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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesYTHDC1, YT521, YT521-B, YTH domain containing 1
External IDsOMIM: 617283 MGI: 2443713 HomoloGene: 15796 GeneCards: YTHDC1
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4q13.2Start68,310,387 bp[1]
End68,350,089 bp[1]
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
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 MbChr 5: 86.8 – 86.84 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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).[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): 1233. 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. S2CID 35669580.
  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". Tumor Biology. 37 (12): 15543–15549. doi:10.1007/s13277-015-3908-y. ISSN 1423-0380. PMID 26289848. S2CID 11257001.
  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


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