NNTM_MOUSE
ID NNTM_MOUSE Reviewed; 1086 AA.
AC Q61941; Q9JK70;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=NAD(P) transhydrogenase, mitochondrial;
DE EC=7.1.1.1 {ECO:0000250|UniProtKB:Q2RSB2};
DE AltName: Full=Nicotinamide nucleotide transhydrogenase;
DE AltName: Full=Pyridine nucleotide transhydrogenase;
DE Flags: Precursor;
GN Name=Nnt;
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=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=8616157; DOI=10.1016/0005-2728(95)00159-x;
RA Lagberg E.M., Betsholtz C., Rydstrom J.;
RT "The cDNA sequence of proton-pumping nicotinamide nucleotide
RT transhydrogenase from man and mouse.";
RL Biochim. Biophys. Acta 1273:203-205(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/SvJ;
RX PubMed=11513952; DOI=10.1016/s0167-4781(01)00257-3;
RA Arkblad E.L., Betsholtz C., Mandoli D., Rydstrom J.;
RT "Characterization of a nicotinamide nucleotide transhydrogenase gene from
RT the green alga Acetabularia acetabulum and comparison of its structure with
RT those of the corresponding genes in mouse and Caenorhabditis elegans.";
RL Biochim. Biophys. Acta 1520:115-123(2001).
RN [3]
RP PROTEIN SEQUENCE OF 72-84; 214-224; 268-279; 367-379; 434-442; 769-777 AND
RP 940-949, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=22634753; DOI=10.1038/ng.2299;
RA Meimaridou E., Kowalczyk J., Guasti L., Hughes C.R., Wagner F.,
RA Frommolt P., Nurnberg P., Mann N.P., Banerjee R., Saka H.N., Chapple J.P.,
RA King P.J., Clark A.J., Metherell L.A.;
RT "Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause
RT familial glucocorticoid deficiency.";
RL Nat. Genet. 44:740-742(2012).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-117; LYS-224; LYS-294; LYS-331
RP AND LYS-1079, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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: The transhydrogenation between NADH and NADP is coupled to
CC respiration and ATP hydrolysis and functions as a proton pump across
CC the membrane (By similarity). May play a role in reactive oxygen
CC species (ROS) detoxification in the adrenal gland (By similarity).
CC {ECO:0000250|UniProtKB:P07001, ECO:0000250|UniProtKB:Q13423}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(in) + NAD(+) + NADPH = H(+)(out) + NADH + NADP(+);
CC Xref=Rhea:RHEA:47992, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57945, ChEBI:CHEBI:58349; EC=7.1.1.1;
CC Evidence={ECO:0000250|UniProtKB:Q2RSB2};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11024}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}; Matrix side {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed with expression most readily
CC detectable in adrenal, heart, kidney, thyroid and adipose tissues.
CC {ECO:0000269|PubMed:22634753}.
CC -!- DISRUPTION PHENOTYPE: Higher levels of adrenocortical cell apoptosis
CC and impaired glucocorticoid production are observed.
CC {ECO:0000269|PubMed:22634753}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the AlaDH/PNT family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the PNT beta subunit
CC family. {ECO:0000305}.
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DR EMBL; Z49204; CAA89065.1; -; mRNA.
DR EMBL; AF257157; AAF72982.2; -; Genomic_DNA.
DR EMBL; AF257137; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257138; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257139; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257140; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257141; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257142; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257143; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257144; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257145; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257146; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257147; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257148; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257149; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257150; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257151; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257152; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257153; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257154; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257155; AAF72982.2; JOINED; Genomic_DNA.
DR EMBL; AF257156; AAF72982.2; JOINED; Genomic_DNA.
DR PIR; S54876; S54876.
DR AlphaFoldDB; Q61941; -.
DR SMR; Q61941; -.
DR IntAct; Q61941; 4.
DR MINT; Q61941; -.
DR iPTMnet; Q61941; -.
DR PhosphoSitePlus; Q61941; -.
DR SwissPalm; Q61941; -.
DR EPD; Q61941; -.
DR jPOST; Q61941; -.
DR MaxQB; Q61941; -.
DR PaxDb; Q61941; -.
DR PeptideAtlas; Q61941; -.
DR PRIDE; Q61941; -.
DR ProteomicsDB; 293697; -.
DR MGI; MGI:109279; Nnt.
DR eggNOG; ENOG502QQ0A; Eukaryota.
DR InParanoid; Q61941; -.
DR Reactome; R-MMU-71403; Citric acid cycle (TCA cycle).
DR ChiTaRS; Nnt; mouse.
DR PRO; PR:Q61941; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q61941; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0051287; F:NAD binding; IBA:GO_Central.
DR GO; GO:0008746; F:NAD(P)+ transhydrogenase activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; ISO:MGI.
DR GO; GO:0045454; P:cell redox homeostasis; ISO:MGI.
DR GO; GO:0098869; P:cellular oxidant detoxification; ISO:MGI.
DR GO; GO:0006740; P:NADPH regeneration; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0032364; P:oxygen homeostasis; ISO:MGI.
DR GO; GO:1903285; P:positive regulation of hydrogen peroxide catabolic process; ISO:MGI.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI.
DR GO; GO:1902600; P:proton transmembrane transport; IEA:InterPro.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; ISS:UniProtKB.
