Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTB5R6M)

• DTT Name: Terminal nucleotidyltransferase 4B (TENT4B)
• Synonyms: Non-canonical poly(A) RNA polymerase PAPD5; PAP-associated domain-containing protein 5; Terminal guanylyltransferase; Terminal uridylyltransferase 3; TUTase 3; Topoisomerase-related function protein 4-2; TRF4-2
• Gene Name: TENT4B
• DTT Type: Clinical trial target; [1]
• BioChemical Class: DNA polymerase type-B
• UniProt ID: PAPD5_HUMAN
• TTD ID: T63241
• EC Number: EC 2.7.7.-; EC 2.7.7.19
• Sequence:
  MYRSGERLLGSHALPAEQRDFLPLETTNNNNNHHQPGAWARRAGSSASSPPSASSSPHPS
  AAVPAADPADSASGSSNKRKRDNKASGGRAAGGGRADGGGVVYSGTPWKRRNYNQGVVGL
  HEEISDFYEYMSPRPEEEKMRMEVVNRIESVIKELWPSADVQIFGSFKTGLYLPTSDIDL
  VVFGKWENLPLWTLEEALRKHKVADEDSVKVLDKATVPIIKLTDSFTEVKVDISFNVQNG
  VRAADLIKDFTKKYPVLPYLVLVLKQFLLQRDLNEVFTGGIGSYSLFLMAVSFLQLHPRE
  DACIPNTNYGVLLIEFFELYGRHFNYLKTGIRIKDGGSYVAKDEVQKNMLDGYRPSMLYI
  EDPLQPGNDVGRSSYGAMQVKQAFDYAYVVLSHAVSPIAKYYPNNETESILGRIIRVTDE
  VATYRDWISKQWGLKNRPEPSCNGPVSSSSATQSSSSDVDSDATPCKTPKQLLCRPSTGN
  RVGSQDVSLESSQAVGKMQSTQTTNTSNSTNKSQHGSARLFRSSSKGFQGTTQTSHGSLM
  TNKQHQGKSNNQYYHGKKRKHKRDAPLSDLCR
• Function: Terminal nucleotidyltransferase that catalyzes preferentially the transfer of ATP and GTP on RNA 3' poly(A) tail creating a heterogeneous 3' poly(A) tail leading to mRNAs stabilization by protecting mRNAs from active deadenylation (PubMed:21788334, PubMed:30026317). Also functions as a catalytic subunit of a TRAMP-like complex which has a poly(A) RNA polymerase activity and is involved in a post-transcriptional quality control mechanism. Polyadenylation with short oligo(A) tails is required for the degradative activity of the exosome on several of its nuclear RNA substrates. Doesn't need a cofactor for polyadenylation activity (in vitro) (PubMed:21788334, PubMed:21855801). Required for cytoplasmic polyadenylation of mRNAs involved in carbohydrate metabolism, including the glucose transporter SLC2A1/GLUT1 (PubMed:28383716). Plays a role in replication-dependent histone mRNA degradation, probably through terminal uridylation of mature histone mRNAs. May play a role in sister chromatid cohesion (PubMed:18172165). Mediates 3' adenylation of the microRNA MIR21 followed by its 3'-to-5' trimming by the exoribonuclease PARN leading to degradation (PubMed:25049417). Mediates 3' adenylation of H/ACA box snoRNAs (small nucleolar RNAs) followed by its 3'-to-5' trimming by the exoribonuclease PARN which enhances snoRNA stability and maturation (PubMed:22442037). {ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:21788334, ECO:0000269|PubMed:21855801, ECO:0000269|PubMed:22442037, ECO:0000269|PubMed:25049417, ECO:0000269|PubMed:28383716, ECO:0000269|PubMed:30026317}.
• KEGG Pathway: 64282 (hsa)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GSK3965193	DMZVEN0	Hepatitis B	1E51	Phase 1	[1]

References

• [1] Clinical pipeline report, company report or official report of GlaxoSmithKline