Molecule Information

General Information of the Molecule (ID: Mol00631)

• Name: Schlafen family member 11 (SLFN11) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: SLFN11
• Gene ID: 91607
• Location: chr17:35350305-35373701[-]
• Sequence:
  MEANQCPLVVEPSYPDLVINVGEVTLGEENRKKLQKIQRDQEKERVMRAACALLNSGGGV
  IRMAKKVEHPVEMGLDLEQSLRELIQSSDLQAFFETKQQGRCFYIFVKSWSSGPFPEDRS
  VKPRLCSLSSSLYRRSETSVRSMDSREAFCFLKTKRKPKILEEGPFHKIHKGVYQELPNS
  DPADPNSDPADLIFQKDYLEYGEILPFPESQLVEFKQFSTKHFQEYVKRTIPEYVPAFAN
  TGGGYLFIGVDDKSREVLGCAKENVDPDSLRRKIEQAIYKLPCVHFCQPQRPITFTLKIV
  NVLKRGELYGYACMIRVNPFCCAVFSEAPNSWIVEDKYVCSLTTEKWVGMMTDTDPDLLQ
  LSEDFECQLSLSSGPPLSRPVYSKKGLEHKKELQQLLFSVPPGYLRYTPESLWRDLISEH
  RGLEELINKQMQPFFRGILIFSRSWAVDLNLQEKPGVICDALLIAQNSTPILYTILREQD
  AEGQDYCTRTAFTLKQKLVNMGGYTGKVCVRAKVLCLSPESSAEALEAAVSPMDYPASYS
  LAGTQHMEALLQSLVIVLLGFRSLLSDQLGCEVLNLLTAQQYEIFSRSLRKNRELFVHGL
  PGSGKTIMAMKIMEKIRNVFHCEAHRILYVCENQPLRNFISDRNICRAETRKTFLRENFE
  HIQHIVIDEAQNFRTEDGDWYGKAKSITRRAKGGPGILWIFLDYFQTSHLDCSGLPPLSD
  QYPREELTRIVRNADPIAKYLQKEMQVIRSNPSFNIPTGCLEVFPEAEWSQGVQGTLRIK
  KYLTVEQIMTCVADTCRRFFDRGYSPKDVAVLVSTAKEVEHYKYELLKAMRKKRVVQLSD
  ACDMLGDHIVLDSVRRFSGLERSIVFGIHPRTADPAILPNVLICLASRAKQHLYIFPWGG
  H
• Function: Inhibitor of DNA replication that promotes cell death in response to DNA damage. Acts as a guardian of the genome by killing cells with defective replication. Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death. Acts independently of ATR. Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis. Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner. Binds to tRNAs and exploits the unique viral codon bias towards A/T nucleotides. The exact inhibition mechanism is unclear: may either sequester tRNAs, prevent their maturation via post-transcriptional processing or may accelerate their deacylation. Does not inhibit reverse transcription, integration or production and nuclear export of viral RNA.
• Uniprot ID: SLN11_HUMAN
• Ensembl ID: ENSG00000172716
• HGNC ID: HGNC:26633

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

Platinum

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Disease Class: Primary prostate cancer [1]

• Resistant Disease: Primary prostate cancer [ICD-11: 2C82.Z]
• Resistant Drug: Platinum
• Molecule Alteration: Alteration; Epigenetic silencing
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vivo Model: A retrospective survey in conducting clinical studies; Homo sapiens
• Experiment for Molecule Alteration: Methyl-CpG binding domain protein-enriched genome sequencing assay;Methylated DNA Immunoprecipitation Sequencing assay
• Mechanism Description: Epigenetic silencing of SLFN11 has been associated with resistance to platinum-based chemotherapies in a number of cell lines including DU-145 and PC3.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.29E-01; Fold-change: 1.64E+00; Z-score: 9.45E-01

References

• Ref 1: The importance of DNA methylation in prostate cancer development. J Steroid Biochem Mol Biol. 2017 Feb;166:1-15. doi: 10.1016/j.jsbmb.2016.04.009. Epub 2016 Apr 24.