Reviewed, UniProtKB/Swiss-Prot P28331 (NDUS1_HUMAN)

Names and origin

Protein names

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 names

Name:

NDUFS1

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	727 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. 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.
Catalytic activity	NADH + ubiquinone = NAD+ + ubiquinol. NADH + acceptor = NAD+ + reduced acceptor.
Cofactor	Binds 1 2Fe-2S cluster per subunit By similarity. Binds 2 4Fe-4S clusters per subunit By similarity.
Subunit structure	Complex I is composed of 45 different subunits.
Subcellular location	Mitochondrion inner membrane.
Involvement in disease	Defects in NDUFS1 are a cause of complex I mitochondrial respiratory chain deficiency [MIM:252010]. Complex I (NADH-ubiquinone oxidoreductase), the largest complex of the mitochondrial respiratory chain, contains more than 40 subunits. It is embedded in the inner mitochondrial membrane and is partly protruding in the matrix. Complex I deficiency is the most common cause of mitochondrial disorders. It represents largely one-third of all cases of respiratory chain deficiency and is responsible for a variety of clinical symptoms, ranging from neurological disorders to cardiomyopathy, liver failure, and myopathy.
Sequence similarities	Belongs to the complex I 75 kDa subunit family. Contains 1 2Fe-2S ferredoxin-type domain.

