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Protein

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

Gene

NDUFS1

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 (By similarity). This is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized.By similarity

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • [2Fe-2S] clusterBy similarityNote: Binds 1 [2Fe-2S] cluster per subunit.By similarity
  • [4Fe-4S] clusterBy similarityNote: Binds 2 [4Fe-4S] clusters per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi64Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi75Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi78Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi92Iron-sulfur 1 (2Fe-2S)By similarity1
Metal bindingi124Iron-sulfur 2 (4Fe-4S); via tele nitrogenPROSITE-ProRule annotation1
Metal bindingi128Iron-sulfur 2 (4Fe-4S)PROSITE-ProRule annotation1
Metal bindingi131Iron-sulfur 2 (4Fe-4S)PROSITE-ProRule annotation1
Metal bindingi137Iron-sulfur 2 (4Fe-4S)PROSITE-ProRule annotation1
Metal bindingi176Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi179Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi182Iron-sulfur 3 (4Fe-4S)By similarity1
Metal bindingi226Iron-sulfur 3 (4Fe-4S)By similarity1

GO - Molecular functioni

  • 2 iron, 2 sulfur cluster binding Source: UniProtKB-KW
  • 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
  • electron transfer activity Source: UniProtKB
  • iron-sulfur cluster binding Source: GO_Central
  • metal ion binding Source: UniProtKB-KW
  • NADH dehydrogenase (ubiquinone) activity Source: UniProtKB

GO - Biological processi

  • apoptotic mitochondrial changes Source: UniProtKB
  • ATP metabolic process Source: UniProtKB
  • cellular respiration Source: UniProtKB
  • mitochondrial electron transport, NADH to ubiquinone Source: UniProtKB
  • mitochondrial respiratory chain complex I assembly Source: Reactome
  • reactive oxygen species metabolic process Source: UniProtKB
  • regulation of mitochondrial membrane potential Source: UniProtKB

Keywordsi

Molecular functionOxidoreductase
Biological processElectron transport, Respiratory chain, Transport
Ligand2Fe-2S, 4Fe-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-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (EC:1.6.5.3, EC:1.6.99.3)
Alternative name(s):
Complex I-75kD
Short name:
CI-75kD
Gene namesi
Name:NDUFS1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000023228.13
HGNCiHGNC:7707 NDUFS1
MIMi157655 gene
neXtProtiNX_P28331

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_019532241R → W in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422225EnsemblClinVar.1
Natural variantiVAR_019533252D → G in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422224EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Primary mitochondrial disease

Organism-specific databases

DisGeNETi4719
MalaCardsiNDUFS1
MIMi252010 phenotype
OpenTargetsiENSG00000023228
Orphaneti2609 Isolated NADH-CoQ reductase deficiency
255241 Leigh syndrome with leukodystrophy
PharmGKBiPA31518

Chemistry databases

ChEMBLiCHEMBL2363065
DrugBankiDB00157 NADH

Polymorphism and mutation databases

BioMutaiNDUFS1
DMDMi92090799

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 23MitochondrionCombined sourcesAdd BLAST23
ChainiPRO_000001996824 – 727NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrialAdd BLAST704

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei84N6-acetyllysineBy similarity1
Modified residuei467N6-acetyllysineBy similarity1
Modified residuei499N6-acetyllysineBy similarity1
Modified residuei709N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP28331
MaxQBiP28331
PaxDbiP28331
PeptideAtlasiP28331
PRIDEiP28331
ProteomicsDBi54470
54471 [P28331-2]
54472 [P28331-3]
54473 [P28331-4]

2D gel databases

REPRODUCTION-2DPAGEiIPI00604664
P28331
UCD-2DPAGEiP28331

PTM databases

CarbonylDBiP28331
iPTMnetiP28331
PhosphoSitePlusiP28331
SwissPalmiP28331

Miscellaneous databases

PMAP-CutDBiP28331

Expressioni

Gene expression databases

BgeeiENSG00000023228
CleanExiHS_NDUFS1
ExpressionAtlasiP28331 baseline and differential
GenevisibleiP28331 HS

