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DnaJ (Hsp40) homolog, subfamily C, member 19
Symbols DNAJC19 ; PAM18; TIM14; TIMM14
External IDs OMIM608977 HomoloGene87176 GeneCards: DNAJC19 Gene
RNA expression pattern
PBB GE DNAJC19 gnf1h09108 at tn.png
More reference expression data
Species Human Mouse
Entrez 131118 67713
Ensembl ENSG00000205981 ENSMUSG00000027679
UniProt Q96DA6 Q9CQV7
RefSeq (mRNA) NM_001190233 NM_001026211
RefSeq (protein) NP_001177162 NP_001021382
Location (UCSC) Chr 3:
180.7 – 180.71 Mb
Chr 3:
34.06 – 34.08 Mb
PubMed search [1] [2]

Mitochondrial import inner membrane translocase subunit TIM14 is an enzyme that in humans is encoded by the DNAJC19 gene.[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]


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[edit]

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][6] 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.[6][7]


TIM14 interacts with:


  1. ^ Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS et al. (Dec 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. ^ "Entrez Gene: DNAJC19 DnaJ (Hsp40) homolog, subfamily C, member 19". 
  3. ^ a b c d e Mokranjac D, Sichting M, Neupert W, Hell K (Oct 2003). "Tim14, a novel key component of the import motor of the TIM23 protein translocase of mitochondria". The EMBO Journal 22 (19). doi:10.1093/emboj/cdg485. PMID 14517234. 
  4. ^ a b 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). doi:10.1136/jmg.2005.036657. PMID 16055927. 
  5. ^ a b c Richter-Dennerlein R, Korwitz A, Haag M, Tatsuta T, Dargazanli S, Baker M et al. (Jul 2014). "DNAJC19, a mitochondrial cochaperone associated with cardiomyopathy, forms a complex with prohibitins to regulate cardiolipin remodeling". Cell Metabolism 20 (1). doi:10.1016/j.cmet.2014.04.016. PMID 24856930. 
  6. ^ a b Ojala T, Polinati P, Manninen T, Hiippala A, Rajantie J, Karikoski R et al. (Oct 2012). "New mutation of mitochondrial DNAJC19 causing dilated and noncompaction cardiomyopathy, anemia, ataxia, and male genital anomalies". Pediatric Research 72 (4). doi:10.1038/pr.2012.92. PMID 22797137. 
  7. ^ Koutras C, Braun JE (Jul 2014). "J protein mutations and resulting proteostasis collapse". Frontiers in Cellular Neuroscience 8. doi:10.3389/fncel.2014.00191. PMID 25071450. 
  8. ^ Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M (Oct 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). doi:10.1038/sj.emboj.7601334. PMID 16977310. 

Further reading[edit]