AGK_HUMAN
ID AGK_HUMAN Reviewed; 422 AA.
AC Q53H12; Q75KN1; Q96GC3; Q9NP48;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Acylglycerol kinase, mitochondrial {ECO:0000303|PubMed:15939762};
DE Short=hAGK {ECO:0000303|PubMed:15939762};
DE EC=2.7.1.107 {ECO:0000269|PubMed:15939762};
DE EC=2.7.1.138 {ECO:0000250|UniProtKB:Q9ESW4};
DE EC=2.7.1.94 {ECO:0000269|PubMed:15939762};
DE AltName: Full=Multiple substrate lipid kinase {ECO:0000303|PubMed:16269826};
DE Short=HsMuLK {ECO:0000303|PubMed:16269826};
DE Short=MuLK {ECO:0000303|PubMed:16269826};
DE Short=Multi-substrate lipid kinase {ECO:0000303|PubMed:16269826};
GN Name=AGK {ECO:0000303|PubMed:15939762, ECO:0000312|HGNC:HGNC:21869};
GN Synonyms=MULK {ECO:0000303|PubMed:16269826};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=16269826; DOI=10.1194/jlr.m500321-jlr200;
RA Van Overloop H., Gijsbers S., Van Veldhoven P.P.;
RT "Further characterization of mammalian ceramide kinase: substrate delivery
RT and (stereo)specificity, tissue distribution, and subcellular localization
RT studies.";
RL J. Lipid Res. 47:268-283(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Gall bladder, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, INDUCTION, AND MUTAGENESIS OF GLY-126.
RX PubMed=15939762; DOI=10.1083/jcb.200407123;
RA Bektas M., Payne S.G., Liu H., Goparaju S., Milstien S., Spiegel S.;
RT "A novel acylglycerol kinase that produces lysophosphatidic acid modulates
RT cross talk with EGFR in prostate cancer cells.";
RL J. Cell Biol. 169:801-811(2005).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP INVOLVEMENT IN MTDPS10.
RX PubMed=22284826; DOI=10.1016/j.ajhg.2011.12.005;
RA Mayr J.A., Haack T.B., Graf E., Zimmermann F.A., Wieland T.,
RA Haberberger B., Superti-Furga A., Kirschner J., Steinmann B.,
RA Baumgartner M.R., Moroni I., Lamantea E., Zeviani M., Rodenburg R.J.,
RA Smeitink J., Strom T.M., Meitinger T., Sperl W., Prokisch H.;
RT "Lack of the mitochondrial protein acylglycerol kinase causes Sengers
RT syndrome.";
RL Am. J. Hum. Genet. 90:314-320(2012).
RN [10]
RP INVOLVEMENT IN CTRCT38.
RX PubMed=22415731; DOI=10.1002/humu.22071;
RA Aldahmesh M.A., Khan A.O., Mohamed J.Y., Alghamdi M.H., Alkuraya F.S.;
RT "Identification of a truncation mutation of acylglycerol kinase (AGK) gene
RT in a novel autosomal recessive cataract locus.";
RL Hum. Mutat. 33:960-962(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP INVOLVEMENT IN MTDPS10.
RX PubMed=22277967; DOI=10.1126/scitranslmed.3003310;
RA Calvo S.E., Compton A.G., Hershman S.G., Lim S.C., Lieber D.S.,
RA Tucker E.J., Laskowski A., Garone C., Liu S., Jaffe D.B., Christodoulou J.,
RA Fletcher J.M., Bruno D.L., Goldblatt J., Dimauro S., Thorburn D.R.,
RA Mootha V.K.;
RT "Molecular diagnosis of infantile mitochondrial disease with targeted next-
RT generation sequencing.";
RL Sci. Transl. Med. 4:118RA10-118RA10(2012).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE TIM22 COMPLEX, AND
RP MUTAGENESIS OF GLY-126.
RX PubMed=28712724; DOI=10.1016/j.molcel.2017.06.013;
RA Vukotic M., Nolte H., Koenig T., Saita S., Ananjew M., Krueger M.,
RA Tatsuta T., Langer T.;
RT "Acylglycerol kinase mutated in Sengers Syndrome is a subunit of the TIM22
RT protein translocase in mitochondria.";
RL Mol. Cell 0:0-0(2017).
RN [16]
RP FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE TIM22 COMPLEX,
RP INVOLVEMENT IN MTDPS10, AND MUTAGENESIS OF GLY-126.
