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Protein

NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial

Gene

NDUFS2

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

Functioni

Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:12611891).1 Publication

Catalytic activityi

NADH + ubiquinone + 5 H+(In) = NAD+ + ubiquinol + 4 H+(Out).
NADH + acceptor = NAD+ + reduced acceptor.

Cofactori

[4Fe-4S] clusterNote: Binds 1 [4Fe-4S] cluster.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi326Iron-sulfur (4Fe-4S)Sequence analysis1
Metal bindingi332Iron-sulfur (4Fe-4S)Sequence analysis1
Metal bindingi347Iron-sulfur (4Fe-4S)Sequence analysis1

GO - Molecular functioni

  • 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  • electron transfer activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • NAD binding Source: InterPro
  • NADH dehydrogenase (ubiquinone) activity Source: UniProtKB
  • quinone binding Source: InterPro
  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • mitochondrial ATP synthesis coupled electron transport Source: CAFA
  • mitochondrial electron transport, NADH to ubiquinone Source: UniProtKB
  • mitochondrial respiratory chain complex I assembly Source: Reactome
  • response to oxidative stress Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
Biological processElectron transport, Respiratory chain, Transport
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding, NAD, Ubiquinone

Enzyme and pathway databases

ReactomeiR-HSA-611105 Respiratory electron transport
R-HSA-6799198 Complex I biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial (EC:1.6.5.3, EC:1.6.99.3)
Alternative name(s):
Complex I-49kD
Short name:
CI-49kD
NADH-ubiquinone oxidoreductase 49 kDa subunit
Gene namesi
Name:NDUFS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000158864.12
HGNCiHGNC:7708 NDUFS2
MIMi602985 gene
neXtProtiNX_O75306

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

Keywords - Cellular componenti

Membrane, Mitochondrion, Mitochondrion inner membrane

Pathology & Biotechi

Involvement in diseasei

Mitochondrial complex I deficiency (MT-C1D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.
See also OMIM:252010
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_019535228R → Q in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434427EnsemblClinVar.1
Natural variantiVAR_019536229P → Q in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434428EnsemblClinVar.1
Natural variantiVAR_019537413S → P in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434429EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Primary mitochondrial disease

Organism-specific databases

DisGeNETi4720
MalaCardsiNDUFS2
MIMi252010 phenotype
OpenTargetsiENSG00000158864
Orphaneti2609 Isolated NADH-CoQ reductase deficiency
PharmGKBiPA31519

Chemistry databases

ChEMBLiCHEMBL2363065
DrugBankiDB00997 Doxorubicin
DB00157 NADH

Polymorphism and mutation databases

BioMutaiNDUFS2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 33MitochondrionBy similarityAdd BLAST33
ChainiPRO_000001998134 – 463NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrialAdd BLAST430

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62N6-acetyllysineBy similarity1
Modified residuei118Symmetric dimethylarginine2 Publications1

Post-translational modificationi

Dimethylation at Arg-118 by NDUFAF7 takes place after NDUFS2 assembles into the complex I, leading to stabilize the early intermediate complex (PubMed:24089531, PubMed:24838397).2 Publications

Keywords - PTMi

Acetylation, Methylation

Proteomic databases

EPDiO75306
MaxQBiO75306
PaxDbiO75306
PeptideAtlasiO75306
PRIDEiO75306
ProteomicsDBi49883
TopDownProteomicsiO75306-1 [O75306-1]

PTM databases

iPTMnetiO75306
PhosphoSitePlusiO75306
SwissPalmiO75306

Expressioni

Gene expression databases

BgeeiENSG00000158864
CleanExiHS_NDUFS2
GenevisibleiO75306 HS

Organism-specific databases

HPAiHPA055140
HPA061953

Interactioni

Subunit structurei

Complex I is composed of 45 different subunits. Component of the iron-sulfur (IP) fragment of the enzyme (PubMed:12611891). Interacts with NDUFAF3 (PubMed:19463981). Interacts with NDUFAF7 (PubMed:20406883, PubMed:24089531).4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NDUFS3O754896EBI-1224806,EBI-1224896

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi110800, 65 interactors
ComplexPortaliCPX-577 Mitochondrial respiratory chain complex I
CORUMiO75306
IntActiO75306, 47 interactors
MINTiO75306
STRINGi9606.ENSP00000356972

Structurei

Secondary structure

1463
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi80 – 82Combined sources3
Beta strandi86 – 88Combined sources3
Turni89 – 94Combined sources6
Beta strandi96 – 105Combined sources10
Beta strandi107 – 112Combined sources6
Helixi120 – 125Combined sources6
Helixi129 – 132Combined sources4
Helixi134 – 137Combined sources4
Beta strandi140 – 142Combined sources3
Helixi145 – 158Combined sources14
Helixi165 – 193Combined sources29
Helixi198 – 218Combined sources21
Beta strandi219 – 223Combined sources5
Beta strandi231 – 234Combined sources4
Helixi240 – 249Combined sources10
Helixi251 – 259Combined sources9
Turni260 – 264Combined sources5
Helixi266 – 272Combined sources7
Helixi280 – 286Combined sources7
Helixi291 – 294Combined sources4
Turni295 – 297Combined sources3
Helixi310 – 312Combined sources3
Beta strandi318 – 320Combined sources3
Helixi326 – 349Combined sources24
Turni361 – 363Combined sources3
Helixi368 – 371Combined sources4
Helixi375 – 384Combined sources10
Turni385 – 387Combined sources3
Beta strandi393 – 402Combined sources10
Beta strandi405 – 413Combined sources9
Beta strandi415 – 423Combined sources9
Helixi427 – 439Combined sources13
Helixi444 – 453Combined sources10
Helixi458 – 461Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5XTBelectron microscopy3.40Q79-463[»]
5XTCelectron microscopy3.70Q34-79[»]
5XTDelectron microscopy3.70Q34-463[»]
5XTHelectron microscopy3.90Q34-463[»]
5XTIelectron microscopy17.40BQ/Q34-463[»]
ProteinModelPortaliO75306
SMRiO75306
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the complex I 49 kDa subunit family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2870 Eukaryota
COG0649 LUCA
GeneTreeiENSGT00390000009529
HOGENOMiHOG000228264
HOVERGENiHBG000760
InParanoidiO75306
KOiK03935
OMAiKKIAWPA
OrthoDBiEOG091G0WWQ
PhylomeDBiO75306
TreeFamiTF300370

