NNRD_MOUSE
ID NNRD_MOUSE Reviewed; 343 AA.
AC Q9CZ42; Q9CQX9; Q9D7G7; Q9DC93;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=ATP-dependent (S)-NAD(P)H-hydrate dehydratase {ECO:0000255|HAMAP-Rule:MF_03157};
DE EC=4.2.1.93 {ECO:0000255|HAMAP-Rule:MF_03157, ECO:0000269|PubMed:21994945};
DE AltName: Full=ATP-dependent NAD(P)HX dehydratase {ECO:0000255|HAMAP-Rule:MF_03157};
DE AltName: Full=Carbohydrate kinase domain-containing protein {ECO:0000255|HAMAP-Rule:MF_03157};
DE AltName: Full=NAD(P)HX dehydratase {ECO:0000250|UniProtKB:Q8IW45};
DE Flags: Precursor;
GN Name=Naxd {ECO:0000250|UniProtKB:Q8IW45}; Synonyms=Carkd;
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 [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Brain, and Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-81, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [4]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=18614015; DOI=10.1016/j.cell.2008.06.016;
RA Pagliarini D.J., Calvo S.E., Chang B., Sheth S.A., Vafai S.B., Ong S.E.,
RA Walford G.A., Sugiana C., Boneh A., Chen W.K., Hill D.E., Vidal M.,
RA Evans J.G., Thorburn D.R., Carr S.A., Mootha V.K.;
RT "A mitochondrial protein compendium elucidates complex I disease biology.";
RL Cell 134:112-123(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-81, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-216, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21994945; DOI=10.1074/jbc.c111.310847;
RA Marbaix A.Y., Noel G., Detroux A.M., Vertommen D., Van Schaftingen E.,
RA Linster C.L.;
RT "Extremely conserved ATP- or ADP-dependent enzymatic system for
RT nicotinamide nucleotide repair.";
RL J. Biol. Chem. 286:41246-41252(2011).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-63, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Catalyzes the dehydration of the S-form of NAD(P)HX at the
CC expense of ATP, which is converted to ADP. Together with NAD(P)HX
CC epimerase, which catalyzes the epimerization of the S- and R-forms, the
CC enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of
CC NAD(P)H that is a result of enzymatic or heat-dependent hydration.
CC {ECO:0000255|HAMAP-Rule:MF_03157, ECO:0000269|PubMed:21994945}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-NADHX + ATP = ADP + H(+) + NADH + phosphate;
CC Xref=Rhea:RHEA:19017, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57945, ChEBI:CHEBI:64074,
CC ChEBI:CHEBI:456216; EC=4.2.1.93; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03157, ECO:0000269|PubMed:21994945};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6S)-NADPHX + ATP = ADP + H(+) + NADPH + phosphate;
CC Xref=Rhea:RHEA:32231, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57783, ChEBI:CHEBI:64076,
CC ChEBI:CHEBI:456216; EC=4.2.1.93;
CC Evidence={ECO:0000269|PubMed:21994945};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03157};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.8 uM for (S)-NADHX {ECO:0000269|PubMed:21994945};
CC KM=2.5 uM for (S)-NADPHX {ECO:0000269|PubMed:21994945};
CC KM=1.8 uM for ATP {ECO:0000269|PubMed:21994945};
CC Vmax=0.43 umol/min/mg enzyme toward (S)-NADHX
CC {ECO:0000269|PubMed:21994945};
CC Vmax=1.6 umol/min/mg enzyme toward (S)-NADPHX
CC {ECO:0000269|PubMed:21994945};
CC Vmax=0.26 umol/min/mg enzyme toward ATP
CC {ECO:0000269|PubMed:21994945};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03157,
CC ECO:0000269|PubMed:18614015}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9CZ42-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9CZ42-2; Sequence=VSP_033831;
CC Name=3;
CC IsoId=Q9CZ42-3; Sequence=VSP_033832;
CC -!- SIMILARITY: Belongs to the NnrD/CARKD family. {ECO:0000255|HAMAP-
CC Rule:MF_03157}.
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; AK003048; BAB22531.1; -; mRNA.
DR EMBL; AK009254; BAB26172.1; -; mRNA.
DR EMBL; AK012456; BAB28251.1; -; mRNA.
DR EMBL; AK013028; BAB28607.1; -; mRNA.
DR EMBL; AK013069; BAB28632.1; -; mRNA.
DR EMBL; AK013420; BAB28847.1; -; mRNA.
DR EMBL; AK154142; BAE32403.1; -; mRNA.
DR EMBL; AK171034; BAE42200.1; -; mRNA.
DR EMBL; BC019538; AAH19538.1; -; mRNA.
