NNTM_BOVIN
ID NNTM_BOVIN Reviewed; 1086 AA.
AC P11024; A4FUB4;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 3.
DT 03-AUG-2022, entry version 180.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-75.
RX PubMed=3196335; DOI=10.1016/s0006-291x(88)80005-6;
RA Yamaguchi M., Hatefi Y., Trach K., Hoch J.A.;
RT "Amino acid sequence of the signal peptide of mitochondrial nicotinamide
RT nucleotide transhydrogenase as determined from the sequence of its
RT messenger RNA.";
RL Biochem. Biophys. Res. Commun. 157:24-29(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 52-1086, AND PROTEIN SEQUENCE OF 44-58.
RX PubMed=3277960; DOI=10.1016/s0021-9258(18)69134-3;
RA Yamaguchi M., Hatefi Y., Trach K., Hoch J.A.;
RT "The primary structure of the mitochondrial energy-linked nicotinamide
RT nucleotide transhydrogenase deduced from the sequence of cDNA clones.";
RL J. Biol. Chem. 263:2761-2767(1988).
RN [4]
RP PROTEIN SEQUENCE OF 280-290 AND 1044-1049.
RX PubMed=3325062;
RA Wakabayashi S., Hatefi Y.;
RT "Characterization of the substrate-binding sites of the mitochondrial
RT nicotinamide nucleotide transhydrogenase.";
RL Biochem. Int. 15:915-924(1987).
RN [5]
RP PROTEIN SEQUENCE OF 291-302.
RX PubMed=3426633;
RA Wakabayashi S., Hatefi Y.;
RT "Amino acid sequence of the NAD (H)-binding region of the mitochondrial
RT nicotinamide nucleotide transhydrogenase modified by N,N'-
RT dicyclohexylcarbodiimide.";
RL Biochem. Int. 15:667-675(1987).
RN [6]
RP SUBUNIT, AND TOPOLOGY.
RX PubMed=2005110; DOI=10.1016/s0021-9258(19)67656-8;
RA Yamaguchi M., Hatefi Y.;
RT "Mitochondrial energy-linked nicotinamide nucleotide transhydrogenase.
RT Membrane topography of the bovine enzyme.";
RL J. Biol. Chem. 266:5728-5735(1991).
RN [7] {ECO:0007744|PDB:1D4O}
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 903-1086.
RX PubMed=10581554; DOI=10.1038/70067;
RA Prasad G.S., Sridhar V., Yamaguchi M., Hatefi Y., Stout C.D.;
RT "Crystal structure of transhydrogenase domain III at 1.2 A resolution.";
RL Nat. Struct. Biol. 6:1126-1131(1999).
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:0000269|PubMed:2005110}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}; Matrix side {ECO:0000305}.
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; BC114660; AAI14661.1; -; mRNA.
DR EMBL; J03534; AAA30660.1; -; mRNA.
DR EMBL; M22754; AAA30717.1; -; mRNA.
DR EMBL; L02543; AAA21440.1; -; mRNA.
DR PIR; A31670; DEBOXM.
DR RefSeq; NP_776368.1; NM_173943.3.
DR RefSeq; XP_005221585.1; XM_005221528.3.
DR RefSeq; XP_005221586.1; XM_005221529.3.
DR RefSeq; XP_005221587.1; XM_005221530.3.
DR PDB; 1D4O; X-ray; 1.21 A; A=903-1086.
DR PDBsum; 1D4O; -.
DR AlphaFoldDB; P11024; -.
DR SMR; P11024; -.
DR STRING; 9913.ENSBTAP00000015769; -.
DR TCDB; 3.D.2.3.1; the proton-translocating transhydrogenase (pth) family.
DR PaxDb; P11024; -.
DR PeptideAtlas; P11024; -.
DR PRIDE; P11024; -.
DR Ensembl; ENSBTAT00000015769; ENSBTAP00000015769; ENSBTAG00000011885.
DR Ensembl; ENSBTAT00000080867; ENSBTAP00000072815; ENSBTAG00000011885.
DR GeneID; 280878; -.
DR KEGG; bta:280878; -.
DR CTD; 23530; -.
DR VEuPathDB; HostDB:ENSBTAG00000011885; -.
DR VGNC; VGNC:32143; NNT.
DR eggNOG; ENOG502QQ0A; Eukaryota.
DR GeneTree; ENSGT00390000004624; -.
DR HOGENOM; CLU_003376_1_0_1; -.
DR InParanoid; P11024; -.
DR OMA; NPAFTTM; -.
DR OrthoDB; 220278at2759; -.
DR TreeFam; TF300636; -.
DR Reactome; R-BTA-71403; Citric acid cycle (TCA cycle).
DR EvolutionaryTrace; P11024; -.
DR Proteomes; UP000009136; Chromosome 20.
DR Bgee; ENSBTAG00000011885; Expressed in corpus luteum and 105 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0006740; P:NADPH regeneration; IBA:GO_Central.
