TIMMDC1

TIMMDC1
Identifikatori
Aliasi	TIMMDC1
Vanjski ID-jevi	OMIM: 615534 MGI: 1922139 HomoloGene: 9578 GeneCards: TIMMDC1
Lokacija gena (čovjek)
Hrom.	Hromosom 3 (čovjek)
Kraj	119,525,090 bp
Lokacija gena (miš)
Hrom.	Hromosom 16 (miš)
Kraj	38,343,025 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• integral component of membrane; • mitochondrial inner membrane; • membrana; • mitohondrija; • mitochondrial membranes; • nukleoplazma; • jedro;
Biološki proces	• mitochondrial respiratory chain complex I assembly;
	Izvori:Amigo / QuickGO
Ortolozi
	51300
	76916
	ENSG00000113845
	ENSMUSG00000002846
	Q9NPL8
	Q8BUY5
	NM_016589
	NM_024273
	NP_057673
	NP_077235
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

TIMMDC1 jest protein koji je kod ljudi kodiran genom TIMMDC1 sa hromosoma 3.^[5]^[6] To je šaaperonski protein uključen u izgradnju membranskog kraka mitohondrijskog kompleksa I.^[7] Pokazalo se da mutacija pomaka okvira u intronu ovog gena uzrokuje neuspjeh u razvoju, zaostajanje psihomotornog razvoja, infantilni početak hipotonije i tešku neurološku disfunkciju.^[8] Visoka ekspresija ovog gena povezana je sa migracijom ćelija raka pluća, dok se pokazalo da iscrpljivanje proteina utiče na regulaciju apoptoza, ćelijski ciklus i migracije ćelija.^[9]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 285 aminokiselina, а molekulska težina 32.178 Da.^[10]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MEVPPPAPRS	FLCRALCLFP	RVFAAEAVTA	DSEVLEERQK	RLPYVPEPYY
PESGWDRLRE	LFGKDEQQRI	SKDLANICKT	AATAGIIGWV	YGGIPAFIHA
KQQYIEQSQA	EIYHNRFDAV	QSAHRAATRG	FIRYGWRWGW	RTAVFVTIFN
TVNTSLNVYR	NKDALSHFVI	AGAVTGSLFR	INVGLRGLVA	GGIIGALLGT
PVGGLLMAFQ	KYSGETVQER	KQKDRKALHE	LKLEEWKGRL	QVTEHLPEKI
ESSLQEDEPE	NDAKKIEALL	NLPRNPSVID	KQDKD

Struktura

Gen TIMMDC1 nalazi se na q kraku hromosoma 3 na poziciji 13.33 i obuhvata 25.760 parova baza, sa sedam egzona.^[6] Gen proizvodi protein od 32,2 kDa sastavljen od 285 aminokiselina.^[11]^[12] Protein TIMMDC1 ima četiri transmembranska domena, sa N– i C-terminalnim ekstenzijama u mitohondrijskom matriksu. TIMMDC1 je multiprolazni protein unutrašnje mitohondrijske membrane , za koji se predviđa da je član 4-prolazne transmembrane porodice proteina TIM17–TIM22–TIM23. Predviđa se da će njegova topologija biti analogna TIMM23.^[13]

Funkcija

TIMMDC1 je proteinski šaperon uključen u sklapanje mitohondrijskog kompleksa I (NADH-ubikvinon-oksidoreduktaze), koji učestvuje u izgradnji membranskog kraka kompleksa I.^[7]

Klinički značaj

Pokazalo se da mutacija pomaka okvira u intronu 5 gena TIMMDC1 uzrokuje tešk neurološke disfunkcije, infantilni početak hipotonija, zaostatak psihomotornog razvoja, i neuspjeh u razvoju.^[8] Dodatno, visoka ekspresija TIMMDC1 povezana je sa metastazama ćelija karcinoma pluća, sa iscrpljivanjem proteina koji inhibira rast i migraciju 95D ćelija karcinoma pluća. Takođe se pokazalo da iscrpljivanje TIMMDC1 mijenja ekspresiju gena uključenih u regulaciju apoptoze, zaustavljanje ćelijskog ciklusa i migraciju ćelija, uključujući CCNG2, PTEN, TIMP3 i COL3A1.^[9]

