Molecule Information

General Information of the Molecule (ID: Mol00578)

• Name: Tyrosine-protein phosphatase non-receptor type 18 (PTPN18) ,Homo sapiens
• Synonyms: Brain-derived phosphatase; BDP1
• Molecule Type: Protein
• Gene Name: PTPN18
• Gene ID: 26469
• Location: chr2:130356045-130375405[+]
• Sequence:
  MSRSLDSARSFLERLEARGGREGAVLAGEFSDIQACSAAWKADGVCSTVAGSRPENVRKN
  RYKDVLPYDQTRVILSLLQEEGHSDYINGNFIRGVDGSLAYIATQGPLPHTLLDFWRLVW
  EFGVKVILMACREIENGRKRCERYWAQEQEPLQTGLFCITLIKEKWLNEDIMLRTLKVTF
  QKESRSVYQLQYMSWPDRGVPSSPDHMLAMVEEARRLQGSGPEPLCVHCSAGCGRTGVLC
  TVDYVRQLLLTQMIPPDFSLFDVVLKMRKQRPAAVQTEEQYRFLYHTVAQMFCSTLQNAS
  PHYQNIKENCAPLYDDALFLRTPQALLAIPRPPGGVLRSISVPGSPGHAMADTYAVVQKR
  GAPAGAGSGTQTGTGTGTGARSAEEAPLYSKVTPRAQRPGAHAEDARGTLPGRVPADQSP
  AGSGAYEDVAGGAQTGGLGFNLRIGRPKGPRDPPAEWTRV
• Function: Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues.
• Uniprot ID: PTN18_HUMAN
• Ensembl ID: ENSG00000072135
• HGNC ID: HGNC:9649

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

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastrointestinal stromal tumor [1]

• Resistant Disease: Gastrointestinal stromal tumor [ICD-11: 2B5B.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: GIST882 cells; Gastric; Homo sapiens (Human); CVCL_7044
• In Vitro Model: GIST48 cells; Gastric; Homo sapiens (Human); CVCL_7041
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: WST-1 assay
• Mechanism Description: miR-125a-5p expression modulated imatinib sensitivity in GIST882 cells with a homozygous kIT mutation but not in GIST48 cells with double kIT mutations. Overexpression of miR-125a-5p suppressed PTPN18 expression, and silencing of PTPN18 expression increased cell viability in GIST882 cells upon imatinib treatment. PTPN18 protein levels were significantly lower in the imatinib-resistant GISTs and inversely correlated with miR-125a-5p. Furthermore, several microRNAs were significantly associated with metastasis, kIT mutational status and survival.

References

• Ref 1: microRNA expression signatures of gastrointestinal stromal tumours: associations with imatinib resistance and patient outcome. Br J Cancer. 2014 Nov 25;111(11):2091-102. doi: 10.1038/bjc.2014.548. Epub 2014 Oct 30.