Molecule Information

General Information of the Molecule (ID: Mol00316)

• Name: Death-associated protein kinase 2 (DAPK2) ,Homo sapiens
• Synonyms: DAP kinase 2; DAP-kinase-related protein 1; DRP-1
• Molecule Type: Protein
• Gene Name: DAPK2
• Gene ID: 23604
• Location: chr15:63907036-64072033[-]
• Sequence:
  MFQASMRSPNMEPFKQQKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRQSR
  ASRRGVSREEIEREVSILRQVLHHNVITLHDVYENRTDVVLILELVSGGELFDFLAQKES
  LSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPIPHIKLIDFGLAHEIED
  GVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANIT
  AVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITPVDNQQAMVRRESV
  VNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHLRPDEDLRNCESDTEEDIARRKA
  LHPRRRSSTS
• Function: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell death signals, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Acts as a mediator of anoikis and a suppressor of beta-catenin-dependent anchorage-independent growth of malignant epithelial cells. May play a role in granulocytic maturation. Regulates granulocytic motility by controlling cell spreading and polarization.
• Uniprot ID: DAPK2_HUMAN
• Ensembl ID: ENSG00000035664
• HGNC ID: HGNC:2675

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) 2 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Epithelial ovarian cancer [1]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• In Vitro Model: OV2008 cells; Ovary; Homo sapiens (Human); CVCL_0473
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: MCAS cells; Ovary; Homo sapiens (Human); CVCL_3020
• In Vitro Model: OVk18 cells; Ovary; Homo sapiens (Human); CVCL_3770
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-520g expression is significantly increased in EOC and high miR-520g expression promotes tumor development, increases chemoresistance to platinum-based chemotherapy and reduces patient survival. miR-520g directly targets and downregulates DAPk2 by binding the DAPk2 3'UTR. DAPk2 suppression, followed by MAPk and AkT pathway activation, promotes the biological processes mediated by miR-520g in EOC.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Epithelial ovarian cancer [1]

• Resistant Disease: Epithelial ovarian cancer [ICD-11: 2B5D.0]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: MAPK/AKT signaling pathway; Regulation; hsa04010
• In Vitro Model: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: A2780 cells; Ovary; Homo sapiens (Human); CVCL_0134
• In Vitro Model: CAOV3 cells; Ovary; Homo sapiens (Human); CVCL_0201
• In Vitro Model: OVCA433 cells; Ovary; Homo sapiens (Human); CVCL_0475
• In Vitro Model: OV2008 cells; Ovary; Homo sapiens (Human); CVCL_0473
• In Vitro Model: ES-2 cells; Ovary; Homo sapiens (Human); CVCL_3509
• In Vitro Model: MCAS cells; Ovary; Homo sapiens (Human); CVCL_3020
• In Vitro Model: OVk18 cells; Ovary; Homo sapiens (Human); CVCL_3770
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-520g expression is significantly increased in EOC and high miR-520g expression promotes tumor development, increases chemoresistance to platinum-based chemotherapy and reduces patient survival. miR-520g directly targets and downregulates DAPk2 by binding the DAPk2 3'UTR. DAPk2 suppression, followed by MAPk and AkT pathway activation, promotes the biological processes mediated by miR-520g in EOC.

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: T47D cells; Breast; Homo sapiens (Human); CVCL_0553
• In Vitro Model: MDA-MB-453 cells; Breast; Homo sapiens (Human); CVCL_0418
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• In Vitro Model: Hs-578T cells; Breast; Homo sapiens (Human); CVCL_0332
• In Vitro Model: HBL-100 cells; Breast; Homo sapiens (Human); CVCL_4362
• In Vitro Model: BT483 cells; Breast; Homo sapiens (Human); CVCL_2319
• In Vitro Model: MDA-MB-361 cells; Breast; Homo sapiens (Human); CVCL_0620
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTS assay; Flow cytometry assay
• Mechanism Description: Through protecting cells from paclitaxel-induced apoptosis, expression of miR-520h promoted the drug resistance of human breast cancer cells. Bioinformatics prediction, compensatory mutation and functional validation further confirmed the essential role of miR-520h-suppressed Death-associated protein kinase 2 (DAPk2) expression, as restoring DAPk2 abolished miR-520h-promoted drug resistance, and knockdown of DAPk2 mitigated cell death caused by the depletion of miR-520h.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.52E-41; Fold-change: -4.93E-01; Z-score: -9.54E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.27E-08; Fold-change: -3.70E-01; Z-score: -7.92E-01

References

• Ref 1: MicroRNA-520g promotes epithelial ovarian cancer progression and chemoresistance via DAPK2 repression. Oncotarget. 2016 May 3;7(18):26516-34. doi: 10.18632/oncotarget.8530.
• Ref 2: miR-520h is crucial for DAPK2 regulation and breast cancer progression. Oncogene. 2016 Mar 3;35(9):1134-42. doi: 10.1038/onc.2015.168. Epub 2015 May 18.