NAD(P) transhydrogenase, mitochondrial

Details

Name
NAD(P) transhydrogenase, mitochondrial
Synonyms
  • 1.6.1.2
  • Nicotinamide nucleotide transhydrogenase
  • Pyridine nucleotide transhydrogenase
Gene Name
NNT
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010129|NAD(P) transhydrogenase, mitochondrial
MANLLKTVVTGCSCPLLSNLGSCKGLRVKKDFLRTFYTHQELWCKAPVKPGIPYKQLTVG
VPKEIFQNEKRVALSPAGVQNLVKQGFNVVVESGAGEASKFSDDHYRVAGAQIQGAKEVL
ASDLVVKVRAPMVNPTLGVHEADLLKTSGTLISFIYPAQNPELLNKLSQRKTTVLAMDQV
PRVTIAQGYDALSSMANIAGYKAVVLAANHFGRFFTGQITAAGKVPPAKILIVGGGVAGL
ASAGAAKSMGAIVRGFDTRAAALEQFKSLGAEPLEVDLKESGEGQGGYAKEMSKEFIEAE
MKLFAQQCKEVDILISTALIPGKKAPVLFNKEMIESMKEGSVVVDLAAEAGGNFETTKPG
ELYIHKGITHIGYTDLPSRMATQASTLYSNNITKLLKAISPDKDNFYFDVKDDFDFGTMG
HVIRGTVVMKDGKVIFPAPTPKNIPQGAPVKQKTVAELEAEKAATITPFRKTMSTASAYT
AGLTGILGLGIAAPNLAFSQMVTTFGLAGIVGYHTVWGVTPALHSPLMSVTNAISGLTAV
GGLALMGGHLYPSTTSQGLAALAAFISSVNIAGGFLVTQRMLDMFKRPTDPPEYNYLYLL
PAGTFVGGYLAALYSGYNIEQIMYLGSGLCCVGALAGLSTQGTARLGNALGMIGVAGGLA
ATLGVLKPGPELLAQMSGAMALGGTIGLTIAKRIQISDLPQLVAAFHSLVGLAAVLTCIA
EYIIEYPHFATDAAANLTKIVAYLGTYIGGVTFSGSLIAYGKLQGLLKSAPLLLPGRHLL
NAGLLAASVGGIIPFMVDPSFTTGITCLGSVSALSAVMGVTLTAAIGGADMPVVITVLNS
YSGWALCAEGFLLNNNLLTIVGALIGSSGAILSYIMCVAMNRSLANVILGGYGTTSTAGG
KPMEISGTHTEINLDNAIDMIREANSIIITPGYGLCAAKAQYPIADLVKMLTEQGKKVRF
GIHPVAGRMPGQLNVLLAEAGVPYDIVLEMDEINHDFPDTDLVLVIGANDTVNSAAQEDP
NSIIAGMPVLEVWKSKQVIVMKRSLGVGYAAVDNPIFYKPNTAMLLGDAKKTCDALQAKV
RESYQK
Number of residues
1086
Molecular Weight
113894.595
Theoretical pI
8.21
GO Classification
Functions
NAD binding / NAD(P)+ transhydrogenase (AB-specific) activity / NAD(P)+ transhydrogenase (B-specific) activity / NAD(P)+ transhydrogenase activity / NADP binding
Processes
cell redox homeostasis / cellular metabolic process / hydrogen ion transmembrane transport / NADPH regeneration / oxidation-reduction process / proton transport / reactive oxygen species metabolic process / small molecule metabolic process / tricarboxylic acid cycle
Components
integral component of membrane / membrane / mitochondrial inner membrane / mitochondrial respiratory chain / mitochondrion
General Function
Nadp binding
Specific Function
The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane. May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland.
