Reviewed, UniProtKB/Swiss-Prot Q53H12 (AGK_HUMAN)

Names and origin

Protein names

Recommended name:
    Acylglycerol kinase, mitochondrial
      Short name=hAGK
    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
      Short name=HsMuLK

Gene names

Name:	AGK
Synonyms:	MULK

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	422 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.6
Catalytic activity	ATP + acylglycerol = ADP + acyl-sn-glycerol 3-phosphate. ATP + 1,2-diacylglycerol = ADP + 1,2-diacyl-sn-glycerol 3-phosphate.
Cofactor	Magnesium. Ref.6
Pathway	Lipid metabolism; glycerolipid metabolism.
Subcellular location	Mitochondrion membrane. Ref.6 Ref.1
Tissue specificity	Highly expressed in muscle, heart, kidney and brain. Ref.6
Miscellaneous	Overexpressed in prostate cancer, suggesting that it may play a role in initiation and progression of prostate cancer, processes in which LPA plays key roles.
Sequence similarities	Contains 1 DAGKc domain.

Ontologies

Keywords
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Gene Ontology (GO)
Biological process	activation of protein kinase C activity Inferred from electronic annotation. Source: InterPro
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 diacylglycerol kinase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q53H12-1)

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: Q53H12-2)

The sequence of this isoform differs from the canonical sequence as follows:
     48-65: VFGNQLIPPNAQVKKATV → HYQDESRWEPTLSRTPGS
     66-422: Missing.

Notes: 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 – 422	391	Acylglycerol kinase, mitochondrial		PRO_0000252380
Regions
	Domain	62 – 193	132	DAGKc
Natural variations
	Alternative sequence	48 – 65	18	VFGNQ…KKATV → HYQDESRWEPTLSRTPGS in isoform 2.		VSP_020925
	Alternative sequence	66 – 422	357	Missing in isoform 2.		VSP_020926
	Natural variant	3	1	V → M: dbSNP rs10262855.		VAR_027848
Experimental info
	Sequence conflict	94	1	D → V in BAD96489. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: F9D85658616B8970	FASTA	422	47,137
	10 20 30 40 50 60 MTVFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQVFG NQLIPPNAQV 70 80 90 100 110 120 KKATVFLNPA ACKGKARTLF EKNAAPILHL SGMDVTIVKT DYEGQAKKLL ELMENTDVII 130 140 150 160 170 180 VAGGDGTLQE VVTGVLRRTD EATFSKIPIG FIPLGETSSL SHTLFAESGN KVQHITDATL 190 200 210 220 230 240 AIVKGETVPL DVLQIKGEKE QPVFAMTGLR WGSFRDAGVK VSKYWYLGPL KIKAAHFFST 250 260 270 280 290 300 LKEWPQTHQA SISYTGPTER PPNEPEETPV QRPSLYRRIL RRLASYWAQP QDALSQEVSP 310 320 330 340 350 360 EVWKDVQLST IELSITTRNN QLDPTSKEDF LNICIEPDTI SKGDFITIGS RKVRNPKLHV 370 380 390 400 410 420 EGTECLQASQ CTLLIPEGAG GSFSIDSEEY EAMPVEVKLL PRKLQFFCDP RKREQMLTSP TQ
	Isoform 2. Checksum: 8F3133CE9A0B6D70		65	7,634
	10 20 30 40 50 60 MTVFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQHYQ DESRWEPTLS RTPGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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), SUBCELLULAR LOCATION.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Liver.
[4]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] (ISOFORMS 1 AND 2). Tissue: Gall bladder and Uterus.
[6]	"A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells." Bektas M., Payne S.G., Liu H., Goparaju S., Milstien S., Spiegel S. J. Cell Biol. 169:801-811(2005) [PubMed: 15939762] [Abstract] Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ278150 mRNA. Translation: CAB93536.1. AK001704 mRNA. Translation: BAA91848.1. AK222769 mRNA. Translation: BAD96489.1. AC004918 Genomic DNA. No translation available. AC073878 Genomic DNA. No translation available. AC099547 Genomic DNA. Translation: AAS07537.1. BC009775 mRNA. Translation: AAH09775.1. BC022777 mRNA. Translation: AAH22777.1.
RefSeq	NP_060708.1.
UniGene	Hs.699361
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q53H12.
Proteomic databases
PeptideAtlas	Q53H12.
PRIDE	Q53H12.
Genome annotation databases
Ensembl	ENSG00000006530. Homo sapiens. [Contig view]
GeneID	55750.
KEGG	hsa:55750.
Organism-specific databases
GeneCards	GC07P140899.
HGNC	HGNC:21869. AGK.
MIM	610345. gene.
PharmGKB	PA31436.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q53H12.
Gene expression databases
ArrayExpress	Q53H12.
CleanEx	HS_AGK.
GermOnline	ENSG00000006530. Homo sapiens.
Family and domain databases
InterPro	IPR001206. DAGKc. [Graphical view]
Pfam	PF00781. DAGK_cat. 1 hit. [Graphical view]
ProDom	PD005043. DAGKc. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00046. DAGKc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	60737.
SOURCE	Search...

Entry information

Entry name

AGK_HUMAN

Accession

Primary (citable) accession number: Q53H12
Secondary accession number(s): Q75KN1, Q96GC3, Q9NP48

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 17, 2006
Last sequence update:	October 17, 2006
Last modified:	December 16, 2008
This is version 33 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)