Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTO0DKT)

• DTT Name: NEDD4-like E3 ubiquitin-protein ligase WWP2 (WWP2)
• Synonyms: WW domaincontaining protein 2; WW domain-containing protein 2; NEDD4like E3 ubiquitinprotein ligaseWWP2; HECT-type E3 ubiquitin transferase WWP2; Atrophin1interacting protein 2; Atrophin-1-interacting protein 2; AIP2
• Gene Name: WWP2
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: WWP2_HUMAN
• TTD ID: T01054
• EC Number: EC 2.3.2.26
• Sequence:
  MASASSSRAGVALPFEKSQLTLKVVSAKPKVHNRQPRINSYVEVAVDGLPSETKKTGKRI
  GSSELLWNEIIILNVTAQSHLDLKVWSCHTLRNELLGTASVNLSNVLKNNGGKMENMQLT
  LNLQTENKGSVVSGGELTIFLDGPTVDLGNVPNGSALTDGSQLPSRDSSGTAVAPENRHQ
  PPSTNCFGGRSRTHRHSGASARTTPATGEQSPGARSRHRQPVKNSGHSGLANGTVNDEPT
  TATDPEEPSVVGVTSPPAAPLSVTPNPNTTSLPAPATPAEGEEPSTSGTQQLPAAAQAPD
  ALPAGWEQRELPNGRVYYVDHNTKTTTWERPLPPGWEKRTDPRGRFYYVDHNTRTTTWQR
  PTAEYVRNYEQWQSQRNQLQGAMQHFSQRFLYQSSSASTDHDPLGPLPPGWEKRQDNGRV
  YYVNHNTRTTQWEDPRTQGMIQEPALPPGWEMKYTSEGVRYFVDHNTRTTTFKDPRPGFE
  SGTKQGSPGAYDRSFRWKYHQFRFLCHSNALPSHVKISVSRQTLFEDSFQQIMNMKPYDL
  RRRLYIIMRGEEGLDYGGIAREWFFLLSHEVLNPMYCLFEYAGKNNYCLQINPASSINPD
  HLTYFRFIGRFIAMALYHGKFIDTGFTLPFYKRMLNKRPTLKDLESIDPEFYNSIVWIKE
  NNLEECGLELYFIQDMEILGKVTTHELKEGGESIRVTEENKEEYIMLLTDWRFTRGVEEQ
  TKAFLDGFNEVAPLEWLRYFDEKELELMLCGMQEIDMSDWQKSTIYRHYTKNSKQIQWFW
  QVVKEMDNEKRIRLLQFVTGTCRLPVGGFAELIGSNGPQKFCIDKVGKETWLPRSHTCFN
  RLDLPPYKSYEQLREKLLYAIEETEGFGQE
• Function: Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation. E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
• KEGG Pathway: Ubiquitin mediated proteolysis (hsa04120)
• Reactome Pathway:
  RHOQ GTPase cycle (R-HSA-9013406)
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOU GTPase cycle (R-HSA-9013420)
  NOTCH3 Activation and Transmission of Signal to the Nucleus (R-HSA-9013507)
  Regulation of PTEN stability and activity (R-HSA-8948751)

References

• [1] Expression of WW domain-containing protein 2 is correlated with pathological grade and recurrence of glioma. J Cancer Res Ther. 2017 Oct-Dec;13(6):1032-1037.