CERK1_HUMAN
ID CERK1_HUMAN Reviewed; 537 AA.
AC Q8TCT0; A0JNT4; A8K611; Q6NX59; Q9BYB3; Q9UGE5;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Ceramide kinase;
DE Short=hCERK;
DE EC=2.7.1.138 {ECO:0000269|PubMed:11956206, ECO:0000269|PubMed:16269826, ECO:0000269|PubMed:19168031};
DE AltName: Full=Acylsphingosine kinase;
DE AltName: Full=Lipid kinase 4;
DE Short=LK4;
GN Name=CERK; Synonyms=KIAA1646;
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), FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE SPECIFICITY.
RC TISSUE=Leukemia;
RX PubMed=11956206; DOI=10.1074/jbc.m201535200;
RA Sugiura M., Kono K., Liu H., Shimizugawa T., Minekura H., Spiegel S.,
RA Kohama T.;
RT "Ceramide kinase, a novel lipid kinase. Molecular cloning and functional
RT characterization.";
RL J. Biol. Chem. 277:23294-23300(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, ACTIVITY
RP REGULATION, AND REGION ESSENTIAL FOR ENZYME ACTIVITY.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=PNS;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 57-537 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11258795; DOI=10.1093/dnares/8.1.1;
RA Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.;
RT "Identification of novel transcribed sequences on human chromosome 22 by
RT expressed sequence tag mapping.";
RL DNA Res. 8:1-9(2001).
RN [9]
RP MUTAGENESIS OF LEU-10.
RX PubMed=16081073; DOI=10.1016/j.febslet.2005.06.079;
RA Kim T.J., Mitsutake S., Kato M., Igarashi Y.;
RT "The leucine 10 residue in the pleckstrin homology domain of ceramide
RT kinase is crucial for its catalytic activity.";
RL FEBS Lett. 579:4383-4388(2005).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP AND REGION REQUIRED FOR BINDING TO SULFATIDE AND PHOSPHOINOSITIDES.
RX PubMed=19168031; DOI=10.1016/j.bbrc.2009.01.075;
RA Don A.S., Rosen H.;
RT "A lipid binding domain in sphingosine kinase 2.";
RL Biochem. Biophys. Res. Commun. 380:87-92(2009).
RN [11]
RP PHOSPHORYLATION AT SER-340 AND SER-408, AND MUTAGENESIS OF SER-340.
RX PubMed=19899769; DOI=10.1021/pr900763z;
RA Chen W.Q., Graf C., Zimmel D., Rovina P., Krapfenbauer K., Jaritz M.,
RA Parker P.J., Lubec G., Bornancin F.;
RT "Ceramide kinase profiling by mass spectrometry reveals a conserved
RT phosphorylation pattern downstream of the catalytic site.";
RL J. Proteome Res. 9:420-429(2010).
RN [12]
RP COFACTOR, AND ACTIVITY REGULATION.
RX PubMed=27725450; DOI=10.1248/bpb.b16-00535;
RA Matsuzaki W., Takahashi H., Nakamura H., Murayama T.;
RT "Effects of glycerophospholipids on ceramide kinase activity: cardiolipin-
RT affected cellular formation of ceramide-1-phosphate.";
RL Biol. Pharm. Bull. 39:1708-1717(2016).
CC -!- FUNCTION: Catalyzes specifically the phosphorylation of ceramide to
CC form ceramide 1-phosphate (PubMed:11956206, PubMed:16269826,
CC PubMed:19168031). Acts efficiently on natural and analog ceramides (C6,
CC C8, C16 ceramides, and C8-dihydroceramide), to a lesser extent on C2-
CC ceramide and C6-dihydroceramide, but not on other lipids, such as
CC various sphingosines (PubMed:11956206, PubMed:16269826,
CC PubMed:19168031). Shows a greater preference for D-erythro isomer of
CC ceramides (PubMed:16269826). Binds phosphoinositides (PubMed:19168031).
CC {ECO:0000269|PubMed:11956206, ECO:0000269|PubMed:16269826,
CC ECO:0000269|PubMed:19168031}.
