DNAJC19: Difference between revisions

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{{Infobox_gene}}
{{Infobox_gene}}
'''Mitochondrial import inner membrane translocase subunit TIM14''' is an [[enzyme]] that in humans is encoded by the ''DNAJC19'' [[gene]] on chromosome 3.<ref name="pmid12477932">{{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16899–903 | date = Dec 2002 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 | displayauthors = 6 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DNAJC19 DnaJ (Hsp40) homolog, subfamily C, member 19| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=131118| accessdate = }}</ref> TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems.<ref name=Mokranjac_2003>{{cite journal | vauthors = Mokranjac D, Sichting M, Neupert W, Hell K | title = Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria | journal = The EMBO Journal | volume = 22 | issue = 19 | date = Oct 2003 | pmid = 14517234 | doi = 10.1093/emboj/cdg485 | pmc=204468 | pages=4945–56}}</ref><ref name=Davey_2006>{{cite journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | date = May 2006 | pmid = 16055927 | doi = 10.1136/jmg.2005.036657 | pmc=2564511 | pages=385–93}}</ref> As a [[mitochondrial]] [[chaperone (protein)|chaperone]], TIM14 functions as part of the [[TIMM23|TIM23]] complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria.<ref name=Mokranjac_2003/> TIM14 also complexes with [[prohibitin]] complexes to regulate mitochondrial [[morphogenesis]], and has been implicated in [[dilated cardiomyopathy]] with ataxia.<ref name=Richter-Dennerlein_2014>{{cite journal | vauthors = Richter-Dennerlein R, Korwitz A, Haag M, Tatsuta T, Dargazanli S, Baker M, Decker T, Lamkemeyer T, Rugarli EI, Langer T | title = DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling | journal = Cell Metabolism | volume = 20 | issue = 1 | date = Jul 2014 | pmid = 24856930 | doi = 10.1016/j.cmet.2014.04.016 | pages=158–71}}</ref>
'''Mitochondrial import inner membrane translocase subunit TIM14''' is an [[enzyme]] that in humans is encoded by the ''DNAJC19'' [[gene]] on chromosome 3.<ref name="pmid12477932">{{cite journal | vauthors = Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA | display-authors = 6 | title = Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 26 | pages = 16899–903 | date = December 2002 | pmid = 12477932 | pmc = 139241 | doi = 10.1073/pnas.242603899 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DNAJC19 DnaJ (Hsp40) homolog, subfamily C, member 19| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=131118| access-date = }}</ref> TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems.<ref name=Mokranjac_2003>{{cite journal | vauthors = Mokranjac D, Sichting M, Neupert W, Hell K | title = Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria | journal = The EMBO Journal | volume = 22 | issue = 19 | pages = 4945–56 | date = October 2003 | pmid = 14517234 | pmc = 204468 | doi = 10.1093/emboj/cdg485 }}</ref><ref name=Davey_2006>{{cite journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | pages = 385–93 | date = May 2006 | pmid = 16055927 | pmc = 2564511 | doi = 10.1136/jmg.2005.036657 }}</ref> As a [[mitochondrial]] [[chaperone (protein)|chaperone]], TIM14 functions as part of the [[TIMM23|TIM23]] complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria.<ref name=Mokranjac_2003/> TIM14 also complexes with [[prohibitin]] complexes to regulate mitochondrial [[morphogenesis]], and has been implicated in [[dilated cardiomyopathy]] with ataxia.<ref name=Richter-Dennerlein_2014>{{cite journal | vauthors = Richter-Dennerlein R, Korwitz A, Haag M, Tatsuta T, Dargazanli S, Baker M, Decker T, Lamkemeyer T, Rugarli EI, Langer T | title = DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling | journal = Cell Metabolism | volume = 20 | issue = 1 | pages = 158–71 | date = July 2014 | pmid = 24856930 | doi = 10.1016/j.cmet.2014.04.016 }}</ref>


== Structure ==
== Structure ==
The ''DNAJC19'' gene is located on the [[Locus (genetics)|q arm]] of [[chromosome 3]] at position 26.33 and it spans 6,065 base pairs.<ref name = entrez /> The ''DNAJC19'' gene produces a 6.29 kDa protein composed of 59 [[amino acids]].<ref name=COPaKB>


