Reviewed, UniProtKB/Swiss-Prot Q9ESW4 (AGK_MOUSE)

Names and origin

Protein names

Recommended name:
    Acylglycerol kinase, mitochondrial
    EC=2.7.1.94
    EC=2.7.1.107
Alternative name(s):
    Multiple substrate lipid kinase
      Short name=Multi-substrate lipid kinase
      Short name=MuLK

Gene names

Name:	Agk
Synonyms:	Mulk

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	421 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Lipid kinase that can phosphorylate both monoacylglycerol and diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively. Does not phosphorylate sphingosine. Overexpression increases the formation and secretion of LPA, resulting in transactivation of EGFR and activation of the downstream MAPK signaling pathway, leading to increased cell growth. Ref.1
Catalytic activity	ATP + acylglycerol = ADP + acyl-sn-glycerol 3-phosphate. ATP + 1,2-diacylglycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
Cofactor	Magnesium By similarity.
Pathway	Lipid metabolism; glycerolipid metabolism.
Subcellular location	Mitochondrion membrane By similarity.
Tissue specificity	Ubiquitously expressed. Ref.1
Sequence similarities	Contains 1 DAGKc domain.
Caution	Was originally (Ref.1) thought to have ceramide kinase activity. Such activity is however unlikely in vivo.
Biophysicochemical properties	Kinetic parameters: KM=45 µM for diacylglycerol Vmax=159 nmol/min/mg enzyme with dioeoylglycerol as substrate

Ontologies

Keywords
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation
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 lipid phosphorylation Ref.1 Inferred from direct assay. Source: MGI
Cellular component	mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acylglycerol kinase activity Inferred from electronic annotation. Source: EC ceramide kinase activity Ref.1 Inferred from direct assay. Source: MGI diacylglycerol kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q9ESW4-1)

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: Q9ESW4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     174-421: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 31	31	Mitochondrion Potential
	Chain	32 – 421	390	Acylglycerol kinase, mitochondrial		PRO_0000252381
Regions
	Domain	58 – 199	142	DAGKc
Amino acid modifications
	Modified residue	6	1	N6-acetyllysine By similarity
Natural variations
	Alternative sequence	174 – 421	248	Missing in isoform 2.		VSP_020927

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: DBBC48C9EB3206FD	FASTA	421	46,976
	10 20 30 40 50 60 MTAFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQVFG NQLIPPNAQV 70 80 90 100 110 120 KKATVFLNPA ACKGKARTLF EKNAAPILHL SGMDVTVVKT DYEGQAKKLL ELMESTDVII 130 140 150 160 170 180 VAGGDGTLQE VVTGVLRRTD EATFSKIPIG FIPLGQTSSL SHTLFAESGN KVQHITDATL 190 200 210 220 230 240 AIVKGETVPL DVLQIKGEKE QPVYAMTGLR WGSFRDAGVK VSKYWYLGPL KTKAAHFFST 250 260 270 280 290 300 LQEWPQTHQA SISYTGPRER PPIEPEETPP RPSLYRRILR RLASFWAQPQ DASSREVSPE 310 320 330 340 350 360 VWKDVQLSTI ELSITTRNTQ LDLMSKEDFM NICIEPDTVS KGDFIIIGSK KVRDPGLRAA 370 380 390 400 410 420 GTECLQASHC TLVLPEGTEG SFSIDSEEYE AMPVEVKLLP RKLRFFCDPR KREQMLPSTS Q
	Isoform 2. Checksum: 54E2CB009875A90B	FASTA	173	18,899
	10 20 30 40 50 60 MTAFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQVFG NQLIPPNAQV 70 80 90 100 110 120 KKATVFLNPA ACKGKARTLF EKNAAPILHL SGMDVTVVKT DYEGQAKKLL ELMESTDVII 130 140 150 160 170 VAGGDGTLQE VVTGVLRRTD EATFSKIPIG FIPLGQTSSL SHTLFAESGN KVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"MuLK, a eukaryotic multi-substrate lipid kinase." Waggoner D.W., Johnson L.B., Mann P.C., Morris V., Guastella J., Bajjalieh S.M. J. Biol. Chem. 279:38228-38235(2004) [PubMed: 15252046] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Strain: FVB/N. Tissue: Carcinoma.
[2]	"Further characterization of mammalian ceramide kinase: substrate delivery and (stereo)specificity, tissue distribution, and subcellular localization studies." Van Overloop H., Gijsbers S., Van Veldhoven P.P. J. Lipid Res. 47:268-283(2006) [PubMed: 16269826] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Head.
[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). Strain: FVB/N. Tissue: Liver and Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY772469 mRNA. Translation: AAV38106.1. AJ401619 mRNA. Translation: CAC06108.1. AK011715 mRNA. Translation: BAB27796.1. AK076224 mRNA. Translation: BAC36260.1. BC019145 mRNA. Translation: AAH19145.1. BC093525 mRNA. Translation: AAH93525.1.
IPI	IPI00113606. IPI00798555.
RefSeq	NP_076027.1.
UniGene	Mm.32840
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q9ESW4.
PTM databases
PhosphoSite	Q9ESW4.
Proteomic databases
PRIDE	Q9ESW4.
Genome annotation databases
Ensembl	ENSMUST00000031977; ENSMUSP00000031977; ENSMUSG00000029916; Mus musculus. [Genome view]
GeneID	69923.
KEGG	mmu:69923.
UCSC	uc009bmm.1. mouse. uc009bmn.1. mouse.
Organism-specific databases
CTD	69923.
MGI	MGI:1917173. Agk.
Phylogenomic databases
eggNOG	roNOG08304.
HOGENOM	HBG278744.
HOVERGEN	Q9ESW4.
InParanoid	Q9ESW4.
OMA	VSKYWYL.
OrthoDB	EOG9HB15W.
PhylomeDB	Q9ESW4.
Enzyme and pathway databases
BRENDA	2.7.1.107. 244. 2.7.1.94. 244.
Gene expression databases
ArrayExpress	Q9ESW4.
Bgee	Q9ESW4.
CleanEx	MM_AGK.
Genevestigator	Q9ESW4.
GermOnline	ENSMUSG00000029916. Mus musculus.
Family and domain databases
InterPro	IPR001206. Diacylglycerol_kinase_cat_dom. [Graphical view]
Pfam	PF00781. DAGK_cat. 1 hit. [Graphical view]
SMART	SM00046. DAGKc. 1 hit. [Graphical view]
PROSITE	PS50146. DAGK. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	330619.
SOURCE	Search...

Entry information

Entry name

AGK_MOUSE

Accession

Primary (citable) accession number: Q9ESW4
Secondary accession number(s): Q9D087

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	March 1, 2001
Last modified:	January 19, 2010
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)