YTHDC1

YTHDC1
Identifiers
Aliases	YTHDC1, YT521, YT521-B, YTH domain containing 1
External IDs	OMIM: 617283; MGI: 2443713; GeneCards: YTHDC1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2YUD, 4R3H, 4R3I
Gene location (Human)
Chr.	Chromosome 4 (human)
End	68,350,090 bp
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)
End	86,984,518 bp
RNA expression pattern
	Top expressed in
	Achilles tendon; ; corpus callosum; ; sural nerve; ; left ovary; ; bone marrow; ; endometrium; ; ventricular zone; ; right ovary; ; right lung; ; vagina;
	Top expressed in
	medullary collecting duct; ; conjunctival fornix; ; renal corpuscle; ; cumulus cell; ; ureter; ; ciliary body; ; pineal gland; ; vestibular membrane of cochlear duct; ; Rostral migratory stream; ; Paneth cell;
	More reference expression data
	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
Databases	NCBI: entry; OMA: entry
	91746
	231386
	ENSG00000275272; ENSG00000083896
	ENSMUSG00000035851
	Q96MU7
	E9Q5K9
	NM_001031732; NM_133370; NM_001330698
	NM_177680; NM_001347375; NM_001347376; NM_001359907; NM_001359908
	NP_001026902; NP_001317627; NP_588611
	NP_001334304; NP_001334305; NP_808348; NP_001346836; NP_001346837
	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:

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.

References

1 2 3 ENSG00000083896 GRCh38: Ensembl release 89: ENSG00000275272, ENSG00000083896 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000035851 – Ensembl, May 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.
↑ Stoilov P, Rafalska I, Stamm S (October 2002). "YTH: a new domain in nuclear proteins". Trends in Biochemical Sciences. 27 (10): 495–497. doi:10.1016/S0968-0004(02)02189-8. PMID 12368078.
1 2 Hartmann AM, Nayler O, Schwaiger FW, Obermeier A, Stamm S (December 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)". Molecular Biology of the Cell. 10 (11): 3909–3926. doi:10.1091/mbc.10.11.3909. PMC 25688. PMID 10564280.
↑ "Entrez Gene: YTHDC1 YTH domain containing 1".
↑ Nayler O, Hartmann AM, Stamm S (September 2000). "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. PMC 2175241. PMID 10973987.
1 2 Rafalska I, Zhang Z, Benderska N, Wolff H, Hartmann AM, Brack-Werner R, et al. (August 2004). "The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation". Human Molecular Genetics. 13 (15): 1535–1549. doi:10.1093/hmg/ddh167. PMID 15175272.
↑ Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, et al. (June 2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". European Journal of Biochemistry. 270 (11): 2459–2466. doi:10.1046/j.1432-1033.2003.03617.x. PMID 12755701.
1 2 Luxton HJ, Simpson BS, Mills IG, Brindle NR, Ahmed Z, Stavrinides V, et al. (August 2019). "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). Basel: 1233. doi:10.3390/cancers11091233. PMC 6770463. PMID 31450747.
↑ Hirschfeld M, Zhang B, Jaeger M, Stamm S, Erbes T, Mayer S, et al. (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. PMID 23765422. S2CID 35669580.
↑ Zhang B, Shao X, Zhou J, Qiu J, Wu Y, Cheng J (December 2016). "YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A". Tumour Biology. 37 (12): 15543–15549. doi:10.1007/s13277-015-3908-y. PMID 26289848. S2CID 11257001.
↑ Yoo BK, Emdad L, Su ZZ, Villanueva A, Chiang DY, Mukhopadhyay ND, et al. (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. PMC 2648696. PMID 19221438.

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 Research. Molecular Brain Research. 53 (1–2): 33–40. doi:10.1016/S0169-328X(97)00262-3. PMID 9473574.
Stoss O, Olbrich M, Hartmann AM, Konig H, Memmott J, Andreadis A, et al. (2001). "The STAR/GSG family protein rSLM-2 regulates the selection of alternative splice sites". The Journal of Biological Chemistry. 276 (12): 8665–8673. 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 Research. 8 (6): 319–327. doi:10.1093/dnares/8.6.319. PMID 11853319.
Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. 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". Molecular and Cellular Neurosciences. 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, et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 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". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–5396. 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". Nature Biotechnology. 24 (10): 1285–1292. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.

This article on a gene on human chromosome 4 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 ENSG00000083896 GRCh38: Ensembl release 89: ENSG00000275272, ENSG00000083896 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[Stoilov_2002-5] Stoilov P, Rafalska I, Stamm S (October 2002). "YTH: a new domain in nuclear proteins". Trends in Biochemical Sciences. 27 (10): 495–497. doi:10.1016/S0968-0004(02)02189-8. PMID 12368078.

[Hartmann_1999-6] 1 2 Hartmann AM, Nayler O, Schwaiger FW, Obermeier A, Stamm S (December 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)". Molecular Biology of the Cell. 10 (11): 3909–3926. doi:10.1091/mbc.10.11.3909. PMC 25688. PMID 10564280.

[entrez-7] "Entrez Gene: YTHDC1 YTH domain containing 1".

[8] Nayler O, Hartmann AM, Stamm S (September 2000). "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. PMC 2175241. PMID 10973987.

[Rafalska_2004-9] 1 2 Rafalska I, Zhang Z, Benderska N, Wolff H, Hartmann AM, Brack-Werner R, et al. (August 2004). "The intranuclear localization and function of YT521-B is regulated by tyrosine phosphorylation". Human Molecular Genetics. 13 (15): 1535–1549. doi:10.1093/hmg/ddh167. PMID 15175272.

[Wilkinson_2003-10] Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, et al. (June 2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". European Journal of Biochemistry. 270 (11): 2459–2466. doi:10.1046/j.1432-1033.2003.03617.x. PMID 12755701.

[Luxton-11] 1 2 Luxton HJ, Simpson BS, Mills IG, Brindle NR, Ahmed Z, Stavrinides V, et al. (August 2019). "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). Basel: 1233. doi:10.3390/cancers11091233. PMC 6770463. PMID 31450747.

[12] Hirschfeld M, Zhang B, Jaeger M, Stamm S, Erbes T, Mayer S, et al. (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. PMID 23765422. S2CID 35669580.

[13] Zhang B, Shao X, Zhou J, Qiu J, Wu Y, Cheng J (December 2016). "YT521 promotes metastases of endometrial cancer by differential splicing of vascular endothelial growth factor A". Tumour Biology. 37 (12): 15543–15549. doi:10.1007/s13277-015-3908-y. PMID 26289848. S2CID 11257001.

[14] Yoo BK, Emdad L, Su ZZ, Villanueva A, Chiang DY, Mukhopadhyay ND, et al. (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. PMC 2648696. PMID 19221438.

YTHDC1

Interactions

Role in disease

Cancer

See also

References

Further reading