Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5G7GKB)

• DOT Name: EF-hand calcium-binding domain-containing protein 6 (EFCAB6)
• Synonyms: CAP-binding protein complex-interacting protein 1; DJ-1-binding protein; DJBP
• Gene Name: EFCAB6
• Related Disease:
  Disorder of sexual differentiation
  Fanconi anemia complementation group A
  Fanconi's anemia
  Myeloproliferative neoplasm
• UniProt ID: EFCB6_HUMAN
• PDB ID: 1WLZ; 5D67
• Pfam ID: PF08976 ; PF13499 ; PF13833
• Sequence:
  MCKMAIIPDWLRSHPHTRKFTHSRPHSSPCRVYSRNGSPNKFRSSSTTAVANPTLSSLDV
  KRILFQKITDRGDELQKAFQLLDTGQNLTVSKSELRRIITDFLMPLTREQFQDVLAQIPL
  STSGTVPYLAFLSRFGGIDLYINGIKRGGGNEMNCCRTLRELEIQVGEKVFKNIKTVMKA
  FELIDVNKTGLVRPQELRRVLETFCMKLRDEEYEKFSKHYNIHKDTAVDYNVFLKNLSIN
  NDLNLRYCMGNQEVSLENQQAKNSKKERLLGSASSEDIWRNYSLDEIERNFCLQLSKSYE
  KVEKALSAGDPCKGGYVSFNYLKIVLDTFVYQIPRRIFIQLMKRFGLKATTKINWKQFLT
  SFHEPQGLQVSSKGPLTKRNSINSRNESHKENIITKLFRHTEDHSASLKKALLIINTKPD
  GPITREEFRYILNCMAVKLSDSEFKELMQMLDPGDTGVVNTSMFIDLIEENCRMRKTSPC
  TDAKTPFLLAWDSVEEIVHDTITRNLQAFYNMLRSYDLGDTGRIGRNNFKKIMHVFCPFL
  TNAHFIKLCSKIQDIGSGRILYKKLLACIGIDGPPTVSPVLVPKDQLLSEHLQKDEQQQP
  DLSERTKLTEDKTTLTKKMTTEEVIEKFKKCIQQQDPAFKKRFLDFSKEPNGKINVHDFK
  KVLEDTGMPMDDDQYALLTTKIGFEKEGMSYLDFAAGFEDPPMRGPETTPPQPPTPSKSY
  VNSHFITAEECLKLFPRRLKESFRDPYSAFFKTDADRDGIINMHDLHRLLLHLLLNLKDD
  EFERFLGLLGLRLSVTLNFREFQNLCEKRPWRTDEAPQRLIRPKQKVADSELACEQAHQY
  LVTKAKNRWSDLSKNFLETDNEGNGILRRRDIKNALYGFDIPLTPREFEKLWARYDTEGK
  GHITYQEFLQKLGINYSPAVHRPCAEDYFNFMGHFTKPQQLQEEMKELQQSTEKAVAARD
  KLMDRHQDISKAFTKTDQSKTNYISICKMQEVLEECGCSLTEGELTHLLNSWGVSRHDNA
  INYLDFLRAVENSKSTGAQPKEKEESMPINFATLNPQEAVRKIQEVVESSQLALSTAFSA
  LDKEDTGFVKATEFGQVLKDFCYKLTDNQYHYFLRKLRIHLTPYINWKYFLQNFSCFLEE
  TADEWAEKMPKGPPPTSPKATADRDILARLHKAVTSHYHAITQEFENFDTMKTNTISREE
  FRAICNRRVQILTDEQFDRLWNEMPVNAKGRLKYPDFLSRFSSETAATPMATGDSAVAQR
  GSSVPDVSEGTRSALSLPTQELRPGSKSQSHPCTPASTTVIPGTPPLQNCDPIESRLRKR
  IQGCWRQLLKECKEKDVARQGDINASDFLALVEKFNLDISKEECQQLIIKYDLKSNGKFA
  YCDFIQSCVLLLKAKESSLMHRMKIQNAHKMKEAGAETPSFYSALLRIQPKIVHCWRPMR
  RTFKSYDEAGTGLLSVADFRTVLRQYSINLSEEEFFHILEYYDKTLSSKISYNDFLRAFL
  Q
• Function: Negatively regulates the androgen receptor by recruiting histone deacetylase complex, and protein DJ-1 antagonizes this inhibition by abrogation of this complex. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (Probable).
• Tissue Specificity: Specifically expressed in the testis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Disorder of sexual differentiation	DISRMAEZ	Strong	Genetic Variation	[1]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Genetic Variation	[1]
Fanconi's anemia	DISGW6Q8	Strong	Genetic Variation	[1]
Myeloproliferative neoplasm	DIS5KAPA	Limited	Genetic Variation	[2]

2 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of EF-hand calcium-binding domain-containing protein 6 (EFCAB6).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of EF-hand calcium-binding domain-containing protein 6 (EFCAB6).	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of EF-hand calcium-binding domain-containing protein 6 (EFCAB6).	[5]

References

• [1] Cytogenetic and molecular diagnosis of Fanconi anemia revealed two hidden phenotypes: Disorder of sex development and cerebro-oculo-facio-skeletal syndrome.Mol Genet Genomic Med. 2019 Jul;7(7):e00694. doi: 10.1002/mgg3.694. Epub 2019 May 23.
• [2] Identification of a HMGA2-EFCAB6 gene rearrangement following next-generation sequencing in a patient with a t(12;22)(q14.3;q13.2) and JAK2V617F-positive myeloproliferative neoplasm.Cancer Genet. 2012 Jun;205(6):295-303. doi: 10.1016/j.cancergen.2012.03.006.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [5] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.