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:0000269|PubMed:11956206, ECO:0000269|PubMed:16269826,
CC ECO:0000269|PubMed:19168031};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17930;
CC Evidence={ECO:0000305|PubMed:11956206, ECO:0000305|PubMed:16269826,
CC ECO:0000305|PubMed:19168031};
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:16269826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43313;
CC Evidence={ECO:0000305|PubMed:16269826};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N-(acetyl)-sphing-4-enine = ADP + H(+) + N-(acetyl)-
CC sphing-4-enine-1-phosphate; Xref=Rhea:RHEA:47904, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:46979, ChEBI:CHEBI:85375,
CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:16269826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47905;
CC Evidence={ECO:0000305|PubMed:16269826};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N-hexadecanoylsphing-4-enine = ADP + H(+) + N-
CC (hexadecanoyl)-sphing-4-enine-1-phosphate; Xref=Rhea:RHEA:46340,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:72959,
CC ChEBI:CHEBI:72963, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16269826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46341;
CC Evidence={ECO:0000305|PubMed:16269826};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + N-hexanoyl-(4R)-hydroxysphinganine = ADP + H(+) + N-
CC hexanoyl-(4R)-hydroxysphinganine-1-phosphate; Xref=Rhea:RHEA:47916,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:88095,
CC ChEBI:CHEBI:88096, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:16269826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47917;
CC Evidence={ECO:0000305|PubMed:16269826};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:16269826, ECO:0000269|PubMed:27725450};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:16269826, ECO:0000269|PubMed:27725450};
CC -!- ACTIVITY REGULATION: Inhibited by sulfatide (PubMed:19168031).
CC Inhibited by sphinganine, sphingenine, and N,N-Dimethylsphingosine
CC (DMS) (PubMed:16269826). Cardiolipin at 0.1 uM significantly increases
CC activity, whereas at concentrations >1 uM has an inhibitory effect
CC (PubMed:27725450). {ECO:0000269|PubMed:16269826,
CC ECO:0000269|PubMed:19168031, ECO:0000269|PubMed:27725450}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=187 uM for C8 ceramide {ECO:0000269|PubMed:11956206};
CC KM=30 uM for C6 ceramide {ECO:0000269|PubMed:16269826};
CC KM=22 uM for C2 ceramide {ECO:0000269|PubMed:16269826};
CC KM=400 uM for ATP (in the presence of 3 mM Mg(2+))
CC {ECO:0000269|PubMed:16269826};
CC KM=32 uM for ATP {ECO:0000269|PubMed:11956206};
CC Vmax=35 nmol/min/mg enzyme for C6 ceramide
CC {ECO:0000269|PubMed:16269826};
CC pH dependence:
CC Optimum pH is 6.0-7.8. {ECO:0000269|PubMed:11956206,
CC ECO:0000269|PubMed:16269826};
CC -!- INTERACTION:
CC Q8TCT0; P13196: ALAS1; NbExp=3; IntAct=EBI-10274247, EBI-3905054;
CC Q8TCT0; P05813: CRYBA1; NbExp=3; IntAct=EBI-10274247, EBI-7043337;
CC Q8TCT0; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10274247, EBI-3867333;
CC Q8TCT0; O76011: KRT34; NbExp=3; IntAct=EBI-10274247, EBI-1047093;
CC Q8TCT0; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-10274247, EBI-11959885;
CC Q8TCT0; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-10274247, EBI-1052037;
CC Q8TCT0; Q8IUB9: KRTAP19-1; NbExp=3; IntAct=EBI-10274247, EBI-12811111;
CC Q8TCT0; Q3LI70: KRTAP19-6; NbExp=3; IntAct=EBI-10274247, EBI-12805508;
CC Q8TCT0; Q9BYR8: KRTAP3-1; NbExp=3; IntAct=EBI-10274247, EBI-9996449;
CC Q8TCT0; Q9BYR7: KRTAP3-2; NbExp=3; IntAct=EBI-10274247, EBI-751260;
CC Q8TCT0; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-10274247, EBI-11962084;
CC Q8TCT0; Q9BYQ4: KRTAP9-2; NbExp=3; IntAct=EBI-10274247, EBI-1044640;
CC Q8TCT0; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-10274247, EBI-742948;
CC Q8TCT0; P0CG21: NHLRC4; NbExp=3; IntAct=EBI-10274247, EBI-12868744;
CC Q8TCT0; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-10274247, EBI-945833;
CC Q8TCT0; P0DPK4: NOTCH2NLC; NbExp=3; IntAct=EBI-10274247, EBI-22310682;
CC Q8TCT0; O43482: OIP5; NbExp=3; IntAct=EBI-10274247, EBI-536879;
CC Q8TCT0; Q9H8W4: PLEKHF2; NbExp=3; IntAct=EBI-10274247, EBI-742388;
CC Q8TCT0; Q8IWZ5: TRIM42; NbExp=3; IntAct=EBI-10274247, EBI-5235829;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19168031}. Cell
CC membrane {ECO:0000269|PubMed:16269826, ECO:0000269|PubMed:19168031};
CC Peripheral membrane protein {ECO:0000269|PubMed:19168031}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TCT0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TCT0-2; Sequence=VSP_056944;
CC -!- TISSUE SPECIFICITY: High level expression in heart, brain, skeletal
CC muscle, kidney and liver; moderate in peripheral blood leukocytes and
CC thymus; very low in spleen, small intestine, placenta and lung.
