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{{Infobox_gene}}
{{PBB_Controls
'''NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13''' is an [[enzyme]] that in humans is encoded by the ''NDUFA13'' [[gene]].<ref name="pmid12837546">{{cite journal | vauthors = Hirst J, Carroll J, Fearnley IM, Shannon RJ, Walker JE | title = The nuclear encoded subunits of complex I from bovine heart mitochondria | journal = Biochim Biophys Acta | volume = 1604 | issue = 3 | pages = 135–50 | date = Jul 2003 | pmid = 12837546 | pmc =  | doi = 10.1016/S0005-2728(03)00059-8 }}</ref><ref name="pmid10924506">{{cite journal | vauthors = Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV | title = Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach | journal = J Biol Chem | volume = 275 | issue = 43 | pages = 33416–26 | date = Nov 2000 | pmid = 10924506 | pmc =  | doi = 10.1074/jbc.M003929200 }}</ref><ref name="pmid15367666">{{cite journal | vauthors = Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K, Lufei C, Zeng Q, Cao X | title = GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I | journal = Mol Cell Biol | volume = 24 | issue = 19 | pages = 8447–56 | date = Sep 2004 | pmid = 15367666 | pmc = 516758 | doi = 10.1128/MCB.24.19.8447-8456.2004 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: NDUFA13 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51079| accessdate = }}</ref> The NDUFA13 protein is a subunit of [[NADH dehydrogenase (ubiquinone)]], which is located in the [[mitochondrial inner membrane]] and is the largest of the five complexes of the [[electron transport chain]].<ref name = Biochem>{{cite book|last1=Pratt|first1=Donald Voet, Judith G. Voet, Charlotte W.|title=Fundamentals of biochemistry : life at the molecular level|date=2013|publisher=Wiley|location=Hoboken, NJ|isbn=9780470547847|chapter = 18 | pages=581–620|edition=4th}}</ref><ref name="pmid9763677">{{cite journal |vauthors=Emahazion T, Beskow A, Gyllensten U, Brookes AJ | title = Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain | journal = Cytogenet Cell Genet | volume = 82 | issue = 1-2 | pages = 115–9 |date=Nov 1998 | pmid = 9763677 | pmc = | doi =10.1159/000015082  }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Structure==
{{GNF_Protein_box
The NDUFA13 gene is located on the p arm of [[chromosome 19]] in position 13.2 and spans 11,995 base pairs.<ref name = "entrez"/> The gene produces a 17 kDa protein composed of 144 [[amino acids]].<ref name="url_COPaKB">{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q9P0J0 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NDUFA13 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 }}</ref> NDUFA13 is a subunit of the enzyme [[NADH dehydrogenase (ubiquinone)]], the largest of the respiratory complexes. The structure is L-shaped with a long, [[hydrophobic]] [[transmembrane]] domain and a [[hydrophilic]] domain for the peripheral arm that includes all the known redox centers and the NADH binding site.<ref name = Biochem /> It has been noted that the [[N-terminus|N-terminal]] hydrophobic domain has the potential to be folded into an [[alpha helix]] spanning the inner [[mitochondrion|mitochondrial membrane]] with a [[C-terminus|C-terminal]] hydrophilic domain interacting with globular subunits of Complex I. The highly [[conserved sequence|conserved]] two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the [[NADH dehydrogenase (ubiquinone)]] complex at the inner mitochondrial membrane. NDUFA13 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.<ref name = UniProt >{{cite web|title=NDUFA13 |url=http://www.uniprot.org/uniprot/Q9P0J0|website=UniProt.org|publisher=The UniProt Consortium}}</ref> The predicted [[secondary structure]] is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.<ref name="entrez"/><ref name="pmid9763677"/><ref name="pmid9425316">{{cite journal |vauthors=Ton C, Hwang DM, Dempsey AA, Liew CC | title = Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits | journal = Biochem Biophys Res Commun | volume = 241 | issue = 2 | pages = 589–94 |date=Jan 1998 | pmid = 9425316 | pmc =  | doi = 10.1006/bbrc.1997.7707 }}</ref>
| image =
| image_source =
| PDB =  
| Name = NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13
| HGNCid = 17194
| Symbol = NDUFA13
| AltSymbols =; B16.6; CDA016; CGI-39; GRIM-19; GRIM19
| OMIM = 609435
| ECnumber = 
| Homologene = 41083
| MGIid = 1914434
| GeneAtlas_image1 = PBB_GE_NDUFA13_220864_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003954 |text = NADH dehydrogenase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0008137 |text = NADH dehydrogenase (ubiquinone) activity}} {{GNF_GO|id=GO:0016491 |text = oxidoreductase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005654 |text = nucleoplasm}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005739 |text = mitochondrion}} {{GNF_GO|id=GO:0005746 |text = mitochondrial respiratory chain}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006606 |text = protein import into nucleus}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0008624 |text = induction of apoptosis by extracellular signals}} {{GNF_GO|id=GO:0017148 |text = negative regulation of protein biosynthetic process}} {{GNF_GO|id=GO:0030262 |text = apoptotic nuclear changes}} {{GNF_GO|id=GO:0030308 |text = negative regulation of cell growth}} {{GNF_GO|id=GO:0045892 |text = negative regulation of transcription, DNA-dependent}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 51079
    | Hs_Ensembl = ENSG00000130288
    | Hs_RefseqProtein = NP_057049
    | Hs_RefseqmRNA = NM_015965
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 19
    | Hs_GenLoc_start = 19487639
    | Hs_GenLoc_end = 19500007
    | Hs_Uniprot = Q9P0J0
    | Mm_EntrezGene = 67184
    | Mm_Ensembl = ENSMUSG00000036199
    | Mm_RefseqmRNA = NM_023312
    | Mm_RefseqProtein = NP_075801
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 72823169
    | Mm_GenLoc_end = 72831547
    | Mm_Uniprot = Q9ERS2
  }}
}}
'''NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13''', also known as '''NDUFA13''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: NDUFA13 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51079| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Function==
{{PBB_Summary
The human NDUFA13 gene codes for a subunit of [[NADH dehydrogenase|Complex I]] of the [[electron transport chain|respiratory chain]], which transfers electrons from [[nicotinamide adenine dinucleotide|NADH]] to [[ubiquinone]].<ref name="entrez"/> [[NADH]] binds to Complex I and transfers two electrons to the [[isoalloxazine ring]] of the [[flavin mononucleotide]] (FMN) prosthetic arm to form FMNH<sub>2</sub>. The electrons are transferred through a series of [[iron-sulfur protein|iron-sulfur (Fe-S) clusters]] in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to [[ubiquinol]] (CoQH<sub>2</sub>). The flow of electrons changes the redox state of the protein, resulting in a conformational change and p''K'' shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.<ref name=Biochem />
| section_title =  
| summary_text =
}}


