P23743 (DGKA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Diacylglycerol kinase alpha
Short name=DAG kinase alpha
EC=2.7.1.107

Alternative name(s):
80 kDa diacylglycerol kinase
Diglyceride kinase alpha
Short name=DGK-alpha

Gene names

Name:	DGKA
Synonyms:	DAGK, DAGK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	735 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Upon cell stimulation converts the second messenger diacylglycerol into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity.
Catalytic activity	ATP + 1,2-diacylglycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
Enzyme regulation	Stimulated by calcium and phosphatidylserine. Phosphorylated by protein kinase C.
Subunit structure	Monomer.
Tissue specificity	Lymphocytes and oligodendroglial cells.
Sequence similarities	Belongs to the eukaryotic diacylglycerol kinase family. Contains 1 DAGKc domain. Contains 2 EF-hand domains. Contains 2 phorbol-ester/DAG-type zinc fingers.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	ATP-binding Calcium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: InterPro intracellular signal transduction Traceable author statement. Source: ProtInc platelet activation Traceable author statement. Source: Reactome
Cellular component	plasma membrane Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: InterPro diacylglycerol kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P23743-1)

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 2 (identifier: P23743-2)

The sequence of this isoform differs from the canonical sequence as follows:
     117-118: FT → WS
     119-735: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 735

735

Diacylglycerol kinase alpha

PRO_0000218453

Regions

Domain

110 – 145

36

EF-hand 1

Domain

155 – 190

36

EF-hand 2

Domain

372 – 506

135

DAGKc

Calcium binding

123 – 134

12

1 Probable

Calcium binding

168 – 179

12

2 Probable

Zinc finger

205 – 253

49

Phorbol-ester/DAG-type 1

Zinc finger

269 – 319

51

Phorbol-ester/DAG-type 2

Amino acid modifications

Modified residue

22

1

Phosphotyrosine Ref.7

Modified residue

484

1

N6-acetyllysine Ref.9

Modified residue

623

1

Phosphotyrosine Ref.8

Natural variations

Alternative sequence

117 – 118

2

FT → WS in isoform 2.

VSP_032212

Alternative sequence

119 – 735

617

Missing in isoform 2.

VSP_032213

Natural variant

538

1

H → Y. Ref.4
Corresponds to variant rs17852990 [ dbSNP | Ensembl ].

VAR_031563

Experimental info

Sequence conflict

339

1

L → P in AAC34804. Ref.2

Sequence conflict

379

1

V → L in AAC34802. Ref.2

Sequence conflict

385

1

S → W in AAC34802. Ref.2

Sequence conflict

684

1

E → G in AAC34803. Ref.2

Sequence conflict

699

1

G → V in CAA44396. Ref.1

Sequence conflict

715

1

N → K in AAC34803. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

735

Helix Strand Turn

Details...

