NNRE_CANLF
ID NNRE_CANLF Reviewed; 288 AA.
AC E2QRY6;
DT 21-MAR-2012, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 63.
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};
GN Synonyms=AIBP {ECO:0000255|HAMAP-Rule:MF_03159},
GN APOA1BP {ECO:0000255|HAMAP-Rule:MF_03159};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
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 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 and APOA2 (By
CC similarity). {ECO:0000250|UniProtKB:Q8K4Z3,
CC ECO:0000250|UniProtKB:Q8NCW5}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03159}.
CC Secreted {ECO:0000255|HAMAP-Rule:MF_03159}. Note=In sperm, secretion
CC gradually increases during capacitation. {ECO:0000255|HAMAP-
CC Rule:MF_03159}.
CC -!- PTM: Undergoes physiological phosphorylation during sperm capacitation,
CC downstream to PKA activation. {ECO:0000255|HAMAP-Rule:MF_03159}.
CC -!- SIMILARITY: Belongs to the NnrE/AIBP family. {ECO:0000255|HAMAP-
CC Rule:MF_03159}.
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DR AlphaFoldDB; E2QRY6; -.
DR SMR; E2QRY6; -.
DR STRING; 9615.ENSCAFP00000024694; -.
DR PaxDb; E2QRY6; -.
DR PRIDE; E2QRY6; -.
DR eggNOG; KOG2585; Eukaryota.
DR InParanoid; E2QRY6; -.
DR Proteomes; UP000002254; Unplaced.
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 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 3: Inferred from homology;
KW Isomerase; Lipid transport; Metal-binding; Mitochondrion; NAD; NADP;
KW Nucleotide-binding; Potassium; Reference proteome; Secreted;
KW Transit peptide; Transport.
FT TRANSIT 1..48
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT CHAIN 49..288
FT /note="NAD(P)H-hydrate epimerase"
FT /id="PRO_0000416308"
FT DOMAIN 65..275
FT /note="YjeF N-terminal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 119..123
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 120
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 185
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 189..195
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 218
FT /ligand="(6S)-NADPHX"
FT /ligand_id="ChEBI:CHEBI:64076"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT BINDING 221
FT /ligand="K(+)"
FT /ligand_id="ChEBI:CHEBI:29103"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03159"
FT MOD_RES 144
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8K4Z3"
SQ SEQUENCE 288 AA; 31175 MW; A72AAB240BA12BA5 CRC64;
MSALRALLGL GLLAAGSRLR RVPGRAGACP AGSAWWEARR PHSGGGGEPA GMASPAVKYL
SQEEAQAVDE ELFNEYQFSV DQLMELAGLS CATAIAKAYP PTSMSRSPPA VLVICGPGNN
GGDGLVCARH LKLFGYQPTI YYPKRPNKPL FTALVTQCQK MDIPFLGEMP PEPMLIDELY
ELVVDAIFGF SFKGDVREPF RTILSVLDGL TVPIASIDIP SGWDVEKGNS GGIQPDLLIS
LTAPKKSATQ FTGRYHYLGG RFVPPALEKK YQLNLPPYPD TECVYRLQ