Family and domain databases

Gene3Di1.10.645.20, 1 hit
HAMAPiMF_01358 NDH1_NuoD, 1 hit
InterProiView protein in InterPro
IPR001135 NADH_Q_OxRdtase_suD
IPR038290 NADH_Q_OxRdtase_suD_sf
IPR014029 NADH_UbQ_OxRdtase_49kDa_CS
IPR022885 NDH1_su_D/H
IPR029014 NiFe-Hase_large
PfamiView protein in Pfam
PF00346 Complex1_49kDa, 1 hit
SUPFAMiSSF56762 SSF56762, 1 hit
TIGRFAMsiTIGR01962 NuoD, 1 hit
PROSITEiView protein in PROSITE
PS00535 COMPLEX1_49K, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75306-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAALRALCGF RGVAAQVLRP GAGVRLPIQP SRGVRQWQPD VEWAQQFGGA
60 70 80 90 100
VMYPSKETAH WKPPPWNDVD PPKDTIVKNI TLNFGPQHPA AHGVLRLVME
110 120 130 140 150
LSGEMVRKCD PHIGLLHRGT EKLIEYKTYL QALPYFDRLD YVSMMCNEQA
160 170 180 190 200
YSLAVEKLLN IRPPPRAQWI RVLFGEITRL LNHIMAVTTH ALDLGAMTPF
210 220 230 240 250
FWLFEEREKM FEFYERVSGA RMHAAYIRPG GVHQDLPLGL MDDIYQFSKN
260 270 280 290 300
FSLRLDELEE LLTNNRIWRN RTIDIGVVTA EEALNYGFSG VMLRGSGIQW
310 320 330 340 350
DLRKTQPYDV YDQVEFDVPV GSRGDCYDRY LCRVEEMRQS LRIIAQCLNK
360 370 380 390 400
MPPGEIKVDD AKVSPPKRAE MKTSMESLIH HFKLYTEGYQ VPPGATYTAI
410 420 430 440 450
EAPKGEFGVY LVSDGSSRPY RCKIKAPGFA HLAGLDKMSK GHMLADVVAI
460
IGTQDIVFGE VDR
Length:463
Mass (Da):52,546
Last modified:April 16, 2002 - v2
Checksum:iA2BF56F008B6312C
GO
Isoform 2 (identifier: O75306-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     454-463: QDIVFGEVDR → RPIV

Note: No experimental confirmation available.
Show »
Length:457
Mass (Da):51,852
Checksum:i312C97A91028FF66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti24V → G in AAC34362 (PubMed:9585441).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03415020P → T. Corresponds to variant dbSNP:rs11538340EnsemblClinVar.1
Natural variantiVAR_071891224A → V1 Publication1
Natural variantiVAR_019535228R → Q in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434427EnsemblClinVar.1
Natural variantiVAR_034151229P → A. Corresponds to variant dbSNP:rs16827493Ensembl.1
Natural variantiVAR_019536229P → Q in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434428EnsemblClinVar.1
Natural variantiVAR_034152352P → A. Corresponds to variant dbSNP:rs11576415EnsemblClinVar.1
Natural variantiVAR_019537413S → P in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs121434429EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046466454 – 463QDIVFGEVDR → RPIV in isoform 2. Curated10

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF050640 mRNA Translation: AAC27453.1
AF013160 mRNA Translation: AAC34362.1
AK314807 mRNA No translation available.
AL590714 Genomic DNA No translation available.
CH471121 Genomic DNA Translation: EAW52625.1
CH471121 Genomic DNA Translation: EAW52626.1
BC000170 mRNA Translation: AAH00170.1
BC001456 mRNA Translation: AAH01456.1
BC008868 mRNA Translation: AAH08868.1
CCDSiCCDS1224.1 [O75306-1]
CCDS53404.1 [O75306-2]
PIRiJE0193
RefSeqiNP_001159631.1, NM_001166159.1 [O75306-2]
NP_004541.1, NM_004550.4 [O75306-1]
XP_005245265.1, XM_005245208.2 [O75306-1]
XP_016856846.1, XM_017001357.1 [O75306-1]
UniGeneiHs.173611

Genome annotation databases

EnsembliENST00000367993; ENSP00000356972; ENSG00000158864 [O75306-1]
ENST00000392179; ENSP00000376018; ENSG00000158864 [O75306-2]
GeneIDi4720
KEGGihsa:4720
UCSCiuc001fyv.4 human [O75306-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNDUS2_HUMAN
AccessioniPrimary (citable) accession number: O75306
Secondary accession number(s): D3DVG7
, J3KPM7, Q5VTW0, Q969P3, Q9UEV3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: April 16, 2002
Last modified: June 20, 2018
This is version 186 of the entry and version 2 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

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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