Z-score: -5.05E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.53E-03; Fold-change: -3.45E-02; Z-score: -1.38E-01

References

• Ref 1: miR-186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer (NSCLC). Mol Biosyst. 2016 Oct 18;12(11):3417-3424. doi: 10.1039/c6mb00576d.
• Ref 2: Regulation of microtubule-associated protein tau (MAPT) by miR-34c-5p determines the chemosensitivity of gastric cancer to paclitaxel. Cancer Chemother Pharmacol. 2013 May;71(5):1159-71. doi: 10.1007/s00280-013-2108-y. Epub 2013 Feb 20.