Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTXHWA7)

• DTT Name: Ubiquitin-activating enzyme E1 (UBAE1)
• Synonyms: Ubiquitin-like modifier-activating enzyme 1; UBE1; Protein A1S9; A1S9T
• Gene Name: UBA1
• DTT Type: Patented-recorded target; [1]
• UniProt ID: UBA1_HUMAN
• TTD ID: T81780
• EC Number: EC 6.2.1.45
• Sequence:
  MSSSPLSKKRRVSGPDPKPGSNCSPAQSVLSEVPSVPTNGMAKNGSEADIDEGLYSRQLY
  VLGHEAMKRLQTSSVLVSGLRGLGVEIAKNIILGGVKAVTLHDQGTAQWADLSSQFYLRE
  EDIGKNRAEVSQPRLAELNSYVPVTAYTGPLVEDFLSGFQVVVLTNTPLEDQLRVGEFCH
  NRGIKLVVADTRGLFGQLFCDFGEEMILTDSNGEQPLSAMVSMVTKDNPGVVTCLDEARH
  GFESGDFVSFSEVQGMVELNGNQPMEIKVLGPYTFSICDTSNFSDYIRGGIVSQVKVPKK
  ISFKSLVASLAEPDFVVTDFAKFSRPAQLHIGFQALHQFCAQHGRPPRPRNEEDAAELVA
  LAQAVNARALPAVQQNNLDEDLIRKLAYVAAGDLAPINAFIGGLAAQEVMKACSGKFMPI
  MQWLYFDALECLPEDKEVLTEDKCLQRQNRYDGQVAVFGSDLQEKLGKQKYFLVGAGAIG
  CELLKNFAMIGLGCGEGGEIIVTDMDTIEKSNLNRQFLFRPWDVTKLKSDTAAAAVRQMN
  PHIRVTSHQNRVGPDTERIYDDDFFQNLDGVANALDNVDARMYMDRRCVYYRKPLLESGT
  LGTKGNVQVVIPFLTESYSSSQDPPEKSIPICTLKNFPNAIEHTLQWARDEFEGLFKQPA
  ENVNQYLTDPKFVERTLRLAGTQPLEVLEAVQRSLVLQRPQTWADCVTWACHHWHTQYSN
  NIRQLLHNFPPDQLTSSGAPFWSGPKRCPHPLTFDVNNPLHLDYVMAAANLFAQTYGLTG
  SQDRAAVATFLQSVQVPEFTPKSGVKIHVSDQELQSANASVDDSRLEELKATLPSPDKLP
  GFKMYPIDFEKDDDSNFHMDFIVAASNLRAENYDIPSADRHKSKLIAGKIIPAIATTTAA
  VVGLVCLELYKVVQGHRQLDSYKNGFLNLALPFFGFSEPLAAPRHQYYNQEWTLWDRFEV
  QGLQPNGEEMTLKQFLDYFKTEHKLEITMLSQGVSMLYSFFMPAAKLKERLDQPMTEIVS
  RVSKRKLGRHVRALVLELCCNDESGEDVEVPYVRYTIR
• Function: Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites.
• KEGG Pathway:
  Ubiquitin mediated proteolysis (hsa04120)
  Parkinson disease (hsa05012)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Synthesis of active ubiquitin (R-HSA-8866652)
• BioCyc Pathway: MetaCyc:HS05465-MON

Molecular Interaction Atlas (MIA) of This DTT

3 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
QCPOIDRINIAUKU-SRBBEKPSSA-N	DM4DJA7	N. A.	N. A.	Patented	[2]
SCHEMBL15198145	DMKQ0GE	N. A.	N. A.	Patented	[2]
SCHEMBL15198146	DMHPQI2	N. A.	N. A.	Patented	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PYZD-4409	DME0NO8	leukaemia	2A60-2B33	Investigative	[3]

References

• [1] Orthogonal ubiquitin transfer identifies ubiquitination substrates under differential control by the two ubiquitin activating enzymes. Nat Commun. 2017 Jan 30;8:14286.
• [2] Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme. US10202389.
• [3] The ubiquitin-activating enzyme E1 as a therapeutic target for the treatment of leukemia and multiple myeloma. Blood. 2010 Mar 18;115(11):2251-9.