CC {ECO:0000269|PubMed:11956206}.
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; AB079066; BAC01154.1; -; mRNA.
DR EMBL; AJ457828; CAD29884.1; -; mRNA.
DR EMBL; CR456404; CAG30290.1; -; mRNA.
DR EMBL; AK291476; BAF84165.1; -; mRNA.
DR EMBL; AL096766; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL118516; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471138; EAW73440.1; -; Genomic_DNA.
DR EMBL; CH471138; EAW73442.1; -; Genomic_DNA.
DR EMBL; BC067255; AAH67255.1; -; mRNA.
DR EMBL; BC126940; AAI26941.1; -; mRNA.
DR EMBL; AB051433; BAB33316.1; -; mRNA.
DR CCDS; CCDS14077.1; -. [Q8TCT0-1]
DR RefSeq; NP_073603.2; NM_022766.5. [Q8TCT0-1]
DR AlphaFoldDB; Q8TCT0; -.
DR SMR; Q8TCT0; -.
DR BioGRID; 122291; 88.
DR IntAct; Q8TCT0; 60.
DR STRING; 9606.ENSP00000216264; -.
DR BindingDB; Q8TCT0; -.
DR ChEMBL; CHEMBL1764936; -.
DR GuidetoPHARMACOLOGY; 2473; -.
DR SwissLipids; SLP:000001354; -.
DR iPTMnet; Q8TCT0; -.
DR PhosphoSitePlus; Q8TCT0; -.
DR BioMuta; CERK; -.
DR DMDM; 30172885; -.
DR EPD; Q8TCT0; -.
DR jPOST; Q8TCT0; -.
DR MassIVE; Q8TCT0; -.
DR MaxQB; Q8TCT0; -.
DR PaxDb; Q8TCT0; -.
DR PeptideAtlas; Q8TCT0; -.
DR PRIDE; Q8TCT0; -.
DR ProteomicsDB; 66749; -.
DR ProteomicsDB; 74154; -. [Q8TCT0-1]
DR Antibodypedia; 326; 325 antibodies from 29 providers.
DR DNASU; 64781; -.
DR Ensembl; ENST00000216264.13; ENSP00000216264.8; ENSG00000100422.14. [Q8TCT0-1]
DR GeneID; 64781; -.
DR KEGG; hsa:64781; -.
DR MANE-Select; ENST00000216264.13; ENSP00000216264.8; NM_022766.6; NP_073603.2.
DR UCSC; uc003bia.4; human. [Q8TCT0-1]
DR CTD; 64781; -.
DR DisGeNET; 64781; -.
DR GeneCards; CERK; -.
DR HGNC; HGNC:19256; CERK.
DR HPA; ENSG00000100422; Low tissue specificity.
DR MIM; 610307; gene.
DR neXtProt; NX_Q8TCT0; -.
DR OpenTargets; ENSG00000100422; -.
DR PharmGKB; PA134958321; -.
DR VEuPathDB; HostDB:ENSG00000100422; -.
DR eggNOG; KOG1115; Eukaryota.
DR GeneTree; ENSGT00940000156976; -.
DR HOGENOM; CLU_013399_2_2_1; -.
DR InParanoid; Q8TCT0; -.
DR OMA; HHKTTAF; -.
DR PhylomeDB; Q8TCT0; -.
DR TreeFam; TF314514; -.
DR BRENDA; 2.7.1.138; 2681.
DR PathwayCommons; Q8TCT0; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SABIO-RK; Q8TCT0; -.
DR SignaLink; Q8TCT0; -.