Organism-specific databases

HPAiCAB070844
HPA064605

Interactioni

Subunit structurei

Complex I is composed of 45 different subunits.1 Publication

Protein-protein interaction databases

BioGridi110799, 104 interactors
ComplexPortaliCPX-577 Mitochondrial respiratory chain complex I
CORUMiP28331
IntActiP28331, 53 interactors
MINTiP28331
STRINGi9606.ENSP00000392709

Structurei

Secondary structure

1727
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi32 – 43Combined sources12
Helixi49 – 56Combined sources8
Turni91 – 93Combined sources3
Helixi107 – 120Combined sources14
Turni134 – 136Combined sources3
Helixi138 – 145Combined sources8
Helixi181 – 186Combined sources6
Turni187 – 190Combined sources4
Beta strandi209 – 211Combined sources3
Helixi221 – 225Combined sources5
Beta strandi227 – 229Combined sources3
Turni235 – 238Combined sources4
Helixi242 – 244Combined sources3
Beta strandi246 – 251Combined sources6
Beta strandi260 – 266Combined sources7
Beta strandi269 – 275Combined sources7
Turni279 – 282Combined sources4
Helixi288 – 291Combined sources4
Helixi293 – 298Combined sources6
Beta strandi306 – 308Combined sources3
Beta strandi314 – 316Combined sources3
Helixi319 – 330Combined sources12
Beta strandi335 – 337Combined sources3
Beta strandi340 – 342Combined sources3
Helixi348 – 360Combined sources13
Beta strandi368 – 370Combined sources3
Beta strandi380 – 382Combined sources3
Turni383 – 385Combined sources3
Turni391 – 393Combined sources3
Helixi394 – 396Combined sources3
Helixi407 – 409Combined sources3
Helixi412 – 423Combined sources12
Helixi448 – 457Combined sources10
Helixi461 – 468Combined sources8
Beta strandi469 – 471Combined sources3
Helixi478 – 481Combined sources4
Turni482 – 485Combined sources4
Helixi486 – 503Combined sources18
Helixi522 – 527Combined sources6
Helixi535 – 537Combined sources3
Beta strandi545 – 548Combined sources4
Beta strandi552 – 554Combined sources3
Helixi576 – 579Combined sources4
Beta strandi581 – 583Combined sources3
Turni589 – 591Combined sources3
Beta strandi595 – 597Combined sources3
Beta strandi603 – 605Combined sources3
Beta strandi613 – 615Combined sources3
Helixi619 – 629Combined sources11
Helixi639 – 647Combined sources9
Helixi652 – 654Combined sources3
Helixi666 – 673Combined sources8
Turni674 – 676Combined sources3
Helixi691 – 695Combined sources5
Helixi699 – 703Combined sources5
Helixi705 – 715Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5XTBelectron microscopy3.40M30-716[»]
5XTDelectron microscopy3.70M30-716[»]
5XTHelectron microscopy3.90M30-716[»]
5XTIelectron microscopy17.40BM/M30-716[»]
ProteinModelPortaliP28331
SMRiP28331
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 1082Fe-2S ferredoxin-typePROSITE-ProRule annotationAdd BLAST79
Domaini108 – 1474Fe-4S His(Cys)3-ligated-typePROSITE-ProRule annotationAdd BLAST40
Domaini245 – 3014Fe-4S Mo/W bis-MGD-typePROSITE-ProRule annotationAdd BLAST57

Sequence similaritiesi

Belongs to the complex I 75 kDa subunit family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2282 Eukaryota
COG1034 LUCA
GeneTreeiENSGT00390000018768
HOGENOMiHOG000031442
HOVERGENiHBG003482
InParanoidiP28331
KOiK03934
OMAiPQASCAM
OrthoDBiEOG091G02C2
PhylomeDBiP28331
TreeFamiTF105756