RX PubMed=28712726; DOI=10.1016/j.molcel.2017.06.014;
RA Kang Y., Stroud D.A., Baker M.J., De Souza D.P., Frazier A.E., Liem M.,
RA Tull D., Mathivanan S., McConville M.J., Thorburn D.R., Ryan M.T.,
RA Stojanovski D.;
RT "Sengers syndrome-associated mitochondrial acylglycerol kinase is a subunit
RT of the human TIM22 protein import complex.";
RL Mol. Cell 0:0-0(2017).
RN [17]
RP VARIANT MTDPS10 327-LYS--GLN-422 DEL.
RX PubMed=23266196; DOI=10.1016/j.ymgme.2012.11.282;
RA Siriwardena K., Mackay N., Levandovskiy V., Blaser S., Raiman J.,
RA Kantor P.F., Ackerley C., Robinson B.H., Schulze A., Cameron J.M.;
RT "Mitochondrial citrate synthase crystals: novel finding in Sengers syndrome
RT caused by acylglycerol kinase (AGK) mutations.";
RL Mol. Genet. Metab. 108:40-50(2013).
RN [18]
RP VARIANTS MTDPS10 137-ARG--GLN-422 DEL AND 291-GLN--GLN-422 DEL.
RX PubMed=25208612; DOI=10.1186/s13023-014-0119-3;
RA Haghighi A., Haack T.B., Atiq M., Mottaghi H., Haghighi-Kakhki H.,
RA Bashir R.A., Ahting U., Feichtinger R.G., Mayr J.A., Roetig A., Lebre A.S.,
RA Klopstock T., Dworschak A., Pulido N., Saeed M.A., Saleh-Gohari N.,
RA Holzerova E., Chinnery P.F., Taylor R.W., Prokisch H.;
RT "Sengers syndrome: six novel AGK mutations in seven new families and review
RT of the phenotypic and mutational spectrum of 29 patients.";
RL Orphanet J. Rare Dis. 9:119-119(2014).
CC -!- FUNCTION: Lipid kinase that can phosphorylate both monoacylglycerol and
CC diacylglycerol to form lysophosphatidic acid (LPA) and phosphatidic
CC acid (PA), respectively (PubMed:15939762). Does not phosphorylate
CC sphingosine (PubMed:15939762). Phosphorylates ceramide (By similarity).
CC Phosphorylates 1,2-dioleoylglycerol more rapidly than 2,3-
CC dioleoylglycerol (By similarity). Independently of its lipid kinase
CC activity, acts as a component of the TIM22 complex (PubMed:28712724,
CC PubMed:28712726). The TIM22 complex mediates the import and insertion
CC of multi-pass transmembrane proteins into the mitochondrial inner
CC membrane by forming a twin-pore translocase that uses the membrane
CC potential as the external driving force (PubMed:28712724,
CC PubMed:28712726). In the TIM22 complex, required for the import of a
CC subset of metabolite carriers into mitochondria, such as ANT1/SLC25A4
CC and SLC25A24, while it is not required for the import of TIMM23
CC (PubMed:28712724). Overexpression increases the formation and secretion
CC of LPA, resulting in transactivation of EGFR and activation of the
CC downstream MAPK signaling pathway, leading to increased cell growth
CC (PubMed:15939762). {ECO:0000250|UniProtKB:Q9ESW4,
CC ECO:0000269|PubMed:15939762, ECO:0000269|PubMed:28712724,
CC ECO:0000269|PubMed:28712726}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a monoacylglycerol + ATP = ADP + H(+) + monoacyl-sn-glycero-3-
CC phosphate; Xref=Rhea:RHEA:19293, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17408, ChEBI:CHEBI:30616, ChEBI:CHEBI:77589,
CC ChEBI:CHEBI:456216; EC=2.7.1.94;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19294;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-
CC phosphate + ADP + H(+); Xref=Rhea:RHEA:10272, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17815, ChEBI:CHEBI:30616, ChEBI:CHEBI:58608,
CC ChEBI:CHEBI:456216; EC=2.7.1.107;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphing-4-enine + ATP = ADP + an N-acylsphing-4-enine
CC 1-phosphate + H(+); Xref=Rhea:RHEA:17929, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:52639, ChEBI:CHEBI:57674,
CC ChEBI:CHEBI:456216; EC=2.7.1.138;
CC Evidence={ECO:0000250|UniProtKB:Q9ESW4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17930;
CC Evidence={ECO:0000250|UniProtKB:Q9ESW4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-(9Z-octadecenoyl)-
CC sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41079,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:74544,
CC ChEBI:CHEBI:75757, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41080;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-
CC octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:40327, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:52333, ChEBI:CHEBI:74546, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-sn-glycerol + ATP = a 1-acyl-sn-glycero-3-phosphate +
