Reviewed, UniProtKB/Swiss-Prot Q16760 (DGKD_HUMAN)

Names and origin

Protein names

Recommended name:
    Diacylglycerol kinase delta
      Short name=DAG kinase delta
    EC=2.7.1.107
Alternative name(s):
    Diglyceride kinase delta
      Short name=DGK-delta
    130 kDa diacylglycerol kinase

Gene names

Name:	DGKD
Synonyms:	KIAA0145

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	1214 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May function as signaling molecule. Isoform 2 may be involved in cell growth and tumorigenesis. Isoform 2 is involved in clathrin-dependent endocytosis. Ref.7
Catalytic activity	ATP + 1,2-diacylglycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
Enzyme regulation	Partially inhibited by phosphatidylserine.
Subunit structure	The two isoforms are able to form homo- and hetero-oligomer structures (at least tetramers). Isoform 2 interacts with AP2A2. Ref.7 Ref.1
Subcellular location	Isoform 2: Cytoplasm. Ref.1 Isoform 1: Membrane; Peripheral membrane protein. Ref.1
Tissue specificity	Isoform 2 is ubiquitously expressed also in tumor tissues. Isoform 1 is expressed in ovary, spleen and some tumor-derived cells. Ref.1
Post-translational modification	Isoform 1 H domain is phosphorylated. Ref.6
Sequence similarities	Belongs to the eukaryotic diacylglycerol kinase family. Contains 1 DAGKc domain. Contains 1 PH domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 SAM (sterile alpha motif) domain.

Ontologies

Keywords
Biological process	Endocytosis Protein transport Transport
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	Phorbol-ester binding Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Ref.1 Non-traceable author statement. Source: UniProtKB cell growth Ref.1 Non-traceable author statement. Source: UniProtKB diacylglycerol metabolic process Ref.1 Non-traceable author statement. Source: UniProtKB epidermal growth factor receptor signaling pathway Ref.1 Non-traceable author statement. Source: UniProtKB multicellular organismal development Ref.1 Non-traceable author statement. Source: UniProtKB protein homooligomerization Ref.1 Inferred from direct assay. Source: UniProtKB response to organic substance Ref.1 Inferred from direct assay. Source: UniProtKB second-messenger-mediated signaling Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	cytoplasmic membrane-bounded vesicle Ref.1 Inferred from direct assay. Source: MGI extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Ref.1 Non-traceable author statement. Source: UniProtKB diacylglycerol kinase activity Ref.1 Ref.4 Traceable author statement. Source: UniProtKB protein heterodimerization activity Ref.1 Inferred from direct assay. Source: MGI protein homodimerization activity Ref.1 Inferred from direct assay. Source: MGI zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 2 (identifier: Q16760-1)

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.

Isoform 1 (identifier: Q16760-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-52: MAAAAGAPPPGPPQPPPPPPPEESSDSEPEAEPGSPQKLIRKVSTSGQIRQK → MNMFLYFQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1214

1214

Diacylglycerol kinase delta

PRO_0000218462

Regions

Domain

53 – 146

94

PH

Domain

317 – 451

135

DAGKc

Domain

1145 – 1208

64

SAM

Zinc finger

163 – 213

51

Phorbol-ester/DAG-type 1

Zinc finger

235 – 286

52

Phorbol-ester/DAG-type 2

Compositional bias

8 – 36

29

Pro-rich

Natural variations

Alternative sequence

1 – 52

52

MAAAA…QIRQK → MNMFLYFQ in isoform 1.

VSP_012891

Experimental info

Mutagenesis

369

1

F → A: Reduces interaction with AP2A2; when associated with A-372. Ref.7

Mutagenesis

372

1

F → A: Reduces interaction with AP2A2; when associated with A-369. Ref.7

Mutagenesis

748

1

F → A: Reduces interaction with AP2A2. Ref.7

Sequence conflict

511

1

V → P in BAA11134. Ref.4

Sequence conflict

828 – 834

7

RPIPLPS → DPSHSPV in BAA11134. Ref.4

Sequence conflict

960

1

L → V in BAC11809. Ref.1

Sequence conflict

960

1

L → V in BAA11134. Ref.4

Sequence conflict

1054

1

Missing in BAA11134. Ref.4

Secondary structure

1

.

.

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.

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.

