Molecule Information

General Information of the Molecule (ID: Mol01961)

• Name: Caspase recruitment domain family member 10 (CARD10) ,Homo sapiens
• Synonyms: CARD10; CARMA3
• Molecule Type: Protein
• Gene Name: CARD10
• Gene ID: 29775
• Location: chr22:37,490,362-37,519,542[-]
• Sequence:
  MPGRAEAGEAEEEAGAGSGSEAEEDALWERIEGVRHRLARALNPAKLTPYLRQCRVIDEQ
  DEEEVLSTYRFPCRVNRTGRLMDILRCRGKRGYEAFLEALEFYYPEHFTLLTGQEPAQRC
  SMILDEEGPEGLTQFLMTEVRRLREARKSQLQREQQLQARGRVLEEERAGLEQRLRDQQQ
  AQERCQRLREDWEAGSLELLRLKDENYMIAMRLAQLSEEKNSAVLRSRDLQLAVDQLKLK
  VSRLEEECALLRRARGPPPGAEEKEKEKEKEKEPDNVDLVSELRAENQRLTASLRELQEG
  LQQEASRPGAPGSERILLDILEHDWREAQDSRQELCQKLHAVQGELQWAEELRDQYLQEM
  EDLRLKHRTLQKDCDLYKHRMATVLAQLEEIEKERDQAIQSRDRIQLQYSQSLIEKDQYR
  KQVRGLEAERDELLTTLTSLEGTKALLEVQLQRAQGGTCLKACASSHSLCSNLSSTWSLS
  EFPSPLGGPEATGEAAVMGGPEPHNSEEATDSEKEINRLSILPFPPSAGSILRRQREEDP
  APPKRSFSSMSDITGSVTLKPWSPGLSSSSSSDSVWPLGKPEGLLARGCGLDFLNRSLAI
  RVSGRSPPGGPEPQDKGPDGLSFYGDRWSGAVVRRVLSGPGSARMEPREQRVEAAGLEGA
  CLEAEAQQRTLLWNQGSTLPSLMDSKACQSFHEALEAWAKGPGAEPFYIRANLTLPERAD
  PHALCVKAQEILRLVDSAYKRRQEWFCTRVDPLTLRDLDRGTVPNYQRAQQLLEVQEKCL
  PSSRHRGPRSNLKKRALDQLRLVRPKPVGAPAGDSPDQLLLEPCAEPERSLRPYSLVRPL
  LVSALRPVVLLPECLAPRLIRNLLDLPSSRLDFQVCPAESLSGEELCPSSAPGAPKAQPA
  TPGLGSRIRAIQESVGKKHCLLELGARGVRELVQNEIYPIVIHVEVTEKNVREVRGLLGR
  PGWRDSELLRQCRGSEQVLWGLPCSWVQVPAHEWGHAEELAKVVRGRILQEQARLVWVEC
  GSSRGCPSSSEA
• Function: Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR.
• Uniprot ID: CAR10_HUMAN
• Ensembl ID: ENSG00000100065
• HGNC ID: HGNC:16422

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; chr22:37891880C>G+chr22:37891912C>G
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: NF-kappaB signaling pathway; Inhibition; hsa04064
• 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