Q9P0J0 (NDUAD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13

Alternative name(s):
Cell death regulatory protein GRIM-19
Complex I-B16.6
Short name=CI-B16.6
Gene associated with retinoic and interferon-induced mortality 19 protein
Short name=GRIM-19
Short name=Gene associated with retinoic and IFN-induced mortality 19 protein
NADH-ubiquinone oxidoreductase B16.6 subunit

Gene names

Name:	NDUFA13
Synonyms:	GRIM19
ORF Names:	CDA016, CGI-39

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	144 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. Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes. May play a role in CARD15-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes. Ref.7 Ref.9 Ref.12
Subunit structure	Complex I is composed of 45 different subunits. Interacts with CARD15, but not with CARD4. Interacts with STAT3, but not with STAT1, STAT2 and STAT5A. Interacts with HHV-8 IRF1, in the nucleus, with HPV-16 E6 and SV40 LT. Interacts with OLFM4. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12
Subcellular location	Mitochondrion inner membrane; Single-pass membrane protein; Matrix side. Nucleus. Note: May be translocated into the nucleus upon IFN/RA treatment. Ref.7 Ref.10 Ref.11
Tissue specificity	Widely expressed, with highest expression in heart, skeletal muscle, liver, kidney and placenta. In intestinal mucosa, down-regulated in areas involved in Crohn disease and ulcerative colitis. Ref.1
Developmental stage	Expressed in numerous fetal tissues.
Induction	By IFNB1/IFN-beta combined with all-trans-retinoic acid (ATRA).
Involvement in disease	Hurthle cell thyroid carcinoma (HCTC) [MIM:607464]: A rare type of thyroid cancer accounting for only about 3-10% of all differentiated thyroid cancers. These neoplasms are considered a variant of follicular carcinoma of the thyroid and are referred to as follicular carcinoma, oxyphilic type. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Sequence similarities	Belongs to the complex I NDUFA13 subunit family.
Sequence caution	The sequence AAD27748.1 differs from that shown. Reason: Erroneous initiation. The sequence AAG44670.1 differs from that shown. Reason: Erroneous initiation. The sequence AAH00589.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Apoptosis Electron transport Respiratory chain Transport
Cellular component	Membrane Mitochondrion Mitochondrion inner membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic nuclear changes Inferred from direct assay Ref.1. Source: UniProtKB apoptotic signaling pathway Inferred from direct assay Ref.1. Source: UniProtKB induction of apoptosis Inferred from mutant phenotype PubMed 16826196. Source: UniProtKB negative regulation of cell growth Inferred from direct assay Ref.1. Source: UniProtKB negative regulation of transcription, DNA-dependent Inferred from direct assay Ref.9. Source: UniProtKB negative regulation of translation Inferred from direct assay Ref.9. Source: UniProtKB protein import into nucleus Non-traceable author statement Ref.1. Source: UniProtKB reactive oxygen species metabolic process Inferred from mutant phenotype PubMed 16826196. Source: UniProtKB respiratory electron transport chain Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial respiratory chain complex I Inferred from direct assay Ref.8PubMed 17209039. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement Ref.1. Source: UniProtKB NADH dehydrogenase (ubiquinone) activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HTRA2	O43464	6	EBI-372742,EBI-517086

