NNRE_MOUSE
ID NNRE_MOUSE Reviewed; 282 AA.
AC Q8K4Z3;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=NAD(P)H-hydrate epimerase {ECO:0000255|HAMAP-Rule:MF_03159};
DE EC=5.1.99.6;
DE AltName: Full=Apolipoprotein A-I-binding protein {ECO:0000255|HAMAP-Rule:MF_03159};
DE Short=AI-BP {ECO:0000255|HAMAP-Rule:MF_03159};
DE AltName: Full=NAD(P)HX epimerase {ECO:0000250|UniProtKB:Q8NCW5};
DE Flags: Precursor;
GN Name=Naxe {ECO:0000250|UniProtKB:Q8NCW5}; Synonyms=Aibp, Apoa1bp;
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].
RC STRAIN=Swiss Webster;
RX PubMed=11991719; DOI=10.1006/geno.2002.6761;
RA Ritter M., Buechler C., Boettcher A., Barlage S., Schmitz-Madry A.,
RA Orso E., Bared S.M., Schmiedeknecht G., Baehr C.H., Fricker G., Schmitz G.;
RT "Cloning and characterization of a novel apolipoprotein A-I-binding
RT protein, AI-BP, secreted by cells of the kidney proximal tubules in
RT response to HDL or ApoA-I.";
RL Genomics 79:693-702(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF
RP 25-282, SUBUNIT, PHOSPHORYLATION AT SER-43, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Testis;
RX PubMed=18202122; DOI=10.1210/en.2007-0582;
RA Jha K.N., Shumilin I.A., Digilio L.C., Chertihin O., Zheng H., Schmitz G.,
RA Visconti P.E., Flickinger C.J., Minor W., Herr J.C.;
RT "Biochemical and structural characterization of apolipoprotein A-I binding
RT protein, a novel phosphoprotein with a potential role in sperm
RT capacitation.";
RL Endocrinology 149:2108-2120(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
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 [4]
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 [5]
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43, 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 [8]
RP FUNCTION, 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 [9]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-138, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Catalyzes the epimerization of the S- and R-forms of
CC NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or
CC heat-dependent hydration. This is a prerequisite for the S-specific
CC NAD(P)H-hydrate dehydratase to allow the repair of both epimers of
CC NAD(P)HX. Accelerates cholesterol efflux from endothelial cells to
CC high-density lipoprotein (HDL) and thereby regulates angiogenesis (By
CC similarity). {ECO:0000250|UniProtKB:Q8NCW5, ECO:0000255|HAMAP-
CC Rule:MF_03159}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-NADHX = (6S)-NADHX; Xref=Rhea:RHEA:32215,
CC ChEBI:CHEBI:64074, ChEBI:CHEBI:64075; EC=5.1.99.6;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(6R)-NADPHX = (6S)-NADPHX; Xref=Rhea:RHEA:32227,
CC ChEBI:CHEBI:64076, ChEBI:CHEBI:64077; EC=5.1.99.6;
CC -!- COFACTOR:
CC Name=K(+); Xref=ChEBI:CHEBI:29103;
CC Note=Binds 1 potassium ion per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.6 uM for (R)-NADHX {ECO:0000269|PubMed:21994945};
CC KM=0.33 uM for (R)-NADPHX {ECO:0000269|PubMed:21994945};
CC Vmax=0.26 umol/min/mg enzyme toward (R)-NADHX
CC {ECO:0000269|PubMed:21994945};
CC Vmax=1.2 umol/min/mg enzyme toward (R)-NADPHX
CC {ECO:0000269|PubMed:21994945};
CC -!- SUBUNIT: Homodimer (PubMed:18202122). Interacts with APOA1 and APOA2
CC (By similarity). {ECO:0000250|UniProtKB:Q8NCW5,
CC ECO:0000269|PubMed:18202122}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03159}.
CC Secreted {ECO:0000255|HAMAP-Rule:MF_03159, ECO:0000269|PubMed:18202122,
CC ECO:0000269|PubMed:18614015}. Note=In sperm, secretion gradually
CC increases during capacitation.
CC -!- TISSUE SPECIFICITY: Detected in testis and sperm (at protein level).
CC Expressed at high levels in heart, liver, kidney, and testis.
CC {ECO:0000269|PubMed:18202122}.
CC -!- PTM: Undergoes physiological phosphorylation during sperm capacitation,
CC downstream to PKA activation. {ECO:0000255|HAMAP-Rule:MF_03159,
CC ECO:0000269|PubMed:18202122}.
CC -!- SIMILARITY: Belongs to the NnrE/AIBP family. {ECO:0000255|HAMAP-
CC Rule:MF_03159}.
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DR EMBL; AJ344092; CAC86966.1; -; mRNA.
DR EMBL; AY566271; AAT70236.1; -; mRNA.
DR EMBL; AK159846; BAE35424.1; -; mRNA.
DR EMBL; BC058362; AAH58362.1; -; mRNA.
DR CCDS; CCDS17464.1; -.
DR RefSeq; NP_659146.1; NM_144897.3.
DR PDB; 2DG2; X-ray; 2.45 A; A/B/C/D/E/F=25-282.
DR PDB; 2O8N; X-ray; 2.00 A; A=25-282.
DR PDB; 3RNO; X-ray; 2.50 A; A=25-282.
DR PDB; 3RO7; X-ray; 2.50 A; A=25-282.
DR PDB; 3ROE; X-ray; 2.11 A; A/B/C/D/E/F=25-282.
DR PDB; 3ROG; X-ray; 2.05 A; A=25-282.
DR PDB; 3ROX; X-ray; 2.40 A; A=25-282.
DR PDB; 3ROZ; X-ray; 2.80 A; A=25-282.