CC ADP + H(+); Xref=Rhea:RHEA:33747, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57970, ChEBI:CHEBI:64683,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33748;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycerol + ATP = 1-hexadecanoyl-sn-glycero-
CC 3-phosphate + ADP + H(+); Xref=Rhea:RHEA:43308, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:57518, ChEBI:CHEBI:75542,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43309;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + ATP = 2-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:43316, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:52392, ChEBI:CHEBI:78209, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43317;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + ATP = 1-
CC (5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+);
CC Xref=Rhea:RHEA:43328, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:34071, ChEBI:CHEBI:74938, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q9ESW4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43329;
CC Evidence={ECO:0000250|UniProtKB:Q9ESW4};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N-(hexanoyl)sphing-4-enine = ADP + H(+) + N-
CC hexanoylsphing-4-enine 1-phosphate; Xref=Rhea:RHEA:43312,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:63867,
CC ChEBI:CHEBI:82959, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:15939762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43313;
CC Evidence={ECO:0000305|PubMed:15939762};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15939762};
CC -!- PATHWAY: Lipid metabolism; glycerolipid metabolism.
CC {ECO:0000269|PubMed:15939762}.
CC -!- SUBUNIT: Component of the TIM22 complex, which core is composed of
CC TIMM22, associated with TIMM10 (TIMM10A and/or TIMM10B), TIMM9, AGK and
CC TIMM29 (PubMed:28712724, PubMed:28712726).
CC {ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726}.
CC -!- INTERACTION:
CC Q53H12; P42858: HTT; NbExp=3; IntAct=EBI-2269837, EBI-466029;
CC Q53H12-2; P42858: HTT; NbExp=12; IntAct=EBI-25944242, EBI-466029;
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15939762, ECO:0000269|PubMed:16269826,
CC ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726}; Peripheral
CC membrane protein {ECO:0000269|PubMed:28712724}. Mitochondrion
CC intermembrane space {ECO:0000269|PubMed:28712724,
CC ECO:0000269|PubMed:28712726}. Note=Localizes in the mitochondrion
CC intermembrane space, where it associates with the inner membrane
CC (PubMed:28712724). It is unclear whether the N-terminal hydrophobic
CC region forms a transmembrane region or associates with the membrane
CC without crossing it (PubMed:28712724, PubMed:28712726).
CC {ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q53H12-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q53H12-2; Sequence=VSP_020925, VSP_020926;
CC -!- TISSUE SPECIFICITY: Highly expressed in muscle, heart, kidney and
CC brain. {ECO:0000269|PubMed:15939762}.
CC -!- INDUCTION: Overexpressed in prostate cancer, suggesting that it may
CC play a role in initiation and progression of prostate cancer, processes
CC in which lysophosphatidic acid (LPA) plays key roles.
CC {ECO:0000269|PubMed:15939762}.
CC -!- DISEASE: Mitochondrial DNA depletion syndrome 10 (MTDPS10)
CC [MIM:212350]: An autosomal recessive mitochondrial disorder
CC characterized by congenital cataracts, hypertrophic cardiomyopathy,
CC skeletal myopathy, exercise intolerance, and lactic acidosis. Mental
CC development is normal, but affected individuals may die early from
CC cardiomyopathy. {ECO:0000269|PubMed:22277967,
CC ECO:0000269|PubMed:22284826, ECO:0000269|PubMed:23266196,
CC ECO:0000269|PubMed:25208612, ECO:0000269|PubMed:28712726}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry. The TIM22 complex and import of proteins into mitochondrion are
CC affected in patients suffering of MTDPS10 (PubMed:28712726).
CC {ECO:0000269|PubMed:28712726}.
CC -!- DISEASE: Cataract 38 (CTRCT38) [MIM:614691]: An opacification of the
CC crystalline lens of the eye becoming evident at birth. It frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. In general, the more posteriorly located and
CC dense an opacity, the greater the impact on visual function.
CC {ECO:0000269|PubMed:22415731}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AGK family. {ECO:0000305}.