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.

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1214

Helix Strand Turn

Details...

Beta strand

238 – 241

4

Beta strand

250 – 252

3

Turn

259 – 261

3

Beta strand

265 – 270

6

Helix

276 – 281

6

Helix

1142 – 1144

3

Helix

1147 – 1156

10

Helix

1160 – 1162

3

Helix

1163 – 1168

6

Helix

1173 – 1176

4

Helix

1181 – 1186

6

Helix

1192 – 1206

15

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified October 17, 2006. Version 4. Checksum: ED114429096D2112	FASTA	1,214	134,525
	10 20 30 40 50 60 MAAAAGAPPP GPPQPPPPPP PEESSDSEPE AEPGSPQKLI RKVSTSGQIR QKTIIKEGML 70 80 90 100 110 120 TKQNNSFQRS KRRYFKLRGR TLYYAKTAKS IIFDEVDLTD ASVAESSTKN VNNSFTVITP 130 140 150 160 170 180 CRKLILCADN RKEMEDWIAA LKTVQNREHF EPTQYSMDHF SGMHNWYACS HARPTYCNVC 190 200 210 220 230 240 REALSGVTSH GLSCEVCKFK AHKRCAVRAT NNCKWTTLAS IGKDIIEDAD GIAMPHQWLE 250 260 270 280 290 300 GNLPVSAKCT VCDKTCGSVL RLQDWRCLWC KAMVHTSCKE SLLTKCPLGL CKVSVIPPTA 310 320 330 340 350 360 LNSIDSDGFW KASCPPSCTS PLLVFVNSKS GDNQGVKFLR RFKQLLNPAQ VFDLMNGGPH 370 380 390 400 410 420 LGLRLFQKFD TFRILVCGGD GSVGWVLSEI DSLNLHKQCQ LGVLPLGTGN DLARVLGWGS 430 440 450 460 470 480 ACDDDTQLPQ ILEKLERAST KMLDRWSVMA YEAKLPRQAS SSTVTEDFSE DSEVQQILFY 490 500 510 520 530 540 EDSVAAHLSK ILTSDQHSVV ISSAKVLCET VKDFVARVGK AYEKTTESSE ESEVMAKKCS 550 560 570 580 590 600 VLKEKLDSLL KTLDDESQAS SSLPNPPPTI AEEAEDGDGS GSICGSTGDR LVASACPARP 610 620 630 640 650 660 QIFRPREQLM LRANSLKKAI RQIIEHTEKA VDEQNAQTQE QEGFVLGLSE SEEKMDHRVC 670 680 690 700 710 720 PPLSHSESFG VPKGRSQRKV SKSPCEKLIS KGSLSLGSSA SLPPQPGSRD GLPALNTKIL 730 740 750 760 770 780 YPNVRAGMSG SLPGGSVISR LLINADPFNS EPETLEYYTE KCVMNNYFGI GLDAKISLDF 790 800 810 820 830 840 NNKRDEHPEK CRSRTKNMMW YGVLGTKELL HRTYKNLEQK VLLECDGRPI PLPSLQGIAV 850 860 870 880 890 900 LNIPSYAGGT NFWGGTKEDD TFAAPSFDDK ILEVVAVFGS MQMAVSRVIR LQHHRIAQCR 910 920 930 940 950 960 TVKISILGDE GVPVQVDGEA WVQPPGYIRI VHKNRAQTLT RDRAFESTLK SWEDKQKCEL 970 980 990 1000 1010 1020 PRPPSCSLHP EMLSEEEATQ MDQFGQAAGV LIHSIREIAQ SHRDMEQELA HAVNASSKSM 1030 1040 1050 1060 1070 1080 DRVYGKPRTT EGLNCSFVLE MVNNFRALRS ETELLLSGKM ALQLDPPQKE QLGSALAEMD 1090 1100 1110 1120 1130 1140 RQLRRLADTP WLCQSAEPGD EESVMLDLAK RSRSGKFRLV TKFKKEKNNK NKEAHSSLGA 1150 1160 1170 1180 1190 1200 PVHLWGTEEV AAWLEHLSLC EYKDIFTRHD IRGSELLHLE RRDLKDLGVT KVGHMKRILC 1210 GIKELSRSAP AVEA
	Isoform 1. Checksum: 00B7946AE15BC0A3	FASTA	1,170	130,326
	10 20 30 40 50 60 MNMFLYFQTI IKEGMLTKQN NSFQRSKRRY FKLRGRTLYY AKTAKSIIFD EVDLTDASVA 70 80 90 100 110 120 ESSTKNVNNS FTVITPCRKL ILCADNRKEM EDWIAALKTV QNREHFEPTQ YSMDHFSGMH 130 140 150 160 170 180 NWYACSHARP TYCNVCREAL SGVTSHGLSC EVCKFKAHKR CAVRATNNCK WTTLASIGKD 190 200 210 220 230 240 IIEDADGIAM PHQWLEGNLP VSAKCTVCDK TCGSVLRLQD WRCLWCKAMV HTSCKESLLT 250 260 270 280 290 300 KCPLGLCKVS VIPPTALNSI DSDGFWKASC PPSCTSPLLV FVNSKSGDNQ GVKFLRRFKQ 310 320 330 340 350 360 LLNPAQVFDL MNGGPHLGLR LFQKFDTFRI LVCGGDGSVG WVLSEIDSLN LHKQCQLGVL 370 380 390 400 410 420 PLGTGNDLAR VLGWGSACDD DTQLPQILEK LERASTKMLD RWSVMAYEAK LPRQASSSTV 430 440 450 460 470 480 TEDFSEDSEV QQILFYEDSV AAHLSKILTS