Family and domain databases

CDDicd00207 fer2, 1 hit
InterProiView protein in InterPro
IPR036010 2Fe-2S_ferredoxin-like_sf
IPR001041 2Fe-2S_ferredoxin-type
IPR006656 Mopterin_OxRdtase
IPR006963 Mopterin_OxRdtase_4Fe-4S_dom
IPR000283 NADH_UbQ_OxRdtase_75kDa_su_CS
IPR010228 NADH_UbQ_OxRdtase_Gsu
IPR019574 NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd
IPR015405 NuoG_C
PfamiView protein in Pfam
PF00384 Molybdopterin, 1 hit
PF10588 NADH-G_4Fe-4S_3, 1 hit
PF09326 NADH_dhqG_C, 1 hit
SMARTiView protein in SMART
SM00929 NADH-G_4Fe-4S_3, 1 hit
SUPFAMiSSF54292 SSF54292, 1 hit
TIGRFAMsiTIGR01973 NuoG, 1 hit
PROSITEiView protein in PROSITE
PS51085 2FE2S_FER_2, 1 hit
PS51839 4FE4S_HC3, 1 hit
PS51669 4FE4S_MOW_BIS_MGD, 1 hit
PS00641 COMPLEX1_75K_1, 1 hit
PS00642 COMPLEX1_75K_2, 1 hit
PS00643 COMPLEX1_75K_3, 1 hit

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P28331-1) [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
MLRIPVRKAL VGLSKSPKGC VRTTATAASN LIEVFVDGQS VMVEPGTTVL
60 70 80 90 100
QACEKVGMQI PRFCYHERLS VAGNCRMCLV EIEKAPKVVA ACAMPVMKGW
110 120 130 140 150
NILTNSEKSK KAREGVMEFL LANHPLDCPI CDQGGECDLQ DQSMMFGNDR
160 170 180 190 200
SRFLEGKRAV EDKNIGPLVK TIMTRCIQCT RCIRFASEIA GVDDLGTTGR
210 220 230 240 250
GNDMQVGTYI EKMFMSELSG NIIDICPVGA LTSKPYAFTA RPWETRKTES
260 270 280 290 300
IDVMDAVGSN IVVSTRTGEV MRILPRMHED INEEWISDKT RFAYDGLKRQ
310 320 330 340 350
RLTEPMVRNE KGLLTYTSWE DALSRVAGML QSFQGKDVAA IAGGLVDAEA
360 370 380 390 400
LVALKDLLNR VDSDTLCTEE VFPTAGAGTD LRSNYLLNTT IAGVEEADVV
410 420 430 440 450
LLVGTNPRFE APLFNARIRK SWLHNDLKVA LIGSPVDLTY TYDHLGDSPK
460 470 480 490 500
ILQDIASGSH PFSQVLKEAK KPMVVLGSSA LQRNDGAAIL AAVSSIAQKI
510 520 530 540 550
RMTSGVTGDW KVMNILHRIA SQVAALDLGY KPGVEAIRKN PPKVLFLLGA
560 570 580 590 600
DGGCITRQDL PKDCFIIYQG HHGDVGAPIA DVILPGAAYT EKSATYVNTE
610 620 630 640 650
GRAQQTKVAV TPPGLAREDW KIIRALSEIA GMTLPYDTLD QVRNRLEEVS
660 670 680 690 700
PNLVRYDDIE GANYFQQANE LSKLVNQQLL ADPLVPPQLT IKDFYMTDSI
710 720
SRASQTMAKC VKAVTEGAQA VEEPSIC
Length:727
Mass (Da):79,468
Last modified:March 7, 2006 - v3
Checksum:i9C35F4B8294771FB
GO
Isoform 2 (identifier: P28331-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MRIRGSSGTLSRINM

Note: No experimental confirmation available.
Show »
Length:741
Mass (Da):80,997
Checksum:iEB7CA8F41E3DF6E2
GO
Isoform 3 (identifier: P28331-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-2: ML → MW
     3-113: Missing.

Note: No experimental confirmation available.
Show »
Length:616
Mass (Da):67,524
Checksum:i16CA2EF571877D03
GO
Isoform 4 (identifier: P28331-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-57: Missing.

Note: No experimental confirmation available.
Show »
Length:670
Mass (Da):73,527
Checksum:iC8B37BF8C954187F
GO
Isoform 5 (identifier: P28331-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     52-87: Missing.

