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Protein

NAD(P) transhydrogenase, mitochondrial

Gene

NNT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.1 Publication

Catalytic activityi

NADPH + NAD+ = NADP+ + NADH.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei933NADP; via amide nitrogen1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi229 – 259NADBy similarityAdd BLAST31
Nucleotide bindingi965 – 970NADP1 Publication6
Nucleotide bindingi1007 – 1011NADP1 Publication5
Nucleotide bindingi1042 – 1049NADP1 Publication8
Nucleotide bindingi1068 – 1069NADP1 Publication2

GO - Molecular functioni

  • NAD(P)+ transhydrogenase (AB-specific) activity Source: GO_Central
  • NAD(P)+ transhydrogenase (B-specific) activity Source: UniProtKB
  • NAD(P)+ transhydrogenase activity Source: Reactome
  • NAD binding Source: UniProtKB
  • NADP binding Source: UniProtKB

GO - Biological processi

  • NADPH regeneration Source: GO_Central
  • oxidation-reduction process Source: UniProtKB
  • proton transmembrane transport Source: UniProtKB
  • reactive oxygen species metabolic process Source: UniProtKB
  • tricarboxylic acid cycle Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
LigandNAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS03639-MONOMER
BRENDAi1.6.1.2 2681
ReactomeiR-HSA-71403 Citric acid cycle (TCA cycle)

Names & Taxonomyi

Protein namesi
Recommended name:
NAD(P) transhydrogenase, mitochondrial (EC:1.6.1.2)
Alternative name(s):
Nicotinamide nucleotide transhydrogenase
Pyridine nucleotide transhydrogenase
Gene namesi
Name:NNT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000112992.16
HGNCiHGNC:7863 NNT
MIMi607878 gene
neXtProtiNX_Q13423

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini44 – 474Mitochondrial matrixAdd BLAST431
Transmembranei475 – 493HelicalSequence analysisAdd BLAST19
Transmembranei501 – 521HelicalSequence analysisAdd BLAST21
Transmembranei527 – 546HelicalSequence analysisAdd BLAST20
Transmembranei558 – 578HelicalSequence analysisAdd BLAST21
Topological domaini579 – 595Mitochondrial matrixAdd BLAST17
Transmembranei596 – 616HelicalSequence analysisAdd BLAST21
Transmembranei622 – 642HelicalSequence analysisAdd BLAST21
Transmembranei646 – 666HelicalSequence analysisAdd BLAST21
Transmembranei672 – 691HelicalSequence analysisAdd BLAST20
Transmembranei702 – 722HelicalSequence analysisAdd BLAST21
Topological domaini723 – 739CytoplasmicAdd BLAST17
Transmembranei740 – 760HelicalSequence analysisAdd BLAST21
Transmembranei778 – 797HelicalSequence analysisAdd BLAST20
Transmembranei801 – 819HelicalSequence analysisAdd BLAST19
Transmembranei833 – 853HelicalSequence analysisAdd BLAST21
Transmembranei857 – 879HelicalSequence analysisAdd BLAST23
Topological domaini880 – 1086Mitochondrial matrixAdd BLAST207

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Glucocorticoid deficiency 4 with or without mineralocorticoid deficiency (GCCD4)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of glucocorticoid deficiency, a rare autosomal recessive disorder characterized by resistance to ACTH action on the adrenal cortex, adrenal insufficiency and an inability of the adrenal cortex to produce cortisol. It usually presents in the neonatal period or in early childhood with episodes of hypoglycemia and other symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, convulsions, and shock. In a small number of patients hypoglycemia can be sufficiently severe and persistent that it leads to serious long-term neurological damage or death. The diagnosis is readily confirmed with a low plasma cortisol measurement in the presence of an elevated ACTH level, and normal aldosterone and plasma renin measurements.
See also OMIM:614736
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068781193S → N in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs867004061Ensembl.1
Natural variantiVAR_068782357T → A in GCCD4. 1 Publication1
Natural variantiVAR_068783365H → P in GCCD4. 1 Publication1
Natural variantiVAR_068784437P → L in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs781183677Ensembl.1
Natural variantiVAR_068785533A → V in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907232Ensembl.1
Natural variantiVAR_068786664G → R in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs371979800Ensembl.1
Natural variantiVAR_068787678G → R in GCCD4. 1 Publication1
Natural variantiVAR_068788862G → D in GCCD4. 1 Publication1
Natural variantiVAR_068789977L → P in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907233Ensembl.1
Natural variantiVAR_0687901008A → P in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907234Ensembl.1
Natural variantiVAR_0687911009N → K in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs370273690Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23530
MalaCardsiNNT
MIMi614736 phenotype
OpenTargetsiENSG00000112992
Orphaneti361 Familial glucocorticoid deficiency
PharmGKBiPA31667

Chemistry databases

DrugBankiDB03461 2'-Monophosphoadenosine 5'-Diphosphoribose
DB01763 7-thionicotinamide-adenine-dinucleotide phosphate
DB00157 NADH

