“TIMMDC1”的意思、由来-开放百科全书

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.^[2] The gene produces a 32.2 kDa protein composed of 285 amino acids.^[6]^[7] 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.^[8]

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.^[3]

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.^[4] 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.^[5]

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.^[9]^[3] TIMMDC1 associates reciprocally with multiple components of the ECSIT-TMEM126B-ACAD9-NDUFAF1 assembly factor complex (MCIA complex).^[8]

References

1. ^{{cite journal | vauthors = Escarceller M, Pluvinet R, Sumoy L, Estivill X | title = Identification and expression analysis of C3orf1, a novel human gene homologous to the Drosophila RP140-upstream gene | journal = DNA Sequence | volume = 11 | issue = 3–4 | pages = 335–8 | date = Mar 2001 | pmid = 11092749 | pmc = | doi = 10.3109/10425170009033252 }}
2. ^¹{{cite web | title = Entrez Gene: C3orf1 chromosome 3 open reading frame 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=51300| access-date = }}{{PD-notice}}
3. ^¹²{{Cite web|url=https://www.uniprot.org/uniprot/Q9NPL8|title=TIMMDC1 - Complex I assembly factor TIMMDC1, mitochondrial - Homo sapiens (Human) - TIMMDC1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-07-27}}{{PD-notice}}
4. ^¹{{cite journal | vauthors = Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, Haack TB, Graf E, Schwarzmayr T, Terrile C, Koňaříková E, Repp B, Kastenmüller G, Adamski J, Lichtner P, Leonhardt C, Funalot B, Donati A, Tiranti V, Lombes A, Jardel C, Gläser D, Taylor RW, Ghezzi D, Mayr JA, Rötig A, Freisinger P, Distelmaier F, Strom TM, Meitinger T, Gagneur J, Prokisch H | display-authors = 6 | title = Genetic diagnosis of Mendelian disorders via RNA sequencing | journal = Nature Communications | volume = 8 | pages = 15824 | date = June 2017 | pmid = 28604674 | pmc = 5499207 | doi = 10.1038/ncomms15824 }}
5. ^¹{{cite journal | vauthors = Wu H, Wang W, Xu H | title = Depletion of C3orf1/TIMMDC1 inhibits migration and proliferation in 95D lung carcinoma cells | journal = International Journal of Molecular Sciences | volume = 15 | issue = 11 | pages = 20555–71 | date = November 2014 | pmid = 25391042 | pmc = 4264183 | doi = 10.3390/ijms151120555 }}
6. ^{{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 }}
7. ^{{cite web|url=https://amino.heartproteome.org/web/protein/Q9NPL8|title=Complex I assembly factor TIMMDC1, mitochondrial|work=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)}}
8. ^¹{{cite journal | vauthors = Guarani V, Paulo J, Zhai B, Huttlin EL, Gygi SP, Harper JW | title = TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex | journal = Molecular and Cellular Biology | volume = 34 | issue = 5 | pages = 847–61 | date = March 2014 | pmid = 24344204 | pmc = 4023825 | doi = 10.1128/MCB.01551-13 }}
9. ^{{Cite web|url=https://thebiogrid.org/119451|title=TIMMDC1 (UNQ247/PRO284) Result Summary {{!}} BioGRID|last=Lab|first=Mike Tyers|website=thebiogrid.org|language=en|access-date=2018-07-27}}

Further reading

{{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}

{{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}

{{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}

{{cite journal | vauthors = Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A | title = Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs | journal = Genome Research | volume = 11 | issue = 3 | pages = 422–35 | date = March 2001 | pmid = 11230166 | pmc = 311072 | doi = 10.1101/gr.GR1547R }}

{{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = September 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}

{{cite journal | vauthors = Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A | title = The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment | journal = Genome Research | volume = 13 | issue = 10 | pages = 2265–70 | date = October 2003 | pmid = 12975309 | pmc = 403697 | doi = 10.1101/gr.1293003 }}

{{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = October 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}