Pfam Domain Function
Transmembrane Regions
475-493 501-521 527-546 558-578 596-616 622-642 646-666 672-691 702-722 740-760 778-797 801-819 833-853 857-879
Cellular Location
Mitochondrion inner membrane
Gene sequence
>lcl|BSEQ0010130|NAD(P) transhydrogenase, mitochondrial (NNT)
ATGGCAAACCTATTGAAAACAGTGGTGACTGGCTGCTCGTGTCCTCTACTTAGCAATTTG
GGGTCCTGTAAGGGTCTACGTGTGAAGAAGGATTTTTTACGAACATTTTATACTCACCAA
GAACTGTGGTGTAAAGCGCCTGTAAAACCAGGAATTCCATATAAGCAACTGACTGTTGGA
GTCCCCAAAGAGATATTCCAAAATGAGAAGCGAGTGGCATTGTCTCCTGCTGGTGTTCAG
AACTTGGTCAAGCAGGGTTTTAATGTTGTCGTGGAATCGGGTGCGGGCGAAGCTTCCAAG
TTCTCAGATGATCACTATAGAGTGGCAGGTGCCCAAATCCAAGGGGCAAAGGAAGTGCTG
GCTTCTGATTTGGTGGTCAAAGTGCGAGCCCCTATGGTTAATCCAACATTAGGTGTTCAT
GAAGCTGACCTTTTAAAGACATCAGGAACGCTGATTAGTTTTATTTACCCAGCCCAAAAT
CCAGAGTTGCTAAATAAACTTTCCCAAAGAAAAACTACAGTTCTGGCAATGGACCAGGTT
CCAAGAGTCACAATTGCTCAGGGATATGATGCGCTAAGCTCCATGGCCAACATTGCGGGT
TATAAGGCTGTTGTCCTAGCAGCAAATCATTTTGGACGTTTTTTTACTGGTCAGATCACA
GCTGCTGGAAAAGTTCCTCCAGCTAAGATTCTGATAGTTGGTGGTGGTGTTGCTGGGCTT
GCTTCTGCAGGCGCAGCAAAGTCGATGGGTGCAATTGTTCGAGGATTTGACACAAGAGCT
GCAGCTTTGGAACAGTTCAAGTCTCTTGGTGCTGAGCCCTTGGAGGTGGACTTGAAGGAA
TCTGGTGAGGGACAAGGAGGATATGCAAAAGAGATGTCCAAAGAGTTCATTGAAGCTGAA
ATGAAACTCTTTGCTCAACAATGCAAGGAGGTAGACATCCTTATCAGCACAGCACTTATT
CCAGGTAAAAAAGCTCCAGTTTTATTTAATAAAGAAATGATTGAGTCAATGAAGGAAGGT
TCAGTTGTTGTGGATTTAGCTGCTGAGGCTGGTGGAAACTTTGAAACCACTAAGCCAGGA
GAACTCTACATTCATAAGGGAATTACTCACATAGGCTACACAGACCTGCCCAGCCGAATG
GCCACTCAGGCCAGCACCCTATATTCCAACAACATCACCAAACTCCTGAAGGCCATCAGC
CCGGACAAAGATAATTTTTATTTTGATGTGAAAGATGACTTTGACTTTGGTACGATGGGT
CATGTCATTAGAGGAACTGTAGTGATGAAAGATGGTAAAGTGATTTTCCCAGCTCCCACA
CCGAAAAATATTCCTCAAGGTGCCCCAGTAAAACAGAAGACAGTGGCTGAGCTGGAAGCT
GAAAAAGCAGCTACCATTACACCCTTCAGGAAGACAATGTCAACGGCTTCTGCATATACA
GCAGGTCTCACAGGGATACTGGGTTTGGGCATTGCGGCTCCCAATCTAGCCTTTTCTCAG
ATGGTGACCACTTTTGGCTTGGCTGGCATTGTGGGGTATCATACCGTCTGGGGAGTGACC
CCTGCTCTCCACTCACCACTGATGTCTGTGACAAATGCAATCTCAGGGCTGACTGCAGTT
GGTGGGTTGGCACTGATGGGAGGACATTTGTATCCTTCCACAACTTCTCAGGGCCTTGCT
GCTCTTGCTGCATTCATATCCTCTGTCAACATTGCAGGTGGCTTTCTGGTGACTCAGAGA
ATGCTGGACATGTTCAAGCGTCCCACTGACCCCCCAGAATACAACTACCTGTACCTGCTC
CCTGCCGGCACCTTTGTTGGTGGATATTTAGCTGCCCTCTACAGTGGTTATAACATTGAA
CAGATCATGTACCTAGGCTCGGGTTTGTGCTGTGTCGGTGCCTTGGCTGGCCTCTCCACC
CAGGGAACAGCACGTCTTGGCAATGCACTGGGCATGATTGGGGTTGCTGGAGGACTGGCA
GCCACCCTCGGAGTCCTAAAACCGGGCCCAGAATTACTAGCTCAGATGTCTGGAGCGATG
GCTTTGGGTGGTACCATTGGATTGACAATTGCCAAACGCATCCAGATTTCTGATTTACCT
CAATTAGTTGCTGCTTTTCACAGTTTAGTGGGTTTGGCAGCTGTACTTACTTGCATAGCT
GAGTACATTATAGAATATCCACATTTTGCTACGGATGCAGCAGCAAATCTCACCAAGATT
GTGGCCTACCTCGGCACTTACATTGGTGGCGTCACCTTTAGTGGGTCTCTCATTGCCTAT
