Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT47RXJ)

• DTT Name: Ubiquitin carboxyl-terminal hydrolase BAP1 (BAP1)
• Synonyms: KIAA0272; Cerebral protein 6; BRCA1-associated protein 1
• Gene Name: BAP1
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Peptidase C12 family. BAP1 subfamily
• UniProt ID: BAP1_HUMAN
• TTD ID: T92628
• EC Number: EC 3.4.19.12
• Sequence:
  MNKGWLELESDPGLFTLLVEDFGVKGVQVEEIYDLQSKCQGPVYGFIFLFKWIEERRSRR
  KVSTLVDDTSVIDDDIVNNMFFAHQLIPNSCATHALLSVLLNCSSVDLGPTLSRMKDFTK
  GFSPESKGYAIGNAPELAKAHNSHARPEPRHLPEKQNGLSAVRTMEAFHFVSYVPITGRL
  FELDGLKVYPIDHGPWGEDEEWTDKARRVIMERIGLATAGEPYHDIRFNLMAVVPDRRIK
  YEARLHVLKVNRQTVLEALQQLIRVTQPELIQTHKSQESQLPEESKSASNKSPLVLEANR
  APAASEGNHTDGAEEAAGSCAQAPSHSPPNKPKLVVKPPGSSLNGVHPNPTPIVQRLPAF
  LDNHNYAKSPMQEEEDLAAGVGRSRVPVRPPQQYSDDEDDYEDDEEDDVQNTNSALRYKG
  KGTGKPGALSGSADGQLSVLQPNTINVLAEKLKESQKDLSIPLSIKTSSGAGSPAVAVPT
  HSQPSPTPSNESTDTASEIGSAFNSPLRSPIRSANPTRPSSPVTSHISKVLFGEDDSLLR
  VDCIRYNRAVRDLGPVISTGLLHLAEDGVLSPLALTEGGKGSSPSIRPIQGSQGSSSPVE
  KEVVEATDSREKTGMVRPGEPLSGEKYSPKELLALLKCVEAEIANYEACLKEEVEKRKKF
  KIDDQRRTHNYDEFICTFISMLAQEGMLANLVEQNISVRRRQGVSIGRLHKQRKPDRRKR
  SRPYKAKRQ
• Function: Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B. Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'-linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains. Deubiquitination of HCFC1 does not lead to increase stability of HCFC1. Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination. It however does not mediate deubiquitination of BRCA1 and BARD1. Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950). Acts as a tumor suppressor.
• Reactome Pathway:
  Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565)
  UCH proteinases (R-HSA-5689603)

References

• [1] Ubiquitin carboxyl-terminal hydrolases: involvement in cancer progression and clinical implications. Cancer Metastasis Rev. 2017 Dec;36(4):669-682.