Polymorphism and mutation databases

BioMutaiNNT
DMDMi51338801

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 43MitochondrionBy similarityAdd BLAST43
ChainiPRO_000000105544 – 1086NAD(P) transhydrogenase, mitochondrialAdd BLAST1043

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei70N6-acetyllysineCombined sources1
Modified residuei117N6-succinyllysineBy similarity1
Modified residuei224N6-succinyllysineBy similarity1
Modified residuei294N6-succinyllysineBy similarity1
Modified residuei331N6-succinyllysineBy similarity1
Modified residuei397N6-acetyllysineCombined sources1
Modified residuei1079N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ13423
MaxQBiQ13423
PaxDbiQ13423
PeptideAtlasiQ13423
PRIDEiQ13423

PTM databases

CarbonylDBiQ13423
iPTMnetiQ13423
PhosphoSitePlusiQ13423
SwissPalmiQ13423

Expressioni

Tissue specificityi

Widely expressed with expression most readily detectable in adrenal, heart, kidney, thyroid and adipose tissues.1 Publication

Gene expression databases

BgeeiENSG00000112992
CleanExiHS_NNT
ExpressionAtlasiQ13423 baseline and differential
GenevisibleiQ13423 HS

Organism-specific databases

HPAiCAB004975
HPA004829

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi117076, 55 interactors
IntActiQ13423, 19 interactors
STRINGi9606.ENSP00000264663

Structurei

Secondary structure

11086
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi914 – 923Combined sources10
Beta strandi925 – 931Combined sources7
Helixi933 – 938Combined sources6
Helixi941 – 953Combined sources13
Beta strandi957 – 962Combined sources6
Beta strandi967 – 969Combined sources3
Helixi972 – 979Combined sources8
Helixi984 – 986Combined sources3
Beta strandi987 – 989Combined sources3
Helixi990 – 993Combined sources4
Helixi994 – 999Combined sources6
Beta strandi1001 – 1007Combined sources7
Helixi1010 – 1012Combined sources3
Helixi1015 – 1018Combined sources4
Turni1023 – 1026Combined sources4
Helixi1032 – 1034Combined sources3
Beta strandi1035 – 1045Combined sources11
Helixi1055 – 1058Combined sources4
Beta strandi1062 – 1067Combined sources6
Helixi1069 – 1081Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DJLX-ray2.00A/B880-1086[»]
1PT9X-ray2.42A/B880-1086[»]
1U31X-ray2.20A/B880-1086[»]
ProteinModelPortaliQ13423
SMRiQ13423
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13423

Family & Domainsi

Sequence similaritiesi

In the N-terminal section; belongs to the AlaDH/PNT family.Curated
In the C-terminal section; belongs to the PNT beta subunit family.Curated

Keywords - Domaini

Transit peptide, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEMU Eukaryota
COG1282 LUCA
COG3288 LUCA
GeneTreeiENSGT00390000004624
HOGENOMiHOG000160623
HOVERGENiHBG006511
InParanoidiQ13423
KOiK00323
OMAiKPGIPYK
OrthoDBiEOG091G01NO
PhylomeDBiQ13423
TreeFamiTF300636