==References==
NDUFA13 has a homologous protein known as '''GRIM-19''', a cell-death regulatory protein. It is involved in [[interferon]]/all-trans-retinoic acid (IFN/RA) induced cell death. This form of [[apoptosis|apoptotic activity]] is inhibited by interaction with viral [[IRF1]]. GRIM-19 prevents the [[transactivation]] of [[STAT3|signal-transducer and activator of transcription 3]] (STAT3) target genes but not other STAT family members.<ref name = UniProt />
{{reflist|2}}
 
==Further reading==
==Clinical significance==
The homologous protein to NDUFA13, GRIM-19, may play a role in [[Chron's disease]] (CD), an [[inflammatory bowel disease]] (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. [[NOD2|Nucleotide-binding oligomerization domain-containing protein 2]] (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for [[NF-κB]] activation, a key component in regulating the immune response to infection.<ref name = UniProt /><ref>{{cite journal | last1=Barnich|first1=N| last2=Hisamatsu|first2=T|last3=Aguirre|first3=JE|last4=Xavier |first4=R |last5=Reinecker|first5=HC|last6=Podolsky| first6=DK | title=GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells.|journal=The Journal of Biological Chemistry|date=13 May 2005|volume=280|issue=19|pages=19021–6|pmid=15753091 | doi=10.1074/jbc.m413776200}}</ref>
 
