DGKH_MOUSE
ID DGKH_MOUSE Reviewed; 1211 AA.
AC D3YXJ0; A0A0B5JC35;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=Diacylglycerol kinase eta {ECO:0000305};
DE Short=DAG kinase eta;
DE EC=2.7.1.107 {ECO:0000269|PubMed:27643686};
DE AltName: Full=Diglyceride kinase eta;
DE Short=DGK-eta;
GN Name=Dgkh {ECO:0000312|MGI:MGI:2444188};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 806-1133 (ISOFORM 3), AND TISSUE SPECIFICITY
RP (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6N;
RX PubMed=25613821; DOI=10.1186/s12861-015-0055-z;
RA Shionoya T., Usuki T., Komenoi S., Isozaki T., Sakai H., Sakane F.;
RT "Distinct expression and localization of the type II diacylglycerol kinase
RT isozymes delta, eta and kappa in the mouse reproductive organs.";
RL BMC Dev. Biol. 15:6-6(2015).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, ALTERNATIVE SPLICING (ISOFORMS 1; 2
RP AND 3), TISSUE SPECIFICITY (ISOFORM 3), AND SUBCELLULAR LOCATION.
RX PubMed=27643686; DOI=10.1371/journal.pone.0162997;
RA Murakami E., Shionoya T., Komenoi S., Suzuki Y., Sakane F.;
RT "Cloning and Characterization of Novel Testis-Specific Diacylglycerol
RT Kinase eta Splice Variants 3 and 4.";
RL PLoS ONE 11:e0162997-e0162997(2016).
CC -!- FUNCTION: Diacylglycerol kinase that converts diacylglycerol/DAG into
CC phosphatidic acid/phosphatidate/PA and regulates the respective levels
CC of these two bioactive lipids (PubMed:27643686). Thereby, acts as a
CC central switch between the signaling pathways activated by these second
CC messengers with different cellular targets and opposite effects in
CC numerous biological processes (Probable). Plays a key role in promoting
CC cell growth. Activates the Ras/B-Raf/C-Raf/MEK/ERK signaling pathway
CC induced by EGF. Regulates the recruitment of RAF1 and BRAF from
CC cytoplasm to membranes and their heterodimerization (By similarity).
CC {ECO:0000250|UniProtKB:Q86XP1, ECO:0000269|PubMed:27643686,
CC ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:10272, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:30616, ChEBI:CHEBI:58608,
CC ChEBI:CHEBI:456216; EC=2.7.1.107;
CC Evidence={ECO:0000269|PubMed:27643686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000305|PubMed:27643686};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40327, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:74546, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:27643686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:27643686};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000305|PubMed:27643686}.
CC -!- SUBUNIT: Interacts with RAF1 and BRAF. {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- SUBUNIT: [Isoform 1]: Homooligomers. Heterooligomers. Oligomerization
CC through the SAM domain inhibits the diacylglycerol kinase activity.
CC Heterooligomerizes with SAM domain-containing isoforms of DGKD.
CC {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- SUBUNIT: [Isoform 2]: Does not form homooligomers.