Interakcije

Protein TIMMDC1 ima interakcije sa srednjim potkompleksom od 315 kDa nepotpuno sastavljenog kompleksa I i ima interakcije sa FATE1, pored oko 60 ostalih proteina.^[7]^[14] TIMMDC1 se recipročno povezuje sa više komponenti ECSIT-TMEM126B-ACAD9-NDUFAF1 faktora sklapanja kompleksa (MCIA-kompleks).^[13]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000113845 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000002846 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ ^a ^b "Entrez Gene: C3orf1 chromosome 3 open reading frame 1".
^ ^a ^b ^c "TIMMDC1 - Complex I assembly factor TIMMDC1, mitochondrial - Homo sapiens (Human) - TIMMDC1 gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 27. 7. 2018.
^ ^a ^b Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, et al. (juni 2017). "Genetic diagnosis of Mendelian disorders via RNA sequencing". Nature Communications. 8: 15824. doi:10.1038/ncomms15824. PMC 5499207. PMID 28604674.
^ ^a ^b Wu H, Wang W, Xu H (novembar 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.
^ "UniProt, Q9NPL8" (jezik: engleski). Pristupljeno 6. 11. 2021.
^ 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 (oktobar 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.
^ "Complex I assembly factor TIMMDC1, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Arhivirano s originala, 2. 8. 2018. Pristupljeno 6. 11. 2021.
^ ^a ^b Guarani V, Paulo J, Zhai B, Huttlin EL, Gygi SP, Harper JW (mart 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.
^ Lab, Mike Tyers. "TIMMDC1 (UNQ247/PRO284) Result Summary | BioGRID". thebiogrid.org (jezik: engleski). Pristupljeno 27. 7. 2018.

Dopunska literatura

Maruyama K, Sugano S (januar 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (oktobar 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
Hartley JL, Temple GF, Brasch MA (novembar 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
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 (mart 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (septembar 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
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 (oktobar 2003). "The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment". Genome Research. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (oktobar 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (januar 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.

Vanjski linkovi

Lokacija ljudskog genoma TIMMDC1 i stranica sa detaljima o genu TIMMDC1 u UCSC Genome Browseru.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000113845 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000002846 - Ensembl, maj 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.

[pmid11092749-5] 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.

[entrez-6] "Entrez Gene: C3orf1 chromosome 3 open reading frame 1".

[:0-7] "TIMMDC1 - Complex I assembly factor TIMMDC1, mitochondrial - Homo sapiens (Human) - TIMMDC1 gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 27. 7. 2018.

[:2-8] Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, et al. (juni 2017). "Genetic diagnosis of Mendelian disorders via RNA sequencing". Nature Communications. 8: 15824. doi:10.1038/ncomms15824. PMC 5499207. PMID 28604674.

[:3-9] Wu H, Wang W, Xu H (novembar 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.

[UniProt-10] "UniProt, Q9NPL8" (jezik: engleski). Pristupljeno 6. 11. 2021.

[COPaKB-11] 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 (oktobar 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.

[url_COPaKB-12] "Complex I assembly factor TIMMDC1, mitochondrial". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Arhivirano s originala, 2. 8. 2018. Pristupljeno 6. 11. 2021.

[:1-13] Guarani V, Paulo J, Zhai B, Huttlin EL, Gygi SP, Harper JW (mart 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.

[14] Lab, Mike Tyers. "TIMMDC1 (UNQ247/PRO284) Result Summary | BioGRID". thebiogrid.org (jezik: engleski). Pristupljeno 27. 7. 2018.

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