P49821 (NDUV1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial
EC=1.6.5.3
EC=1.6.99.3

Alternative name(s):
Complex I-51kD
Short name=CI-51kD
NADH dehydrogenase flavoprotein 1
NADH-ubiquinone oxidoreductase 51 kDa subunit

Gene names

Name:	NDUFV1
Synonyms:	UQOR1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	464 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	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.
Catalytic activity	NADH + ubiquinone = NAD+ + ubiquinol. NADH + acceptor = NAD+ + reduced acceptor.
Cofactor	Binds 1 FMN Potential. Binds 1 4Fe-4S cluster Potential.
Subunit structure	Complex I is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme. Ref.9
Subcellular location	Mitochondrion inner membrane; Peripheral membrane protein; Matrix side.
Involvement in disease	Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Mitochondrial complex I deficiency (MT-C1D) [MIM:252010]: A 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12
Sequence similarities	Belongs to the complex I 51 kDa subunit family.

Ontologies

Keywords
Biological process	Electron transport Respiratory chain Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Leigh syndrome
Domain	Transit peptide
Ligand	4Fe-4S FMN Flavoprotein Iron Iron-sulfur Metal-binding NAD Ubiquinone
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mitochondrial electron transport, NADH to ubiquinone Non-traceable author statement PubMed 9878551. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial respiratory chain complex I Inferred from direct assay Ref.9. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW FMN binding Inferred from electronic annotation. Source: InterPro NAD binding Inferred from electronic annotation. Source: InterPro NADH dehydrogenase (ubiquinone) activity Non-traceable author statement Ref.8PubMed 9878551. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49821-1)

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.

Isoform 2 (identifier: P49821-2)