== Interactions ==
 
NDUFA13 has been shown to [[Protein-protein interaction|interact]] with [[STAT3]].<ref name=pmid12867595>{{cite journal | vauthors = Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV | title = The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3 | language =  | journal = [[PNAS|Proc. Natl. Acad. Sci. U.S.A.]] | volume = 100 | issue = 16 | pages = 9342–7 | date = Aug 2003 | pmid = 12867595 | pmc = 170920 | doi = 10.1073/pnas.1633516100  }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W | title = Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. | journal = Genome Res. | volume = 10 | issue = 5 | pages = 703–13 | year = 2000 | pmid = 10810093 | pmc = 310876 | doi = 10.1101/gr.10.5.703 }}
| citations =
* {{cite journal | vauthors = Chidambaram NV, Angell JE, Ling W, Hofmann ER, Kalvakolanu DV | title = Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death. | journal = J. Interferon Cytokine Res. | volume = 20 | issue = 7 | pages = 661–5 | year = 2000 | pmid = 10926209 | doi = 10.1089/107999000414844 }}
*{{cite journal | author=Hirst J, Carroll J, Fearnley IM, ''et al.'' |title=The nuclear encoded subunits of complex I from bovine heart mitochondria. |journal=Biochim. Biophys. Acta |volume=1604 |issue= 3 |pages= 135-50 |year= 2003 |pmid= 12837546 |doi= }}
* {{cite journal | vauthors = Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL | title = Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 17 | pages = 9543–8 | year = 2000 | pmid = 10931946 | pmc = 16901 | doi = 10.1073/pnas.160270997 }}
*{{cite journal | author=Lai CH, Chou CY, Ch'ang LY, ''et al.'' |title=Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. |journal=Genome Res. |volume=10 |issue= 5 |pages= 703-13 |year= 2000 |pmid= 10810093 |doi= }}
* {{cite journal | vauthors = Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE, Hirst J | title = GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). | journal = J. Biol. Chem. | volume = 276 | issue = 42 | pages = 38345–8 | year = 2001 | pmid = 11522775 | doi = 10.1074/jbc.C100444200 }}
*{{cite journal | author=Angell JE, Lindner DJ, Shapiro PS, ''et al.'' |title=Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. |journal=J. Biol. Chem. |volume=275 |issue= 43 |pages= 33416-26 |year= 2000 |pmid= 10924506 |doi= 10.1074/jbc.M003929200 }}
* {{cite journal | vauthors = Seo T, Lee D, Shim YS, Angell JE, Chidambaram NV, Kalvakolanu DV, Choe J | title = 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. | journal = J. Virol. | volume = 76 | issue = 17 | pages = 8797–807 | year = 2002 | pmid = 12163600 | pmc = 136415 | doi = 10.1128/JVI.76.17.8797-8807.2002 }}
*{{cite journal  | author=Chidambaram NV, Angell JE, Ling W, ''et al.'' |title=Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid-activated regulator of cell death. |journal=J. Interferon Cytokine Res. |volume=20 |issue= 7 |pages= 661-5 |year= 2000 |pmid= 10926209 |doi= 10.1089/107999000414844 }}
* {{cite journal | vauthors = Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, Ghosh SS, Capaldi RA | title = The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. | journal = J. Biol. Chem. | volume = 278 | issue = 16 | pages = 13619–22 | year = 2003 | pmid = 12611891 | doi = 10.1074/jbc.C300064200 }}
*{{cite journal  | author=Hu RM, Han ZG, Song HD, ''et al.'' |title=Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 17 |pages= 9543-8 |year= 2000 |pmid= 10931946 |doi= 10.1073/pnas.160270997 }}
* {{cite journal | vauthors = Lufei C, Ma J, Huang G, Zhang T, Novotny-Diermayr V, Ong CT, Cao X | title = GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. | journal = EMBO J. | volume = 22 | issue = 6 | pages = 1325–35 | year = 2003 | pmid = 12628925 | pmc = 151078 | doi = 10.1093/emboj/cdg135 }}
*{{cite journal | author=Fearnley IM, Carroll J, Shannon RJ, ''et al.'' |title=GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). |journal=J. Biol. Chem. |volume=276 |issue= 42 |pages= 38345-8 |year= 2001 |pmid= 11522775 |doi= 10.1074/jbc.C100444200 }}
* {{cite journal | vauthors = Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV | title = The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 16 | pages = 9342–7 | year = 2003 | pmid = 12867595 | pmc = 170920 | doi = 10.1073/pnas.1633516100 }}
