YTHDC1

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) Band 4q13.2 Start 68,310,387 bp End 68,350,090 bp
Gene location (Mouse) Chr. Chromosome 5 (mouse) Band 5|5 E1 Start 86,952,080 bp End 86,984,518 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon corpus callosum sural nerve bone marrow endometrium right lung vagina lymph node canal of the cervix body of pancreas Top expressed in medullary collecting duct conjunctival fornix renal corpuscle cumulus cell ureter ciliary body pineal gland Paneth cell blood iris More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding RNA binding N6-methyladenosine-containing RNA binding Cellular component nucleus nuclear speck plasma 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: 86.95 – 86.98 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

YTH domain-containing protein 1 is a protein that in humans is encoded by the YTHDC1 gene. 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.

Interactions

YTHDC1 has been shown to interact with:

• Abl gene,
• C-src tyrosine kinase,
• Emerin,
• KHDRBS1. and
• Metadherin

Role in disease

Alternative splicing is altered in a number of diseases and is particularly 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).

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.

See also

N⁶-Methyladenosine

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. Bibcode:2004PNAS..10112130B. 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. S2CID 31339890.
• 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. Bibcode:2006PNAS..103.5391N. 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. S2CID 14294292.
• 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. S2CID 7827573.