The sequence of this isoform differs from the canonical sequence as follows:
     16-24: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 20	20	Mitochondrion By similarity
	Chain	21 – 464	444	NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial		PRO_0000019976
Regions
	Nucleotide binding	87 – 96	10	NAD(H) By similarity
	Nucleotide binding	199 – 247	49	FMN By similarity
Sites
	Metal binding	379	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	382	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	385	1	Iron-sulfur (4Fe-4S) Potential
	Metal binding	425	1	Iron-sulfur (4Fe-4S) Potential
Amino acid modifications
	Modified residue	81	1	N6-acetyllysine By similarity
	Modified residue	104	1	N6-acetyllysine By similarity
	Modified residue	375	1	N6-acetyllysine By similarity
Natural variations
	Alternative sequence	16 – 24	9	Missing in isoform 2.		VSP_003730
	Natural variant	76	1	I → V. Corresponds to variant rs1800670 [ dbSNP | Ensembl ].		VAR_014480
	Natural variant	214	1	E → K in MT-C1D. Ref.12		VAR_019534
	Natural variant	277	1	N → Y. Corresponds to variant rs1043770 [ dbSNP | Ensembl ].		VAR_014481
	Natural variant	341	1	A → V in MT-C1D. Ref.11		VAR_008846
	Natural variant	423	1	T → M in LS. Ref.11		VAR_008847
Experimental info
	Sequence conflict	80	1	I → V in AAB24883. Ref.7
	Sequence conflict	150	1	G → A in AAB29698. Ref.8
	Sequence conflict	306	1	G → F in CAA76757. Ref.1
	Sequence conflict	313	1	N → Y in CAA76757. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 2, 2002. Version 4. Checksum: 8C261EA3B0267256	FASTA	464	50,817
	10 20 30 40 50 60 MLATRRLLGW SLPARVSVRF SGDTTAPKKT SFGSLKDEDR IFTNLYGRHD WRLKGSLSRG 70 80 90 100 110 120 DWYKTKEILL KGPDWILGEI KTSGLRGRGG AGFPTGLKWS FMNKPSDGRP KYLVVNADEG 130 140 150 160 170 180 EPGTCKDREI LRHDPHKLLE GCLVGGRAMG ARAAYIYIRG EFYNEASNLQ VAIREAYEAG 190 200 210 220 230 240 LIGKNACGSG YDFDVFVVRG AGAYICGEET ALIESIEGKQ GKPRLKPPFP ADVGVFGCPT 250 260 270 280 290 300 TVANVETVAV SPTICRRGGT WFAGFGRERN SGTKLFNISG HVNHPCTVEE EMSVPLKELI 310 320 330 340 350 360 EKHAGGVTGG WDNLLAVIPG GSSTPLIPKS VCETVLMDFD ALVQAQTGLG TAAVIVMDRS 370 380 390 400 410 420 TDIVKAIARL IEFYKHESCG QCTPCREGVD WMNKVMARFV RGDARPAEID SLWEISKQIE 430 440 450 460 GHTICALGDG AAWPVQGLIR HFRPELEERM QRFAQQHQAR QAAS
	Isoform 2 [UniParc]. Checksum: 14B14974F7966121	FASTA	455	49,868
	10 20 30 40 50 60 MLATRRLLGW SLPARTAPKK TSFGSLKDED RIFTNLYGRH DWRLKGSLSR GDWYKTKEIL 70 80 90 100 110 120 LKGPDWILGE IKTSGLRGRG GAGFPTGLKW SFMNKPSDGR PKYLVVNADE GEPGTCKDRE 130 140 150 160 170 180 ILRHDPHKLL EGCLVGGRAM GARAAYIYIR GEFYNEASNL QVAIREAYEA GLIGKNACGS 190 200 210 220 230 240 GYDFDVFVVR GAGAYICGEE TALIESIEGK QGKPRLKPPF PADVGVFGCP TTVANVETVA 250 260 270 280 290 300 VSPTICRRGG TWFAGFGRER NSGTKLFNIS GHVNHPCTVE EEMSVPLKEL IEKHAGGVTG 310 320 330 340 350 360 GWDNLLAVIP GGSSTPLIPK SVCETVLMDF DALVQAQTGL GTAAVIVMDR STDIVKAIAR 370 380 390 400 410 420 LIEFYKHESC GQCTPCREGV DWMNKVMARF VRGDARPAEI DSLWEISKQI EGHTICALGD 430 440 450 GAAWPVQGLI RHFRPELEER MQRFAQQHQA RQAAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The structure of the human NDUFV1 gene encoding the 51-kDa subunit of mitochondrial complex I." de Coo R.F.M., Buddiger P.A., Smeets H.J.M., van Oost B.A. Mamm. Genome 10:49-53(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning of the human mitochondrial 51 kDa subunit (NDUFV1) reveals a 100% antisense homology of its 3'UTR with the 5'UTR of the gamma-interferon inducible protein (IP-30) precursor: is this a link between mitochondrial myopathy and inflammation?" Schuelke M., Loeffen J., Mariman E., Smeitink J., van den Heuvel L. Biochem. Biophys. Res. Commun. 245:599-606(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning." Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L. Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pituitary.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Brain and Eye.
[7]	"The human mitochondrial NADH: ubiquinone oxidoreductase 51-kDa subunit maps adjacent to the glutathione S-transferase P1-1 gene on chromosome 11q13." Spencer S.R., Taylor J.B., Cowell I.G., Xia C.L., Pemble S.E., Ketterer B. Genomics 14:1116-1118(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-130.
