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Protein

NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial

Gene

NDUFS1

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 (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 nitrogen1
Metal bindingi128Iron-sulfur 2 (4Fe-4S)1
Metal bindingi131Iron-sulfur 2 (4Fe-4S)1
Metal bindingi137Iron-sulfur 2 (4Fe-4S)1
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 carrier 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: Reactome
  • 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.

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:rs199422225Ensembl.1
Natural variantiVAR_019533252D → G in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422224Ensembl.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.

2D gel databases

REPRODUCTION-2DPAGEiIPI00604664.
P28331.
UCD-2DPAGEiP28331.

PTM databases

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. 101 interactors.
CORUMiP28331.
IntActiP28331. 43 interactors.
MINTiMINT-3011123.
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-typeAdd BLAST79
Domaini108 – 1474Fe-4S His(Cys)3-ligated-typeAdd BLAST40
Domaini245 – 3014Fe-4S Mo/W bis-MGD-typeAdd 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.
Gene3Di3.10.20.30. 1 hit.
InterProiView protein in InterPro
IPR036010. 2Fe-2S_ferredoxin-like_sf.
IPR001041. 2Fe-2S_ferredoxin-type.
IPR012675. Beta-grasp_dom_sf.
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:rs199422225Ensembl.1
Natural variantiVAR_019533252D → G in MT-C1D. 1 PublicationCorresponds to variant dbSNP:rs199422224Ensembl.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: November 22, 2017
This is version 194 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

Documents

  1. Human chromosome 2
    Human chromosome 2: 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