CC {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27643686}. Cell
CC membrane {ECO:0000269|PubMed:27643686}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:27643686}. Note=Translocated from the cytoplasm to
CC endosomes in response to stress stimuli. Isoform 2 is rapidly relocated
CC back to the cytoplasm upon removal of stress stimuli, whereas isoform 1
CC exhibits sustained endosomal association. Translocates from the
CC cytoplasm to the cell membrane in the presence of active GTP-bound form
CC of HRAS. {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=DAG kinase eta-2 {ECO:0000303|PubMed:27643686};
CC IsoId=D3YXJ0-1; Sequence=Displayed;
CC Name=2; Synonyms=DAG kinase eta-1 {ECO:0000303|PubMed:27643686};
CC IsoId=D3YXJ0-2; Sequence=VSP_060669, VSP_060670;
CC Name=3; Synonyms=DAG kinase eta-3 {ECO:0000303|PubMed:25613821};
CC IsoId=D3YXJ0-3; Sequence=VSP_060668, VSP_060669, VSP_060670;
CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:27643686). Detected in the
CC granulosa cells of the primary and secondary follicles
CC (PubMed:25613821). Expressed in mature follicles and corpus lutea
CC (PubMed:25613821). Expressed in the oviductal epithelium
CC (PubMed:25613821). In the uterus, strongly expressed in the luminal
CC epithelium (PubMed:25613821). Detected in the uterine glands
CC (PubMed:25613821). {ECO:0000269|PubMed:25613821,
CC ECO:0000269|PubMed:27643686}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Detected in ovary and uterus (at
CC protein level). {ECO:0000269|PubMed:25613821}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Specifically expressed in testis
CC (PubMed:25613821, PubMed:27643686). Detected in the inner area of the
CC testis (PubMed:25613821). Strongly expressed in the secondary
CC spermatocytes and the round spermatids and weakly detected in the
CC primary spermatocytes (PubMed:25613821). {ECO:0000269|PubMed:25613821,
CC ECO:0000269|PubMed:27643686}.
CC -!- DOMAIN: The SAM domain mediates homooligomerization.
CC {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- PTM: Phosphorylated. Phosphorylation does not inhibit catalytic
CC activity. {ECO:0000250|UniProtKB:Q86XP1}.
CC -!- SIMILARITY: Belongs to the eukaryotic diacylglycerol kinase family.
CC {ECO:0000305}.
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DR EMBL; AC124715; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC126251; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC161608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KP329574; AJF98606.1; -; mRNA.
DR RefSeq; NP_001074805.1; NM_001081336.1.
DR AlphaFoldDB; D3YXJ0; -.
DR SMR; D3YXJ0; -.
DR iPTMnet; D3YXJ0; -.
DR PhosphoSitePlus; D3YXJ0; -.
DR EPD; D3YXJ0; -.
DR MaxQB; D3YXJ0; -.
DR PaxDb; D3YXJ0; -.
DR PRIDE; D3YXJ0; -.
DR ProteomicsDB; 331287; -. [D3YXJ0-1]
DR Antibodypedia; 23454; 129 antibodies from 26 providers.
DR Ensembl; ENSMUST00000074729; ENSMUSP00000074290; ENSMUSG00000034731. [D3YXJ0-2]
DR GeneID; 380921; -.
DR KEGG; mmu:380921; -.
DR UCSC; uc007uso.1; mouse. [D3YXJ0-1]
DR CTD; 160851; -.
DR MGI; MGI:2444188; Dgkh.
DR VEuPathDB; HostDB:ENSMUSG00000034731; -.
DR eggNOG; KOG1170; Eukaryota.
DR GeneTree; ENSGT00940000158106; -.
DR HOGENOM; CLU_001799_3_0_1; -.
DR InParanoid; D3YXJ0; -.
DR OMA; EKEMICE; -.
DR OrthoDB; 43384at2759; -.
DR PhylomeDB; D3YXJ0; -.
DR TreeFam; TF313104; -.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 380921; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Dgkh; mouse.
DR PRO; PR:D3YXJ0; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; D3YXJ0; protein.
DR Bgee; ENSMUSG00000034731; Expressed in dorsal root ganglion and 206 other tissues.
DR ExpressionAtlas; D3YXJ0; baseline and differential.
DR Genevisible; D3YXJ0; MM.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019900; F:kinase binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0032093; F:SAM domain binding; ISO:MGI.
DR GO; GO:0046339; P:diacylglycerol metabolic process; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046834; P:lipid phosphorylation; IDA:UniProtKB.
DR GO; GO:0043086; P:negative regulation of catalytic activity; ISO:MGI.
DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0046473; P:phosphatidic acid metabolic process; ISO:MGI.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISO:MGI.
DR CDD; cd00029; C1; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR037607; DGK.
DR InterPro; IPR000756; Diacylglycerol_kin_accessory.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR PANTHER; PTHR11255; PTHR11255; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00609; DAGK_acc; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF07647; SAM_2; 1.