The protein encoded by the ''DNAJC19'' gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the [[C-terminal]] rather than the [[N-terminal]], and the [[transmembrane]] domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 [[ortholog]]s in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.<ref>{{vcite2 journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | pages = 385–93 | date = May 2006 | pmid = 16055927 | doi = 10.1136/jmg.2005.036657 | pmc=2564511}}</ref>
{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}
 
</ref><ref name="url_COPaKB">
 
{{cite web | url = https://amino.heartproteome.org/web/protein/F2Z3A7 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = Mitochondrial import inner membrane translocase subunit TIM14
}}
 
</ref> The protein encoded by the ''DNAJC19'' gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the [[C-terminal]] rather than the [[N-terminal]], and the [[transmembrane]] domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 [[ortholog]]s in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.<ref>{{vcite2 journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | pages = 385–93 | date = May 2006 | pmid = 16055927 | doi = 10.1136/jmg.2005.036657 | pmc=2564511}}</ref>


== Function ==
== Function ==
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== Clinical significance ==
== Clinical significance ==


Defects in DNAJC19 have been observed primarily in cases of [[dilated cardiomyopathy]] with ataxia (DCMA), though it has also been associated with [[growth failure]], [[microcytic anemia]], and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations.<ref name="Davey_2006"/><ref name=Ojala_2012>{{cite journal | vauthors = Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T | title = New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies | journal = Pediatric Research | volume = 72 | issue = 4 | date = Oct 2012 | pmid = 22797137 | doi = 10.1038/pr.2012.92 | pages=432–7}}</ref> In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of [[3-methylglutaconic acid]], mitochondrial distress, dilated cardiomyopathy, prolongation of the [[QT interval]] in the [[electrocardiogram]], and [[cerebellar ataxia]].<ref name=Ojala_2012/><ref name="Koutras">{{cite journal | vauthors = Koutras C, Braun JE | title = J protein mutations and resulting proteostasis collapse | journal = Frontiers in Cellular Neuroscience | volume = 8 | date = Jul 2014 | pmid = 25071450 | doi = 10.3389/fncel.2014.00191 | pages=191 | pmc=4086201}}</ref>
Defects in DNAJC19 have been observed primarily in cases of [[dilated cardiomyopathy]] with ataxia (DCMA), though it has also been associated with [[growth failure]], [[microcytic anemia]], and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations.<ref name="Davey_2006"/><ref name=Ojala_2012>{{cite journal | vauthors = Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T | title = New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies | journal = Pediatric Research | volume = 72 | issue = 4 | pages = 432–7 | date = October 2012 | pmid = 22797137 | doi = 10.1038/pr.2012.92 }}</ref> In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of [[3-methylglutaconic acid]], mitochondrial distress, dilated cardiomyopathy, prolongation of the [[QT interval]] in the [[electrocardiogram]], and [[cerebellar ataxia]].<ref name=Ojala_2012/><ref name="Koutras">{{cite journal | vauthors = Koutras C, Braun JE | title = J protein mutations and resulting proteostasis collapse | journal = Frontiers in Cellular Neuroscience | volume = 8 | pages = 191 | date = Jul 2014 | pmid = 25071450 | pmc = 4086201 | doi = 10.3389/fncel.2014.00191 }}</ref>


== Interactions ==
== Interactions ==
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* [[TIMM44]],<ref name=Mokranjac_2003/>
* [[TIMM44]],<ref name=Mokranjac_2003/>
* [[HSPA9|mtHsp70]],<ref name=Mokranjac_2003/>
* [[HSPA9|mtHsp70]],<ref name=Mokranjac_2003/>
* TIMM16/[[PAM16]],<ref name ="Mokranjac_2006">{{cite journal | vauthors = Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M | title = Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor | journal = The EMBO Journal | volume = 25 | issue = 19 | date = Oct 2006 | pmid = 16977310 | doi = 10.1038/sj.emboj.7601334 | pages=4675–85 | pmc=1590002}}</ref> and
* TIMM16/[[PAM16]],<ref name ="Mokranjac_2006">{{cite journal | vauthors = Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M | title = Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor | journal = The EMBO Journal | volume = 25 | issue = 19 | pages = 4675–85 | date = October 2006 | pmid = 16977310 | pmc = 1590002 | doi = 10.1038/sj.emboj.7601334 }}</ref> and
* [[PHB2]].<ref name=Richter-Dennerlein_2014/>
* [[PHB2]].<ref name=Richter-Dennerlein_2014/>