CC -!- CAUTION: According to a report, the N-terminal hydrophobic region forms
CC a transmembrane region that crosses the mitochondrion inner membrane
CC (PubMed:28712726). According to another report, the N-terminal
CC hydrophobic region associates with the membrane without crossing it
CC (PubMed:28712724). {ECO:0000269|PubMed:28712724,
CC ECO:0000269|PubMed:28712726}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ278150; CAB93536.1; -; mRNA.
DR EMBL; AK001704; BAA91848.1; -; mRNA.
DR EMBL; AK222769; BAD96489.1; -; mRNA.
DR EMBL; AC004918; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073878; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC099547; AAS07537.1; -; Genomic_DNA.
DR EMBL; BC009775; AAH09775.1; -; mRNA.
DR EMBL; BC022777; AAH22777.1; -; mRNA.
DR CCDS; CCDS5865.1; -. [Q53H12-1]
DR RefSeq; NP_060708.1; NM_018238.3. [Q53H12-1]
DR RefSeq; XP_011514699.1; XM_011516397.2. [Q53H12-1]
DR PDB; 7CGP; EM; 3.70 A; B=1-422.
DR PDBsum; 7CGP; -.
DR AlphaFoldDB; Q53H12; -.
DR SMR; Q53H12; -.
DR BioGRID; 120868; 111.
DR ComplexPortal; CPX-6124; TIM22 mitochondrial inner membrane twin-pore carrier translocase complex.
DR IntAct; Q53H12; 49.
DR MINT; Q53H12; -.
DR STRING; 9606.ENSP00000347581; -.
DR ChEMBL; CHEMBL2417354; -.
DR SwissLipids; SLP:000000638; -.
DR iPTMnet; Q53H12; -.
DR PhosphoSitePlus; Q53H12; -.
DR SwissPalm; Q53H12; -.
DR BioMuta; AGK; -.
DR DMDM; 116248550; -.
DR EPD; Q53H12; -.
DR jPOST; Q53H12; -.
DR MassIVE; Q53H12; -.
DR MaxQB; Q53H12; -.
DR PaxDb; Q53H12; -.
DR PeptideAtlas; Q53H12; -.
DR PRIDE; Q53H12; -.
DR ProteomicsDB; 62491; -. [Q53H12-1]
DR ProteomicsDB; 62492; -. [Q53H12-2]
DR Antibodypedia; 18305; 202 antibodies from 32 providers.
DR DNASU; 55750; -.
DR Ensembl; ENST00000492693.5; ENSP00000418789.1; ENSG00000006530.18. [Q53H12-2]
DR Ensembl; ENST00000575872.2; ENSP00000458417.2; ENSG00000262327.7.
DR Ensembl; ENST00000648068.1; ENSP00000498112.1; ENSG00000006530.18. [Q53H12-1]
DR Ensembl; ENST00000649286.2; ENSP00000497280.1; ENSG00000006530.18. [Q53H12-1]
DR Ensembl; ENST00000650547.1; ENSP00000496789.1; ENSG00000006530.18. [Q53H12-1]
DR GeneID; 55750; -.
DR KEGG; hsa:55750; -.
DR MANE-Select; ENST00000649286.2; ENSP00000497280.1; NM_018238.4; NP_060708.1.
DR UCSC; uc003vwi.3; human. [Q53H12-1]
DR CTD; 55750; -.
DR DisGeNET; 55750; -.
DR GeneCards; AGK; -.
DR HGNC; HGNC:21869; AGK.
DR HPA; ENSG00000006530; Low tissue specificity.
DR MalaCards; AGK; -.
DR MIM; 212350; phenotype.
DR MIM; 610345; gene.
DR MIM; 614691; phenotype.
DR neXtProt; NX_Q53H12; -.
DR OpenTargets; ENSG00000006530; -.
DR Orphanet; 1369; Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA162375851; -.
DR VEuPathDB; HostDB:ENSG00000006530; -.
DR eggNOG; KOG4435; Eukaryota.
DR GeneTree; ENSGT00940000154961; -.
DR HOGENOM; CLU_042458_0_0_1; -.
DR InParanoid; Q53H12; -.
DR OMA; FFCDPRR; -.
DR OrthoDB; 1312024at2759; -.
DR PhylomeDB; Q53H12; -.
DR TreeFam; TF320485; -.
DR BRENDA; 2.7.1.94; 2681.
DR PathwayCommons; Q53H12; -.
DR Reactome; R-HSA-1483206; Glycerophospholipid biosynthesis.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR SABIO-RK; Q53H12; -.