*{{cite journal | author=Seo T, Lee D, Shim YS, ''et al.'' |title=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. |journal=J. Virol. |volume=76 |issue= 17 |pages= 8797-807 |year= 2002 |pmid= 12163600 |doi= }}
* {{cite journal | vauthors = Lehner B, Sanderson CM | title = A protein interaction framework for human mRNA degradation. | journal = Genome Res. | volume = 14 | issue = 7 | pages = 1315–23 | year = 2004 | pmid = 15231747 | pmc = 442147 | doi = 10.1101/gr.2122004 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. | journal = Genome Res. | volume = 14 | issue = 9 | pages = 1711–8 | year = 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }}
*{{cite journal | author=Murray J, Zhang B, Taylor SW, ''et al.'' |title=The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. |journal=J. Biol. Chem. |volume=278 |issue= 16 |pages= 13619-22 |year= 2003 |pmid= 12611891 |doi= 10.1074/jbc.C300064200 }}
* {{cite journal | vauthors = Barnich N, Hisamatsu T, Aguirre JE, Xavier R, Reinecker HC, Podolsky DK | title = GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. | journal = J. Biol. Chem. | volume = 280 | issue = 19 | pages = 19021–6 | year = 2005 | pmid = 15753091 | doi = 10.1074/jbc.M413776200 }}
*{{cite journal | author=Lufei C, Ma J, Huang G, ''et al.'' |title=GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. |journal=EMBO J. |volume=22 |issue= 6 |pages= 1325-35 |year= 2003 |pmid= 12628925 |doi= 10.1093/emboj/cdg135 }}
* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network. | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | year = 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
*{{cite journal | author=Zhang J, Yang J, Roy SK, ''et al.'' |title=The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=100 |issue= 16 |pages= 9342-7 |year= 2003 |pmid= 12867595 |doi= 10.1073/pnas.1633516100 }}
* {{cite journal | vauthors = Huang G, Chen Y, Lu H, Cao X | title = Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death. | journal = Cell Death Differ. | volume = 14 | issue = 2 | pages = 327–37 | year = 2007 | pmid = 16826196 | doi = 10.1038/sj.cdd.4402004 }}
*{{cite journal | author=Lehner B, Sanderson CM |title=A protein interaction framework for human mRNA degradation. |journal=Genome Res. |volume=14 |issue= 7 |pages= 1315-23 |year= 2004 |pmid= 15231747 |doi= 10.1101/gr.2122004 }}
* {{cite journal | vauthors = Vogel RO, Dieteren CE, van den Heuvel LP, Willems PH, Smeitink JA, Koopman WJ, Nijtmans LG | title = Identification of mitochondrial complex I assembly intermediates by tracing tagged NDUFS3 demonstrates the entry point of mitochondrial subunits. | journal = J. Biol. Chem. | volume = 282 | issue = 10 | pages = 7582–90 | year = 2007 | pmid = 17209039 | doi = 10.1074/jbc.M609410200 }}
*{{cite journal  | author=Suzuki Y, Yamashita R, Shirota M, ''et al.'' |title=Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. |journal=Genome Res. |volume=14 |issue= 9 |pages= 1711-8 |year= 2004 |pmid= 15342556 |doi= 10.1101/gr.2435604 }}
*{{cite journal | author=Huang G, Lu H, Hao A, ''et al.'' |title=GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I. |journal=Mol. Cell. Biol. |volume=24 |issue= 19 |pages= 8447-56 |year= 2004 |pmid= 15367666 |doi= 10.1128/MCB.24.19.8447-8456.2004 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  | author=Barnich N, Hisamatsu T, Aguirre JE, ''et al.'' |title=GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. |journal=J. Biol. Chem. |volume=280 |issue= 19 |pages= 19021-6 |year= 2005 |pmid= 15753091 |doi= 10.1074/jbc.M413776200 }}
*{{cite journal  | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
*{{cite journal  | author=Huang G, Chen Y, Lu H, Cao X |title=Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death. |journal=Cell Death Differ. |volume=14 |issue= 2 |pages= 327-37 |year= 2007 |pmid= 16826196 |doi= 10.1038/sj.cdd.4402004 }}
*{{cite journal  | author=Vogel RO, Dieteren CE, van den Heuvel LP, ''et al.'' |title=Identification of mitochondrial complex I assembly intermediates by tracing tagged NDUFS3 demonstrates the entry point of mitochondrial subunits. |journal=J. Biol. Chem. |volume=282 |issue= 10 |pages= 7582-90 |year= 2007 |pmid= 17209039 |doi= 10.1074/jbc.M609410200 }}
}}
{{refend}}
{{refend}}


