SMYD3

SMYD3 is a lysine methyltransferase{{cite journal | vauthors = Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, McDevitt P, Sinnamon R, Le B, Mas G, Annan R, Sage J, Garcia BA, Tummino PJ, Gozani O, Kruger RG | display-authors = 6 | title = Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation | journal = Epigenetics | volume = 7 | issue = 4 | pages = 340–3 | date = April 2012 | pmid = 22419068 | pmc = 3368817 | doi = 10.4161/epi.19506 }} which specifically methylates H3K4 and H4K5.{{cite journal | vauthors = Liu Y, Liu H, Luo X, Deng J, Pan Y, Liang H | title = Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer | journal = Tumour Biology | volume = 36 | issue = 6 | pages = 4377–86 | date = June 2015 | pmid = 25627005 | doi = 10.1007/s13277-015-3077-z | s2cid = 21827212 }} SMYD3 plays a role in transcriptional regulation as a member of an RNA polymerase complex. It is also involved in cancer regulation.

SMYD3 is predominantly expressed in skeletal muscles and the testis.

SMYD3 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1{{cite journal | vauthors = Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y | display-authors = 6 | title = SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells | journal = Nature Cell Biology | volume = 6 | issue = 8 | pages = 731–40 | date = August 2004 | pmid = 15235609 | doi = 10.1038/ncb1151 | s2cid = 13456531 }} and POLR2A.

SMYD3 trimethylates a lysine residue on MAP3K2, which causes crosstalk into the MAP kinase signaling pathway in Ras-driven cancers.{{cite journal | vauthors = Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, Barbash O, Van Aller GS, Huddleston M, Dhanak D, Tummino PJ, Kruger RG, Garcia BA, Butte AJ, Vermeulen M, Sage J, Gozani O | display-authors = 6 | title = SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer | journal = Nature | volume = 510 | issue = 7504 | pages = 283–7 | date = June 2014 | pmid = 24847881 | pmc = 4122675 | doi = 10.1038/nature13320 | bibcode = 2014Natur.510..283M }}

SMYD3 plays an important role in the progression of cancers in humans. It is highly over expressed in a number of cancers such as liver, breast, and colorectal carcinomas.{{cite journal | vauthors = Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y | display-authors = 6 | title = SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells | journal = Nature Cell Biology | volume = 6 | issue = 8 | pages = 731–40 | date = August 2004 | pmid = 15235609 | doi = 10.1038/ncb1151 | s2cid = 13456531 }} SMYD3 is known to play a role in lung, esophageal and prostate cancers also.{{cite journal | vauthors = Giakountis A, Moulos P, Sarris ME, Hatzis P, Talianidis I | title = Smyd3-associated regulatory pathways in cancer | journal = Seminars in Cancer Biology | volume = 42 | pages = 70–80 | date = February 2017 | pmid = 27554136 | doi = 10.1016/j.semcancer.2016.08.008 }}

It has been noted that in lung and colorectal cancers, MAP3K2 methylation by SMYD3 ameliorates PPA2's inhibitory control, which leads to the overriding of apoptosis signals via the activation of the MEK/ERK signalling cascade.{{cite journal | vauthors = Colón-Bolea P, Crespo P | title = Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway | journal = BioEssays | volume = 36 | issue = 12 | pages = 1162–9 | date = December 2014 | pmid = 25382779 | doi = 10.1002/bies.201400120 | s2cid = 25659263 }} Meanwhile, in colon and liver cancers, SMYD3-mediated methylation of H3 promotes RNAP II recruitment and the associated transcription factors from proto-oncogenic regions.

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• {{cite journal | vauthors = Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM | title = Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region | journal = Genomics | volume = 83 | issue = 1 | pages = 153–67 | date = January 2004 | pmid = 14667819 | doi = 10.1016/S0888-7543(03)00235-0 }}
• {{cite journal | vauthors = Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, Yagyu R, Nakamura Y | display-authors = 6 | title = SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells | journal = Nature Cell Biology | volume = 6 | issue = 8 | pages = 731–40 | date = August 2004 | pmid = 15235609 | doi = 10.1038/ncb1151 | s2cid = 13456531 }}
• {{cite journal | vauthors = Zhou Z, Ren X, Huang X, Lu L, Xu M, Yin L, Li J, Sha J | display-authors = 6 | title = SMYD3-NY, a novel SMYD3 mRNA transcript variant, may have a role in human spermatogenesis | journal = Annals of Clinical and Laboratory Science | volume = 35 | issue = 3 | pages = 270–7 | year = 2006 | pmid = 16081583 }}
• {{cite journal | vauthors = Tsuge M, Hamamoto R, Silva FP, Ohnishi Y, Chayama K, Kamatani N, Furukawa Y, Nakamura Y | display-authors = 6 | title = A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5' flanking region of SMYD3 is a risk factor for human cancers | journal = Nature Genetics | volume = 37 | issue = 10 | pages = 1104–7 | date = October 2005 | pmid = 16155568 | doi = 10.1038/ng1638 | s2cid = 40468351 }}
• {{cite journal | vauthors = Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, Furukawa Y | title = Enhanced SMYD3 expression is essential for the growth of breast cancer cells | journal = Cancer Science | volume = 97 | issue = 2 | pages = 113–8 | date = February 2006 | pmid = 16441421 | doi = 10.1111/j.1349-7006.2006.00146.x | doi-access = free | pmc = 11159510 }}
• {{cite journal | vauthors = Wang XQ, Miao X, Cai Q, Garcia-Barcelo MM, Fan ST | title = SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population | journal = Experimental Oncology | volume = 29 | issue = 1 | pages = 71–3 | date = March 2007 | pmid = 17431393 }}

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Category:Genes mutated in mice