Reviewed, UniProtKB/Swiss-Prot Q13574 (DGKZ_HUMAN)

Names and origin

Protein names

Recommended name:
    Diacylglycerol kinase zeta
      Short name=DAG kinase zeta
    EC=2.7.1.107
Alternative name(s):
    Diglyceride kinase zeta
      Short name=DGK-zeta

Gene names

Name:	DGKZ
Synonyms:	DAGK6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1117 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Displays a strong preference for 1,2-diacylglycerols over 1,3-diacylglycerols, but lacks substrate specificity among molecular species of long chain diacylglycerols. Isoform 2 but not isoform 1 regulates RASGRP1 activity. Ref.6
Catalytic activity	ATP + 1,2-diacylglycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
Subunit structure	Interacts with the PDZ domain of the syntrophin SNTG1 and that of SNX27. Isoform 2 forms a signaling complex with RASGRP1 and HRAS. Ref.5 Ref.7
Subcellular location	Cytoplasm. Nucleus. Cell membrane. Ref.6 Ref.4
Tissue specificity	Highest levels in brain, and substantial levels in skeletal muscle, heart, and pancreas. Isoform 1 is predominantly expressed in muscle.
Post-translational modification	Phosphorylation of the MARCKS homology domain by PKC reduces nuclear accumulation of DGK-zeta.
Sequence similarities	Belongs to the eukaryotic diacylglycerol kinase family. Contains 2 ANK repeats. Contains 1 DAGKc domain. Contains 2 phorbol-ester/DAG-type zinc fingers.
Sequence caution	The sequence AAB60859.1 differs from that shown. Reason: Frameshift at positions 166 and 167.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Phorbol-ester binding Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	G1 DNA damage checkpoint Inferred from genetic interaction. Source: UniProtKB activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro intracellular signaling cascade Inferred from electronic annotation. Source: InterPro negative regulation of mitotic cell cycle Inferred from genetic interaction. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Ref.1 Traceable author statement. Source: ProtInc diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol kinase activity Inferred from direct assay. Source: UniProtKB lipid kinase activity Inferred from direct assay. Source: UniProtKB protein C-terminus binding Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RB1	P06400	5	EBI-715527,EBI-491274
RBL1	P28749	2	EBI-715527,EBI-971402
RBL2	Q08999	2	EBI-715527,EBI-971439

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13574-1)

Also known as: Long; zeta2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Note: Minor isoform.

Isoform 2 (identifier: Q13574-2)

Also known as: Short;