DR SIGNOR; Q8TCT0; -.
DR BioGRID-ORCS; 64781; 9 hits in 1088 CRISPR screens.
DR ChiTaRS; CERK; human.
DR GeneWiki; CERK; -.
DR GenomeRNAi; 64781; -.
DR Pharos; Q8TCT0; Tchem.
DR PRO; PR:Q8TCT0; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; Q8TCT0; protein.
DR Bgee; ENSG00000100422; Expressed in islet of Langerhans and 185 other tissues.
DR ExpressionAtlas; Q8TCT0; baseline and differential.
DR Genevisible; Q8TCT0; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0001729; F:ceramide 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:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0003951; F:NAD+ kinase activity; IEA:InterPro.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:UniProtKB.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR GO; GO:0006665; P:sphingolipid metabolic process; IBA:GO_Central.
DR Gene3D; 3.40.50.10330; -; 1.
DR InterPro; IPR017438; ATP-NAD_kinase_N.
DR InterPro; IPR045363; CERK_C.
DR InterPro; IPR001206; Diacylglycerol_kinase_cat_dom.
DR InterPro; IPR016064; NAD/diacylglycerol_kinase_sf.
DR Pfam; PF19280; CERK_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 Alternative splicing; ATP-binding; Calcium; Cell membrane; Cytoplasm;
KW Kinase; Lipid metabolism; Magnesium; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..537
FT /note="Ceramide kinase"
FT /id="PRO_0000181354"
FT DOMAIN 128..278
FT /note="DAGKc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT REGION 1..125
FT /note="Required for binding to sulfatide and
FT phosphoinositides"
FT /evidence="ECO:0000269|PubMed:19168031"
FT REGION 1..115
FT /note="Essential for enzyme activity"
FT /evidence="ECO:0000269|PubMed:16269826"
FT ACT_SITE 197
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 138..140
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 170..174
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 195..198
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9NYA1"
FT BINDING 202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 239..241
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 310
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT BINDING 502..504
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00783"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19899769"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19899769"
FT VAR_SEQ 1..198
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056944"
FT VARIANT 191
FT /note="I -> V (in dbSNP:rs16995615)"
FT /id="VAR_053685"
FT VARIANT 211
FT /note="T -> M (in dbSNP:rs9306515)"
FT /id="VAR_053686"
FT VARIANT 306
FT /note="L -> F (in dbSNP:rs13057352)"
FT /id="VAR_053687"
FT MUTAGEN 10
FT /note="L->A: 99% decrease in catalytic activity but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:16081073"
FT MUTAGEN 10
FT /note="L->I: 71% decrease in catalytic activity but no
FT effect on substrate affinity."
FT /evidence="ECO:0000269|PubMed:16081073"
FT MUTAGEN 340
FT /note="S->A: 15% decrease in catalytic activity and
FT decreased stability."
FT /evidence="ECO:0000269|PubMed:19899769"
SQ SEQUENCE 537 AA; 59977 MW; 3DBFC0ED8D679F7F CRC64;
MGATGAAEPL QSVLWVKQQR CAVSLEPARA LLRWWRSPGP GAGAPGADAC SVPVSEIIAV
EETDVHGKHQ GSGKWQKMEK PYAFTVHCVK RARRHRWKWA QVTFWCPEEQ LCHLWLQTLR
EMLEKLTSRP KHLLVFINPF GGKGQGKRIY ERKVAPLFTL ASITTDIIVT EHANQAKETL
YEINIDKYDG IVCVGGDGMF SEVLHGLIGR TQRSAGVDQN HPRAVLVPSS LRIGIIPAGS
TDCVCYSTVG TSDAETSALH IVVGDSLAMD VSSVHHNSTL LRYSVSLLGY GFYGDIIKDS
EKKRWLGLAR YDFSGLKTFL SHHCYEGTVS FLPAQHTVGS PRDRKPCRAG CFVCRQSKQQ
LEEEQKKALY GLEAAEDVEE WQVVCGKFLA INATNMSCAC RRSPRGLSPA AHLGDGSSDL
ILIRKCSRFN FLRFLIRHTN QQDQFDFTFV EVYRVKKFQF TSKHMEDEDS DLKEGGKKRF
GHICSSHPSC CCTVSNSSWN CDGEVLHSPA IEVRVHCQLV RLFARGIEEN PKPDSHS
