P28331 · NDUS1_HUMAN
- ProteinNADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
- GeneNDUFS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids727 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:30879903, PubMed:31557978).
Essential for catalysing the entry and efficient transfer of electrons within complex I (PubMed:31557978).
Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:30879903, PubMed:31557978).
Essential for catalysing the entry and efficient transfer of electrons within complex I (PubMed:31557978).
Plays a key role in the assembly and stability of complex I and participates in the association of complex I with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:30879903, PubMed:31557978).
Catalytic activity
- a ubiquinone + 5 H+(in) + NADH = a ubiquinol + 4 H+(out) + NAD+
a ubiquinone RHEA-COMP:9565 + 5 H+ (in)CHEBI:15378+ CHEBI:57945 = a ubiquinol RHEA-COMP:9566 + 4 H+ (out)CHEBI:15378+ CHEBI:57540
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 [2Fe-2S] cluster per subunit.
Note: Binds 2 [4Fe-4S] clusters per subunit.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 64 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 75 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 78 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 92 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 124 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 128 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 131 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 137 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 176 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 179 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 182 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 226 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial inner membrane | |
Cellular Component | mitochondrial intermembrane space | |
Cellular Component | mitochondrial matrix | |
Cellular Component | mitochondrial respiratory chain complex I | |
Cellular Component | mitochondrion | |
Cellular Component | respiratory chain complex I | |
Molecular Function | 2 iron, 2 sulfur cluster binding | |
Molecular Function | 4 iron, 4 sulfur cluster binding | |
Molecular Function | electron transfer activity | |
Molecular Function | metal ion binding | |
Molecular Function | NADH dehydrogenase (ubiquinone) activity | |
Biological Process | aerobic respiration | |
Biological Process | cellular respiration | |
Biological Process | mitochondrial electron transport, NADH to ubiquinone | |
Biological Process | mitochondrial respiratory chain complex I assembly | |
Biological Process | proton motive force-driven mitochondrial ATP synthesis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP28331
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion inner membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Mitochondrial complex I deficiency, nuclear type 5 (MC1DN5)
- Note
- DescriptionA form of mitochondrial complex I deficiency, the most common biochemical signature of mitochondrial disorders, a group of highly heterogeneous conditions characterized by defective oxidative phosphorylation, which collectively affects 1 in 5-10000 live births. Clinical disorders have variable severity, ranging 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. MC1DN5 transmission pattern is consistent with autosomal recessive inheritance.
- See alsoMIM:618226
Natural variants in MC1DN5
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_084177 | 228 | V>A | in MC1DN5; loss of catalytic activity | |
VAR_019532 | 241 | R>W | in MC1DN5; uncertain significance; dbSNP:rs199422225 | |
VAR_019533 | 252 | D>G | in MC1DN5; also found in a patient with muscular hypotonia; loss of catalytic activity; dbSNP:rs199422224 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_084177 | 228 | in MC1DN5; loss of catalytic activity | |||
Sequence: V → A | ||||||
Natural variant | VAR_025511 | 241 | in dbSNP:rs17856901 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_019532 | 241 | in MC1DN5; uncertain significance; dbSNP:rs199422225 | |||
Sequence: R → W | ||||||
Natural variant | VAR_019533 | 252 | in MC1DN5; also found in a patient with muscular hypotonia; loss of catalytic activity; dbSNP:rs199422224 | |||
Sequence: D → G | ||||||
Natural variant | VAR_069506 | 253 | in dbSNP:rs786205666 | |||
Sequence: V → G | ||||||
Natural variant | VAR_018463 | 649 | in dbSNP:rs1044049 | |||
Sequence: V → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 1,531 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-23 | Mitochondrion | ||||
Sequence: MLRIPVRKALVGLSKSPKGCVRT | ||||||
Chain | PRO_0000019968 | 24-727 | NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial | |||
Sequence: TATAASNLIEVFVDGQSVMVEPGTTVLQACEKVGMQIPRFCYHERLSVAGNCRMCLVEIEKAPKVVAACAMPVMKGWNILTNSEKSKKAREGVMEFLLANHPLDCPICDQGGECDLQDQSMMFGNDRSRFLEGKRAVEDKNIGPLVKTIMTRCIQCTRCIRFASEIAGVDDLGTTGRGNDMQVGTYIEKMFMSELSGNIIDICPVGALTSKPYAFTARPWETRKTESIDVMDAVGSNIVVSTRTGEVMRILPRMHEDINEEWISDKTRFAYDGLKRQRLTEPMVRNEKGLLTYTSWEDALSRVAGMLQSFQGKDVAAIAGGLVDAEALVALKDLLNRVDSDTLCTEEVFPTAGAGTDLRSNYLLNTTIAGVEEADVVLLVGTNPRFEAPLFNARIRKSWLHNDLKVALIGSPVDLTYTYDHLGDSPKILQDIASGSHPFSQVLKEAKKPMVVLGSSALQRNDGAAILAAVSSIAQKIRMTSGVTGDWKVMNILHRIASQVAALDLGYKPGVEAIRKNPPKVLFLLGADGGCITRQDLPKDCFIIYQGHHGDVGAPIADVILPGAAYTEKSATYVNTEGRAQQTKVAVTPPGLAREDWKIIRALSEIAGMTLPYDTLDQVRNRLEEVSPNLVRYDDIEGANYFQQANELSKLVNQQLLADPLVPPQLTIKDFYMTDSISRASQTMAKCVKAVTEGAQAVEEPSIC | ||||||
Modified residue | 84 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 467 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 499 | N6-acetyllysine | ||||
Sequence: K | ||||||
Modified residue | 709 | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits (PubMed:12611891).