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: METFFRRHFR...GPQAWSALLA → MEPRDGSPEA...FPGLRLFGHR

Note: Major isoform.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1117	1117	Diacylglycerol kinase zeta		PRO_0000218468
Regions
	Domain	480 – 614	135	DAGKc
	Repeat	1011 – 1041	31	ANK 1
	Repeat	1046 – 1075	30	ANK 2
	Zinc finger	287 – 341	55	Phorbol-ester/DAG-type 1
	Zinc finger	361 – 419	59	Phorbol-ester/DAG-type 2
	Region	448 – 462	15	MARCKS homology
	Region	467 – 605	139	Mediates interaction with RASGRP1
	Compositional bias	256 – 261	6	Poly-Pro
	Compositional bias	448 – 451	4	Poly-Lys
	Compositional bias	560 – 563	4	Poly-Pro
Amino acid modifications
	Modified residue	686	1	Phosphoserine Ref.8
Natural variations
	Alternative sequence	1 – 243	243	METFF…SALLA → MEPRDGSPEARSSDSESASA SSSGSERDAGPEPDKAPRRL NKRRFPGLRLFGHR in isoform 2.		VSP_001268
	Natural variant	21	1	Q → R: dbSNP rs1317826. Ref.2		VAR_047371
Experimental info
	Mutagenesis	1115 – 1116	2	TA → NS: Loss of interaction with SNTG1. Ref.5
	Sequence conflict	159	1	L → V in AAB60859. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) (zeta2) [UniParc]. Last modified November 25, 2008. Version 3. Checksum: F3A7C2382ECF549B	FASTA	1,117	124,128
	10 20 30 40 50 60 METFFRRHFR GKVPGPGEGQ QRPSSVGLPT GKARRRSPAG QASSSLAQRR RSSAQLQGCL 70 80 90 100 110 120 LSCGVRAQGS SRRRSSTVPP SCNPRFIVDK VLTPQPTTVG AQLLGAPLLL TGLVGMNEEE 130 140 150 160 170 180 GVQEDVVAEA SSAIQPGTKT PGPPPPRGAQ PLLPLPRYLR RASSHLLPAD AVYDHALWGL 190 200 210 220 230 240 HGYYRRLSQR RPSGQHPGPG GRRASGTTAG TMLPTRVRPL SRRRQVALRR KAAGPQAWSA 250 260 270 280 290 300 LLAKAITKSG LQHLAPPPPT PGAPCSESER QIRSTVDWSE SATYGEHIWF ETNVSGDFCY 310 320 330 340 350 360 VGEQYCVARM LKSVSRRKCA ACKIVVHTPC IEQLEKINFR CKPSFRESGS RNVREPTFVR 370 380 390 400 410 420 HHWVHRRRQD GKCRHCGKGF QQKFTFHSKE IVAISCSWCK QAYHSKVSCF MLQQIEEPCS 430 440 450 460 470 480 LGVHAAVVIP PTWILRARRP QNTLKASKKK KRASFKRKSS KKGPEEGRWR PFIIRPTPSP 490 500 510 520 530 540 LMKPLLVFVN PKSGGNQGAK IIQSFLWYLN PRQVFDLSQG GPKEALEMYR KVHNLRILAC 550 560 570 580 590 600 GGDGTVGWIL STLDQLRLKP PPPVAILPLG TGNDLARTLN WGGGYTDEPV SKILSHVEEG 610 620 630 640 650 660 NVVQLDRWDL HAEPNPEAGP EDRDEGATDR LPLDVFNNYF SLGFDAHVTL EFHESREANP 670 680 690 700 710 720 EKFNSRFRNK MFYAGTAFSD FLMGSSKDLA KHIRVVCDGM DLTPKIQDLK PQCVVFLNIP 730 740 750 760 770 780 RYCAGTMPWG HPGEHHDFEP QRHDDGYLEV IGFTMTSLAA LQVGGHGERL TQCREVVLTT 790 800 810 820 830 840 SKAIPVQVDG EPCKLAASRI RIALRNQATM VQKAKRRSAA PLHSDQQPVP EQLRIQVSRV 850 860 870 880 890 900 SMHDYEALHY DKEQLKEASV PLGTVVVPGD SDLELCRAHI ERLQQEPDGA GAKSPTCQKL 910 920 930 940 950 960 SPKWCFLDAT TASRFYRIDR AQEHLNYVTE IAQDEIYILD PELLGASARP DLPTPTSPLP 970 980 990 1000 1010 1020 TSPCSPTPRS LQGDAAPPQG EELIEAAKRN DFCKLQELHR AGGDLMHRDE QSRTLLHHAV 1030 1040 1050 1060 1070 1080 STGSKDVVRY LLDHAPPEIL DAVEENGETC LHQAAALGQR TICHYIVEAG ASLMKTDQQG 1090 1100 1110 DTPRQRAEKA QDTELAAYLE NRQHYQMIQR EDQETAV
	Isoform 2 (Short). Checksum: 7936A979CB3D35AA	FASTA	928	103,981
