ID CERK1_MOUSE Reviewed; 531 AA.
AC Q8K4Q7; Q52KP2;
DT 23-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 24-JAN-2024, entry version 152.
DE RecName: Full=Ceramide kinase;
DE Short=mCERK;
DE EC=2.7.1.138 {ECO:0000269|PubMed:16269826};
DE AltName: Full=Acylsphingosine kinase;
GN Name=Cerk;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Brain;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Heart, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
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).
CC -!- FUNCTION: Catalyzes specifically the phosphorylation of ceramide to
CC form ceramide 1-phosphate (PubMed:16269826). Acts efficiently on
CC natural and analog ceramides (C6, C8, C16 ceramides, and C8-
CC dihydroceramide), to a lesser extent on C2-ceramide and C6-
CC dihydroceramide, but not on other lipids, such as various sphingosines
CC (PubMed:16269826). Shows a greater preference for D-erythro isomer of
CC ceramides (By similarity). Binds phosphoinositides (By similarity).
CC {ECO:0000250|UniProtKB:Q8TCT0, ECO:0000269|PubMed:16269826}.
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:16269826};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17930;
CC Evidence={ECO:0000305|PubMed:16269826};
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:0000250|UniProtKB:Q8TCT0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43313;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
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:0000250|UniProtKB:Q8TCT0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47905;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
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:0000250|UniProtKB:Q8TCT0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46341;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
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:0000250|UniProtKB:Q8TCT0};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47917;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8TCT0};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q8TCT0}. Cell
CC membrane {ECO:0000250|UniProtKB:Q8TCT0}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8TCT0}.
CC -!- TISSUE SPECIFICITY: High level expression in heart, brain, testis and
CC pancreas; low expression in spleen, liver and lung; not detected in
CC skeletal muscle. {ECO:0000269|PubMed:11956206,
CC ECO:0000269|PubMed:16269826}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed at 7 dpc and decreases rapidly
CC thereafter. {ECO:0000269|PubMed:11956206}.
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DR EMBL; AB079067; BAC01155.1; -; mRNA.
DR EMBL; AK042077; BAC31157.1; -; mRNA.
DR EMBL; AK052269; BAC34908.1; -; mRNA.
DR EMBL; AK169528; BAE41212.1; -; mRNA.
DR EMBL; BC094253; AAH94253.1; -; mRNA.
DR CCDS; CCDS27728.1; -.
DR RefSeq; NP_663450.3; NM_145475.4.
DR AlphaFoldDB; Q8K4Q7; -.
DR SMR; Q8K4Q7; -.
DR BioGRID; 230189; 2.
DR STRING; 10090.ENSMUSP00000038203; -.
DR PhosphoSitePlus; Q8K4Q7; -.
DR SwissPalm; Q8K4Q7; -.
DR MaxQB; Q8K4Q7; -.
DR PaxDb; 10090-ENSMUSP00000038203; -.
DR ProteomicsDB; 281382; -.
DR Antibodypedia; 326; 355 antibodies from 30 providers.
DR DNASU; 223753; -.
DR Ensembl; ENSMUST00000044332.16; ENSMUSP00000038203.10; ENSMUSG00000035891.17.
DR GeneID; 223753; -.
DR KEGG; mmu:223753; -.
DR UCSC; uc007xdx.2; mouse.
DR AGR; MGI:2386052; -.
DR CTD; 64781; -.
DR MGI; MGI:2386052; Cerk.
DR VEuPathDB; HostDB:ENSMUSG00000035891; -.
DR eggNOG; KOG1115; Eukaryota.
DR GeneTree; ENSGT00940000156976; -.
DR HOGENOM; CLU_013399_2_2_1; -.
DR InParanoid; Q8K4Q7; -.
DR OMA; GSQTYER; -.
DR OrthoDB; 7645at2759; -.
DR PhylomeDB; Q8K4Q7; -.
DR TreeFam; TF314514; -.
DR BRENDA; 2.7.1.138; 3474.
DR Reactome; R-MMU-9840309; Glycosphingolipid biosynthesis.
DR BioGRID-ORCS; 223753; 3 hits in 79 CRISPR screens.
DR ChiTaRS; Cerk; mouse.
DR PRO; PR:Q8K4Q7; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K4Q7; Protein.
DR Bgee; ENSMUSG00000035891; Expressed in cerebellum lobe and 223 other cell types or tissues.
DR ExpressionAtlas; Q8K4Q7; baseline and differential.
DR Genevisible; Q8K4Q7; MM.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS: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:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0006672; P:ceramide metabolic process; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IBA:GO_Central.
DR Gene3D; 2.60.200.40; -; 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 PANTHER; PTHR12358:SF25; CERAMIDE KINASE; 1.
DR PANTHER; PTHR12358; SPHINGOSINE KINASE; 1.
DR Pfam; PF19280; CERK_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 ATP-binding; Calcium; Cell membrane; Cytoplasm; Kinase; Lipid metabolism;
KW Magnesium; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..531
FT /note="Ceramide kinase"
FT /id="PRO_0000181355"
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:0000250|UniProtKB:Q8TCT0"
FT REGION 1..115
FT /note="Essential for enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT0"
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:0000250|UniProtKB:Q8TCT0"
FT MOD_RES 408
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8TCT0"
FT CONFLICT 378
FT /note="M -> V (in Ref. 1; BAC01155)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="D -> Y (in Ref. 2; BAC34908)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 531 AA; 59843 MW; C5A030D422E3AA10 CRC64;
MGAMGAAEPL HSVLWVKRRR CAVSLEPARA LLRWWRSPEP GPSAPGADAR SVLVSEIIAV
EEKDDCEKHA SSGRWHKMEN PFAFTVHRVK RVRHHRWKWA RVTFWSADEQ LCHLWLQTLR
GLLESLTSRP KHLLVFINPF GGKGQGKRIY EKTVAPLFTL ASITTEIIIT EHANQAKETL
YEINTDSYDG IVCVGGDGMF SEVLHGVIGR TQQSAGIDPN HPRAVLVPST LRIGIIPAGS
TDCVCYSTVG TNDAETSALH IIIGDSLAID VSSVHYHNTL LRYSVSLLGY GFYGDLIKDS
EKKRWMGLVR YDFSGLKTFL SHQYYEGTLS FLPAQHTVGS PRDNKPCRAG CFVCRQSKQQ
LEEEEKKALY GLENAEEMEE WQVTCGKFLA INATNMSCAC PRSPGGLSPF AHLGDGSSDL
ILIRKCSRFN FLRFLIRHTN QEDQFDFTFV EVYRVKKFHF TSKHVEDEDN DSKEQEKQKF
GKICKDRPSC TCSASRSSWN CDGEVMHSPA IEVRVHCQLV RLFARGIEEE S
//