Note: No experimental confirmation available.
Show »
Length:691
Mass (Da):75,375
Checksum:i522872E0D6EB9E09
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti8K → R in CAA43412 (PubMed:1935949).Curated1
Sequence conflicti417R → W in CAA43412 (PubMed:1935949).Curated1
Sequence conflicti572H → L in BAG58551 (PubMed:14702039).Curated1
Sequence conflicti691I → L in CAA43412 (PubMed:1935949).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025511241R → Q1 PublicationCorresponds to variant dbSNP:rs17856901Ensembl.1
Natural variantiVAR_019532241R → W in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422225EnsemblClinVar.1
Natural variantiVAR_019533252D → G in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422224EnsemblClinVar.1
Natural variantiVAR_069506253V → G1 PublicationCorresponds to variant dbSNP:rs786205666Ensembl.1
Natural variantiVAR_018463649V → F1 PublicationCorresponds to variant dbSNP:rs1044049Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0437271 – 57Missing in isoform 4. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_0437281 – 2ML → MW in isoform 3. 1 Publication2
Alternative sequenceiVSP_0426821M → MRIRGSSGTLSRINM in isoform 2. Curated1
Alternative sequenceiVSP_0437293 – 113Missing in isoform 3. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_04586452 – 87Missing in isoform 5. 1 PublicationAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X61100 mRNA Translation: CAA43412.1
AK295705 mRNA Translation: BAG58551.1
AK295987 mRNA Translation: BAG58762.1
AK298320 mRNA Translation: BAG60573.1
AK300585 mRNA Translation: BAG62283.1
AC007383 Genomic DNA Translation: AAY15061.1
CH471063 Genomic DNA Translation: EAW70379.1
BC022368 mRNA Translation: AAH22368.1
BC030833 mRNA Translation: AAH30833.1
CCDSiCCDS2366.1 [P28331-1]
CCDS56162.1 [P28331-4]
CCDS56163.1 [P28331-3]
CCDS56164.1 [P28331-5]
CCDS56165.1 [P28331-2]
PIRiS17854
RefSeqiNP_001186910.1, NM_001199981.1 [P28331-5]
NP_001186911.1, NM_001199982.1 [P28331-3]
NP_001186912.1, NM_001199983.1 [P28331-4]
NP_001186913.1, NM_001199984.1 [P28331-2]
NP_004997.4, NM_005006.6 [P28331-1]
UniGeneiHs.471207
Hs.598436

Genome annotation databases

EnsembliENST00000233190; ENSP00000233190; ENSG00000023228 [P28331-1]
ENST00000423725; ENSP00000397760; ENSG00000023228 [P28331-4]
ENST00000432169; ENSP00000409689; ENSG00000023228 [P28331-3]
ENST00000440274; ENSP00000409766; ENSG00000023228 [P28331-5]
ENST00000449699; ENSP00000399912; ENSG00000023228 [P28331-1]
ENST00000455934; ENSP00000392709; ENSG00000023228 [P28331-2]
ENST00000635748; ENSP00000489640; ENSG00000283447 [P28331-1]
ENST00000636505; ENSP00000490898; ENSG00000283447 [P28331-1]
ENST00000637298; ENSP00000490583; ENSG00000283447 [P28331-4]
ENST00000637631; ENSP00000489705; ENSG00000283447 [P28331-3]
ENST00000637733; ENSP00000490092; ENSG00000283447 [P28331-2]
ENST00000637990; ENSP00000490766; ENSG00000283447 [P28331-5]
GeneIDi4719
KEGGihsa:4719
UCSCiuc002vbe.4 human [P28331-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNDUS1_HUMAN
AccessioniPrimary (citable) accession number: P28331
Secondary accession number(s): B4DIN9
, B4DJA0, B4DPG1, B4DUC1, E7ENF3, Q53TR8, Q8N1C4, Q8TCC9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: March 7, 2006
Last modified: June 20, 2018
This is version 199 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, Direct protein sequencing, Reference proteome

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