NNRE_DANRE
ID NNRE_DANRE Reviewed; 283 AA.
AC Q6DHK1;
DT 26-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 106.
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;
GN ORFNames=si:dkeyp-84f11.6, zgc:92263;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH APOA1, BINDS TO HDL, AND DISRUPTION PHENOTYPE.
RX PubMed=23719382; DOI=10.1038/nature12166;
RA Fang L., Choi S.H., Baek J.S., Liu C., Almazan F., Ulrich F., Wiesner P.,
RA Taleb A., Deer E., Pattison J., Torres-Vazquez J., Li A.C., Miller Y.I.;
RT "Control of angiogenesis by AIBP-mediated cholesterol efflux.";
RL Nature 498:118-122(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. {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 Evidence={ECO:0000255|HAMAP-Rule:MF_03159};
CC Note=Binds 1 potassium ion per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_03159};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with APOA1
CC (PubMed:23719382). Binds to HDL (PubMed:23719382).
CC {ECO:0000250|UniProtKB:Q8NCW5, ECO:0000269|PubMed:23719382}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03159}.
CC Secreted {ECO:0000255|HAMAP-Rule:MF_03159}.
CC -!- DISRUPTION PHENOTYPE: Mutants do not show increased levels of free
CC (unesterified) cholesterol. {ECO:0000269|PubMed:23719382}.
CC -!- SIMILARITY: Belongs to the NnrE/AIBP family. {ECO:0000255|HAMAP-
CC Rule:MF_03159}.
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DR EMBL; BX890617; CAK11463.1; -; Genomic_DNA.
DR EMBL; BC075969; AAH75969.1; -; mRNA.
DR RefSeq; NP_001002618.1; NM_001002618.1.
DR AlphaFoldDB; Q6DHK1; -.
DR SMR; Q6DHK1; -.
DR STRING; 7955.ENSDARP00000076185; -.
DR PaxDb; Q6DHK1; -.
DR PRIDE; Q6DHK1; -.
DR Ensembl; ENSDART00000081746; ENSDARP00000076185; ENSDARG00000058806.
DR GeneID; 436891; -.
DR KEGG; dre:436891; -.
DR CTD; 128240; -.
DR ZFIN; ZDB-GENE-040718-362; naxe.
DR eggNOG; KOG2585; Eukaryota.
DR GeneTree; ENSGT00390000007227; -.
DR HOGENOM; CLU_024853_3_0_1; -.
DR InParanoid; Q6DHK1; -.
DR OMA; SMFRGRY; -.
DR OrthoDB; 1030667at2759; -.
DR PhylomeDB; Q6DHK1; -.
DR TreeFam; TF300197; -.
DR Reactome; R-DRE-197264; Nicotinamide salvaging.
DR PRO; PR:Q6DHK1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000058806; Expressed in testis and 28 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0052856; F:NADHX epimerase activity; IBA:GO_Central.
DR GO; GO:0052857; F:NADPHX epimerase activity; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
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 Isomerase; Lipid transport; Metal-binding; Mitochondrion; NAD; NADP;
KW Nucleotide-binding; Potassium; Reference proteome; Secreted;
KW Transit peptide; Transport.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT CHAIN 29..283
FT /note="NAD(P)H-hydrate epimerase"
FT /id="PRO_0000292425"
FT DOMAIN 61..270
FT /note="YjeF N-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 115..119
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 116
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 180
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 184..190
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 213
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 216
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
SQ SEQUENCE 283 AA; 30882 MW; 036930E12F0324BC CRC64;
MLGVRALFGI GLLVTSRGGF VLTHTRACSS AASNIYSKHL THRPTCTMAN TGVKYLGQEE
AQQIDEELFS DFSFSVDQLM ELAGLSCATA VAKGYPVTSL LKSPARVLVI CGPGNNGGDG
LVCARHLKLF GYEPSVLYPK RPNKQLFQNL SIQCQKMEIP FLTEMPEADL IDEAYSLVVD
AIFGFSFKGA VREPFGEILS QLKKITVPIA SVDIPSGWDV EKGCPDGIQP DMLISLTAPK
KSAALFKGRF HFLGGRFVPP VLEQKYQLNL PQYPGTECVF QLN
