MKL1

MKL/megakaryoblastic leukemia 1 (also termed MRTFA/myocardin related transcription factor A) is a protein that in humans is encoded by the MKL1 gene.^[5][6][7][8]

MRTFA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KVU, 2KW9
Identifiers
Aliases	MRTFA, BSAC, MAL, MRTF-A, megakaryoblastic leukemia (translocation) 1, MKL, MKL1, myocardin related transcription factor A
External IDs	OMIM: 606078; MGI: 2384495; HomoloGene: 32487; GeneCards: MRTFA; OMA:MRTFA - orthologs
Gene ___location (Human) Chr. Chromosome 22 (human)[1] Band 22q13.1-q13.2 Start 40,410,281 bp[1] End 40,636,719 bp[1]
Gene ___location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15|15 E1 Start 80,896,482 bp[2] End 81,074,958 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte granulocyte popliteal artery tibial arteries right testis bone marrow cell left testis body of uterus blood stromal cell of endometrium Top expressed in granulocyte layer of dentate gyrus granular layer of dentate gyrus olfactory tubercle pyramidal layer of hippocampus mesenteric lymph nodes Ileal epithelium dentate gyrus of hippocampal formation granule cell CA3 field blood More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coactivator activity actin monomer binding leucine zipper ___domain binding protein binding actin binding Cellular component cytoplasm nucleoplasm nucleus cytosol Biological process regulation of transcription, DNA-templated smooth muscle cell differentiation transcription, DNA-templated positive regulation of transcription by RNA polymerase II transcription by RNA polymerase II actin cytoskeleton organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 57591 223701 Ensembl ENSG00000196588 ENSMUSG00000042292 UniProt Q969V6 Q8K4J6 RefSeq (mRNA) NM_001282660 NM_001282661 NM_001282662 NM_020831 NM_001318139 NM_001082536 NM_153049 RefSeq (protein) NP_001269589 NP_001269590 NP_001269591 NP_001305068 NP_065882 NP_001076005 NP_694629 Location (UCSC) Chr 22: 40.41 – 40.64 Mb Chr 15: 80.9 – 81.07 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is regulated by the actin cytoskeleton and is shuttled between the cytoplasm and the nucleus as a result of actin dynamics.^[9] In the nucleus, it coactivates the transcription factor serum response factor,^[10] a key regulator of smooth muscle cell differentiation, in an interaction mediated by its Basic ___domain. It is closely related to MKL2 and myocardin, with which it shares five key conserved structural domains.^[11]

Clinical significance

This gene is involved in a specific translocation event that creates a fusion of this gene and the RNA-binding motif protein-15 gene. This translocation has been associated with acute megakaryocytic leukemia.^[8] It also functions in the process of normal megakaryocyte maturation.^[12]

Research

Evalarted MKL1 expression is observed in breast cancer and can predict chemosensitivity and patient survival. MKL1 may be a promising biomarker of clinical value for breast cancer.^[13]

See also

• Serum response factor

References

1. GRCh38: Ensembl release 89: ENSG00000196588 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000042292 – 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. Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, et al. (July 2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics. 28 (3): 220–221. doi:10.1038/90054. PMID 11431691. S2CID 36236342.
6. Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, et al. (August 2002). "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death". The Journal of Biological Chemistry. 277 (32): 28853–28860. doi:10.1074/jbc.M203190200. PMID 12019265.
7. Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS (April 2004). "Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells". The Journal of Biological Chemistry. 279 (17): 17578–17586. doi:10.1074/jbc.M400961200. PMID 14970199.
8. "Entrez Gene: MKL1 megakaryoblastic leukemia (translocation) 1".
9. Vartiainen MK, Guettler S, Larijani B, Treisman R (June 2007). "Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL". Science. 316 (5832): 1749–1752. Bibcode:2007Sci...316.1749V. doi:10.1126/science.1141084. PMID 17588931. S2CID 44910416.
10. Miralles F, Posern G, Zaromytidou AI, Treisman R (May 2003). "Actin dynamics control SRF activity by regulation of its coactivator MAL". Cell. 113 (3): 329–342. doi:10.1016/S0092-8674(03)00278-2. PMID 12732141.
11. Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
12. Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, et al. (March 2009). "Role for MKL1 in megakaryocytic maturation". Blood. 113 (12): 2826–2834. doi:10.1182/blood-2008-09-180596. PMC 2661865. PMID 19136660.
13. Hua Y, Yang M (June 2022). "The prognostic value of MKL1 in predicting breast cancer immune infiltrates and chemosensitivity". Bosnian Journal of Basic Medical Sciences. 22 (3): 382–394. doi:10.17305/bjbms.2021.6306. PMC 9162751. PMID 34761735.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, et al. (December 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–495. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (February 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
• Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, et al. (May 2001). "Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 98 (10): 5776–5779. Bibcode:2001PNAS...98.5776M. doi:10.1073/pnas.101001498. PMC 33289. PMID 11344311.
• Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. (June 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–862. doi:10.1016/S0092-8674(01)00404-4. PMID 11439182.
• Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. (November 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–14860. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
• Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R (September 2003). "Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes". Molecular and Cellular Biology. 23 (18): 6597–6608. doi:10.1128/MCB.23.18.6597-6608.2003. PMC 193697. PMID 12944485.
• Selvaraj A, Prywes R (October 2003). "Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation". The Journal of Biological Chemistry. 278 (43): 41977–41987. doi:10.1074/jbc.M305679200. PMID 14565952.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 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.
• Selvaraj A, Prywes R (August 2004). "Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent". BMC Molecular Biology. 5: 13. doi:10.1186/1471-2199-5-13. PMC 516031. PMID 15329155.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
• Hsiao HH, Yang MY, Liu YC, Hsiao HP, Tseng SB, Chao MC, et al. (May 2005). "RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient". American Journal of Hematology. 79 (1): 43–45. doi:10.1002/ajh.20298. PMID 15849773. S2CID 30859557.
• Nakagawa K, Kuzumaki N (August 2005). "Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification". Genes to Cells. 10 (8): 835–850. doi:10.1111/j.1365-2443.2005.00880.x. PMID 16098147.