DR SignaLink; Q53H12; -.
DR SIGNOR; Q53H12; -.
DR UniPathway; UPA00230; -.
DR BioGRID-ORCS; 55750; 26 hits in 1088 CRISPR screens.
DR ChiTaRS; AGK; human.
DR GeneWiki; AGK_(gene); -.
DR GenomeRNAi; 55750; -.
DR Pharos; Q53H12; Tbio.
DR PRO; PR:Q53H12; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q53H12; protein.
DR Bgee; ENSG00000006530; Expressed in adrenal tissue and 92 other tissues.
DR ExpressionAtlas; Q53H12; baseline and differential.
DR Genevisible; Q53H12; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031305; C:integral component of mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0042721; C:TIM22 mitochondrial import inner membrane insertion complex; IDA:UniProtKB.
DR GO; GO:0047620; F:acylglycerol kinase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0001729; F:ceramide kinase activity; IBA:GO_Central.
DR GO; GO:0004143; F:diacylglycerol kinase activity; IDA:UniProtKB.
DR GO; GO:0102773; F:dihydroceramide kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0001727; F:lipid kinase activity; IBA:GO_Central.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0046486; P:glycerolipid metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0006665; P:sphingolipid metabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR045579; AGK_C.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR Pfam; PF19712; AGK_C; 1.
DR Pfam; PF00781; DAGK_cat; 1.
DR SMART; SM00046; DAGKc; 1.
DR SUPFAM; SSF111331; SSF111331; 1.
DR PROSITE; PS50146; DAGK; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cardiomyopathy; Cataract; Disease variant; Kinase; Lipid metabolism;
KW Membrane; Mitochondrion; Mitochondrion inner membrane; Nucleotide-binding;
KW Primary mitochondrial disease; Reference proteome; Transferase.
FT CHAIN 1..422
FT /note="Acylglycerol kinase, mitochondrial"
FT /id="PRO_0000252380"
FT DOMAIN 58..199
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REGION 15..31
FT /note="Hydrophobic"
FT /evidence="ECO:0000305"
FT REGION 249..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 6
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 48..65
FT /note="VFGNQLIPPNAQVKKATV -> HYQDESRWEPTLSRTPGS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020925"
FT VAR_SEQ 66..422
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020926"
FT VARIANT 3
FT /note="V -> M (in dbSNP:rs10262855)"
FT /id="VAR_027848"
FT VARIANT 137..422
FT /note="Missing (in MTDPS10)"
FT /evidence="ECO:0000269|PubMed:25208612"
FT /id="VAR_079050"
FT VARIANT 291..422
FT /note="Missing (in MTDPS10)"
FT /evidence="ECO:0000269|PubMed:25208612"
FT /id="VAR_079051"
FT VARIANT 327..422
FT /note="Missing (in MTDPS10)"
FT /evidence="ECO:0000269|PubMed:23266196"
FT /id="VAR_079052"
FT MUTAGEN 126
FT /note="G->E: Abolishes lipid kinase activity. Does not
FT affect ability to associate with the TIM22 complex and
FT mediate import of transmembrane proteins into the
FT mitochondrial inner membrane."
FT /evidence="ECO:0000269|PubMed:15939762,
FT ECO:0000269|PubMed:28712724, ECO:0000269|PubMed:28712726"
FT CONFLICT 94
FT /note="D -> V (in Ref. 3; BAD96489)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 422 AA; 47137 MW; F9D85658616B8970 CRC64;
MTVFFKTLRN HWKKTTAGLC LLTWGGHWLY GKHCDNLLRR AACQEAQVFG NQLIPPNAQV
KKATVFLNPA ACKGKARTLF EKNAAPILHL SGMDVTIVKT DYEGQAKKLL ELMENTDVII
VAGGDGTLQE VVTGVLRRTD EATFSKIPIG FIPLGETSSL SHTLFAESGN KVQHITDATL
AIVKGETVPL DVLQIKGEKE QPVFAMTGLR WGSFRDAGVK VSKYWYLGPL KIKAAHFFST
LKEWPQTHQA SISYTGPTER PPNEPEETPV QRPSLYRRIL RRLASYWAQP QDALSQEVSP
EVWKDVQLST IELSITTRNN QLDPTSKEDF LNICIEPDTI SKGDFITIGS RKVRNPKLHV
EGTECLQASQ CTLLIPEGAG GSFSIDSEEY EAMPVEVKLL PRKLQFFCDP RKREQMLTSP
TQ
