Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Diacylglycerol kinase zeta (DGKZ)
• Synonyms: DAG kinase zeta; Diglyceride kinase zeta; DGK-zeta
• Gene Name: DGKZ
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: DGKZ_HUMAN
• TTD ID: T63193
• EC Number: EC 2.7.1.107
• Sequence:
  MEPRDGSPEARSSDSESASASSSGSERDAGPEPDKAPRRLNKRRFPGLRLFGHRKAITKS
  GLQHLAPPPPTPGAPCSESERQIRSTVDWSESATYGEHIWFETNVSGDFCYVGEQYCVAR
  MLKSVSRRKCAACKIVVHTPCIEQLEKINFRCKPSFRESGSRNVREPTFVRHHWVHRRRQ
  DGKCRHCGKGFQQKFTFHSKEIVAISCSWCKQAYHSKVSCFMLQQIEEPCSLGVHAAVVI
  PPTWILRARRPQNTLKASKKKKRASFKRKSSKKGPEEGRWRPFIIRPTPSPLMKPLLVFV
  NPKSGGNQGAKIIQSFLWYLNPRQVFDLSQGGPKEALEMYRKVHNLRILACGGDGTVGWI
  LSTLDQLRLKPPPPVAILPLGTGNDLARTLNWGGGYTDEPVSKILSHVEEGNVVQLDRWD
  LHAEPNPEAGPEDRDEGATDRLPLDVFNNYFSLGFDAHVTLEFHESREANPEKFNSRFRN
  KMFYAGTAFSDFLMGSSKDLAKHIRVVCDGMDLTPKIQDLKPQCVVFLNIPRYCAGTMPW
  GHPGEHHDFEPQRHDDGYLEVIGFTMTSLAALQVGGHGERLTQCREVVLTTSKAIPVQVD
  GEPCKLAASRIRIALRNQATMVQKAKRRSAAPLHSDQQPVPEQLRIQVSRVSMHDYEALH
  YDKEQLKEASVPLGTVVVPGDSDLELCRAHIERLQQEPDGAGAKSPTCQKLSPKWCFLDA
  TTASRFYRIDRAQEHLNYVTEIAQDEIYILDPELLGASARPDLPTPTSPLPTSPCSPTPR
  SLQGDAAPPQGEELIEAAKRNDFCKLQELHRAGGDLMHRDEQSRTLLHHAVSTGSKDVVR
  YLLDHAPPEILDAVEENGETCLHQAAALGQRTICHYIVEAGASLMKTDQQGDTPRQRAEK
  AQDTELAAYLENRQHYQMIQREDQETAV
• Function: Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:9159104, PubMed:15544348, PubMed:18004883, PubMed:19744926, PubMed:22108654, PubMed:22627129, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:9159104, PubMed:15544348, PubMed:18004883, PubMed:19744926, PubMed:22108654, PubMed:22627129, PubMed:23949095). Also plays an important role in the biosynthesis of complex lipids (Probable). Does not exhibit an acyl chain-dependent substrate specificity among diacylglycerol species (PubMed:9159104, PubMed:19744926, PubMed:22108654). Can also phosphorylate 1-alkyl-2-acylglycerol in vitro but less efficiently and with a preference for alkylacylglycerols containing an arachidonoyl group (PubMed:15544348, PubMed:19744926, PubMed:22627129). The biological processes it is involved in include T cell activation since it negatively regulates T-cell receptor signaling which is in part mediated by diacylglycerol (By similarity). By generating phosphatidic acid, stimulates PIP5KIA activity which regulates actin polymerization (PubMed:15157668). Through the same mechanism could also positively regulate insulin-induced translocation of SLC2A4 to the cell membrane (By similarity). {ECO:0000250|UniProtKB:Q80UP3, ECO:0000269|PubMed:15157668, ECO:0000269|PubMed:15544348, ECO:0000269|PubMed:18004883, ECO:0000269|PubMed:19744926, ECO:0000269|PubMed:22108654, ECO:0000269|PubMed:22627129, ECO:0000269|PubMed:23949095, ECO:0000269|PubMed:9159104, ECO:0000305|PubMed:8626588}.; [Isoform 1]: Regulates RASGRP1 activity. {ECO:0000269|PubMed:11257115}.; [Isoform 2]: Does not regulate RASGRP1 activity. {ECO:0000269|PubMed:11257115}.
• KEGG Pathway: 8525 (hsa)
• Reactome Pathway: (R-HSA-114508)

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
ASP1570	DMBUOUV	Aggressive cancer	2A00-2F9Z	Phase 1/2	[1]

References

• [1] Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8(+) T cell responses during chronic viral infection. Front Immunol. 2022 Nov 24;13:1032113.