NNTM_SHEEP
ID NNTM_SHEEP Reviewed; 1086 AA.
AC W5PFI3;
DT 31-JUL-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 2.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=NAD(P) transhydrogenase, mitochondrial {ECO:0000305};
DE EC=7.1.1.1 {ECO:0000250|UniProtKB:Q2RSB2};
DE AltName: Full=Nicotinamide nucleotide transhydrogenase {ECO:0000305};
DE Flags: Precursor;
GN Name=NNT;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940 {ECO:0000312|Proteomes:UP000002356};
RN [1] {ECO:0000312|Proteomes:UP000002356}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Texel;
RX PubMed=20809919; DOI=10.1111/j.1365-2052.2010.02100.x;
RA Archibald A.L., Cockett N.E., Dalrymple B.P., Faraut T., Kijas J.W.,
RA Maddox J.F., McEwan J.C., Hutton Oddy V., Raadsma H.W., Wade C., Wang J.,
RA Wang W., Xun X.;
RT "The sheep genome reference sequence: a work in progress.";
RL Anim. Genet. 41:449-453(2010).
RN [2] {ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE, ECO:0007744|PDB:6S59}
RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) IN COMPLEX WITH NADPH AND
RP NADP, AND SUBUNIT.
RX PubMed=31462775; DOI=10.1038/s41586-019-1519-2;
RA Kampjut D., Sazanov L.A.;
RT "Structure and mechanism of mitochondrial proton-translocating
RT transhydrogenase.";
RL Nature 573:291-295(2019).
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:0000305|PubMed:31462775};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:31462775}.
CC -!- INTERACTION:
CC W5PFI3; W5PFI3: NNT; NbExp=2; IntAct=EBI-22054528, EBI-22054528;
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; AMGL01034992; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AMGL01034993; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 6QTI; X-ray; 2.90 A; A/B=1-1086.
DR PDB; 6QUE; X-ray; 3.70 A; A/B=1-1086.
DR PDB; 6S59; X-ray; 3.70 A; A/B=1-1086.
DR PDBsum; 6QTI; -.
DR PDBsum; 6QUE; -.
DR PDBsum; 6S59; -.
DR AlphaFoldDB; W5PFI3; -.
DR SMR; W5PFI3; -.
DR STRING; 9940.ENSOARP00000009198; -.
DR PRIDE; W5PFI3; -.
DR eggNOG; ENOG502QQ0A; Eukaryota.
DR HOGENOM; CLU_003376_1_0_1; -.
DR OrthoDB; 220278at2759; -.
DR Proteomes; UP000002356; Unplaced.
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:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0008746; F:NAD(P)+ transhydrogenase activity; IEA:InterPro.
DR GO; GO:1902600; P:proton transmembrane transport; IEA:InterPro.
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; 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_0000447642"
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:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
FT BINDING 237
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QUE"
FT BINDING 257..259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
FT BINDING 287
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
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:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
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:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
FT BINDING 1007..1011
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
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:31462775,
FT ECO:0007744|PDB:6QTI, ECO:0007744|PDB:6QUE"
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: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 STRAND 58..61
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 88..92
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 93..100
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 117..119
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 161..169
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 173..176
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 191..207
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 211..213
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 229..233
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 238..247
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 285..289
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 294..306
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 307..310
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 342..345
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 348..351
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 364..367
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 377..380
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 381..398
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 402..404
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 419..426
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 427..430
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 455..462
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 468..491
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 496..517
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 524..534
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 535..537
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 538..544
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 555..582
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 595..598
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 599..614
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 620..636
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 637..639
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 640..643
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 646..666
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 670..690
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 691..694
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 696..698
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 699..724
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 726..728
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 735..764
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 765..767
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 775..778
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 779..790
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 792..795
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 802..823
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 828..830
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 831..852
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 856..864
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 869..879
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 884..888
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 914..923
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 925..931
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 933..937
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 941..953
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 957..962
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 967..969
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 972..980
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 984..986
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 987..989
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 990..993
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 1001..1007
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 1015..1018
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 1023..1026
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 1032..1034
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 1038..1041
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 1043..1045
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 1048..1050
FT /evidence="ECO:0007829|PDB:6QTI"
FT TURN 1055..1058
FT /evidence="ECO:0007829|PDB:6QTI"
FT STRAND 1062..1064
FT /evidence="ECO:0007829|PDB:6QTI"
FT HELIX 1069..1084
FT /evidence="ECO:0007829|PDB:6QTI"
SQ SEQUENCE 1086 AA; 113879 MW; 19643A143F74626C CRC64;
MANLLKTVVT GCSCPFLSNL GSCKVLPGKK NFLRAFHTHR ILWCKAPVKP GIPYKQLTVG
VPKEIFQNEK RVALSPAGVQ ALVKQGFNVV VESGAGEASK FSDDHYRAAG AQIQGAKEVL
ASDLVVKVRA PMLNPTLGIH EADLLKTSGT LISFIYPAQN PDLLNKLSKR NTTVLAMDQV
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
NAGLLAASVG 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