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[[Category:Human proteins]]

Revision as of 12:44, 5 September 2017

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 is an enzyme that in humans is encoded by the NDUFA13 gene.[1][2][3][4] The NDUFA13 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[5][6]

Structure

The NDUFA13 gene is located on the p arm of chromosome 19 in position 13.2 and spans 11,995 base pairs.[4] The gene produces a 17 kDa protein composed of 144 amino acids.[7] NDUFA13 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[5] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA13 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[8] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[4][6][9]

Function

The human NDUFA13 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[5]

NDUFA13 has a homologous protein known as GRIM-19, a cell-death regulatory protein. It is involved in interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This form of apoptotic activity is inhibited by interaction with viral IRF1. GRIM-19 prevents the transactivation of signal-transducer and activator of transcription 3 (STAT3) target genes but not other STAT family members.[8]

Clinical significance

The homologous protein to NDUFA13, GRIM-19, may play a role in Chron's disease (CD), an inflammatory bowel disease (IBD) characterized by chronic inflammation of the intestinal epithelium. Its expression is decreased in the inflamed mucosa of patients with these diseases. Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), also known as caspase recruitment domain-containing protein 15 (CARD15) or inflammatory bowel disease protein 1 (IBD1), functions as a mammalian cytosolic pathogen recognition molecule and plays an anti-bacterial role by limiting survival of intracellular invasive bacteria. GRIM-19 acts as a downstream anti-bacterial effector in CARD15-mediated innate mucosal responses by regulating intestinal epithelial cell responses to microbes. Following NOD2-mediated recognition of bacterial muramyl dipeptide, GRIM-19 is required for NF-κB activation, a key component in regulating the immune response to infection.[8][10]

Interactions

NDUFA13 has been shown to interact with STAT3.[11]

References

  1. ↑ Hirst J, Carroll J, Fearnley IM, Shannon RJ, Walker JE (Jul 2003). "The nuclear encoded subunits of complex I from bovine heart mitochondria". Biochim Biophys Acta. 1604 (3): 135–50. doi:10.1016/S0005-2728(03)00059-8. PMID 12837546.
  2. ↑ Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV (Nov 2000). "Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach". J Biol Chem. 275 (43): 33416–26. doi:10.1074/jbc.M003929200. PMID 10924506.
  3. ↑ Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K, Lufei C, Zeng Q, Cao X (Sep 2004). "GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I". Mol Cell Biol. 24 (19): 8447–56. doi:10.1128/MCB.24.19.8447-8456.2004. PMC 516758. PMID 15367666.
  4. ↑ 4.0 4.1 4.2 4.3 "Entrez Gene: NDUFA13 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 13".
  5. ↑ 5.0 5.1 5.2 Pratt, Donald Voet, Judith G. Voet, Charlotte W. (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847.
  6. ↑ 6.0 6.1 Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenet Cell Genet. 82 (1–2): 115–9. doi:10.1159/000015082. PMID 9763677.
  7. ↑ "NDUFA13 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  8. ↑ 8.0 8.1 8.2 "NDUFA13". UniProt.org. The UniProt Consortium.
  9. ↑ Ton C, Hwang DM, Dempsey AA, Liew CC (Jan 1998). "Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits". Biochem Biophys Res Commun. 241 (2): 589–94. doi:10.1006/bbrc.1997.7707. PMID 9425316.
  10. ↑ Barnich, N; Hisamatsu, T; Aguirre, JE; Xavier, R; Reinecker, HC; Podolsky, DK (13 May 2005). "GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells". The Journal of Biological Chemistry. 280 (19): 19021–6. doi:10.1074/jbc.m413776200. PMID 15753091.
  11. ↑ Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, Poli V, Stark GR, Kalvakolanu DV (Aug 2003). "The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3". Proc. Natl. Acad. Sci. U.S.A. 100 (16): 9342–7. doi:10.1073/pnas.1633516100. PMC 170920. PMID 12867595.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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