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Q16760 (DGKD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Diacylglycerol kinase delta
Short name=DAG kinase delta
EC=2.7.1.107
Alternative name(s):
130 kDa diacylglycerol kinase
Diglyceride kinase delta
Short name=DGK-delta
Gene names
Name:DGKD
Synonyms:KIAA0145
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length1214 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May function as signaling molecule. Ref.7

Isoform 2 may be involved in cell growth and tumorigenesis. 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.1 Ref.7

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 processEndocytosis
Protein transport
Transport
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell growth

Non-traceable author statement Ref.1. Source: UniProtKB

diacylglycerol metabolic process

Non-traceable author statement Ref.1. Source: UniProtKB

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

epidermal growth factor receptor signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

multicellular organismal development

Non-traceable author statement Ref.1. Source: UniProtKB

platelet activation

Traceable author statement. Source: Reactome

protein homooligomerization

Inferred from direct assay Ref.1. Source: UniProtKB

protein kinase C-activating G-protein coupled receptor signaling pathway

Non-traceable author statement Ref.1. Source: UniProtKB

protein transport

Inferred from electronic annotation. Source: UniProtKB-KW

response to organic substance

Inferred from direct assay Ref.1. Source: UniProtKB

second-messenger-mediated signaling

Non-traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay Ref.1. Source: UniProtKB

cytoplasmic membrane-bounded vesicle

Inferred from direct assay Ref.1. Source: MGI

plasma membrane

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

diacylglycerol binding

Non-traceable author statement Ref.1. Source: UniProtKB

diacylglycerol kinase activity

Traceable author statement Ref.1Ref.4. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phospholipid binding

Inferred from electronic annotation. Source: InterPro

protein heterodimerization activity

Inferred from direct assay Ref.1. Source: MGI

protein homodimerization activity

Inferred from direct assay Ref.1. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

DYSFO759233EBI-719333,EBI-2799016

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12141214Diacylglycerol kinase delta
PRO_0000218462

Regions

Domain53 – 14694PH
Domain317 – 451135DAGKc
Domain1145 – 120864SAM
Zinc finger163 – 21351Phorbol-ester/DAG-type 1
Zinc finger235 – 28652Phorbol-ester/DAG-type 2
Compositional bias8 – 3629Pro-rich

Natural variations

Alternative sequence1 – 5252MAAAA…QIRQK → MNMFLYFQ in isoform 1.
VSP_012891

Experimental info

Mutagenesis3691F → A: Reduces interaction with AP2A2; when associated with A-372. Ref.7
Mutagenesis3721F → A: Reduces interaction with AP2A2; when associated with A-369. Ref.7
Mutagenesis7481F → A: Reduces interaction with AP2A2. Ref.7
Sequence conflict5111V → P in BAA11134. Ref.4
Sequence conflict828 – 8347RPIPLPS → DPSHSPV in BAA11134. Ref.4
Sequence conflict9601L → V in BAC11809. Ref.1
Sequence conflict9601L → V in BAA11134. Ref.4
Sequence conflict10541Missing in BAA11134. Ref.4

Secondary structure

1 ........................ 1214
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 2 [UniParc].

Last modified October 17, 2006. Version 4.
Checksum: ED114429096D2112

FASTA1,214134,525
        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

« Hide

Isoform 1 [UniParc].

Checksum: 00B7946AE15BC0A3
Show »

FASTA1,170130,326

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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

EMBL
GenBank
DDBJ		AB078966 mRNA. Translation: BAC11809.1.
D63479 mRNA. Translation: BAA09766.3.
D73409 mRNA. Translation: BAA11134.1.
BC006561 mRNA. Translation: AAH06561.1.
IPIIPI00303136.
IPI00374804.
RefSeqNP_003639.2. NM_003648.2.
NP_690618.2. NM_152879.2.
UniGeneHs.471675.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1R79NMR-A216-286[»]
3BQ7X-ray2.90A/B/C/D/E/F1141-1208[»]
ProteinModelPortalQ16760.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-29646N.
IntActQ16760. 5 interactions.
MINTMINT-87709.
STRING9606.ENSP00000264057.

PTM databases

PhosphoSiteQ16760.

Polymorphism databases

DMDM116241328.

Proteomic databases

PaxDbQ16760.
PRIDEQ16760.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264057; ENSP00000264057; ENSG00000077044.
ENST00000409813; ENSP00000386455; ENSG00000077044.
GeneID8527.
KEGGhsa:8527.
UCSCuc002vui.1. human.
uc002vuj.1. human.

Organism-specific databases

CTD8527.
GeneCardsGC02P234279.
H-InvDBHIX0002934.
HGNCHGNC:2851. DGKD.
HPAHPA049101.
MIM601826. gene.
neXtProtNX_Q16760.
PharmGKBPA27312.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG328046.
HOGENOMHOG000234676.
HOVERGENHBG051346.
InParanoidQ16760.
KOK00901.
OMANCSFVLE.
OrthoDBEOG42NHZQ.
PhylomeDBQ16760.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ16760.
BgeeQ16760.
CleanExHS_DGKD.
GenevestigatorQ16760.
GermOnlineENSG00000077044. Homo sapiens.

Family and domain databases

Gene3D1.10.150.50. 1 hit.
2.30.29.30. 1 hit.
InterProIPR000756. Diacylglycerol_kin_accessory.
IPR001206. Diacylglycerol_kinase_cat_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR011510. SAM_2.
[Graphical view]
PfamPF00130. 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]
SMARTSM00109. C1. 2 hits.
SM00045. DAGKa. 1 hit.
SM00046. DAGKc. 1 hit.
SM00233. PH. 1 hit.
SM00454. SAM. 1 hit.
[Graphical view]
SUPFAMSSF47769. SAM_homology. 1 hit.
PROSITEPS50146. 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]
ProtoNetSearch...

Other

ChEMBLCHEMBL1075120.
ChiTaRSDGKD. human.
DrugBankDB00144. Phosphatidylserine.
EvolutionaryTraceQ16760.
GenomeRNAi8527.
NextBio31928.
SOURCESearch...

Entry information

Entry nameDGKD_HUMAN
AccessionPrimary (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: May 1, 2013
This is version 147 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

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