[8]	"Chromosomal localization of the human gene encoding the 51-kDa subunit of mitochondrial complex I (NDUFV1) to 11q13." Ali S.T., Duncan A.M.V., Schappert K.T., Heng H.H.Q., Tsui L.-C., Chow W., Robinson B.H. Genomics 18:435-439(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 87-305. Tissue: Kidney.
[9]	"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] [Europe PMC] [Abstract] Cited for: MASS SPECTROMETRY, IDENTIFICATION IN THE NADH-UBIQUINONE OXIDOREDUCTASE COMPLEX.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Mutant NDUFV1 subunit of mitochondrial complex I causes leukodystrophy and myoclonic epilepsy." Schuelke M., Smeitink J., Mariman E., Loeffen J., Plecko B., Trijbels F., Stockler-Ipsiroglu S., van den Heuvel L. Nat. Genet. 21:260-261(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MT-C1D VAL-341, VARIANT LS MET-423.
[12]	"Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency." Benit P., Chretien D., Kadhom N., de Lonlay-Debeney P., Cormier-Daire V., Cabral A., Peudenier S., Rustin P., Munnich A., Roetig A. Am. J. Hum. Genet. 68:1344-1352(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MT-C1D LYS-214.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y17379 , Y17380, Y17381, Y17382, Y17383 Genomic DNA. Translation: CAA76757.1. AF053069 Genomic DNA. Translation: AAC39750.1. AF053070 mRNA. Translation: AAC39722.1. AF092131 mRNA. Translation: AAD40373.1. CR456739 mRNA. Translation: CAG33020.1. CH471076 Genomic DNA. Translation: EAW74655.1. BC008146 mRNA. Translation: AAH08146.1. BC015645 mRNA. Translation: AAH15645.1. AH004147 Genomic DNA. Translation: AAB24883.1. S67973 mRNA. Translation: AAB29698.2. Sequence problems.
IPI	IPI00028520. IPI00978187.
PIR	JE0092.
RefSeq	NP_001159574.1. NM_001166102.1. NP_009034.2. NM_007103.3.
UniGene	Hs.7744.
3D structure databases
ProteinModelPortal	P49821.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49821. 2 interactions.
MINT	MINT-1444762.
STRING	9606.ENSP00000322450.
PTM databases
PhosphoSite	P49821.
Polymorphism databases
DMDM	20455501.
2D gel databases
REPRODUCTION-2DPAGE	IPI00028520. IPI00221298.
Proteomic databases
PaxDb	P49821.
PRIDE	P49821.
Protocols and materials databases
DNASU	4723.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322776; ENSP00000322450; ENSG00000167792. ENST00000529927; ENSP00000436766; ENSG00000167792.
GeneID	4723.
KEGG	hsa:4723.
UCSC	uc001omj.2. human. uc001omk.4. human.
Organism-specific databases
CTD	4723.
GeneCards	GC11P067374.
HGNC	HGNC:7716. NDUFV1.
HPA	HPA045211.
MIM	161015. gene. 252010. phenotype. 256000. phenotype.
neXtProt	NX_P49821.
Orphanet	58. Alexander disease. 2609. Isolated NADH-CoQ reductase deficiency. 255241. Leigh syndrome with leukodystrophy.
PharmGKB	PA31526.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1894.
HOVERGEN	HBG006542.
InParanoid	P49821.
KO	K03942.
OMA	PSGMKWS.
OrthoDB	EOG444KK9.
PhylomeDB	P49821.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P49821.
Bgee	P49821.
CleanEx	HS_NDUFV1.
Genevestigator	P49821.
GermOnline	ENSG00000167792. Homo sapiens.
Family and domain databases
InterPro	IPR001949. NADH-UbQ_OxRdtase_51kDa_CS. IPR019575. NADH-UbQ_OxRdtase_Fsu_4Fe4S-bd. IPR011537. NADH-UbQ_OxRdtase_suF. IPR011538. NADH_UbQ_OxRdtase_51kDa_su. IPR019554. Soluble_ligand-bd. [Graphical view]
Pfam	PF01512. Complex1_51K. 1 hit. PF10589. NADH_4Fe-4S. 1 hit. PF10531. SLBB. 1 hit. [Graphical view]
SMART	SM00928. NADH_4Fe-4S. 1 hit. [Graphical view]
TIGRFAMs	TIGR01959. nuoF_fam. 1 hit.
PROSITE	PS00644. COMPLEX1_51K_1. 1 hit. PS00645. COMPLEX1_51K_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NDUFV1. human.
DrugBank	DB00157. NADH.
GenomeRNAi	4723.
NextBio	18214.
SOURCE	Search...

Entry information

Entry name

NDUV1_HUMAN

Accession

Primary (citable) accession number: P49821
Secondary accession number(s): O60924 , O60940, Q16104, Q6IBR3, Q96BF8, Q96HS7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	May 2, 2002
Last modified:	May 1, 2013
This is version 139 of the entry and version 4 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.