NNT

Protein identityUniProt · HPA

UniProt accession

Q13423

Gene

NNT

Ensembl

ENSG00000112992

Chromosome

5

Canonical length

1086 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an integral protein of the inner mitochondrial membrane. The enzyme couples hydride transfer between NAD(H) and NADP(+) to proton translocation across the inner mitochondrial membrane. Under most physiological conditions, the enzyme uses energy from the mitochondrial proton gradient to produce high concentrations of NADPH. The resulting NADPH is used for biosynthesis and in free radical detoxification. [provided by RefSeq, Sep 2016]

Canonical amino-acid sequenceUniProt

1086 residues, UniProt reviewed canonical sequence.

>Q13423|NNT
     1  MANLLKTVVT GCSCPLLSNL GSCKGLRVKK DFLRTFYTHQ ELWCKAPVKP GIPYKQLTVG
    61  VPKEIFQNEK RVALSPAGVQ NLVKQGFNVV VESGAGEASK FSDDHYRVAG AQIQGAKEVL
   121  ASDLVVKVRA PMVNPTLGVH EADLLKTSGT LISFIYPAQN PELLNKLSQR KTTVLAMDQV
   181  PRVTIAQGYD ALSSMANIAG YKAVVLAANH FGRFFTGQIT AAGKVPPAKI LIVGGGVAGL
   241  ASAGAAKSMG AIVRGFDTRA AALEQFKSLG AEPLEVDLKE SGEGQGGYAK EMSKEFIEAE
   301  MKLFAQQCKE VDILISTALI PGKKAPVLFN KEMIESMKEG SVVVDLAAEA GGNFETTKPG
   361  ELYIHKGITH IGYTDLPSRM ATQASTLYSN NITKLLKAIS PDKDNFYFDV KDDFDFGTMG
   421  HVIRGTVVMK DGKVIFPAPT PKNIPQGAPV KQKTVAELEA EKAATITPFR KTMSTASAYT
   481  AGLTGILGLG IAAPNLAFSQ MVTTFGLAGI VGYHTVWGVT PALHSPLMSV TNAISGLTAV
   541  GGLALMGGHL YPSTTSQGLA ALAAFISSVN IAGGFLVTQR MLDMFKRPTD PPEYNYLYLL
   601  PAGTFVGGYL AALYSGYNIE QIMYLGSGLC CVGALAGLST QGTARLGNAL GMIGVAGGLA
   661  ATLGVLKPGP ELLAQMSGAM ALGGTIGLTI AKRIQISDLP QLVAAFHSLV GLAAVLTCIA
   721  EYIIEYPHFA TDAAANLTKI VAYLGTYIGG VTFSGSLIAY GKLQGLLKSA PLLLPGRHLL
   781  NAGLLAASVG GIIPFMVDPS FTTGITCLGS VSALSAVMGV TLTAAIGGAD MPVVITVLNS
   841  YSGWALCAEG FLLNNNLLTI VGALIGSSGA ILSYIMCVAM NRSLANVILG GYGTTSTAGG
   901  KPMEISGTHT EINLDNAIDM IREANSIIIT PGYGLCAAKA QYPIADLVKM LTEQGKKVRF
   961  GIHPVAGRMP GQLNVLLAEA GVPYDIVLEM DEINHDFPDT DLVLVIGAND TVNSAAQEDP
  1021  NSIIAGMPVL EVWKSKQVIV MKRSLGVGYA AVDNPIFYKP NTAMLLGDAK KTCDALQAKV
  1081  RESYQK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NNT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

14

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

359 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NNT.

Disease | AllUniProt

Conditions NNT is implicated in, by any mechanism.

• Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4) MIM:614736

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 326 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Glucocorticoid deficiency 4
• GLUCOCORTICOID DEFICIENCY 4 WITH MINERALOCORTICOID DEFICIENCY
• Inborn genetic diseases

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.31

gnomAD pLI

0.97

gnomAD missense Z

2.08

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell redox homeostasis
• cellular oxidant detoxification
• intracellular oxygen homeostasis
• NADPH regeneration
• negative regulation of apoptotic process
• positive regulation of hydrogen peroxide catabolic process
• positive regulation of mitochondrial membrane potential
• proton transmembrane transport
• reactive oxygen species metabolic process
• response to vitamin
• tricarboxylic acid cycle

Molecular functions

• NAD binding
• NADP binding
• NAD(P)+ transhydrogenase (Si-specific) activity
• proton-translocating NAD(P)+ transhydrogenase activity

Cellular components

• membrane
• mitochondrial inner membrane
• mitochondrion
• respiratory chain complex

Protein domainsUniProt · Pfam · InterPro

• Alanine dehydrogenase/pyridine nucleotide transhydrogenase, NAD(H)-binding domain
• Alanine dehydrogenase/pyridine nucleotide transhydrogenase, N-terminal
• DHS-like NAD/FAD-binding domain superfamily
• NAD(P)-binding domain superfamily
• Alanine dehydrogenase/PNT, N-terminal domain
• Alanine dehydrogenase/NAD(P) transhydrogenase, conserved site-1
• Alanine dehydrogenase/pyridine nucleotide transhydrogenase, conserved site-2
• NAD(P) transhydrogenase, alpha subunit, C-terminal
• NAD(P) transhydrogenase, alpha subunit
• NADP transhydrogenase beta-like domain
• Alanine dehydrogenase/PNT, C-terminal domain
• NAD(P) transhydrogenase beta subunit
• 4TM region of pyridine nucleotide transhydrogenase, mitoch

KeywordsUniProt

• Acetylation
• Membrane
• Mitochondrion
• Mitochondrion inner membrane
• NAD
• NADP
• Nucleotide-binding
• Transit peptide
• Translocase
• Transmembrane
• Transmembrane helix