Molecule Information

General Information of the Molecule (ID: Mol01936)

• Name: Zinc finger FYVE-type containing 9 (ZFYVE9) ,Homo sapiens
• Synonyms: ZFYVE9; MADHIP; SARA; SMADIP
• Molecule Type: Protein
• Gene Name: ZFYVE9
• Gene ID: 9372
• Location: chr1:52,142,089-52,348,671[+]
• Sequence:
  MENYFQAEAYNLDKVLDEFEQNEDETVSSTLLDTKWNKILDPPSHRLSFNPTLASVNESA
  VSNESQPQLKVFSLAHSAPLTTEEEDHCANGQDCNLNPEIATMWIDENAVAEDQLIKRNY
  SWDDQCSAVEVGEKKCGNLACLPDEKNVLVVAVMHNCDKRTLQNDLQDCNNYNSQSLMDA
  FSCSLDNENRQTDQFSFSINESTEKDMNSEKQMDPLNRPKTEGRSVNHLCPTSSDSLASV
  CSPSQLKDDGSIGRDPSMSAITSLTVDSVISSQGTDGCPAVKKQENYIPDEDLTGKISSP
  RTDLGSPNSFSHMSEGILMKKEPAEESTTEESLRSGLPLLLKPDMPNGSGRNNDCERCSD
  CLVPNEVRADENEGYEHEETLGTTEFLNMTEHFSESQDMTNWKLTKLNEMNDSQVNEEKE
  KFLQISQPEDTNGDSGGQCVGLADAGLDLKGTCISESEECDFSTVIDTPAANYLSNGCDS
  YGMQDPGVSFVPKTLPSKEDSVTEEKEIEESKSECYSNIYEQRGNEATEGSGLLLNSTGD
  LMKKNYLHNFCSQVPSVLGQSSPKVVASLPSISVPFGGARPKQPSNLKLQIPKPLSDHLQ
  NDFPANSGNNTKNKNDILGKAKLGENSATNVCSPSLGNISNVDTNGEHLESYEAEISTRP
  CLALAPDSPDNDLRAGQFGISARKPFTTLGEVAPVWVPDSQAPNCMKCEARFTFTKRRHH
  CRACGKVFCASCCSLKCKLLYMDRKEARVCVICHSVLMNAQAWENMMSASSQSPNPNNPA
  EYCSTIPPLQQAQASGALSSPPPTVMVPVGVLKHPGAEVAQPREQRRVWFADGILPNGEV
  ADAAKLTMNGTSSAGTLAVSHDPVKPVTTSPLPAETDICLFSGSITQVGSPVGSAMNLIP
  EDGLPPILISTGVKGDYAVEEKPSQISVMQQLEDGGPDPLVFVLNANLLSMVKIVNYVNR
  KCWCFTTKGMHAVGQSEIVILLQCLPDEKCLPKDIFNHFVQLYRDALAGNVVSNLGHSFF
  SQSFLGSKEHGGFLYVTSTYQSLQDLVLPTPPYLFGILIQKWETPWAKVFPIRLMLRLGA
  EYRLYPCPLFSVRFRKPLFGETGHTIMNLLADFRNYQYTLPVVQGLVVDMEVRKTSIKIP
  SNRYNEMMKAMNKSNEHVLAGGACFNEKADSHLVCVQNDDGNYQTQAISIHNQPRKVTGA
  SFFVFSGALKSSSGYLAKSSIVEDGVMVQITAENMDSLRQALREMKDFTITCGKADAEEP
  QEHIHIQWVDDDKNVSKGVVSPIDGKSMETITNVKIFHGSEYKANGKVIRWTEVFFLEND
  DQHNCLSDPADHSRLTEHVAKAFCLALCPHLKLLKEDGMTKLGLRVTLDSDQVGYQAGSN
  GQPLPSQYMNDLDSALVPVIHGGACQLSEGPVVMELIFYILENIV
• Function: Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization.
• Uniprot ID: ZFYV9_HUMAN
• Ensembl ID: ENSG00000157077
• HGNC ID: HGNC:6775

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; chr1:52704185G>T
• 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