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 28-JAN-2026, entry version 167. 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 INTERACTION WITH SMIM26. RX PubMed=37009826; DOI=10.15252/embr.202256282; RA Meng K., Lu S., Li Y.Y., Hu L.L., Zhang J., Cao Y., Wang Y., Zhang C.Z., RA He Q.Y.; RT "LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in RT renal cell carcinoma."; RL EMBO Rep. 24:e56282-e56282(2023). RN [18] 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 [19] 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 = a monoacyl-sn-glycero-3-phosphate + CC ADP + H(+); 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 = an N-acylsphing-4-enine 1- CC phosphate + ADP + 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=a 2-acylglycerol + ATP = a 2-acyl-sn-glycerol 3-phosphate + CC ADP + H(+); Xref=Rhea:RHEA:39847, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17389, ChEBI:CHEBI:30616, ChEBI:CHEBI:64982, CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:15939762}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39848; 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=N-(hexanoyl)sphing-4-enine + ATP = N-hexanoylsphing-4-enine 1- CC phosphate + ADP + H(+); Xref=Rhea:RHEA:43312, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:63867, ChEBI:CHEBI:82959, CC ChEBI:CHEBI:456216; 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). Interacts with SMIM26 CC (PubMed:37009826). {ECO:0000269|PubMed:28712724, CC ECO:0000269|PubMed:28712726, ECO:0000269|PubMed:37009826}. CC -!- INTERACTION: CC Q53H12; P53701: HCCS; NbExp=4; IntAct=EBI-2269837, EBI-10763431; CC Q53H12; P42858: HTT; NbExp=3; IntAct=EBI-2269837, EBI-466029; CC Q53H12; A0A096LP01: SMIM26; NbExp=18; IntAct=EBI-2269837, EBI-50428917; 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_018238.4. [Q53H12-1] DR RefSeq; XP_011514699.1; XM_011516397.4. [Q53H12-1] DR RefSeq; XP_024302603.1; XM_024446835.2. [Q53H12-1] DR RefSeq; XP_054214618.1; XM_054358643.1. [Q53H12-1] DR RefSeq; XP_054214619.1; XM_054358644.1. [Q53H12-1] DR PDB; 7CGP; EM; 3.70 A; B=1-422. DR PDBsum; 7CGP; -. DR AlphaFoldDB; Q53H12; -. DR EMDB; EMD-9958; -. DR SMR; Q53H12; -. DR BioGRID; 120868; 159. DR ComplexPortal; CPX-6124; TIM22 mitochondrial inner membrane twin-pore carrier translocase complex. DR CORUM; Q53H12; -. DR FunCoup; Q53H12; 1820. DR IntAct; Q53H12; 90. DR MINT; Q53H12; -. DR STRING; 9606.ENSP00000497280; -. DR ChEMBL; CHEMBL2417354; -. DR SwissLipids; SLP:000000638; -. DR iPTMnet; Q53H12; -. DR PhosphoSitePlus; Q53H12; -. DR SwissPalm; Q53H12; -. DR BioMuta; AGK; -. DR DMDM; 116248550; -. DR jPOST; Q53H12; -. DR MassIVE; Q53H12; -. DR PaxDb; 9606-ENSP00000347581; -. DR PeptideAtlas; Q53H12; -. DR ProteomicsDB; 62491; -. [Q53H12-1] DR ProteomicsDB; 62492; -. [Q53H12-2] DR Pumba; Q53H12; -. DR Antibodypedia; 18305; 195 antibodies from 31 providers. DR DNASU; 55750; -. DR Ensembl; ENST00000492693.5; ENSP00000418789.1; ENSG00000006530.19. [Q53H12-2] DR Ensembl; ENST00000575872.2; ENSP00000458417.2; ENSG00000262327.7. DR Ensembl; ENST00000648068.1; ENSP00000498112.1; ENSG00000006530.19. [Q53H12-1] DR Ensembl; ENST00000649286.2; ENSP00000497280.1; ENSG00000006530.19. [Q53H12-1] DR Ensembl; ENST00000650547.1; ENSP00000496789.1; ENSG00000006530.19. [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 AGR; HGNC:21869; -. DR ClinPGx; PA162375851; -. 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 OpenTargets; ENSG00000006530; -. DR Orphanet; 1369; Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome. DR Orphanet; 98994; Total early-onset cataract. DR VEuPathDB; HostDB:ENSG00000006530; -. DR eggNOG; KOG4435; Eukaryota. DR GeneTree; ENSGT00940000154961; -. DR HOGENOM; CLU_042458_0_0_1; -. DR InParanoid; Q53H12; -. DR OMA; HWKKTTF; -. DR OrthoDB; 9979394at2759; -. DR PAN-GO; Q53H12; 8 GO annotations based on evolutionary models. DR PhylomeDB; Q53H12; -. 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 Agora; ENSG00000006530; -. DR BioGRID-ORCS; 55750; 26 hits in 1168 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. 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 94 other cell types or tissues. DR ExpressionAtlas; Q53H12; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0004143; F:ATP-dependent diacylglycerol kinase activity; IDA:UniProtKB. DR GO; GO:0001729; F:ceramide kinase activity; IBA:GO_Central. 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:0046834; P:lipid phosphorylation; IEA:Ensembl. DR GO; GO:0045039; P:protein insertion into mitochondrial inner membrane; IDA:UniProtKB. DR GO; GO:0046512; P:sphingosine biosynthetic process; IBA:GO_Central. DR FunFam; 3.40.50.10330:FF:000015; acylglycerol kinase, mitochondrial; 1. DR Gene3D; 3.40.50.10330; Probable inorganic polyphosphate/atp-NAD kinase, domain 1; 1. DR InterPro; IPR045579; AGK_C. DR InterPro; IPR017438; ATP-NAD_kinase_N. DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom. DR InterPro; IPR050187; Lipid_Phosphate_FormReg. DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf. DR PANTHER; PTHR12358:SF31; ACYLGLYCEROL KINASE, MITOCHONDRIAL; 1. DR PANTHER; PTHR12358; SPHINGOSINE KINASE; 1. DR Pfam; PF19712; AGK_C; 1. DR Pfam; PF00781; DAGK_cat; 1. DR SMART; SM00046; DAGKc; 1. DR SUPFAM; SSF111331; NAD kinase/diacylglycerol kinase-like; 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; Proteomics identification; KW 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 //