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
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 81,012,281 bp[2] End 81,190,757 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001105 transcription coactivator activity • actin monomer binding • leucine zipper domain binding • GO:0001948 protein binding • actin binding Cellular component • cytoplasm • nucleoplasm • cell nucleus • cytosol Biological process • regulation of transcription, DNA-templated • smooth muscle cell differentiation • transcription, DNA-templated • positive regulation of transcription via serum response element binding • positive regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • 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: 81.01 – 81.19 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene interacts with the transcription factor serum response factor,[9] a key regulator of smooth muscle cell differentiation. It is closely related to MKL2 and myocardin.[10] The encoded protein can shuttle between the cytoplasm and the nucleus, and may help this way transduce signals from the cytoskeleton to the nucleus.[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]

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, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK (Jul 2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics. 28 (3): 220–1. doi:10.1038/90054. PMID 11431691.
6. Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, Katano M, Tanaka M, Watanabe M, Yagita H, Okumura K, Nakano H (Aug 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): 28853–60. doi:10.1074/jbc.M203190200. PMID 12019265.
7. Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS (Apr 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): 17578–86. doi:10.1074/jbc.M400961200. PMID 14970199.
8. "Entrez Gene: MKL1 megakaryoblastic leukemia (translocation) 1".
9. Miralles F, Posern G, Zaromytidou AI, Treisman R (May 2003). "Actin dynamics control SRF activity by regulation of its coactivator MAL". Cell. 113 (3): 329–42. doi:10.1016/S0092-8674(03)00278-2. PMID 12732141.
10. Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN (Nov 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): 14855–60. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
11. Vartiainen MK, Guettler S, Larijani B, Treisman R (Jun 2007). "Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL". Science. 316 (5832): 1749–52. doi:10.1126/science.1141084. PMID 17588931.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 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, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
• Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (Feb 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, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA (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): 5776–9. doi:10.1073/pnas.101001498. PMC 33289. PMID 11344311.
• Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN (Jun 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–62. doi:10.1016/S0092-8674(01)00404-4. PMID 11439182.
• Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN (Nov 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): 14855–60. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
• Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R (Sep 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): 6597–608. doi:10.1128/MCB.23.18.6597-6608.2003. PMC 193697. PMID 12944485.
• Selvaraj A, Prywes R (Oct 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): 41977–87. doi:10.1074/jbc.M305679200. PMID 14565952.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Selvaraj A, Prywes R (Aug 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, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (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, Liu TC, Lin SF (May 2005). "RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient". American Journal of Hematology. 79 (1): 43–5. doi:10.1002/ajh.20298. PMID 15849773.
• Nakagawa K, Kuzumaki N (Aug 2005). "Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification". Genes to Cells. 10 (8): 835–50. doi:10.1111/j.1365-2443.2005.00880.x. PMID 16098147.