TIMMDC1
Identifiers
AliasesTIMMDC1, C3orf1, translocase of inner mitochondrial membrane domain containing 1, MC1DN31
External IDsOMIM: 615534 MGI: 1922139 HomoloGene: 9578 GeneCards: TIMMDC1
Orthologs
SpeciesHumanMouse
Entrez

51300

76916

Ensembl

ENSG00000113845

ENSMUSG00000002846

UniProt

Q9NPL8

Q8BUY5

RefSeq (mRNA)

NM_016589

NM_024273

RefSeq (protein)

NP_057673

NP_077235

Location (UCSC)Chr 3: 119.5 – 119.53 MbChr 16: 38.32 – 38.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

TIMMDC1 is a protein that in humans is encoded by the TIMMDC1 gene.[5][6] It is a chaperone protein involved in constructing the membrane arm of mitochondrial Complex I.[7] A frameshift mutation in an intron of this gene has been shown to cause failure to thrive, retardation of psychomotor development, infantile-onset hypotonia, and severe neurologic dysfunction.[8] High expression of this gene has been associated with migration of lung cancer cells while depletion of the protein has been shown to affect regulation of apoptosis, the cell cycle, and cell migration.[9]

Structure

The TIMMDC1 gene is located on the q arm of chromosome 3 in position 13.33 and spans 25,760 base pairs, with 7 exons.[6] The gene produces a 32.2 kDa protein composed of 285 amino acids.[10][11] The TIMMDC1 protein has 4 transmembrane domains, with the N-terminal and C-terminal extensions localized in the mitochondrial matrix. TIMMDC1 is a multipass mitochondrial inner membrane protein, predicted to be a member of the 4-pass transmembrane protein family of TIM17-TIM22-TIM23. Its topology is predicted to be analogous to TIMM23.[12]

Function

TIMMDC1 is a chaperone protein involved in the assembly of the mitochondrial Complex I (NADH-ubiquinone oxidoreductase), participating in the construction of the membrane arm of complex I.[7]

Clinical Significance

A frameshift mutation in intron 5 of the TIMMDC1 gene has been shown to cause severe neurologic dysfunction, infantile-onset hypotonia, retardation of psychomotor development, and failure to thrive.[8] Additionally, high expression of TIMMDC1 has been associated with metastasis of lung carcinoma cells, with depletion of the protein inhibiting growth and migration of 95D lung carcinoma cells. Depletion of TIMMDC1 has also been shown to alter expression of genes involved in the regulation of apoptosis, cell-cycle arrest, and cell migration, including CCNG2, PTEN, TIMP3, and COL3A1.[9]

Interactions

The TIMMDC1 protein interacts with the intermediate 315 kDa subcomplex of incompletely assembled complex I and has interactions with FATE1, in addition to about 60 other proteins.[13][7] TIMMDC1 associates reciprocally with multiple components of the ECSIT-TMEM126B-ACAD9-NDUFAF1 assembly factor complex (MCIA complex).[12]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000113845 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000002846 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Escarceller M, Pluvinet R, Sumoy L, Estivill X (Mar 2001). "Identification and expression analysis of C3orf1, a novel human gene homologous to the Drosophila RP140-upstream gene". DNA Sequence. 11 (3–4): 335–8. doi:10.3109/10425170009033252. PMID 11092749. S2CID 20254976.
  6. 1 2 "Entrez Gene: C3orf1 chromosome 3 open reading frame 1".Public Domain This article incorporates text from this source, which is in the public domain.
  7. 1 2 3 "TIMMDC1 - Complex I assembly factor TIMMDC1, mitochondrial - Homo sapiens (Human) - TIMMDC1 gene & protein". www.uniprot.org. Retrieved 2018-07-27.Public Domain This article incorporates text from this source, which is in the public domain.
  8. 1 2 Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, et al. (June 2017). "Genetic diagnosis of Mendelian disorders via RNA sequencing". Nature Communications. 8: 15824. Bibcode:2017NatCo...815824K. doi:10.1038/ncomms15824. PMC 5499207. PMID 28604674.
  9. 1 2 Wu H, Wang W, Xu H (November 2014). "Depletion of C3orf1/TIMMDC1 inhibits migration and proliferation in 95D lung carcinoma cells". International Journal of Molecular Sciences. 15 (11): 20555–71. doi:10.3390/ijms151120555. PMC 4264183. PMID 25391042.
  10. ↑ 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.
  11. ↑ "Complex I assembly factor TIMMDC1, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 2018-08-02. Retrieved 2018-08-02.
  12. 1 2 Guarani V, Paulo J, Zhai B, Huttlin EL, Gygi SP, Harper JW (March 2014). "TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex". Molecular and Cellular Biology. 34 (5): 847–61. doi:10.1128/MCB.01551-13. PMC 4023825. PMID 24344204.
  13. ↑ Lab, Mike Tyers. "TIMMDC1 (UNQ247/PRO284) Result Summary | BioGRID". thebiogrid.org. Retrieved 2018-07-27.

Further reading

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