YTHDC1

YTH domain-containing protein 1 is a protein that in humans is encoded by the YTHDC1 gene.[5][6][7] YTHDC1 is a nuclear protein involved in splice site selection that localises to YT bodies; dynamic subnuclear compartments, which first appear at the beginning of S-phase in the cell cycle and disperse during mitosis.[8]

YTHDC1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2YUD, 4R3H, 4R3I
Identifiers
Aliases	YTHDC1, YT521, YT521-B, YTH domain containing 1
External IDs	OMIM: 617283 MGI: 2443713 HomoloGene: 15796 GeneCards: YTHDC1
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q13.2 Start 68,310,387 bp[1] End 68,350,089 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5|5 E1 Start 86,804,221 bp[2] End 86,836,659 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • RNA binding • N6-methyladenosine-containing RNA binding Cellular component • cell nucleus • nuclear speck • cell membrane • nucleoplasm Biological process • mRNA processing • mRNA splice site selection • RNA splicing • regulation of mRNA splicing, via spliceosome • mRNA export from nucleus • dosage compensation by inactivation of X chromosome • posttranscriptional regulation of gene expression Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	91746	231386
Ensembl	ENSG00000275272 ENSG00000083896	ENSMUSG00000035851
UniProt	Q96MU7	E9Q5K9
RefSeq (mRNA)	NM_001031732 NM_133370 NM_001330698	NM_177680 NM_001347375 NM_001347376 NM_001359907 NM_001359908
RefSeq (protein)	NP_001026902 NP_001317627 NP_588611	NP_001334304 NP_001334305 NP_808348 NP_001346836 NP_001346837
Location (UCSC)	Chr 4: 68.31 – 68.35 Mb	Chr 5: 86.8 – 86.84 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

YTHDC1 has been shown to interact with:

• Abl gene,[9]
• C-src tyrosine kinase,[9]
• Emerin,[10]
• KHDRBS1.[6] and
• Metadherin [11]

Role in disease

Alternative splicing is altered in a number of diseases and is particuarly relevant to cancer.

Cancer

YTHDC1 has been shown to splice mRNA transcripts which have oncological importance, regulating tumour functions such as hypoxia associated vascular endothelial growth factor (VEGF), DNA damage associated breast cancer 1 (BRCA1) and hormonal growth driver; the progesterone receptor (PGR).[12][13]

In prostate cancer, YTHDC1 has also been shown to interact with the protein metadherin, encoded by the oncogene MTDH acting to influence alternative splicing of tumour-related genes such as CD44.[11][14]