DR SMART; SM00109; C1; 2.
DR SMART; SM00045; DAGKa; 1.
DR SMART; SM00046; DAGKc; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50146; DAGK; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Cytoskeleton;
KW Kinase; Lipid metabolism; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..1211
FT /note="Diacylglycerol kinase eta"
FT /id="PRO_0000450665"
FT DOMAIN 62..155
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 325..460
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT DOMAIN 1143..1206
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT ZN_FING 172..222
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 244..295
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 562..613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 634..694
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..66
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..694
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1033..1063
FT /note="Missing (in isoform 3)"
FT /id="VSP_060668"
FT VAR_SEQ 1140..1156
FT /note="VQNWGTEEVAAWLDLLN -> GPGDSESGSYEANSPGN (in isoform 2
FT and isoform 3)"
FT /id="VSP_060669"
FT VAR_SEQ 1157..1211
FT /note="Missing (in isoform 2 and isoform 3)"
FT /id="VSP_060670"
SQ SEQUENCE 1211 AA; 134132 MW; 477C73A1142B3BB1 CRC64;
MAGAGSQHHP QGVAGGAVAG ASAVSPTAAG PGEDSSDSEA EQEGPQKLIR KVSTSGQMRT
KTSIKEGQLL KQTSSFQRWK KRYFKLRGRT LYYAKDSKSL IFDEVDLSDA SVAEASTKNA
NNSFTIITPF RRLMLCAENR KEMEVWISSL KSVQSREPYE VAQFNVEHFS GMHNWYACSH
ARPTFCNVCR ESLSGVTSHG LSCEVCKFKA HKRCAVRATN NCKWTTLASI GKDIIEDEDG
VAMPHQWLEG NLPVSAKCAV CDKTCGSVLR LQDWKCLWCK TMVHTACKDV YHPVCPLGQC
KVSIIPPIAL NSTDSDGFCR ATFSFCVSPL LVFVNSKSGD NQGVKFLRRF KQLLNPAQVF
DLMNGGPYLG LRLFQKFDNF RILVCGGDGS VGWVLSEIDK LNLHKQCQLG VLPLGTGNDL
ARVLGWGGSY DDDTQLPQIL EKLERASTKM LDRWSIMTYE LKLPAKSSLL PEPVAATEEF
YMTIYEDSVA NHLTKIVNSD EHAVVISSAK ILCETVKDFV AKVEKAQDRT LENTVVAEAV
ASKCSVLNEK LEQLLQALHA DSQASRVPPG IGPAIPEEDT VESASDESLG ESKDQLVNDI
GKPSSQKAVK PREIMLRANS LKKAVRQVIE EAEKVMDEPA VQPSEPVSPS CDYDTETDEA
KEDDAKESLS AKTTSQSPDA QASCGHPQTD SVAGPAMATT KENLPVLNTR IICPGLRAGL
AASIAGSSII NKMLLANIDP FGATPFIDPD LDSLDGYSEK CVMNNYFGIG LDAKISLEFN
NKREEHPEKC RSRTKNLMWY GVLGTRELLQ RSYKNLEQRV QLECDGQYIP LPSLQGIAVL
NIPSYAGGTN FWGGTKEDDI FAAPSFDDKI LEVVAVFDSV QMAVSRVIKL QHHRIAQCRT
VKITIFGDEG VPVQVDGEAW VQPPGIIKIV HKNRAQMLTR DRAFESTLKS WEDKQKCDSG
KPVLRTNLYI HPAPDLATEE VSQMRLCSQA AEELITRICD AATIHCLLEQ ELAHAVNACS
HALNKANPRF PESLTRDTAT EIAINVKALY NETEALLVGR VPLHLESPHE ERVSSALHSV
EMELQKLTEI PWLYYILRPS EDEEPPLDCT KRNNKSTVFR IVPKFKKEKA QKQKTSSQPV
QNWGTEEVAA WLDLLNLGEY KEIFIRHDVR GAELLHLERR DLKDLGIPKV GHMKRILQGI
KELERNPPNL V
