Target Information
Target General Information | Top | |||||
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Target ID |
T63193
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Target Name |
Diacylglycerol kinase zeta (DGKZ)
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Synonyms |
DAG kinase zeta; Diglyceride kinase zeta; DGK-zeta
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Gene Name |
DGKZ
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
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}.
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BioChemical Class |
Kinase
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UniProt ID | ||||||
EC Number |
EC 2.7.1.107
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Sequence |
MEPRDGSPEARSSDSESASASSSGSERDAGPEPDKAPRRLNKRRFPGLRLFGHRKAITKS
GLQHLAPPPPTPGAPCSESERQIRSTVDWSESATYGEHIWFETNVSGDFCYVGEQYCVAR MLKSVSRRKCAACKIVVHTPCIEQLEKINFRCKPSFRESGSRNVREPTFVRHHWVHRRRQ DGKCRHCGKGFQQKFTFHSKEIVAISCSWCKQAYHSKVSCFMLQQIEEPCSLGVHAAVVI PPTWILRARRPQNTLKASKKKKRASFKRKSSKKGPEEGRWRPFIIRPTPSPLMKPLLVFV NPKSGGNQGAKIIQSFLWYLNPRQVFDLSQGGPKEALEMYRKVHNLRILACGGDGTVGWI LSTLDQLRLKPPPPVAILPLGTGNDLARTLNWGGGYTDEPVSKILSHVEEGNVVQLDRWD LHAEPNPEAGPEDRDEGATDRLPLDVFNNYFSLGFDAHVTLEFHESREANPEKFNSRFRN KMFYAGTAFSDFLMGSSKDLAKHIRVVCDGMDLTPKIQDLKPQCVVFLNIPRYCAGTMPW GHPGEHHDFEPQRHDDGYLEVIGFTMTSLAALQVGGHGERLTQCREVVLTTSKAIPVQVD GEPCKLAASRIRIALRNQATMVQKAKRRSAAPLHSDQQPVPEQLRIQVSRVSMHDYEALH YDKEQLKEASVPLGTVVVPGDSDLELCRAHIERLQQEPDGAGAKSPTCQKLSPKWCFLDA TTASRFYRIDRAQEHLNYVTEIAQDEIYILDPELLGASARPDLPTPTSPLPTSPCSPTPR SLQGDAAPPQGEELIEAAKRNDFCKLQELHRAGGDLMHRDEQSRTLLHHAVSTGSKDVVR YLLDHAPPEILDAVEENGETCLHQAAALGQRTICHYIVEAGASLMKTDQQGDTPRQRAEK AQDTELAAYLENRQHYQMIQREDQETAV Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | ASP1570 | Drug Info | Phase 1/2 | Aggressive cancer | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | ASP1570 | Drug Info | [1] |
References | Top | |||||
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REF 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. | |||||
REF 2 | ClinicalTrials.gov (NCT05083481) A Phase 1/2 Study of ASP1570 as Monotherapy and in Combination With Pembrolizumab in Participants With Locally Advanced or Metastatic Solid Tumors. U.S.National Institutes of Health. |
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