SETD3

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SETD3
Properties of human protein
Mass / length primary structure 594 amino acids , 67,257 Da
Identifier
External IDs
Enzyme classification
EC, category 2.1.1.85
Orthologue (human)
Entrez 84193
Ensemble ENSG00000183576
UniProt Q86TU7
Refseq (mRNA) NM_032233.3
Refseq (protein) NP_115609.2
PubMed search 84193

SET domain containing 3 (SETD3) is an actin histidine methyl transferase which is encoded by the SETD3 gene of the same name.

properties

SETD3 is a protein histidine N -methyltransferase that methylates histidine at position 73 of actin . This methylation is necessary for muscle contraction of the smooth muscle of the uterus during labor. Lysine is not methylated by SETD3. In the human genome, the gene is located at locus 14q32.2.

The results of a CRISPR screening were published in September 2019 . Enterovirus EV-D68 and rhinovirus RV-C15 could no longer multiply in cell cultures with human cell lines that lack SETD3. It was found that SETD3 interacts with the 2A protease of enteroviruses and is essential for the replication of the viruses.

A mouse line that does not have SETD3 has been shown to be resistant to some enteroviruses , including CV-A10 ( hand-foot-mouth disease ), EV-A71 ( aseptic meningitis , encephalitis and polio- like diseases) and EV -D68 (respiratory diseases). The mice then had problems giving birth to their young. Since colds and runny nose are often caused by rhinoviruses and other enteroviruses, this opens up a potential avenue for combating these diseases.

In breast cancer , the expression of SETD3 has a subtype-dependent prognostic value: While a high expression in the estrogen receptor-positive and in the luminal A subtype shows a positive prognosis , a high expression in the triple-negative and p53-positive breast cancer has a associated negative prognosis. In triple-negative breast carcinoma cells, the siRNA -mediated inhibition of SETD3 expression leads to changes in the cytoskeleton which are associated with a reduced invasiveness.

swell

Individual evidence

  1. ↑ S. Kwiatkowski, AK Seliga, D. Vertommen, M. Terreri, T. Ishikawa, I. Grabowska, M. Tiebe, AA Teleman, AK Jagielski, M. Veiga-da-Cunha, J. Drozak: SETD3 protein is the actin-specific histidine -methyltransferase. In: eLife. Volume 7, 12 2018, S., doi: 10.7554 / eLife.37921 . PMID 30526847 , PMC 6289574 (free full text).
  2. ↑ AW Wilkinson, J. Diep, S. Dai, S. Liu, YS Ooi, D. Song, TM Li, JR Horton, X. Zhang, C. Liu, DV Trivedi, KM Ruppel, JG Vilches-Moure, KM Casey , J. Mak, T. Cowan, JE Elias, CM Nagamine, JA Spudich, X. Cheng, JE Carette, O. Gozani: SETD3 is an actin histidine methyltransferase that prevents primary dystocia. In: Nature . Volume 565, number 7739, 01 2019, pp. 372-376, doi: 10.1038 / s41586-018-0821-8 . PMID 30626964 , PMC 6511263 (free full text).
  3. ↑ Q. Guo, S. Liao, S. Kwiatkowski, W. Tomaka, H. Yu, G. Wu, X. Tu, J. Min, J. Drozak, C. Xu: Structural insights into SETD3-mediated histidine methylation on β-actin. In: eLife. Volume 8, February 2019, p., Doi: 10.7554 / eLife.43676 . PMID 30785395 , PMC 6400499 (free full text).
  4. ↑ a b AW Wilkinson, J. Diep, S. Dai, S. Liu, YS Ooi, D. Song, TM Li, JR Horton, X. Zhang, C. Liu, DV Trivedi, KM Ruppel, JG Vilches-Moure, KM Casey, J. Mak, T. Cowan, JE Elias, CM Nagamine, JA Spudich, X. Cheng, JE Carette, O. Gozani: SETD3 is an actin histidine methyltransferase that prevents primary dystocia. In: Nature . Volume 565, number 7739, 01 2019, pp. 372-376, doi: 10.1038 / s41586-018-0821-8 . PMID 30626964 , PMC 6511263 (free full text).
  5. ↑ Q. Guo, S. Liao, S. Kwiatkowski, W. Tomaka, H. Yu, G. Wu, X. Tu, J. Min, J. Drozak, C. Xu: Structural insights into SETD3-mediated histidine methylation on β-actin. In: eLife. Volume 8, February 2019, p., Doi: 10.7554 / eLife.43676 . PMID 30785395 , PMC 6400499 (free full text).
  6. ↑ a b N. Hassan, N. Rutsch, B. Győrffy, NA Espinoza-Sánchez, M. Götte: SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells . In: Scientific Reports . tape 10 , no. 1 , February 10, 2020, ISSN  2045-2322 , p. 2262 , doi : 10.1038 / s41598-020-59057-5 , PMID 32042016 ( nature.com [accessed February 13, 2020]).

en: SETD3 (gene)