This is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme (By similarity).
Complex I associates with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:30879903, PubMed:31557978).
Interacts with MDM2 (PubMed:30879903).
Interacts with AKAP1 (By similarity).
This is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme (By similarity).
Complex I associates with ubiquinol-cytochrome reductase complex (Complex III) to form supercomplexes (PubMed:30879903, PubMed:31557978).
Interacts with MDM2 (PubMed:30879903).
Interacts with AKAP1 (By similarity).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 30-108 | 2Fe-2S ferredoxin-type | ||||
Sequence: NLIEVFVDGQSVMVEPGTTVLQACEKVGMQIPRFCYHERLSVAGNCRMCLVEIEKAPKVVAACAMPVMKGWNILTNSEK | ||||||
Domain | 108-147 | 4Fe-4S His(Cys)3-ligated-type | ||||
Sequence: KSKKAREGVMEFLLANHPLDCPICDQGGECDLQDQSMMFG | ||||||
Domain | 245-301 | 4Fe-4S Mo/W bis-MGD-type | ||||
Sequence: TRKTESIDVMDAVGSNIVVSTRTGEVMRILPRMHEDINEEWISDKTRFAYDGLKRQR |
Sequence similarities
Belongs to the complex I 75 kDa subunit family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 5 isoforms produced by Alternative splicing.
P28331-1
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.
- Name1
- Length727
- Mass (Da)79,468
- Last updated2006-03-07 v3
- Checksum9C35F4B8294771FB
P28331-2
- Name2
- Differences from canonical
- 1-1: M → MRIRGSSGTLSRINM
P28331-3
- Name3
P28331-4
- Name4
- Differences from canonical
- 1-57: Missing
P28331-5
- Name5
- Differences from canonical
- 52-87: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_042682 | 1 | in isoform 2 | |||
Sequence: M → MRIRGSSGTLSRINM | ||||||
Alternative sequence | VSP_043728 | 1-2 | in isoform 3 | |||
Sequence: ML → MW | ||||||
Alternative sequence | VSP_043727 | 1-57 | in isoform 4 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_043729 | 3-113 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 8 | in Ref. 1; CAA43412 | ||||
Sequence: K → R | ||||||
Alternative sequence | VSP_045864 | 52-87 | in isoform 5 | |||
Sequence: Missing | ||||||
Sequence conflict | 417 | in Ref. 1; CAA43412 | ||||
Sequence: R → W | ||||||
Sequence conflict | 572 | in Ref. 2; BAG58551 | ||||
Sequence: H → L | ||||||
Sequence conflict | 691 | in Ref. 1; CAA43412 | ||||
Sequence: I → L |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X61100 EMBL· GenBank· DDBJ | CAA43412.1 EMBL· GenBank· DDBJ | mRNA | ||
AK295705 EMBL· GenBank· DDBJ | BAG58551.1 EMBL· GenBank· DDBJ | mRNA | ||
AK295987 EMBL· GenBank· DDBJ | BAG58762.1 EMBL· GenBank· DDBJ | mRNA | ||
AK298320 EMBL· GenBank· DDBJ | BAG60573.1 EMBL· GenBank· DDBJ | mRNA | ||
AK300585 EMBL· GenBank· DDBJ | BAG62283.1 EMBL· GenBank· DDBJ | mRNA | ||
AC007383 EMBL· GenBank· DDBJ | AAY15061.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471063 EMBL· GenBank· DDBJ | EAW70379.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC022368 EMBL· GenBank· DDBJ | AAH22368.1 EMBL· GenBank· DDBJ | mRNA | ||
BC030833 EMBL· GenBank· DDBJ | AAH30833.1 EMBL· GenBank· DDBJ | mRNA |