DR EMBL; BC021955; AAH21955.1; -; mRNA.
DR CCDS; CCDS57604.1; -. [Q9CZ42-3]
DR RefSeq; NP_001177286.1; NM_001190357.1.
DR RefSeq; NP_081271.2; NM_026995.4.
DR AlphaFoldDB; Q9CZ42; -.
DR SMR; Q9CZ42; -.
DR BioGRID; 213302; 8.
DR IntAct; Q9CZ42; 1.
DR MINT; Q9CZ42; -.
DR STRING; 10090.ENSMUSP00000033901; -.
DR GlyConnect; 2143; 2 N-Linked glycans (1 site).
DR GlyGen; Q9CZ42; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q9CZ42; -.
DR PhosphoSitePlus; Q9CZ42; -.
DR SwissPalm; Q9CZ42; -.
DR EPD; Q9CZ42; -.
DR jPOST; Q9CZ42; -.
DR MaxQB; Q9CZ42; -.
DR PaxDb; Q9CZ42; -.
DR PeptideAtlas; Q9CZ42; -.
DR PRIDE; Q9CZ42; -.
DR ProteomicsDB; 252976; -. [Q9CZ42-1]
DR ProteomicsDB; 252977; -. [Q9CZ42-2]
DR ProteomicsDB; 252978; -. [Q9CZ42-3]
DR GeneID; 69225; -.
DR KEGG; mmu:69225; -.
DR CTD; 55739; -.
DR MGI; MGI:1913353; Naxd.
DR eggNOG; KOG3974; Eukaryota.
DR InParanoid; Q9CZ42; -.
DR OrthoDB; 1337331at2759; -.
DR PhylomeDB; Q9CZ42; -.
DR BRENDA; 4.2.1.93; 3474.
DR Reactome; R-MMU-197264; Nicotinamide salvaging.
DR SABIO-RK; Q9CZ42; -.
DR BioGRID-ORCS; 69225; 5 hits in 71 CRISPR screens.
DR ChiTaRS; Carkd; mouse.
DR PRO; PR:Q9CZ42; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9CZ42; protein.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0052855; F:ADP-dependent NAD(P)H-hydrate dehydratase activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0047453; F:ATP-dependent NAD(P)H-hydrate dehydratase activity; ISO:MGI.
DR GO; GO:0110051; P:metabolite repair; IBA:GO_Central.
DR GO; GO:0046496; P:nicotinamide nucleotide metabolic process; IEA:UniProtKB-UniRule.
DR CDD; cd01171; YXKO-related; 1.
DR Gene3D; 3.40.1190.20; -; 1.
DR HAMAP; MF_01965; NADHX_dehydratase; 1.
DR InterPro; IPR000631; CARKD.
DR InterPro; IPR029056; Ribokinase-like.
DR Pfam; PF01256; Carb_kinase; 1.
DR SUPFAM; SSF53613; SSF53613; 1.
DR TIGRFAMs; TIGR00196; yjeF_cterm; 1.
DR PROSITE; PS51383; YJEF_C_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Lyase; Mitochondrion; NAD;
KW NADP; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..42
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT CHAIN 43..343
FT /note="ATP-dependent (S)-NAD(P)H-hydrate dehydratase"
FT /id="PRO_0000337022"
FT DOMAIN 49..340
FT /note="YjeF C-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT BINDING 149
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT BINDING 202..208
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT BINDING 242..246
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT BINDING 261..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT BINDING 271
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03157"
FT MOD_RES 63
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 81
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 216
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..45
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_033831"
FT VAR_SEQ 1..29
FT /note="MAVHACGAAAAVVALLSAAIALQWSPLYA -> MGFRCVAIRACGG (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_033832"
FT CONFLICT 203
FT /note="H -> N (in Ref. 1; BAB22531)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 36717 MW; D0202FE6716F80D5 CRC64;
MAVHACGAAA AVVALLSAAI ALQWSPLYAV LQRALSLHTA HATKDMENLF QLVRNIVPAL
TSKKHKGQDG RIGIVGGCQE YTGAPYFAGI SALKVGADLT HVFCAREAAP VIKSYSPELI
VHPVLDSSNA VEEVEKWLPR LHALVVGPGL GRDDLLLNNV RGILESTKAR DIPVVIDADG
LWLVAQQPAL IHSYHKAILT PNHVEFSRLW EAVLSSPMDS NDLKGSTLKL SQALGNITVV
QKGEQDLISN GQQVLVCNQE GSSRRCGGQG DLLSGSLGVM VHWALRAGPE KTNGSSPLLV
AAWGACTLTR ECNRQAFQKY GRSTTTTDMI TEVGTAFSRL FTT