See also

N⁶-Methyladenosine

References

1. ENSG00000083896 GRCh38: Ensembl release 89: ENSG00000275272, ENSG00000083896 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035851 - 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. Stoilov P, Rafalska I, Stamm S (Oct 2002). "YTH: a new domain in nuclear proteins". Trends Biochem Sci. 27 (10): 495–7. doi:10.1016/S0968-0004(02)02189-8. PMID 12368078.
6. Hartmann AM, Nayler O, Schwaiger FW, Obermeier A, Stamm S (Dec 1999). "The interaction and colocalization of Sam68 with the splicing-associated factor YT521-B in nuclear dots is regulated by the Src family kinase p59(fyn)". Mol Biol Cell. 10 (11): 3909–26. doi:10.1091/mbc.10.11.3909. PMC 25688. PMID 10564280.
7. "Entrez Gene: YTHDC1 YTH domain containing 1".
8. Nayler, O.; Hartmann, A. M.; Stamm, S. (2000-09-04). "The ER repeat protein YT521-B localizes to a novel subnuclear compartment". The Journal of Cell Biology. 150 (5): 949–962. doi:10.1083/jcb.150.5.949. ISSN 0021-9525. PMC 2175241. PMID 10973987.
9. Rafalska I, Zhang Z, Benderska N, Wolff H, Hartmann AM, Brack-Werner R, Stamm S (Aug 2004). "The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation". Hum. Mol. Genet. 13 (15): 1535–49. doi:10.1093/hmg/ddh167. PMID 15175272.
10. Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE (Jun 2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". Eur. J. Biochem. 270 (11): 2459–66. doi:10.1046/j.1432-1033.2003.03617.x. PMID 12755701.
11. Luxton, Hayley J.; Simpson, Benjamin S.; Mills, Ian G.; Brindle, Nicola R.; Ahmed, Zeba; Stavrinides, Vasilis; Heavey, Susan; Stamm, Stefan; Whitaker, Hayley C. (2019-08-23). "The Oncogene Metadherin Interacts with the Known Splicing Proteins YTHDC1, Sam68 and T-STAR and Plays a Novel Role in Alternative mRNA Splicing". Cancers. 11 (9). doi:10.3390/cancers11091233. ISSN 2072-6694. PMC 6770463. PMID 31450747.
12. Hirschfeld, Marc; Zhang, Bo; Jaeger, Markus; Stamm, Stefan; Erbes, Thalia; Mayer, Sebastian; Tong, Xiaowen; Stickeler, Elmar (November 2014). "Hypoxia-dependent mRNA expression pattern of splicing factor YT521 and its impact on oncological important target gene expression". Molecular Carcinogenesis. 53 (11): 883–892. doi:10.1002/mc.22045. ISSN 1098-2744. PMID 23765422.
13. Zhang, Bo; Shao, Xiaowen; Zhou, Jianhong; Qiu, Jin; Wu, Yi; Cheng, Jiajing (2015-08-21). "YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A". Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine. doi:10.1007/s13277-015-3908-y. ISSN 1423-0380. PMID 26289848.
14. Yoo, Byoung Kwon; Emdad, Luni; Su, Zao-zhong; Villanueva, Augusto; Chiang, Derek Y.; Mukhopadhyay, Nitai D.; Mills, Alan Scott; Waxman, Samuel; Fisher, Robert A.; Llovet, Josep M.; Fisher, Paul B. (March 2009). "Astrocyte elevated gene-1 regulates hepatocellular carcinoma development and progression". The Journal of Clinical Investigation. 119 (3): 465–477. doi:10.1172/JCI36460. ISSN 1558-8238. PMC 2648696. PMID 19221438.

Further reading

• Imai Y, Matsuo N, Ogawa S, Tohyama M, Takagi T (1998). "Cloning of a gene, YT521, for a novel RNA splicing-related protein induced by hypoxia/reoxygenation". Brain Res. Mol. Brain Res. 53 (1–2): 33–40. doi:10.1016/S0169-328X(97)00262-3. PMID 9473574.
• Nayler O, Hartmann AM, Stamm S (2000). "The ER repeat protein YT521-B localizes to a novel subnuclear compartment". J. Cell Biol. 150 (5): 949–62. doi:10.1083/jcb.150.5.949. PMC 2175241. PMID 10973987.
• Stoss O, Olbrich M, Hartmann AM, Konig H, Memmott J, Andreadis A, Stamm S (2001). "The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites". J. Biol. Chem. 276 (12): 8665–73. doi:10.1074/jbc.M006851200. PMID 11118435.
• Nagase T, Kikuno R, Ohara O (2002). "Prediction of the coding sequences of unidentified human genes. XXII. The complete sequences of 50 new cDNA clones which code for large proteins". DNA Res. 8 (6): 319–27. doi:10.1093/dnares/8.6.319. PMID 11853319.
• Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE (2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". Eur. J. Biochem. 270 (11): 2459–66. doi:10.1046/j.1432-1033.2003.03617.x. PMID 12755701.
• Rafalska I, Zhang Z, Benderska N, Wolff H, Hartmann AM, Brack-Werner R, Stamm S (2005). "The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation". Hum. Mol. Genet. 13 (15): 1535–49. doi:10.1093/hmg/ddh167. PMID 15175272.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Stoss O, Novoyatleva T, Gencheva M, Olbrich M, Benderska N, Stamm S (2005). "p59(fyn)-mediated phosphorylation regulates the activity of the tissue-specific splicing factor rSLM-1". Mol. Cell. Neurosci. 27 (1): 8–21. doi:10.1016/j.mcn.2004.04.011. PMID 15345239.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (2006). "Phosphoproteome analysis of the human mitotic spindle". Proc. Natl. Acad. Sci. U.S.A. 103 (14): 5391–6. doi:10.1073/pnas.0507066103. PMC 1459365. PMID 16565220.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. Biotechnol. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.