GGAAAATTGCAGGGTCTCCTGAAATCTGCCCCTCTCCTACTGCCTGGAAGGCACTTACTC
AATGCAGGCTTACTGGCTGCTAGTGTGGGCGGGATAATCCCATTCATGGTGGACCCAAGC
TTTACTACTGGCATCACCTGTCTGGGTTCAGTGTCTGCTCTCTCTGCTGTCATGGGTGTG
ACTTTGACAGCTGCTATTGGGGGTGCTGACATGCCCGTCGTTATCACTGTGCTGAACAGC
TACTCAGGCTGGGCCCTGTGTGCAGAGGGCTTCCTGCTCAACAACAATCTGCTGACCATC
GTGGGTGCACTCATAGGCTCGTCTGGTGCTATCCTGTCATACATCATGTGTGTGGCAATG
AATCGCTCCCTGGCTAATGTGATTCTTGGAGGCTATGGCACCACTTCAACAGCTGGTGGA
AAACCCATGGAAATTTCTGGCACACATACGGAAATCAACCTTGACAATGCAATTGACATG
ATTCGAGAAGCTAATAGCATTATTATTACACCAGGCTATGGTCTCTGTGCAGCCAAAGCT
CAATACCCCATTGCTGATTTGGTAAAGATGCTCACTGAGCAAGGCAAAAAAGTCAGGTTT
GGAATTCACCCAGTTGCAGGCCGAATGCCTGGTCAGCTTAATGTGCTGCTGGCTGAGGCT
GGTGTGCCATATGACATTGTGTTGGAAATGGATGAGATCAACCATGATTTTCCAGATACT
GATTTGGTCCTTGTAATTGGAGCTAATGACACTGTTAATTCAGCAGCTCAAGAAGATCCC
AACTCTATTATTGCAGGCATGCCAGTCCTTGAGGTCTGGAAATCAAAGCAGGTGATTGTT
ATGAAGAGGTCTTTGGGTGTTGGCTATGCTGCAGTGGACAATCCAATCTTCTACAAACCT
AACACGGCCATGCTTCTAGGTGATGCCAAGAAAACATGTGACGCGCTCCAGGCGAAAGTT
AGAGAATCCTATCAGAAGTAA
Chromosome Location
5
Locus
5p13.1-5cen
External Identifiers
ResourceLink
UniProtKB IDQ13423
UniProtKB Entry NameNNTM_HUMAN
GenBank Protein ID1110520
GenBank Gene IDU40490
GenAtlas IDNNT
HGNC IDHGNC:7863
General References
  1. Zieger B, Ware J: Cloning and deduced amino acid sequence of human nicotinamide nucleotide transhydrogenase. DNA Seq. 1997;7(6):369-73. [Article]
  2. Arkblad EL, Betsholtz C, Rydstrom J: The cDNA sequence of proton-pumping nicotinamide nucleotide transhydrogenase from man and mouse. Biochim Biophys Acta. 1996 Mar 28;1273(3):203-5. [Article]
  3. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  6. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  7. Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nurnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJ, Metherell LA: Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet. 2012 May 27;44(7):740-2. doi: 10.1038/ng.2299. [Article]
  8. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  9. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  10. White SA, Peake SJ, McSweeney S, Leonard G, Cotton NP, Jackson JB: The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria. Structure. 2000 Jan 15;8(1):1-12. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00157NADHapproved, nutraceuticalunknownDetails
DB017637-thionicotinamide-adenine-dinucleotide phosphateexperimentalunknownDetails
DB03461Nicotinamide adenine dinucleotide phosphateexperimentalunknownDetails
DB09092Xanthinolapproved, withdrawnyescofactorDetails
DB09072Sodium oxybateapprovedunknownsubstrateDetails