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Protein

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

Gene

NDUFS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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 carrier 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 electron transport, NADH to ubiquinone Source: UniProtKB
  • mitochondrial respiratory chain complex I assembly Source: Reactome
  • response to oxidative stress Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Electron transport, Respiratory chain, Transport

Keywords - Ligandi

4Fe-4S, Iron, Iron-sulfur, Metal-binding, NAD, Ubiquinone

Enzyme and pathway databases

BioCyciZFISH:HS08339-MONOMER.
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

HGNCiHGNC:7708. NDUFS2.

Subcellular locationi

GO - Cellular componenti

  • mitochondrial matrix Source: Reactome
  • mitochondrial respiratory chain complex I Source: UniProtKB
  • mitochondrion Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

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 rs121434427dbSNPEnsembl.1
Natural variantiVAR_019536229P → Q in MT-C1D. 1 PublicationCorresponds to variant rs121434428dbSNPEnsembl.1
Natural variantiVAR_019537413S → P in MT-C1D. 1 PublicationCorresponds to variant rs121434429dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

ChEMBLiCHEMBL2363065.
DrugBankiDB00997. Doxorubicin.

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.
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. 64 interactors.
IntActiO75306. 33 interactors.
STRINGi9606.ENSP00000356972.

Structurei

3D structure databases

ProteinModelPortaliO75306.
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.
OMAiMADVITI.
OrthoDBiEOG091G0WWQ.
PhylomeDBiO75306.
TreeFamiTF300370.

Family and domain databases

Gene3Di1.10.645.10. 1 hit.
HAMAPiMF_01358. NDH1_NuoD. 1 hit.
InterProiIPR001135. NADH_Q_OxRdtase_suD.
IPR014029. NADH_UbQ_OxRdtase_49kDa_CS.
IPR022885. NDH1_su_D/H.
IPR029014. NiFe_Hase-like.
[Graphical view]
PfamiPF00346. Complex1_49kDa. 1 hit.
[Graphical view]
SUPFAMiSSF56762. SSF56762. 1 hit.
TIGRFAMsiTIGR01962. NuoD. 1 hit.
PROSITEiPS00535. COMPLEX1_49K. 1 hit.
[Graphical view]

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 rs11538340dbSNPEnsembl.1
Natural variantiVAR_071891224A → V.1 Publication1
Natural variantiVAR_019535228R → Q in MT-C1D. 1 PublicationCorresponds to variant rs121434427dbSNPEnsembl.1
Natural variantiVAR_034151229P → A.Corresponds to variant rs16827493dbSNPEnsembl.1
Natural variantiVAR_019536229P → Q in MT-C1D. 1 PublicationCorresponds to variant rs121434428dbSNPEnsembl.1
Natural variantiVAR_034152352P → A.Corresponds to variant rs11576415dbSNPEnsembl.1
Natural variantiVAR_019537413S → P in MT-C1D. 1 PublicationCorresponds to variant rs121434429dbSNPEnsembl.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. Translation: CAH72148.1.
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

Cross-referencesi

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. Translation: CAH72148.1.
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.

3D structure databases

ProteinModelPortaliO75306.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110800. 64 interactors.
IntActiO75306. 33 interactors.
STRINGi9606.ENSP00000356972.

Chemistry databases

ChEMBLiCHEMBL2363065.
DrugBankiDB00997. Doxorubicin.

PTM databases

iPTMnetiO75306.
PhosphoSitePlusiO75306.
SwissPalmiO75306.

Polymorphism and mutation databases

BioMutaiNDUFS2.

Proteomic databases

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

Protocols and materials databases

DNASUi4720.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4720.
DisGeNETi4720.
GeneCardsiNDUFS2.
HGNCiHGNC:7708. NDUFS2.
HPAiHPA055140.
HPA061953.
MalaCardsiNDUFS2.
MIMi252010. phenotype.
602985. gene.
neXtProtiNX_O75306.
OpenTargetsiENSG00000158864.
Orphaneti2609. Isolated NADH-CoQ reductase deficiency.
PharmGKBiPA31519.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS08339-MONOMER.
ReactomeiR-HSA-611105. Respiratory electron transport.
R-HSA-6799198. Complex I biogenesis.

Miscellaneous databases

ChiTaRSiNDUFS2. human.
GeneWikiiNDUFS2.
GenomeRNAii4720.
PROiO75306.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158864.
CleanExiHS_NDUFS2.
GenevisibleiO75306. HS.

Family and domain databases

Gene3Di1.10.645.10. 1 hit.
HAMAPiMF_01358. NDH1_NuoD. 1 hit.
InterProiIPR001135. NADH_Q_OxRdtase_suD.
IPR014029. NADH_UbQ_OxRdtase_49kDa_CS.
IPR022885. NDH1_su_D/H.
IPR029014. NiFe_Hase-like.
[Graphical view]
PfamiPF00346. Complex1_49kDa. 1 hit.
[Graphical view]
SUPFAMiSSF56762. SSF56762. 1 hit.
TIGRFAMsiTIGR01962. NuoD. 1 hit.
PROSITEiPS00535. COMPLEX1_49K. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNDUS2_HUMAN
AccessioniPrimary (citable) accession number: O75306
Secondary accession number(s): D3DVG7
, J3KPM7, Q5VTW0, Q969P3, Q9UEV3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: April 16, 2002
Last modified: November 30, 2016
This is version 173 of the entry and version 2 of the sequence. [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

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. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.