	10 20 30 40 50 60 MEPRDGSPEA RSSDSESASA SSSGSERDAG PEPDKAPRRL NKRRFPGLRL FGHRKAITKS 70 80 90 100 110 120 GLQHLAPPPP TPGAPCSESE RQIRSTVDWS ESATYGEHIW FETNVSGDFC YVGEQYCVAR 130 140 150 160 170 180 MLKSVSRRKC AACKIVVHTP CIEQLEKINF RCKPSFRESG SRNVREPTFV RHHWVHRRRQ 190 200 210 220 230 240 DGKCRHCGKG FQQKFTFHSK EIVAISCSWC KQAYHSKVSC FMLQQIEEPC SLGVHAAVVI 250 260 270 280 290 300 PPTWILRARR PQNTLKASKK KKRASFKRKS SKKGPEEGRW RPFIIRPTPS PLMKPLLVFV 310 320 330 340 350 360 NPKSGGNQGA KIIQSFLWYL NPRQVFDLSQ GGPKEALEMY RKVHNLRILA CGGDGTVGWI 370 380 390 400 410 420 LSTLDQLRLK PPPPVAILPL GTGNDLARTL NWGGGYTDEP VSKILSHVEE GNVVQLDRWD 430 440 450 460 470 480 LHAEPNPEAG PEDRDEGATD RLPLDVFNNY FSLGFDAHVT LEFHESREAN PEKFNSRFRN 490 500 510 520 530 540 KMFYAGTAFS DFLMGSSKDL AKHIRVVCDG MDLTPKIQDL KPQCVVFLNI PRYCAGTMPW 550 560 570 580 590 600 GHPGEHHDFE PQRHDDGYLE VIGFTMTSLA ALQVGGHGER LTQCREVVLT TSKAIPVQVD 610 620 630 640 650 660 GEPCKLAASR IRIALRNQAT MVQKAKRRSA APLHSDQQPV PEQLRIQVSR VSMHDYEALH 670 680 690 700 710 720 YDKEQLKEAS VPLGTVVVPG DSDLELCRAH IERLQQEPDG AGAKSPTCQK LSPKWCFLDA 730 740 750 760 770 780 TTASRFYRID RAQEHLNYVT EIAQDEIYIL DPELLGASAR PDLPTPTSPL PTSPCSPTPR 790 800 810 820 830 840 SLQGDAAPPQ GEELIEAAKR NDFCKLQELH RAGGDLMHRD EQSRTLLHHA VSTGSKDVVR 850 860 870 880 890 900 YLLDHAPPEI LDAVEENGET CLHQAAALGQ RTICHYIVEA GASLMKTDQQ GDTPRQRAEK 910 920 AQDTELAAYL ENRQHYQMIQ REDQETAV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of a novel human diacylglycerol kinase zeta." Bunting M., Tang W., Zimmerman G.A., McIntyre T.M., Prescott S.M. J. Biol. Chem. 271:10230-10236(1996) [PubMed: 8626588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Endothelial cell.
[2]	"Alternative splicing of the human diacylglycerol kinase zeta gene in muscle." Ding L., Bunting M., Topham M.K., McIntyre T.M., Zimmerman G.A., Prescott S.M. Proc. Natl. Acad. Sci. U.S.A. 94:5519-5524(1997) [PubMed: 9159104] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ARG-21. Tissue: Skeletal muscle.
[3]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed: 16554811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Protein kinase C regulates the nuclear localization of diacylglycerol kinase-zeta." Topham M.K., Bunting M., Zimmerman G.A., McIntyre T.M., Blackshear P.J., Prescott S.M. Nature 394:697-700(1998) [PubMed: 9716136] [Abstract] Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION.
[5]	"Interaction of gamma 1-syntrophin with diacylglycerol kinase-zeta. Regulation of nuclear localization by PDZ interactions." Hogan A., Shepherd L., Chabot J., Quenneville S., Prescott S.M., Topham M.K., Gee S.H. J. Biol. Chem. 276:26526-26533(2001) [PubMed: 11352924] [Abstract] Cited for: INTERACTION WITH SNTG1, MUTAGENESIS OF 1115-THR-ALA-1116.
[6]	"Diacylglycerol kinase zeta regulates Ras activation by a novel mechanism." Topham M.K., Prescott S.M. J. Cell Biol. 152:1135-1143(2001) [PubMed: 11257115] [Abstract] Cited for: FUNCTION AS A RASGRP1 REGULATOR, IDENTIFICATION IN A COMPLEX WITH RASGRP1 AND HRAS, SUBCELLULAR LOCATION.