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 144	143	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13		PRO_0000118804
Regions
	Transmembrane	30 – 51	22	Helical; Potential
	Region	102 – 144	43	Important for inducing cell death
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
Natural variations
	Natural variant	5	1	K → N in a Hurthle cell variant of papillary carcinoma sample. Ref.14		VAR_045984
	Natural variant	115	1	R → P in a Hurthle cell variant of papillary carcinoma sample. Ref.14		VAR_045985
Experimental info
	Sequence conflict	2	1	A → P Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9P0J0 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 058F608B235FF856	FASTA	144	16,698
	10 20 30 40 50 60 MAASKVKQDM PPPGGYGPID YKRNLPRRGL SGYSMLAIGI GTLIYGHWSI MKWNRERRRL 70 80 90 100 110 120 QIEDFEARIA LLPLLQAETD RRTLQMLREN LEEEAIIMKD VPDWKVGESV FHTTRWVPPL 130 140 IGELYGLRTT EEALHASHGF MWYT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach." Angell J.E., Lindner D.J., Shapiro P.S., Hofmann E.R., Kalvakolanu D.V. J. Biol. Chem. 275:33416-33426(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Mammary carcinoma.
[2]	"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: Adrenal gland.
[3]	"Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics." Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C. Genome Res. 10:703-713(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"A novel gene expressed in human pheochromocytoma." Xu X., Yang Y., Gao G., Xiao H., Chen Z., Han Z. Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Pheochromocytoma.
[5]	"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]. Tissue: Placenta and Skin.
[6]	"Viral interferon regulatory factor 1 of Kaposi's sarcoma-associated herpesvirus interacts with a cell death regulator, GRIM19, and inhibits interferon/retinoic acid-induced cell death." Seo T., Lee D., Shim Y.S., Angell J.E., Chidambaram N.V., Kalvakolanu D.V., Choe J. J. Virol. 76:8797-8807(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HHV-8 IRF1; HPV-16 E6 AND SV40 LT.
[7]	"GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction." Lufei C., Ma J., Huang G., Zhang T., Novotny-Diermayr V., Ong C.T., Cao X. EMBO J. 22:1325-1335(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STAT3, SUBCELLULAR LOCATION.
[8]	"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.
[9]	"The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3." Zhang J., Yang J., Roy S.K., Tininini S., Hu J., Bromberg J.F., Poli V., Stark G.R., Kalvakolanu D.V. Proc. Natl. Acad. Sci. U.S.A. 100:9342-9347(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STAT3.
[10]	"GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I." Huang G., Lu H., Hao A., Ng D.C.H., Ponniah S., Guo K., Lufei C., Zeng Q., Cao X. Mol. Cell. Biol. 24:8447-8456(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"GW112, a novel antiapoptotic protein that promotes tumor growth." Zhang X., Huang Q., Yang Z., Li Y., Li C.-Y. Cancer Res. 64:2474-2481(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH OLFM4.
[12]	"GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells." Barnich N., Hisamatsu T., Aguirre J.E., Xavier R., Reinecker H.-C., Podolsky D.K. J. Biol. Chem. 280:19021-19026(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH CARD15.
[13]	"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].
[14]	"Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid." Maximo V., Botelho T., Capela J., Soares P., Lima J., Taveira A., Amaro T., Barbosa A.P., Preto A., Harach H.R., Williams D., Sobrinho-Simoes M. Br. J. Cancer 92:1892-1898(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASN-5 AND PRO-115, INVOLVEMENT IN SUSCEPTIBILITY TO HURTHLE CELL THYROID CARCINOMA.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF286697 mRNA. Translation: AAG28167.1. AF155662 mRNA. Translation: AAF67481.1. AF132973 mRNA. Translation: AAD27748.1. Different initiation. AF261134 mRNA. Translation: AAG44670.1. Different initiation. BC000589 mRNA. Translation: AAH00589.2. Different initiation. BC009189 mRNA. Translation: AAH09189.1.
IPI	IPI00942935.
RefSeq	NP_057049.5. NM_015965.6.
UniGene	Hs.534453.
3D structure databases
ProteinModelPortal	Q9P0J0.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-31180N.
IntAct	Q9P0J0. 5 interactions.
PTM databases
PhosphoSite	Q9P0J0.
Polymorphism databases
DMDM	20139242.
Proteomic databases
PaxDb	Q9P0J0.
PRIDE	Q9P0J0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000507754; ENSP00000423673; ENSG00000186010.
GeneID	51079.
KEGG	hsa:51079.
UCSC	uc021uqu.1. human.
Organism-specific databases
CTD	51079.
GeneCards	GC19P019626.
H-InvDB	HIX0213010.
HGNC	HGNC:17194. NDUFA13.
HPA	HPA041213.
MIM	607464. phenotype. 609435. gene.
neXtProt	NX_Q9P0J0.
PharmGKB	PA142671270.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0062.
HOGENOM	HOG000195836.
HOVERGEN	HBG019074.
InParanoid	Q9P0J0.
KO	K11353.
OrthoDB	EOG4JQ3ZG.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9P0J0.
Bgee	Q9P0J0.
CleanEx	HS_NDUFA13.
Genevestigator	Q9P0J0.
GermOnline	ENSG00000130288. Homo sapiens.
Family and domain databases
InterPro	IPR009346. GRIM-19. [Graphical view]
PANTHER	PTHR12966. PTHR12966. 1 hit.
Pfam	PF06212. GRIM-19. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NDUFA13. human.
DrugBank	DB00157. NADH.
GenomeRNAi	51079.
NextBio	53719.
SOURCE	Search...

Entry information

Entry name

NDUAD_HUMAN

Accession

Primary (citable) accession number: Q9P0J0
Secondary accession number(s): Q6PKI0, Q9H2L3, Q9Y327

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 123 of the entry and version 3 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.