DQHSVVISSA KVLCETVKDF VARVGKAYEK 490 500 510 520 530 540 TTESSEESEV MAKKCSVLKE KLDSLLKTLD DESQASSSLP NPPPTIAEEA EDGDGSGSIC 550 560 570 580 590 600 GSTGDRLVAS ACPARPQIFR PREQLMLRAN SLKKAIRQII EHTEKAVDEQ NAQTQEQEGF 610 620 630 640 650 660 VLGLSESEEK MDHRVCPPLS HSESFGVPKG RSQRKVSKSP CEKLISKGSL SLGSSASLPP 670 680 690 700 710 720 QPGSRDGLPA LNTKILYPNV RAGMSGSLPG GSVISRLLIN ADPFNSEPET LEYYTEKCVM 730 740 750 760 770 780 NNYFGIGLDA KISLDFNNKR DEHPEKCRSR TKNMMWYGVL GTKELLHRTY KNLEQKVLLE 790 800 810 820 830 840 CDGRPIPLPS LQGIAVLNIP SYAGGTNFWG GTKEDDTFAA PSFDDKILEV VAVFGSMQMA 850 860 870 880 890 900 VSRVIRLQHH RIAQCRTVKI SILGDEGVPV QVDGEAWVQP PGYIRIVHKN RAQTLTRDRA 910 920 930 940 950 960 FESTLKSWED KQKCELPRPP SCSLHPEMLS EEEATQMDQF GQAAGVLIHS IREIAQSHRD 970 980 990 1000 1010 1020 MEQELAHAVN ASSKSMDRVY GKPRTTEGLN CSFVLEMVNN FRALRSETEL LLSGKMALQL 1030 1040 1050 1060 1070 1080 DPPQKEQLGS ALAEMDRQLR RLADTPWLCQ SAEPGDEESV MLDLAKRSRS GKFRLVTKFK 1090 1100 1110 1120 1130 1140 KEKNNKNKEA HSSLGAPVHL WGTEEVAAWL EHLSLCEYKD IFTRHDIRGS ELLHLERRDL 1150 1160 1170 KDLGVTKVGH MKRILCGIKE LSRSAPAVEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Alternative splicing of the human diacylglycerol kinase delta gene generates two isoforms differing in their expression patterns and in regulatory functions." Sakane F., Imai S., Yamada K., Murakami T., Tsushima S., Kanoh H. J. Biol. Chem. 277:43519-43526(2002) [PubMed: 12200442] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. DNA Res. 2:167-174(1995) [PubMed: 8590280] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 17-1214 (ISOFORM 2). Tissue: Bone marrow.
[3]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"Molecular cloning of a novel diacylglycerol kinase isozyme with a pleckstrin homology domain and a C-terminal tail similar to those of the EPH family of protein-tyrosine kinases." Sakane F., Imai S., Kai M., Wada I., Kanoh H. J. Biol. Chem. 271:8394-8401(1996) [PubMed: 8626538] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-1214 (ISOFORM 1). Tissue: Hepatoma and Testis.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1068-1214. Tissue: Lymph.
[6]	"Phorbol ester-regulated oligomerization of diacylglycerol kinase delta linked to its phosphorylation and translocation." Imai S., Sakane F., Kanoh H. J. Biol. Chem. 277:35323-35332(2002) [PubMed: 12084710] [Abstract] Cited for: PHOSPHORYLATION.
[7]	"Regulation of clathrin-dependent endocytosis by diacylglycerol kinase delta: importance of kinase activity and binding to AP2alpha." Kawasaki T., Kobayashi T., Ueyama T., Shirai Y., Saito N. Biochem. J. 409:471-479(2008) [PubMed: 17880279] [Abstract] Cited for: FUNCTION, INTERACTION WITH AP2A2, MUTAGENESIS OF PHE-369; PHE-372 AND PHE-748.
[8]	"Solution structure of the C1 domain of the human diacylglycerol kinase delta." RIKEN structural genomics initiative (RSGI) Submitted (APR-2004) to the PDB data bank Cited for: STRUCTURE BY NMR OF 216-286.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB078966 mRNA. Translation: BAC11809.1.
D63479 mRNA. Translation: BAA09766.3.
D73409 mRNA. Translation: BAA11134.1.
BC006561 mRNA. Translation: AAH06561.1.