DR GO; GO:1902600; P:proton transmembrane transport; IEA:InterPro.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
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 3D-structure; Acetylation; Direct protein sequencing; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; NAD; NADP; Nucleotide-binding;
KW Reference proteome; Transit peptide; Translocase; Transmembrane;
KW Transmembrane helix.
FT TRANSIT 1..43
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:3277960"
FT CHAIN 44..1086
FT /note="NAD(P) transhydrogenase, mitochondrial"
FT /id="PRO_0000001054"
FT TOPO_DOM 44..474
FT /note="Mitochondrial matrix"
FT /evidence="ECO:0000269|PubMed:2005110"
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:0000269|PubMed:2005110"
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:0000269|PubMed:2005110"
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:0000269|PubMed:2005110"
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:0000269|PubMed:10581554,
FT ECO:0007744|PDB:1D4O"
FT BINDING 965..970
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10581554,
FT ECO:0007744|PDB:1D4O"
FT BINDING 1009..1011
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10581554,
FT ECO:0007744|PDB:1D4O"
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:0000269|PubMed:10581554,
FT ECO:0007744|PDB:1D4O"
FT BINDING 1068..1069
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:10581554,
FT ECO:0007744|PDB:1D4O"
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:0000250|UniProtKB:Q61941"
FT MOD_RES 224
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61941"
FT MOD_RES 294
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61941"
FT MOD_RES 331
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q61941"
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:0000250|UniProtKB:Q61941"
FT HELIX 914..923
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 925..931
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 933..937
FT /evidence="ECO:0007829|PDB:1D4O"
FT TURN 938..940
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 941..953
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 957..962
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 972..980
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 984..986
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 987..989
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 990..993
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 994..999
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 1001..1007
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 1010..1012
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 1015..1018
FT /evidence="ECO:0007829|PDB:1D4O"
FT TURN 1023..1026
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 1032..1034
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 1038..1045
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 1055..1058
FT /evidence="ECO:0007829|PDB:1D4O"
FT STRAND 1062..1067
FT /evidence="ECO:0007829|PDB:1D4O"
FT HELIX 1069..1081
FT /evidence="ECO:0007829|PDB:1D4O"
SQ SEQUENCE 1086 AA; 113854 MW; E3663B533B8E7E35 CRC64;
MANLLKTVVT GCSCPFLSNL GSCKVLPGKK NFLRTFHTHR ILWCSAPVKP GIPYKQLTVG
VPKEIFQNEK RVALSPAGVQ ALVKQGFNVV VESGAGEASK FSDDHYRAAG AQIQGAKEVL
ASDLVVKVRA PMLNPTLGVH EADLLKTSGT LISFIYPAQN PDLLNKLSKR KTTVLAMDQV
PRVTIAQGYD ALSSMANIAG YKAVVLAANH FGRFFTGQIT AAGKVPPAKI LIVGGGVAGL
ASAGAAKSMG AIVRGFDTRA AALEQFKSLG AEPLEVDLKE SGEGQGGYAK EMSKEFIEAE
MKLFAQQCKE VDILISTALI PGKKAPILFN KEMIESMKEG SVVVDLAAEA GGNFETTKPG
ELYVHKGITH IGYTDLPSRM ATQASTLYSN NITKLLKAIS PDKDNFYFEV KDDFDFGTMG
HVIRGTVVMK DGQVIFPAPT PKNIPQGAPV KQKTVAELEA EKAATITPFR KTMTSASVYT
AGLTGILGLG IAAPNLAFSQ MVTTFGLAGI VGYHTVWGVT PALHSPLMSV TNAISGLTAV
GGLVLMGGHL YPSTTSQGLA ALATFISSVN IAGGFLVTQR MLDMFKRPTD PPEYNYLYLL
PAGTFVGGYL ASLYSGYNIE QIMYLGSGLC CVGALAGLST QGTARLGNAL GMIGVAGGLA
ATLGGLKPCP ELLAQMSGAM ALGGTIGLTI AKRIQISDLP QLVAAFHSLV GLAAVLTCIA
EYIIEYPHFA TDAAANLTKI VAYLGTYIGG VTFSGSLVAY GKLQGILKSA PLLLPGRHLL
NAGLLAGSVG GIIPFMMDPS FTTGITCLGS VSALSAVMGV TLTAAIGGAD MPVVITVLNS
YSGWALCAEG FLLNNNLLTI VGALIGSSGA ILSYIMCVAM NRSLANVILG GYGTTSTAGG
KPMEISGTHT EINLDNAIDM IREANSIIIT PGYGLCAAKA QYPIADLVKM LSEQGKKVRF
GIHPVAGRMP GQLNVLLAEA GVPYDIVLEM DEINHDFPDT DLVLVIGAND TVNSAAQEDP
NSIIAGMPVL EVWKSKQVIV MKRSLGVGYA AVDNPIFYKP NTAMLLGDAK KTCDALQAKV
RESYQK