Helix

10 – 22

13

Helix

27 – 35

9

Helix

38 – 42

5

Helix

50 – 60

11

Helix

68 – 77

10

Helix

96 – 107

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 15, 2009. Version 3. Checksum: ACAA0AD186EE64A0	FASTA	735	82,630
	10 20 30 40 50 60 MAKERGLISP SDFAQLQKYM EYSTKKVSDV LKLFEDGEMA KYVQGDAIGY EGFQQFLKIY 70 80 90 100 110 120 LEVDNVPRHL SLALFQSFET GHCLNETNVT KDVVCLNDVS CYFSLLEGGR PEDKLEFTFK 130 140 150 160 170 180 LYDTDRNGIL DSSEVDKIIL QMMRVAEYLD WDVSELRPIL QEMMKEIDYD GSGSVSQAEW 190 200 210 220 230 240 VRAGATTVPL LVLLGLEMTL KDDGQHMWRP KRFPRPVYCN LCESSIGLGK QGLSCNLCKY 250 260 270 280 290 300 TVHDQCAMKA LPCEVSTYAK SRKDIGVQSH VWVRGGCESG RCDRCQKKIR IYHSLTGLHC 310 320 330 340 350 360 VWCHLEIHDD CLQAVGHECD CGLLRDHILP PSSIYPSVLA SGPDRKNSKT SQKTMDDLNL 370 380 390 400 410 420 STSEALRIDP VPNTHPLLVF VNPKSGGKQG QRVLWKFQYI LNPRQVFNLL KDGPEIGLRL 430 440 450 460 470 480 FKDVPDSRIL VCGGDGTVGW ILETIDKANL PVLPPVAVLP LGTGNDLARC LRWGGGYEGQ 490 500 510 520 530 540 NLAKILKDLE MSKVVHMDRW SVEVIPQQTE EKSDPVPFQI INNYFSIGVD ASIAHRFHIM 550 560 570 580 590 600 REKYPEKFNS RMKNKLWYFE FATSESIFST CKKLEESLTV EICGKPLDLS NLSLEGIAVL 610 620 630 640 650 660 NIPSMHGGSN LWGDTRRPHG DIYGINQALG ATAKVITDPD ILKTCVPDLS DKRLEVVGLE 670 680 690 700 710 720 GAIEMGQIYT KLKNAGRRLA KCSEITFHTT KTLPMQIDGE PWMQTPCTIK ITHKNQMPML 730 MGPPPRSTNF FGFLS
	Isoform 2 [UniParc]. Checksum: DC47336F5D8B584F	FASTA	118	13,486
	10 20 30 40 50 60 MAKERGLISP SDFAQLQKYM EYSTKKVSDV LKLFEDGEMA KYVQGDAIGY EGFQQFLKIY 70 80 90 100 110 LEVDNVPRHL SLALFQSFET GHCLNETNVT KDVVCLNDVS CYFSLLEGGR PEDKLEWS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Purification, cDNA-cloning and expression of human diacylglycerol kinase." Schaap D., de Widt J., van der Wal J., Vandekerckhove J., van Damme J., Gussow D., Ploegh H.L., van Blitterswijk W.J., van der Bendl R.L. FEBS Lett. 275:151-158(1990) [PubMed: 2175712] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lymphocyte.
[2]	"Alternative splicing of diacylglycerol kinase alpha expressed in human neutrophils." Champagne C.M.E., Maeda H., Takashiba S., van Dyke T.E. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING. Tissue: Uterus.
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed: 16541075] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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] (ISOFORM 1), VARIANT TYR-538. Tissue: Brain.
[5]	"Assignment of the gene for diacylglycerol kinase (DAGK) to human chromosome 12." Hart T.C., Champagne C., Zhou J., van Dyke T.E. Mamm. Genome 5:123-124(1994) [PubMed: 8180475] [Abstract] Cited for: CHROMOSOMAL LOCATION.
[6]	"Assignment of the human diacylglycerol kinase gene (DAGK) to 12q13.3 using fluorescence in situ hybridization analysis." Hart T.C., Zhou J., Champagne C., van Dyke T.E., Rao P.N., Pettenati M.J. Genomics 22:246-247(1994) [PubMed: 7959783] [Abstract] Cited for: CHROMOSOMAL LOCATION.
[7]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-22, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[8]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-623, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-484, MASS SPECTROMETRY.
[10]	"NMR structure of diacylglycerol kinase alpha, NESGC target HR532." Northeast structural genomics consortium (NESG) Submitted (JAN-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 1-118.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X62535 mRNA. Translation: CAA44396.1.
AF064767 mRNA. Translation: AAC34802.1.
AF064768 mRNA. Translation: AAC34803.1.
AF064769 mRNA. Translation: AAC34804.1.
AF064771 mRNA. Translation: AAC34806.1.
AC025162 Genomic DNA. No translation available.
BC023523 mRNA. Translation: AAH23523.1.
BC031870 mRNA. Translation: AAH31870.1.

IPI

IPI00333143.
IPI01026253.

PIR

S12969.

RefSeq

NP_001336.2. NM_001345.4.
NP_958852.1. NM_201444.2.
NP_958853.1. NM_201445.1.
NP_963848.1. NM_201554.1.

UniGene

Hs.524488.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TUZ	NMR	-	A	1-116	[»]

ProteinModelPortal

P23743.

SMR

P23743. Positions 1-184, 200-324.

ModBase

Search...

Protein-protein interaction databases

IntAct

P23743. 2 interactions.

STRING

P23743.

PTM databases

PhosphoSite

P23743.

Polymorphism databases

DMDM

281185505.

Proteomic databases

PRIDE

P23743.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000331886; ENSP00000328405; ENSG00000065357.
ENST00000394145; ENSP00000377701; ENSG00000065357.
ENST00000394147; ENSP00000377703; ENSG00000065357.
ENST00000402956; ENSP00000385792; ENSG00000065357.
ENST00000412897; ENSP00000395713; ENSG00000065357.

GeneID

1606.

KEGG

hsa:1606.

UCSC

uc001sij.1. human.

Organism-specific databases

CTD

1606.

GeneCards

GC12P056324.

HGNC

HGNC:2849. DGKA.

MIM

125855. gene.

neXtProt

NX_P23743.

PharmGKB

PA27310.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04926.

HOVERGEN

HBG051345.

InParanoid

P23743.

OMA

GDTKRPH.

OrthoDB

EOG4T782Q.

PhylomeDB

P23743.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpress

P23743.

Bgee

P23743.

CleanEx

HS_DGKA.

Genevestigator

P23743.

GermOnline

ENSG00000065357. Homo sapiens.

Family and domain databases

InterPro

IPR000756. Diacylglycerol_kin_accessory.
IPR001206. Diacylglycerol_kinase_cat_dom.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR018249. EF_HAND_2.
IPR002048. EF_hand_Ca-bd.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

KO

K00901.

Pfam

PF00130. C1_1. 2 hits.
PF00609. DAGK_acc. 1 hit.
PF00781. DAGK_cat. 1 hit.
[Graphical view]

SMART

SM00109. C1. 2 hits.
SM00045. DAGKa. 1 hit.
SM00046. DAGKc. 1 hit.
SM00054. EFh. 2 hits.
[Graphical view]

PROSITE

PS50146. DAGK. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00163. Vitamin E.

NextBio

6590.

SOURCE

Search...

Entry information

Entry name

DGKA_HUMAN

Accession

Primary (citable) accession number: P23743
Secondary accession number(s): O75481 , O75482, O75483, O95217, Q8IZ56, Q8N5Q2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	December 15, 2009
Last modified:	January 25, 2012
This is version 128 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.