[7]	"Proteomics identification of sorting nexin 27 as a diacylglycerol kinase zeta-associated protein: new diacylglycerol kinase roles in endocytic recycling." Rincon E., Santos T., Avila-Flores A., Albar J.P., Lalioti V., Lei C., Hong W., Merida I. Mol. Cell. Proteomics 6:1073-1087(2007) [PubMed: 17351151] [Abstract] Cited for: INTERACTION WITH SNX27.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686, MASS SPECTROMETRY. Tissue: Epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	U51477 mRNA. Translation: AAC50478.1. U94905 mRNA. Translation: AAB60859.1. Frameshift. AC116021 Genomic DNA. No translation available.
IPI	IPI00013835. IPI00300125.
RefSeq	NP_001099010.1. NP_003637.2. NP_963291.1.
UniGene	Hs.502461
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13574. 8 interactions.
STRING	Q13574.
PTM databases
PhosphoSite	Q13574.
Proteomic databases
PRIDE	Q13574.
Genome annotation databases
Ensembl	ENST00000318201; ENSP00000320340; ENSG00000149091; Homo sapiens. [Genome view] ENST00000343674; ENSP00000343065; ENSG00000149091; Homo sapiens. [Genome view] ENST00000395574; ENSP00000378941; ENSG00000149091; Homo sapiens. [Genome view] ENST00000421244; ENSP00000391021; ENSG00000149091; Homo sapiens. [Genome view] ENST00000454345; ENSP00000412178; ENSG00000149091; Homo sapiens. [Genome view] ENST00000456247; ENSP00000395684; ENSG00000149091; Homo sapiens. [Genome view]
GeneID	8525.
KEGG	hsa:8525.
UCSC	uc001ncm.2. human. uc001ncn.1. human.
Organism-specific databases
CTD	8525.
GeneCards	GC11P046311.
H-InvDB	HIX0009600.
HGNC	HGNC:2857. DGKZ.
MIM	601441. gene.
PharmGKB	PA27318.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q13574.
HOVERGEN	Q13574.
OMA	GDLMHRD.
Enzyme and pathway databases
BRENDA	2.7.1.107. 247.
Gene expression databases
ArrayExpress	Q13574.
Bgee	Q13574.
CleanEx	HS_DGKZ.
Genevestigator	Q13574.
GermOnline	ENSG00000149091. Homo sapiens.
Family and domain databases
InterPro	IPR002110. ANK. IPR000756. Diacylglycerol_kinase_access. IPR001206. Diacylglycerol_kinase_cat. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit.
Pfam	PF00023. Ank. 2 hits. PF00130. C1_1. 1 hit. PF00609. DAGK_acc. 1 hit. PF00781. DAGK_cat. 1 hit. [Graphical view]
ProDom	PD002939. DAGKa. 1 hit. PD005043. DAGKc. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00248. ANK. 2 hits. SM00109. C1. 2 hits. SM00045. DAGKa. 1 hit. SM00046. DAGKc. 1 hit. [Graphical view]
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 2 hits. PS50146. DAGK. 1 hit. PS00479. ZF_DAG_PE_1. False negative. PS50081. ZF_DAG_PE_2. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	31916.
SOURCE	Search...

Entry information

Entry name

DGKZ_HUMAN

Accession

Primary (citable) accession number: Q13574
Secondary accession number(s): O00542

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 25, 2008
Last modified:	November 3, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.