Family and domain databases

InterProiView protein in InterPro
IPR008143 Ala_DH/PNT_CS2
IPR008142 AlaDH/PNT_CS1
IPR007886 AlaDH/PNT_N
IPR007698 AlaDH/PNT_NAD(H)-bd
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR036291 NAD(P)-bd_dom_sf
IPR026255 NADP_transhyd_a
IPR024605 NADP_transhyd_a_C
IPR034300 PNTB-like
PfamiView protein in Pfam
PF01262 AlaDh_PNT_C, 1 hit
PF05222 AlaDh_PNT_N, 1 hit
PF02233 PNTB, 1 hit
PF12769 PNTB_4TM, 1 hit
SMARTiView protein in SMART
SM01002 AlaDh_PNT_C, 1 hit
SM01003 AlaDh_PNT_N, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
SSF52467 SSF52467, 1 hit
TIGRFAMsiTIGR00561 pntA, 1 hit
PROSITEiView protein in PROSITE
PS00836 ALADH_PNT_1, 1 hit
PS00837 ALADH_PNT_2, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q13423-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MANLLKTVVT GCSCPLLSNL GSCKGLRVKK DFLRTFYTHQ ELWCKAPVKP
60 70 80 90 100
GIPYKQLTVG VPKEIFQNEK RVALSPAGVQ NLVKQGFNVV VESGAGEASK
110 120 130 140 150
FSDDHYRVAG AQIQGAKEVL ASDLVVKVRA PMVNPTLGVH EADLLKTSGT
160 170 180 190 200
LISFIYPAQN PELLNKLSQR KTTVLAMDQV PRVTIAQGYD ALSSMANIAG
210 220 230 240 250
YKAVVLAANH FGRFFTGQIT AAGKVPPAKI LIVGGGVAGL ASAGAAKSMG
260 270 280 290 300
AIVRGFDTRA AALEQFKSLG AEPLEVDLKE SGEGQGGYAK EMSKEFIEAE
310 320 330 340 350
MKLFAQQCKE VDILISTALI PGKKAPVLFN KEMIESMKEG SVVVDLAAEA
360 370 380 390 400
GGNFETTKPG ELYIHKGITH IGYTDLPSRM ATQASTLYSN NITKLLKAIS
410 420 430 440 450
PDKDNFYFDV KDDFDFGTMG HVIRGTVVMK DGKVIFPAPT PKNIPQGAPV
460 470 480 490 500
KQKTVAELEA EKAATITPFR KTMSTASAYT AGLTGILGLG IAAPNLAFSQ
510 520 530 540 550
MVTTFGLAGI VGYHTVWGVT PALHSPLMSV TNAISGLTAV GGLALMGGHL
560 570 580 590 600
YPSTTSQGLA ALAAFISSVN IAGGFLVTQR MLDMFKRPTD PPEYNYLYLL
610 620 630 640 650
PAGTFVGGYL AALYSGYNIE QIMYLGSGLC CVGALAGLST QGTARLGNAL
660 670 680 690 700
GMIGVAGGLA ATLGVLKPGP ELLAQMSGAM ALGGTIGLTI AKRIQISDLP
710 720 730 740 750
QLVAAFHSLV GLAAVLTCIA EYIIEYPHFA TDAAANLTKI VAYLGTYIGG
760 770 780 790 800
VTFSGSLIAY GKLQGLLKSA PLLLPGRHLL NAGLLAASVG GIIPFMVDPS
810 820 830 840 850
FTTGITCLGS VSALSAVMGV TLTAAIGGAD MPVVITVLNS YSGWALCAEG
860 870 880 890 900
FLLNNNLLTI VGALIGSSGA ILSYIMCVAM NRSLANVILG GYGTTSTAGG
910 920 930 940 950
KPMEISGTHT EINLDNAIDM IREANSIIIT PGYGLCAAKA QYPIADLVKM
960 970 980 990 1000
LTEQGKKVRF GIHPVAGRMP GQLNVLLAEA GVPYDIVLEM DEINHDFPDT
1010 1020 1030 1040 1050
DLVLVIGAND TVNSAAQEDP NSIIAGMPVL EVWKSKQVIV MKRSLGVGYA
1060 1070 1080
AVDNPIFYKP NTAMLLGDAK KTCDALQAKV RESYQK
Length:1,086
Mass (Da):113,896
Last modified:August 16, 2004 - v3
Checksum:i8A437658CA0EB41B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti176A → T in CAA90428 (PubMed:8616157).Curated1
Sequence conflicti212G → E in CAD38536 (PubMed:17974005).Curated1
Sequence conflicti246A → E in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti262A → S in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti706F → S in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti731T → P in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti810S → A in CAA90428 (PubMed:8616157).Curated1
Sequence conflicti824A → P in CAA90428 (PubMed:8616157).Curated1
Sequence conflicti871I → P in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti929I → F in AAC51914 (PubMed:9524818).Curated1
Sequence conflicti1059K → R in CAD38536 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068781193S → N in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs867004061Ensembl.1
Natural variantiVAR_068782357T → A in GCCD4. 1 Publication1
Natural variantiVAR_068783365H → P in GCCD4. 1 Publication1
Natural variantiVAR_068784437P → L in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs781183677Ensembl.1
Natural variantiVAR_068785533A → V in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907232Ensembl.1
Natural variantiVAR_068786664G → R in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs371979800Ensembl.1
Natural variantiVAR_068787678G → R in GCCD4. 1 Publication1
Natural variantiVAR_068788862G → D in GCCD4. 1 Publication1
Natural variantiVAR_068789977L → P in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907233Ensembl.1
Natural variantiVAR_0687901008A → P in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs387907234Ensembl.1
Natural variantiVAR_0687911009N → K in GCCD4. 1 PublicationCorresponds to variant dbSNP:rs370273690Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U40490 mRNA Translation: AAC51914.1
Z50101 mRNA Translation: CAA90428.1
AL831822 mRNA Translation: CAD38536.1
BC110543 mRNA Translation: AAI10544.1
CCDSiCCDS3949.1
PIRiG02257
RefSeqiNP_036475.3, NM_012343.3
NP_892022.2, NM_182977.2
XP_005248331.1, XM_005248274.4
XP_011512303.1, XM_011514001.2
XP_016864782.1, XM_017009293.1
UniGeneiHs.482043

Genome annotation databases

EnsembliENST00000264663; ENSP00000264663; ENSG00000112992
ENST00000344920; ENSP00000343873; ENSG00000112992
GeneIDi23530
KEGGihsa:23530
UCSCiuc003joe.4 human

Similar proteinsi

Entry informationi

Entry nameiNNTM_HUMAN
AccessioniPrimary (citable) accession number: Q13423
Secondary accession number(s): Q16796, Q2TB60, Q8N3V4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: August 16, 2004
Last modified: April 25, 2018
This is version 180 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health