DR InterPro; IPR008143; Ala_DH/PNT_CS2.
DR InterPro; IPR008142; AlaDH/PNT_CS1.
DR InterPro; IPR007886; AlaDH/PNT_N.
DR InterPro; IPR007698; AlaDH/PNT_NAD(H)-bd.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR026255; NADP_transhyd_a.
DR InterPro; IPR024605; NADP_transhyd_a_C.
DR InterPro; IPR034300; PNTB-like.
DR Pfam; PF01262; AlaDh_PNT_C; 1.
DR Pfam; PF05222; AlaDh_PNT_N; 1.
DR Pfam; PF02233; PNTB; 1.
DR Pfam; PF12769; PNTB_4TM; 1.
DR SMART; SM01002; AlaDh_PNT_C; 1.
DR SMART; SM01003; AlaDh_PNT_N; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR TIGRFAMs; TIGR00561; pntA; 1.
DR PROSITE; PS00836; ALADH_PNT_1; 1.
DR PROSITE; PS00837; ALADH_PNT_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; NAD; NADP; Reference proteome;
KW Transit peptide; Translocase; Transmembrane; Transmembrane helix.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P11024"
FT CHAIN 44..1086
FT /note="NAD(P) transhydrogenase, mitochondrial"
FT /id="PRO_0000001056"
FT TOPO_DOM 44..474
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P11024"
FT TRANSMEM 475..493
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 501..521
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 527..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 558..578
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..595
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P11024"
FT TRANSMEM 596..616
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 622..642
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 646..666
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 672..691
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 702..722
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 723..739
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P11024"
FT TRANSMEM 740..760
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 778..797
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 801..819
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 857..879
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 880..1086
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000250|UniProtKB:P11024"
FT BINDING 182..184
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P07001"
FT BINDING 237
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P07001"
FT BINDING 257..259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P07001"
FT BINDING 287
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:W5PFI3"
FT BINDING 300
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P07001"
FT BINDING 319
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P07001"
FT BINDING 933
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT BINDING 965..970
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT BINDING 1007..1011
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT BINDING 1026..1027
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT BINDING 1042..1049
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT BINDING 1068..1069
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT MOD_RES 70
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT MOD_RES 117
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 224
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 294
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 331
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 397
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13423"
FT MOD_RES 1079
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CONFLICT 35
FT /note="T -> M (in Ref. 1; CAA89065)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="P -> L (in Ref. 1; CAA89065)"
FT /evidence="ECO:0000305"
FT CONFLICT 813
FT /note="G -> A (in Ref. 1; CAA89065)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1086 AA; 113838 MW; A023285169834D07 CRC64;
MAHLLKTVVA GCSCPFLSNL GSSKVLPGKR DFVRTLRTHQ ALWCKSPVKP GIPYKQLTVG
VPKEIFQNEK RVALSPAGVQ ALVKQGFNVV VESGAGEASK FPDDLYRAAG AQIQGMKEVL
ASDLVVKVRA PMVNPTLGAH EADFLKPSGT LISFIYPAQN PDLLNKLSER KTTVLAMDQV
PRVTIAQGYD ALSSMANISG YKAVVLAANH FGRFFTGQIT AAGKVPPAKI LIVGGGVAGL
ASAGAAKSMG AVVRGFDTRA AALEQFKSLG AEPLEVDLKE SGEGQGGYAK EMSKEFIEAE
MKLFAQQCKE VDILISTALI PGKKAPVLFS KEMIESMKEG SVVVDLAAEA GGNFETTKPG
ELYVHKGITH IGYTDLPSRM ATQASTLYSN NITKLLKAIS PDKDNFHFEV KDDFDFGTMS
HVIRGTVVMK DGKVIFPAPT PKNIPEEAPV KPKTVAELEA EKAGTVSMYT KTLTTASVYS
AGLTGMLGLG IVAPNVAFSQ MVTTFGLAGI IGYHTVWGVT PALHSPLMSV TNAISGLTAV
GGLALMGGHF YPSTTSQSLA ALATFISSVN IAGGFLVTQR MLDMFKRPTD PPEYNYLYLL
PGGTFVGGYL AALYGGYNIE EIMYLGSGLC CVGALGGLST QGTARLGNAL GMIGVAGGLA
ATLGGLKPDP QLLAQMSGAM AMGGTIGLTI AKRIQISDLP QLVAAFHSLV GLAAVLTCMA
EYIVEYPHFA MDATSNFTKI VAYLGTYIGG VTFSGSLVAY GKLQGILKSA PLLLPGRHAL
NAGLLAASVG GIIPFMADPS FTTGITCLGS VSGLSTLMGV TLTAAIGGAD MPVVITVLNS
YSGWALCAEG FLLNNNLLTI VGALIGSSGA ILSYIMCVAM NRSLANVILG GYGTTSTAGG
KPMEISGTHT EINLDNAVEM IREANSIVIT PGYGLCAAKA QYPIADLVKM LTEQGKKVRF
GIHPVAGRMP GQLNVLLAEA GVPYDIVLEM DEINSDFPDT DLVLVIGAND TVNSAAQEDP
NSIIAGMPVL EVWKSKQVIV MKRSLGVGYA AVDNPIFYKP NTAMLLGDAK KTCDALQAKV
RESYQK
