Q53H12 (AGK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acylglycerol kinase, mitochondrial
Short name=hAGK
EC=2.7.1.107
EC=2.7.1.94

Alternative name(s):
Multiple substrate lipid kinase
Short name=HsMuLK
Short name=MuLK
Short name=Multi-substrate lipid kinase

Gene names

Name:	AGK
Synonyms:	MULK

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.1 Ref.6.
Tissue specificity	Highly expressed in muscle, heart, kidney and brain. Ref.6
Involvement in disease	Mitochondrial DNA depletion syndrome 10 (MTDPS10) [MIM:212350]: An autosomal recessive mitochondrial disorder characterized by congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, exercise intolerance, and lactic acidosis. Mental development is normal, but affected individuals may die early from cardiomyopathy. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.11 Cataract, congenital, autosomal recessive 5 (CATC5) [MIM:614691]: An opacification of the crystalline lens of the eye becoming evident at birth. It frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
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
Disease	Cardiomyopathy Cataract
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ceramide biosynthetic process Inferred from electronic annotation. Source: Compara glycerolipid metabolic process Inferred from electronic annotation. Source: UniProtKB-UniPathway protein kinase C-activating G-protein coupled receptor signaling pathway 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 ceramide kinase activity Inferred from electronic annotation. Source: Compara 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: 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.

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 – 422	391	Acylglycerol kinase, mitochondrial		PRO_0000252380
Regions
	Domain	58 – 199	142	DAGKc
Amino acid modifications
	Modified residue	6	1	N6-acetyllysine Ref.7
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. Corresponds to variant rs10262855 [ dbSNP | Ensembl ].		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 [UniParc]. Checksum: 8F3133CE9A0B6D70	FASTA	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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, MASS SPECTROMETRY.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome." Mayr J.A., Haack T.B., Graf E., Zimmermann F.A., Wieland T., Haberberger B., Superti-Furga A., Kirschner J., Steinmann B., Baumgartner M.R., Moroni I., Lamantea E., Zeviani M., Rodenburg R.J., Smeitink J., Strom T.M., Meitinger T., Sperl W., Prokisch H. Am. J. Hum. Genet. 90:314-320(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MTDPS10.
[10]	"Identification of a truncation mutation of acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus." Aldahmesh M.A., Khan A.O., Mohamed J.Y., Alghamdi M.H., Alkuraya F.S. Hum. Mutat. 33:960-962(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CATC5.
[11]	"Molecular diagnosis of infantile mitochondrial disease with targeted next-generation sequencing." Calvo S.E., Compton A.G., Hershman S.G., Lim S.C., Lieber D.S., Tucker E.J., Laskowski A., Garone C., Liu S., Jaffe D.B., Christodoulou J., Fletcher J.M., Bruno D.L., Goldblatt J., Dimauro S., Thorburn D.R., Mootha V.K. Sci. Transl. Med. 4:118ra10-118ra10(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MTDPS10.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00019353. IPI00553233.
RefSeq	NP_060708.1. NM_018238.3.
UniGene	Hs.743318.
3D structure databases
ProteinModelPortal	Q53H12.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q53H12. 3 interactions.
MINT	MINT-1378485.
STRING	9606.ENSP00000347581.
PTM databases
PhosphoSite	Q53H12.
Polymorphism databases
DMDM	116248550.
Proteomic databases
PaxDb	Q53H12.
PeptideAtlas	Q53H12.
PRIDE	Q53H12.
Protocols and materials databases
DNASU	55750.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355413; ENSP00000347581; ENSG00000006530. ENST00000492693; ENSP00000418789; ENSG00000006530. ENST00000573470; ENSP00000459040; ENSG00000262327. ENST00000575872; ENSP00000458417; ENSG00000262327.
GeneID	55750.
KEGG	hsa:55750.
UCSC	uc003vwi.2. human.
Organism-specific databases
CTD	55750.
GeneCards	GC07P141250.
HGNC	HGNC:21869. AGK.
HPA	HPA020959. HPA053471.
MIM	212350. phenotype. 610345. gene. 614691. phenotype.
neXtProt	NX_Q53H12.
Orphanet	1369. Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathy. 91492. Non-syndromic congenital cataract.
PharmGKB	PA162375851.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1597.
HOGENOM	HOG000252977.
HOVERGEN	HBG080751.
InParanoid	Q53H12.
KO	K09881.
OMA	ELSITTR.
OrthoDB	EOG48D0VC.
PhylomeDB	Q53H12.
Enzyme and pathway databases
SABIO-RK	Q53H12.
UniPathway	UPA00230.
Gene expression databases
ArrayExpress	Q53H12.
Bgee	Q53H12.
CleanEx	HS_AGK.
Genevestigator	Q53H12.
GermOnline	ENSG00000006530. Homo sapiens.
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
ChiTaRS	AGK. human.
GenomeRNAi	55750.
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:	May 29, 2013
This is version 78 of the entry and version 2 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.