Molecule Information

General Information of the Molecule (ID: Mol01845)

• Name: Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) ,Homo sapiens
• Synonyms: Protein phosphatase 1 regulatory subunit 15A; Growth arrest and DNA damage-inducible protein GADD34; Myeloid differentiation primary response protein MyD116 homolog
• Molecule Type: Protein
• Gene Name: PPP1R15A
• Gene ID: 23645
• Location: chr19:48,872,421-48,876,058[+]
• Sequence:
  MAPGQAPHQATPWRDAHPFFLLSPVMGLLSRAWSRLRGLGPLEPWLVEAVKGAALVEAGL
  EGEARTPLAIPHTPWGRRPEEEAEDSGGPGEDRETLGLKTSSSLPEAWGLLDDDDGMYGE
  REATSVPRGQGSQFADGQRAPLSPSLLIRTLQGSDKNPGEEKAEEEGVAEEEGVNKFSYP
  PSHRECCPAVEEEDDEEAVKKEAHRTSTSALSPGSKPSTWVSCPGEEENQATEDKRTERS
  KGARKTSVSPRSSGSDPRSWEYRSGEASEEKEEKAHKETGKGEAAPGPQSSAPAQRPQLK
  SWWCQPSDEEEGEVKALGAAEKDGEAECPPCIPPPSAFLKAWVYWPGEDTEEEEDEEEDE
  DSDSGSDEEEGEAEASSSTPATGVFLKSWVYQPGEDTEEEEDEDSDTGSAEDEREAETSA
  STPPASAFLKAWVYRPGEDTEEEEDEDVDSEDKEDDSEAALGEAESDPHPSHPDQRAHFR
  GWGYRPGKETEEEEAAEDWGEAEPCPFRVAIYVPGEKPPPPWAPPRLPLRLQRRLKRPET
  PTHDPDPETPLKARKVRFSEKVTVHFLAVWAGPAQAARQGPWEQLARDRSRFARRITQAQ
  EELSPCLTPAARARAWARLRNPPLAPIPALTQTLPSSSVPSSPVQTTPLSQAVATPSRSS
  AAAAAALDLSGRRG
• Function: Recruits the serine/threonine-protein phosphatase PPP1CA to prevents excessive phosphorylation of the translation initiation factor eIF-2A/EIF2S1, thereby reversing the shut-off of protein synthesis initiated by stress-inducible kinases and facilitating recovery of cells from stress. Down-regulates the TGF-beta signaling pathway by promoting dephosphorylation of TGFB1 by PP1. May promote apoptosis by inducing p53/TP53 phosphorylation on 'Ser-15'. Plays an essential role in autophagy by tuning translation during starvation, thus enabling lysosomal biogenesis and a sustained autophagic flux. Acts also a viral restriction factor by attenuating HIV-1 replication. Mechanistically, mediates the inhibition of HIV-1 TAR RNA-mediated translation.
• Uniprot ID: PR15A_HUMAN
• Ensembl ID: ENSG00000087074
• HGNC ID: HGNC:14375

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Investigative Drug(s) 1 drug(s) in total

Bevacizumab/FOLFIRI Regimen

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Colorectal cancer [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Sensitive Drug: Bevacizumab/FOLFIRI Regimen
• Molecule Alteration: Missense mutation; p.R251P (c.752G>C)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vivo Model: BALB/c nude mouse PDX model; Mus musculus
• Experiment for Drug Resistance: MTT assay

References

• Ref 1: Feasibility of novel PPP1R15A and proposed ANXA11 single nucleotide polymorphisms as predictive markers for bevacizumab regimen in metastatic colorectal cancerJ Cancer Res Clin Oncol. 2016 Aug;142(8):1705-14. doi: 10.1007/s00432-016-2177-5. Epub 2016 May 13.