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== Further reading ==
== Further reading ==
{{refbegin|33em}}
{{refbegin|33em}}
* {{cite journal | vauthors = Sparkes R, Patton D, Bernier F | title = Cardiac features of a novel autosomal recessive dilated cardiomyopathic syndrome due to defective importation of mitochondrial protein | journal = Cardiology in the Young | volume = 17 | issue = 2 | pages = 215–7 | date = Apr 2007 | pmid = 17244376 | doi = 10.1017/S1047951107000042 }}
* {{cite journal | vauthors = Sparkes R, Patton D, Bernier F | title = Cardiac features of a novel autosomal recessive dilated cardiomyopathic syndrome due to defective importation of mitochondrial protein | journal = Cardiology in the Young | volume = 17 | issue = 2 | pages = 215–7 | date = April 2007 | pmid = 17244376 | doi = 10.1017/S1047951107000042 }}
* {{cite journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | pages = 385–93 | date = May 2006 | pmid = 16055927 | pmc = 2564511 | doi = 10.1136/jmg.2005.036657 }}
* {{cite journal | vauthors = Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP | title = Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition | journal = Journal of Medical Genetics | volume = 43 | issue = 5 | pages = 385–93 | date = May 2006 | pmid = 16055927 | pmc = 2564511 | doi = 10.1136/jmg.2005.036657 }}
* {{cite journal | vauthors = Mokranjac D, Sichting M, Neupert W, Hell K | title = Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria | journal = The EMBO Journal | volume = 22 | issue = 19 | pages = 4945–56 | date = Oct 2003 | pmid = 14517234 | pmc = 204468 | doi = 10.1093/emboj/cdg485 }}
* {{cite journal | vauthors = Mokranjac D, Sichting M, Neupert W, Hell K | title = Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria | journal = The EMBO Journal | volume = 22 | issue = 19 | pages = 4945–56 | date = October 2003 | pmid = 14517234 | pmc = 204468 | doi = 10.1093/emboj/cdg485 }}
* {{cite journal | vauthors = Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS | title = Characterization of the human heart mitochondrial proteome | journal = Nature Biotechnology | volume = 21 | issue = 3 | pages = 281–6 | date = Mar 2003 | pmid = 12592411 | doi = 10.1038/nbt793 }}
* {{cite journal | vauthors = Taylor SW, Fahy E, Zhang B, Glenn GM, Warnock DE, Wiley S, Murphy AN, Gaucher SP, Capaldi RA, Gibson BW, Ghosh SS | title = Characterization of the human heart mitochondrial proteome | journal = Nature Biotechnology | volume = 21 | issue = 3 | pages = 281–6 | date = March 2003 | pmid = 12592411 | doi = 10.1038/nbt793 }}
* {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–6 | date = Mar 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 }}
* {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–6 | date = March 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = September 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
{{refend}}
{{refend}}


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[[Category:Heat shock proteins]]
[[Category:Heat shock proteins]]
{{Portal bar|Mitochondria|Gene Wiki|border=no}}
{{NLM content}}

Latest revision as of 20:09, 21 August 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
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Mitochondrial import inner membrane translocase subunit TIM14 is an enzyme that in humans is encoded by the DNAJC19 gene on chromosome 3.[1][2] TIM14 belongs to the DnaJ family, which has been involved in Hsp40/Hsp70 chaperone systems.[3][4] As a mitochondrial chaperone, TIM14 functions as part of the TIM23 complex import motor to facilitate the import of nuclear-encoded proteins into the mitochondria.[3] TIM14 also complexes with prohibitin complexes to regulate mitochondrial morphogenesis, and has been implicated in dilated cardiomyopathy with ataxia.[5]

