Molecule Information

General Information of the Molecule (ID: Mol00559)

• Name: PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2) ,Homo sapiens
• Synonyms: PH domain leucine-rich repeat-containing protein phosphatase-like; PHLPP-like; KIAA0931; PHLPPL
• Molecule Type: Protein
• Gene Name: PHLPP2
• Gene ID: 23035
• Location: chr16:71637835-71724701[-]
• Sequence:
  MKRNGSRNCLNRRSRFGSRERDWLREDVKRGCVYLYGADTTTATTTTTTSSSSSSSSSSS
  DLHLVLCTVETPASEICAGEGRESLYLQLHGDLVRRLEPTERPLQIVYDYLSRLGFDDPV
  RIQEEATNPDLGCMIRFYGEKPCHMDRLDRILLSGIYNVRKGKTQLHKWAERLVVLCGTC
  LIVSSVKDCQTGKMHILPLVGGKIEEVKRRQYSLAFSSAGAQAQTYHVSFETLAEYQRWQ
  RQASKVVSQRISTVDLSCYSLEEVPEHLFYSQDITYLNLRHNFMQLERPGGLDTLYKFSQ
  LKGLNLSHNKLGLFPILLCEISTLTELNLSCNGFHDLPSQIGNLLNLQTLCLDGNFLTTL
  PEELGNLQQLSSLGISFNNFSQIPEVYEKLTMLDRVVMAGNCLEVLNLGVLNRMNHIKHV
  DLRMNHLKTMVIENLEGNKHITHVDLRDNRLTDLDLSSLCSLEQLHCGRNQLRELTLSGF
  SLRTLYASSNRLTAVNVYPVPSLLTFLDLSRNLLECVPDWACEAKKIEVLDVSYNLLTEV
  PVRILSSLSLRKLMLGHNHVQNLPTLVEHIPLEVLDLQHNALTRLPDTLFSKALNLRYLN
  ASANSLESLPSACTGEESLSMLQLLYLTNNLLTDQCIPVLVGHLHLRILHLANNQLQTFP
  ASKLNKLEQLEELNLSGNKLKTIPTTIANCKRLHTLVAHSNNISIFPEILQLPQIQFVDL
  SCNDLTEILIPEALPATLQDLDLTGNTNLVLEHKTLDIFSHITTLKIDQKPLPTTDSTVT
  STFWSHGLAEMAGQRNKLCVSALAMDSFAEGVGAVYGMFDGDRNEELPRLLQCTMADVLL
  EEVQQSTNDTVFMANTFLVSHRKLGMAGQKLGSSALLCYIRPDTADPASSFSLTVANVGT
  CQAVLCRGGKPVPLSKVFSLEQDPEEAQRVKDQKAIITEDNKVNGVTCCTRMLGCTYLYP
  WILPKPHISSTPLTIQDELLILGNKALWEHLSYTEAVNAVRHVQDPLAAAKKLCTLAQSY
  GCQDNVGAMVVYLNIGEEGCTCEMNGLTLPGPVGFASTTTIKDAPKPATPSSSSGIASEF
  SSEMSTSEVSSEVGSTASDEHNAGGLDTALLPRPERRCSLHPTPTSGLFQRQPSSATFSS
  NQSDNGLDSDDDQPVEGVITNGSKVEVEVDIHCCRGRDLENSPPLIESSPTLCSEEHARG
  SCFGIRRQNSVNSGMLLPMSKDRMELQKSPSTSCLYGKKLSNGSIVPLEDSLNLIEVATE
  VPKRKTGYFAAPTQMEPEDQFVVPHDLEEEVKEQMKQHQDSRLEPEPHEEDRTEPPEEFD
  TAL
• Function: Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT1, 'Ser-660' of PRKCB isoform beta-II and 'Ser-657' of PRKCA. Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and decreases cell proliferation. Also controls the phosphorylation of AKT3. Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis. Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation. Inhibits cancer cell proliferation and may act as a tumor suppressor. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation. Dephosphorylates RAF1 inhibiting its kinase activity.
• Uniprot ID: PHLP2_HUMAN
• Ensembl ID: ENSG00000040199
• HGNC ID: HGNC:29149

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) 3 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Z138c cells; Blood; Homo sapiens (Human); CVCL_B077
• In Vivo Model: CB-17/SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Xenograft experiments assay
• Mechanism Description: The protein phosphatase PHLPP2, an important negative regulator of the PI3k/AkT pathway, was a direct target of miR-17 92 miRNAs, miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3k/AkT pathway activation.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Z138c cells; Blood; Homo sapiens (Human); CVCL_B077
• In Vivo Model: CB-17/SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Xenograft experiments assay
• Mechanism Description: The protein phosphatase PHLPP2, an important negative regulator of the PI3k/AkT pathway, was a direct target of miR-17 92 miRNAs, miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3k/AkT pathway activation.

Topotecan

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Mantle cell lymphoma [1]

• Resistant Disease: Mantle cell lymphoma [ICD-11: 2A85.0]
• Resistant Drug: Topotecan
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Activation; hsa04151
• In Vitro Model: Jeko-1 cells; Blood; Homo sapiens (Human); CVCL_1865
• In Vitro Model: Granta-519 cells; Blood; Homo sapiens (Human); CVCL_1818
• In Vitro Model: Z138c cells; Blood; Homo sapiens (Human); CVCL_B077
• In Vivo Model: CB-17/SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Luciferase assay
• Experiment for Drug Resistance: Xenograft experiments assay
• Mechanism Description: The protein phosphatase PHLPP2, an important negative regulator of the PI3k/AkT pathway, was a direct target of miR-17 92 miRNAs, miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3k/AkT pathway activation.

References

• Ref 1: The miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3K/AKT pathway activation. Leukemia. 2012 May;26(5):1064-72. doi: 10.1038/leu.2011.305. Epub 2011 Nov 25.