DR PDBsum; 2DG2; -.
DR PDBsum; 2O8N; -.
DR PDBsum; 3RNO; -.
DR PDBsum; 3RO7; -.
DR PDBsum; 3ROE; -.
DR PDBsum; 3ROG; -.
DR PDBsum; 3ROX; -.
DR PDBsum; 3ROZ; -.
DR AlphaFoldDB; Q8K4Z3; -.
DR SMR; Q8K4Z3; -.
DR BioGRID; 232930; 3.
DR DIP; DIP-59952N; -.
DR ELM; Q8K4Z3; -.
DR STRING; 10090.ENSMUSP00000029708; -.
DR iPTMnet; Q8K4Z3; -.
DR PhosphoSitePlus; Q8K4Z3; -.
DR SwissPalm; Q8K4Z3; -.
DR REPRODUCTION-2DPAGE; Q8K4Z3; -.
DR EPD; Q8K4Z3; -.
DR jPOST; Q8K4Z3; -.
DR MaxQB; Q8K4Z3; -.
DR PaxDb; Q8K4Z3; -.
DR PeptideAtlas; Q8K4Z3; -.
DR PRIDE; Q8K4Z3; -.
DR ProteomicsDB; 253089; -.
DR TopDownProteomics; Q8K4Z3; -.
DR Antibodypedia; 34221; 220 antibodies from 29 providers.
DR DNASU; 246703; -.
DR Ensembl; ENSMUST00000029708; ENSMUSP00000029708; ENSMUSG00000028070.
DR GeneID; 246703; -.
DR KEGG; mmu:246703; -.
DR UCSC; uc008ptu.1; mouse.
DR CTD; 128240; -.
DR MGI; MGI:2180167; Naxe.
DR VEuPathDB; HostDB:ENSMUSG00000028070; -.
DR eggNOG; KOG2585; Eukaryota.
DR GeneTree; ENSGT00390000007227; -.
DR HOGENOM; CLU_024853_3_0_1; -.
DR InParanoid; Q8K4Z3; -.
DR OMA; TIYYPKP; -.
DR OrthoDB; 1030667at2759; -.
DR PhylomeDB; Q8K4Z3; -.
DR TreeFam; TF300197; -.
DR BRENDA; 5.1.99.6; 3474.
DR Reactome; R-MMU-197264; Nicotinamide salvaging.
DR SABIO-RK; Q8K4Z3; -.
DR BioGRID-ORCS; 246703; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Apoa1bp; mouse.
DR EvolutionaryTrace; Q8K4Z3; -.
DR PRO; PR:Q8K4Z3; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8K4Z3; protein.
DR Bgee; ENSMUSG00000028070; Expressed in choroid plexus of fourth ventricle and 256 other tissues.
DR Genevisible; Q8K4Z3; MM.
DR GO; GO:0044297; C:cell body; IDA:MGI.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052856; F:NADHX epimerase activity; ISO:MGI.
DR GO; GO:0052857; F:NADPHX epimerase activity; ISO:MGI.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0031580; P:membrane raft distribution; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0046496; P:nicotinamide nucleotide metabolic process; ISS:UniProtKB.
DR GO; GO:0010874; P:regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR Gene3D; 3.40.50.10260; -; 1.
DR HAMAP; MF_01966; NADHX_epimerase; 1.
DR InterPro; IPR004443; YjeF_N_dom.
DR InterPro; IPR036652; YjeF_N_dom_sf.
DR InterPro; IPR032976; YJEFN_prot_NAXE-like.
DR PANTHER; PTHR13232; PTHR13232; 1.
DR Pfam; PF03853; YjeF_N; 1.
DR SUPFAM; SSF64153; SSF64153; 1.
DR TIGRFAMs; TIGR00197; yjeF_nterm; 1.
DR PROSITE; PS51385; YJEF_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isomerase; Lipid transport; Metal-binding; Mitochondrion;
KW NAD; NADP; Nucleotide-binding; Phosphoprotein; Potassium;
KW Reference proteome; Secreted; Transit peptide; Transport.
FT TRANSIT 1..53
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT CHAIN 54..282
FT /note="NAD(P)H-hydrate epimerase"
FT /id="PRO_0000292423"
FT DOMAIN 59..269
FT /note="YjeF N-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 113..117
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 114
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 179
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 183..189
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 212
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 215
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT MOD_RES 43
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:18202122,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 138
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT HELIX 56..67
FT /evidence="ECO:0007829|PDB:2O8N"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 74..92
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 98..102
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 104..109
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 113..127
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 131..135
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 143..154
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:3ROZ"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 175..181
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 194..202
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 208..213
FT /evidence="ECO:0007829|PDB:2O8N"
FT TURN 219..221
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 230..237
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 240..244
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 247..253
FT /evidence="ECO:0007829|PDB:2O8N"
FT HELIX 259..264
FT /evidence="ECO:0007829|PDB:2O8N"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:2O8N"
SQ SEQUENCE 282 AA; 30973 MW; DFD95155755D8D96 CRC64;
MSGLRTLLGL GLLVAGSRLP RVISQQSVCR ARPIWWGTQR RGSETMAGAA VKYLSQEEAQ
AVDQELFNEY QFSVDQLMEL AGLSCATAIA KAYPPTSMSK SPPTVLVICG PGNNGGDGLV
CARHLKLFGY QPTIYYPKRP NKPLFTGLVT QCQKMDIPFL GEMPPEPMMV DELYELVVDA
IFGFSFKGDV REPFHSILSV LSGLTVPIAS IDIPSGWDVE KGNPSGIQPD LLISLTAPKK
SATHFTGRYH YLGGRFVPPA LEKKYQLNLP SYPDTECVYR LQ