Structure

The DNAJC19 gene is located on the q arm of chromosome 3 at position 26.33 and it spans 6,065 base pairs.[2] The DNAJC19 gene produces a 6.29 kDa protein composed of 59 amino acids.[6][7] The protein encoded by the DNAJC19 gene possesses an unusual structure compared to the rest of the DNAJ protein family. Notably, the DNAJ domain of TIM14 is located at the C-terminal rather than the N-terminal, and the transmembrane domain confers membrane-bound localization for TIM14 while other DNAJ proteins are cytosolic. TIM14 orthologs in other species, such as the yeast Tim14 and Mdj2p proteins, confirm localization to the mitochondrial inner membrane.[8]

Function

TIM14 is required for the ATP-dependent import of mitochondrial pre-proteins into the mitochondrial matrix.The J-domain of TIM14 stimulates mtHsp70 ATPase activity to power this transport.[3]

Additionally, TIM14 helps regulate mitochondrial morphology by complexing with prohibitins to perform disphosphoglycerolipid cardiolipin (CL) remodeling. CL is a key phospholipid in mitochondrial membranes that modulates the fusion and fission of mitochondrial membranes, as well as mitophagy and apoptosis.[5]

Clinical significance

Defects in DNAJC19 have been observed primarily in cases of dilated cardiomyopathy with ataxia (DCMA), though it has also been associated with growth failure, microcytic anemia, and male genital anomalies. DNAJC19 was first implicated in DCMA in a study on the consanguineous Hutterite population, which has since been confirmed in other European populations.[4][9] In the clinic, DNAJC19 mutations can be detected by screening for elevated levels of 3-methylglutaconic acid, mitochondrial distress, dilated cardiomyopathy, prolongation of the QT interval in the electrocardiogram, and cerebellar ataxia.[9][10]

Interactions

TIM14 interacts with:

References

  1. ↑ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  2. ↑ 2.0 2.1 "Entrez Gene: DNAJC19 DnaJ (Hsp40) homolog, subfamily C, member 19".
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Mokranjac D, Sichting M, Neupert W, Hell K (October 2003). "Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria". The EMBO Journal. 22 (19): 4945–56. doi:10.1093/emboj/cdg485. PMC 204468. PMID 14517234.
  4. ↑ 4.0 4.1 Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, Snyder FF, Bridge PJ, Bernier FP (May 2006). "Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition". Journal of Medical Genetics. 43 (5): 385–93. doi:10.1136/jmg.2005.036657. PMC 2564511. PMID 16055927.
  5. ↑ 5.0 5.1 5.2 Richter-Dennerlein R, Korwitz A, Haag M, Tatsuta T, Dargazanli S, Baker M, Decker T, Lamkemeyer T, Rugarli EI, Langer T (July 2014). "DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling". Cell Metabolism. 20 (1): 158–71. doi:10.1016/j.cmet.2014.04.016. PMID 24856930.
  6. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  7. ↑ "Mitochondrial import inner membrane translocase subunit TIM14". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  8. ↑ Davey KM, Parboosingh JS, McLeod DR, Chan A, Casey R, Ferreira P, et al. (May 2006). "Mutation of DNAJC19, a human homologue of yeast inner mitochondrial membrane co-chaperones, causes DCMA syndrome, a novel autosomal recessive Barth syndrome-like condition". Journal of Medical Genetics. 43 (5): 385–93. doi:10.1136/jmg.2005.036657. PMC 2564511. PMID 16055927.
  9. ↑ 9.0 9.1 Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R, Suomalainen A, Tyni T (October 2012). "New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies". Pediatric Research. 72 (4): 432–7. doi:10.1038/pr.2012.92. PMID 22797137.
  10. ↑ Koutras C, Braun JE (Jul 2014). "J protein mutations and resulting proteostasis collapse". Frontiers in Cellular Neuroscience. 8: 191. doi:10.3389/fncel.2014.00191. PMC 4086201. PMID 25071450.
  11. ↑ Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M (October 2006). "Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor". The EMBO Journal. 25 (19): 4675–85. doi:10.1038/sj.emboj.7601334. PMC 1590002. PMID 16977310.

Further reading

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

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