O43181 (NDUS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial

Alternative name(s):
Complex I-18 kDa
Short name=CI-18 kDa
Complex I-AQDQ
Short name=CI-AQDQ
NADH-ubiquinone oxidoreductase 18 kDa subunit

Gene names

Name:

NDUFS4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	175 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in 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.
Subunit structure	Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Involvement in disease	Defects in NDUFS4 are a cause of mitochondrial complex I deficiency (MT-C1D) [MIM:252010]. A disorder of the mitochondrial respiratory chain that causes a wide range of clinical disorders, 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. Ref.1
Sequence similarities	Belongs to the complex I NDUFS4 subunit family.

Ontologies

Keywords
Biological process	Electron transport Respiratory chain Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Domain	Transit peptide
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	brain development Inferred from mutant phenotype. Source: UniProtKB cAMP-mediated signaling Inferred from mutant phenotype. Source: UniProtKB mitochondrial electron transport, NADH to ubiquinone Non-traceable author statement Ref.1. Source: UniProtKB mitochondrial respiratory chain complex I assembly Inferred from mutant phenotype. Source: UniProtKB positive regulation of fibroblast proliferation Inferred from mutant phenotype. Source: UniProtKB reactive oxygen species metabolic process Inferred from mutant phenotype. Source: UniProtKB regulation of protein phosphorylation Inferred from mutant phenotype. Source: MGI response to cAMP Inferred from mutant phenotype. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial respiratory chain complex I Inferred from direct assay Ref.3. Source: UniProtKB
Molecular function	NADH dehydrogenase (ubiquinone) activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 42	42	Mitochondrion By similarity
	Chain	43 – 175	133	NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial		PRO_0000020038
Amino acid modifications
	Modified residue	32	1	Phosphothreonine Ref.4
	Modified residue	34	1	Phosphoserine Ref.4
Natural variations
	Natural variant	174	1	T → P. Corresponds to variant rs1044692 [ dbSNP | Ensembl ].		VAR_012037
Experimental info
	Sequence conflict	39	1	T → S in AAH05270. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O43181 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: DE5B51DBDD76231E	FASTA	175	20,108
	10 20 30 40 50 60 MAAVSMSVVL RQTLWRRRAV AVAALSVSRV PTRSLRTSTW RLAQDQTQDT QLITVDEKLD 70 80 90 100 110 120 ITTLTGVPEE HIKTRKVRIF VPARNNMQSG VNNTKKWKME FDTRERWENP LMGWASTADP 130 140 150 160 170 LSNMVLTFST KEDAVSFAEK NGWSYDIEER KVPKPKSKSY GANFSWNKRT RVSTK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Demonstration of a new pathogenic mutation in human complex I deficiency: a 5-bp duplication in the nuclear gene encoding the 18-kD (AQDQ) subunit." van den Heuvel L., Ruitenbeek W., Smeets R., Gelman-Kohan Z., Elpeleg O., Loeffen J., Trijbels F., Mariman E., de Bruijn D., Smeitink J. Am. J. Hum. Genet. 62:262-268(1998) [PubMed: 9463323] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Urinary bladder.
[3]	"The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification." Murray J., Zhang B., Taylor S.W., Oglesbee D., Fahy E., Marusich M.F., Ghosh S.S., Capaldi R.A. J. Biol. Chem. 278:13619-13622(2003) [PubMed: 12611891] [Abstract] Cited for: MASS SPECTROMETRY, IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX.
[4]	"Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry." Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., Bodenmiller B., Watts J.D., Hood L., Aebersold R. Nat. Methods 2:591-598(2005) [PubMed: 16094384] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32 AND SER-34, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[5]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF020351 mRNA. Translation: AAB87865.1. BC005270 mRNA. Translation: AAH05270.1.
IPI	IPI00011217.
RefSeq	NP_002486.1. NM_002495.2.
UniGene	Hs.528222.
3D structure databases
ProteinModelPortal	O43181.
SMR	O43181. Positions 75-152.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43181. 2 interactions.
STRING	O43181.
PTM databases
PhosphoSite	O43181.
2D gel databases
UCD-2DPAGE	O43181.
Proteomic databases
PeptideAtlas	O43181.
PRIDE	O43181.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000296684; ENSP00000296684; ENSG00000164258.
GeneID	4724.
KEGG	hsa:4724.
UCSC	uc003jpe.2. human.
Organism-specific databases
CTD	4724.
GeneCards	GC05P052892.
H-InvDB	HIX0004857.
HGNC	HGNC:7711. NDUFS4.
HPA	HPA003884.
MIM	252010. phenotype. 602694. gene.
neXtProt	NX_O43181.
Orphanet	2609. Isolated NADH-CoQ reductase deficiency. 255241. Leigh syndrome with leukodystrophy.
PharmGKB	PA31521.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16208.
GeneTree	ENSGT00390000013835.
HOGENOM	HBG600003.
HOVERGEN	HBG003007.
InParanoid	O43181.
OMA	ERNGWRW.
PhylomeDB	O43181.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O43181.
Bgee	O43181.
CleanEx	HS_NDUFS4.
Genevestigator	O43181.
GermOnline	ENSG00000164258. Homo sapiens.
Family and domain databases
InterPro	IPR006885. NADH_UbQ_FeS_4_mit. [Graphical view]
KO	K03937.
PANTHER	PTHR12219. ETC_CI_21. 1 hit.
Pfam	PF04800. ETC_C1_NDUFA4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00157. NADH.
NextBio	18218.
SOURCE	Search...

Entry information

Entry name

NDUS4_HUMAN

Accession

Primary (citable) accession number: O43181
Secondary accession number(s): Q9BS69

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 1, 1998
Last modified:	January 25, 2012
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.