IPI

IPI00303136.
IPI00374804.

RefSeq

NP_003639.2.
NP_690618.2.

UniGene

Hs.471675

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R79	NMR	-	A	216-286	[»]
3BQ7	X-ray	2.90	A/B/C/D/E/F	1141-1208	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16760. 2 interactions.

STRING

Q16760.

PTM databases

PhosphoSite

Q16760.

Proteomic databases

PRIDE

Q16760.

Genome annotation databases

Ensembl

ENST00000264057; ENSP00000264057; ENSG00000077044; Homo sapiens. [Genome view]
ENST00000409813; ENSP00000386455; ENSG00000077044; Homo sapiens. [Genome view]
ENST00000427930; ENSP00000407938; ENSG00000077044; Homo sapiens. [Genome view]
ENST00000430834; ENSP00000390970; ENSG00000077044; Homo sapiens. [Genome view]
ENST00000447484; ENSP00000395530; ENSG00000077044; Homo sapiens. [Genome view]

GeneID

8527.

KEGG

hsa:8527.

UCSC

uc002vui.1. human.
uc002vuj.1. human.

Organism-specific databases

CTD

8527.

GeneCards

GC02P233927.

H-InvDB

HIX0002934.

HGNC

HGNC:2851. DGKD.

MIM

601826. gene.

PharmGKB

PA27312.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q16760.

HOVERGEN

Q16760.

OMA

SLCEYKD.

Enzyme and pathway databases

BRENDA

2.7.1.107. 247.

Gene expression databases

ArrayExpress

Q16760.

Bgee

Q16760.

CleanEx

HS_DGKD.

Genevestigator

Q16760.

GermOnline

ENSG00000077044. Homo sapiens.

Family and domain databases

InterPro

IPR000756. Diacylglycerol_kinase_access.
IPR001206. Diacylglycerol_kinase_cat.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG_bd.
IPR001660. SAM.
IPR011510. SAM_2.
IPR013761. SAM_type.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:1.10.150.50. SAM_type. 1 hit.

Pfam

PF00130. C1_1. 2 hits.
PF00609. DAGK_acc. 1 hit.
PF00781. DAGK_cat. 1 hit.
PF00169. PH. 1 hit.
PF07647. SAM_2. 1 hit.
[Graphical view]

ProDom

PD002939. DAGKa. 1 hit.
PD005043. DAGKc. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00109. C1. 2 hits.
SM00045. DAGKa. 1 hit.
SM00046. DAGKc. 1 hit.
SM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]

PROSITE

PS50146. DAGK. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00144. Phosphatidylserine.

NextBio

31928.

SOURCE

Search...

Entry information

Entry name

DGKD_HUMAN

Accession

Primary (citable) accession number: Q16760
Secondary accession number(s): Q14158, Q6PK55, Q8NG53

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	November 3, 2009
This is version 110 of the entry and version 4 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.