Ontologies

Keywords
Biological process	Electron transport Respiratory chain Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	2Fe-2S 4Fe-4S Iron Iron-sulfur Metal-binding NAD Ubiquinone
Molecular function	Oxidoreductase
PTM	Acetylation
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	ATP metabolic process Inferred from mutant phenotype. Source: UniProtKB apoptosis Inferred from direct assay. Source: UniProtKB mitochondrial electron transport, NADH to ubiquinone Non-traceable author statement. Source: UniProtKB oxygen and reactive oxygen species metabolic process Inferred from mutant phenotype. Source: UniProtKB regulation of mitochondrial membrane potential Inferred from mutant phenotype. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrial intermembrane space Inferred from direct assay. Source: UniProtKB mitochondrial respiratory chain complex I Inferred from mutant phenotype. Source: UniProtKB
Molecular function	2 iron, 2 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW 4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW NADH dehydrogenase (ubiquinone) activity Non-traceable author statement. Source: UniProtKB electron carrier activity Ref.1 Non-traceable author statement. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 23	23	Mitochondrion By similarity
	Chain	24 – 727	704	NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial		PRO_0000019968
Regions
	Domain	30 – 108	79	2Fe-2S ferredoxin-type
Sites
	Metal binding	64	1	Iron-sulfur 1 (2Fe-2S) By similarity
	Metal binding	75	1	Iron-sulfur 1 (2Fe-2S) By similarity
	Metal binding	78	1	Iron-sulfur 1 (2Fe-2S) By similarity
	Metal binding	92	1	Iron-sulfur 1 (2Fe-2S) By similarity
	Metal binding	124	1	Iron-sulfur 2 (4Fe-4S); via pros nitrogen By similarity
	Metal binding	128	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	131	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	137	1	Iron-sulfur 2 (4Fe-4S) By similarity
	Metal binding	176	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	179	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	182	1	Iron-sulfur 3 (4Fe-4S) By similarity
	Metal binding	226	1	Iron-sulfur 3 (4Fe-4S) By similarity
Amino acid modifications
	Modified residue	84	1	N6-acetyllysine By similarity
Natural variations
	Natural variant	241	1	R → Q: dbSNP rs17856901. Ref.3 Ref.6		VAR_025511
	Natural variant	241	1	R → W in complex I deficiency. Ref.3 Ref.6		VAR_019532
	Natural variant	252	1	D → G in complex I deficiency. Ref.6		VAR_019533
	Natural variant	649	1	V → F: dbSNP rs1044049. Ref.1		VAR_018463
Experimental info
	Sequence conflict	8	1	K → R in CAA43412. Ref.1
	Sequence conflict	417	1	R → W in CAA43412. Ref.1
	Sequence conflict	691	1	I → L in CAA43412. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P28331-1 [UniParc]. Last modified March 7, 2006. Version 3. Checksum: 9C35F4B8294771FB	FASTA	727	79,468
	10 20 30 40 50 60 MLRIPVRKAL VGLSKSPKGC VRTTATAASN LIEVFVDGQS VMVEPGTTVL QACEKVGMQI 70 80 90 100 110 120 PRFCYHERLS VAGNCRMCLV EIEKAPKVVA ACAMPVMKGW NILTNSEKSK KAREGVMEFL 130 140 150 160 170 180 LANHPLDCPI CDQGGECDLQ DQSMMFGNDR SRFLEGKRAV EDKNIGPLVK TIMTRCIQCT 190 200 210 220 230 240 RCIRFASEIA GVDDLGTTGR GNDMQVGTYI EKMFMSELSG NIIDICPVGA LTSKPYAFTA 250 260 270 280 290 300 RPWETRKTES IDVMDAVGSN IVVSTRTGEV MRILPRMHED INEEWISDKT RFAYDGLKRQ 310 320 330 340 350 360 RLTEPMVRNE KGLLTYTSWE DALSRVAGML QSFQGKDVAA IAGGLVDAEA LVALKDLLNR 370 380 390 400 410 420 VDSDTLCTEE VFPTAGAGTD LRSNYLLNTT IAGVEEADVV LLVGTNPRFE APLFNARIRK 430 440 450 460 470 480 SWLHNDLKVA LIGSPVDLTY TYDHLGDSPK ILQDIASGSH PFSQVLKEAK KPMVVLGSSA 490 500 510 520 530 540 LQRNDGAAIL AAVSSIAQKI RMTSGVTGDW KVMNILHRIA SQVAALDLGY KPGVEAIRKN 550 560 570 580 590 600 PPKVLFLLGA DGGCITRQDL PKDCFIIYQG HHGDVGAPIA DVILPGAAYT EKSATYVNTE 610 620 630 640 650 660 GRAQQTKVAV TPPGLAREDW KIIRALSEIA GMTLPYDTLD QVRNRLEEVS PNLVRYDDIE 670 680 690 700 710 720 GANYFQQANE LSKLVNQQLL ADPLVPPQLT IKDFYMTDSI SRASQTMAKC VKAVTEGAQA VEEPSIC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase." Chow W., Ragan I., Robinson B.H. Eur. J. Biochem. 201:547-550(1991) [PubMed: 1935949] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PHE-649.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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], VARIANT GLN-241. Tissue: Brain and Liver.
[4]	Lubec G., Vishwanath V., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 185-200; 247-266; 277-289; 312-325; 361-382; 451-467; 471-499; 519-538; 544-557 AND 625-655, MASS SPECTROMETRY. Tissue: Brain, Cajal-Retzius cell and Fetal brain cortex.
[5]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]	"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: 11349233] [Abstract] Cited for: VARIANTS COMPLEX I DEFICIENCY TRP-241 AND GLY-252.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	X61100 mRNA. Translation: CAA43412.1. AC007383 Genomic DNA. Translation: AAY15061.1. BC022368 mRNA. Translation: AAH22368.1. BC030833 mRNA. Translation: AAH30833.1.
IPI	IPI00604664.
PIR	S17854.
RefSeq	NP_004997.4.
UniGene	Hs.471207
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	P28331. 3 interactions.
PTM databases
PhosphoSite	P28331.
2-D gel databases
REPRODUCTION-2DPAGE	IPI00604664. P28331.
Proteomic databases
PeptideAtlas	P28331.
PRIDE	P28331.
Genome annotation databases
Ensembl	ENSG00000023228. Homo sapiens. [Contig view]
GeneID	4719.
KEGG	hsa:4719.
NMPDR	fig|9606.3.peg.19217.
Organism-specific databases
GeneCards	GC02M206695.
H-InvDB	HIX0002769.
HGNC	HGNC:7707. NDUFS1.
MIM	157655. gene. 252010. phenotype.
Orphanet	506. Leigh syndrome. 2609. NADH-CoQ reductase deficiency.
PharmGKB	PA31518.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P28331.
OMA	P28331. RMSSGVT.
Enzyme and pathway databases
BRENDA	1.6.5.3. 247. 1.6.99.3. 247.
Reactome	REACT_6305. Electron Transport Chain.
Gene expression databases
ArrayExpress	P28331.
CleanEx	HS_NDUFS1.
GermOnline	ENSG00000023228. Homo sapiens.
Family and domain databases
InterPro	IPR006058. 2Fe2S_fd_BS. IPR001041. Ferredoxin. IPR006656. Mopterin_OxRdtase. IPR000283. NADH_UbQ_OxRdtase_75KDa_su_CS. IPR010228. NADH_UbQ_OxRdtase_Gsu. IPR019574. NADH_UbQ_OxRdtase_Gsu_4Fe4S-bd. IPR015405. NuoG_C. [Graphical view]
Pfam	PF09326. DUF1982. 1 hit. PF00111. Fer2. 1 hit. PF00384. Molybdopterin. 1 hit. PF10588. NADH-G_4Fe-4S_3. 1 hit. [Graphical view]
TIGRFAMs	TIGR01973. NuoG. 1 hit.
PROSITE	PS00197. 2FE2S_FER_1. False negative. PS51085. 2FE2S_FER_2. 1 hit. PS00641. COMPLEX1_75K_1. 1 hit. PS00642. COMPLEX1_75K_2. 1 hit. PS00643. COMPLEX1_75K_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	18202.
PMAP-CutDB	P28331.
SOURCE	Search...

Entry information

Entry name

NDUS1_HUMAN

Accession

Primary (citable) accession number: P28331
Secondary accession number(s): Q53TR8, Q8N1C4, Q8TCC9

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	March 7, 2006
Last modified:	June 16, 2009
This is version 103 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)