Molecule Information

General Information of the Molecule (ID: Mol01985)

• Name: SH3 domain containing ring finger 2 (SH3RF2) ,Homo sapiens
• Synonyms: SH3RF2; POSH3; POSHER; PPP1R39; RNF158
• Molecule Type: Protein
• Gene Name: SH3RF2
• Gene ID: 153769
• Location: chr5:145,936,578-146,081,791[+]
• Sequence:
  MDDLTLLDLLECPVCFEKLDVTAKVLPCQHTFCKPCLQRVFKAHKELRCPECRTPVFSNI
  EALPANLLLVRLLDGVRSGQSSGRGGSFRRPGTMTLQDGRKSRTNPRRLQASPFRLVPNV
  RIHMDGVPRAKALCNYRGQNPGDLRFNKGDIILLRRQLDENWYQGEINGISGNFPASSVE
  VIKQLPQPPPLCRALYNFDLRGKDKSENQDCLTFLKDDIITVISRVDENWAEGKLGDKVG
  IFPILFVEPNLTARHLLEKNKGRQSSRTKNLSLVSSSSRGNTSTLRRGPGSRRKVPGQFS
  ITTALNTLNRMVHSPSGRHMVEISTPVLISSSNPSVITQPMEKADVPSSCVGQVSTYHPA
  PVSPGHSTAVVSLPGSQQHLSANMFVALHSYSAHGPDELDLQKGEGVRVLGKCQDGWLRG
  VSLVTGRVGIFPNNYVIPIFRKTSSFPDSRSPGLYTTWTLSTSSVSSQGSISEGDPRQSR
  PFKSVFVPTAIVNPVRSTAGPGTLGQGSLRKGRSSMRKNGSLQRPLQSGIPTLVVGSLRR
  SPTMVLRPQQFQFYQPQGIPSSPSAVVVEMGSKPALTGEPALTCISRGSEAWIHSAASSL
  IMEDKEIPIKSEPLPKPPASAPPSILVKPENSRNGIEKQVKTVRFQNYSPPPTKHYTSHP
  TSGKPEQPATLKASQPEAASLGPEMTVLFAHRSGCHSGQQTDLRRKSALGKATTLVSTAS
  GTQTVFPSK
• Function: Has E3 ubiquitin-protein ligase activity. Acts as an anti-apoptotic regulator of the JNK pathway by ubiquitinating and promoting the degradation of SH3RF1, a scaffold protein that is required for pro-apoptotic JNK activation. Facilitates TNF-alpha-mediated recruitment of adapter proteins TRADD and RIPK1 to TNFRSF1A and regulates PAK4 protein stability via inhibition of its ubiquitin-mediated proteasomal degradation. Inhibits PPP1CA phosphatase activity.
• Uniprot ID: SH3R2_HUMAN
• Ensembl ID: ENSG00000156463
• HGNC ID: HGNC:26299

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

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Dermatofibrosarcoma protuberans [1]

• Resistant Disease: Dermatofibrosarcoma protuberans [ICD-11: 2B53.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Missense mutation; chr5:145435750G>A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Dermatofibrosarcoma protuberans tissue; .
• Experiment for Molecule Alteration: Sequencing assay
• Mechanism Description: This finding includes mutations in the CARD10, PPP1R39, SAFB2, and STARD9 genes. CARD10 is associated with the activation of the NK-kB signaling pathway and is known to have clinical implications in gastric cancer, colon cancer, and non-small cell lung cance. A potential role for changes in the PPP1R39 gene has also been suggested in the development of human cancers. Further, the SAFB2 gene product is involved in a variety of cellular process, such as cell growth, apoptosis, and stress response and is associated with breast tumorigenesis. In a recent in vitro study, the STARD9 gene product was shown to be associated with mitotic microtubule formation and cell division and might be a potential candidate target to extend the reach of cancer therapeutics. Among the studies mentioned above, Crone et al. demonstrated that targeting CARD10 by microRNA-146a inhibited NF-kB signaling pathway activation in gastric cancer cell lines via reduction of tumor-promoting cytokines and growth factors including PDGFRB. This study showed the possible association between CARD10 inhibition and decreased level of PDGFR and also implied CARD10 activating mutation may be one of the possible resistance mechanism to PBGFR inhibition by imatinib in DFSP.

References

• Ref 1: Genetic aberrations in imatinib-resistant dermatofibrosarcoma protuberans revealed by whole genome sequencing .PLoS One. 2013 Jul 29;8(7):e69752. doi: 10.1371/journal.pone.0069752. Print 2013. 10.1371/journal.pone.0069752