Molecule Information

General Information of the Molecule (ID: Mol01849)

• Name: Protein kinase C eta type (PRKCH) ,Homo sapiens
• Synonyms: Protein kinase C eta type; PKC-L; nPKC-eta
• Molecule Type: Protein
• Gene Name: PRKCH
• Gene ID: 5583
• Location: chr14:61,187,559-61,550,976[+]
• Sequence:
  MSSGTMKFNGYLRVRIGEAVGLQPTRWSLRHSLFKKGHQLLDPYLTVSVDQVRVGQTSTK
  QKTNKPTYNEEFCANVTDGGHLELAVFHETPLGYDHFVANCTLQFQELLRTTGASDTFEG
  WVDLEPEGKVFVVITLTGSFTEATLQRDRIFKHFTRKRQRAMRRRVHQINGHKFMATYLR
  QPTYCSHCREFIWGVFGKQGYQCQVCTCVVHKRCHHLIVTACTCQNNINKVDSKIAEQRF
  GINIPHKFSIHNYKVPTFCDHCGSLLWGIMRQGLQCKICKMNVHIRCQANVAPNCGVNAV
  ELAKTLAGMGLQPGNISPTSKLVSRSTLRRQGKESSKEGNGIGVNSSNRLGIDNFEFIRV
  LGKGSFGKVMLARVKETGDLYAVKVLKKDVILQDDDVECTMTEKRILSLARNHPFLTQLF
  CCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARFYAAEIISALMFLHDKGIIYRDL
  KLDNVLLDHEGHCKLADFGMCKEGICNGVTTATFCGTPDYIAPEILQEMLYGPAVDWWAM
  GVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLHEDATGILKSFMTKNPTMRLGSL
  TQGGEHAILRHPFFKEIDWAQLNHRQIEPPFRPRIKSREDVSNFDPDFIKEEPVLTPIDE
  GHLPMINQDEFRNFSYVSPELQP
• Function: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization.
• Uniprot ID: KPCL_HUMAN
• Ensembl ID: ENSG00000027075
• HGNC ID: HGNC:9403

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

Trametinib

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Atypical chronic myeloid leukemia [1]

• Sensitive Disease: Atypical chronic myeloid leukemia [ICD-11: 2A41.1]
• Sensitive Drug: Trametinib
• Molecule Alteration: Copy number gain; .
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human CML cells; Peripheral blood; Homo sapiens (Human); CVCL_E508
• In Vitro Model: BCR-ABL mouse primary bone marrow cells; N.A.; Mus musculus (Mouse); N.A.
• In Vivo Model: Mouse model of BCR-ABL-independent IM-resistant CML; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis; qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay

References

• Ref 1: A therapeutically targetable mechanism of BCR-ABL-independent imatinib resistance in chronic myeloid leukemiaSci Transl Med. 2014 Sep 3;6(252):252ra121. doi: 10.1126/scitranslmed.3009073.