MKL1

Protein-coding gene in the species Homo sapiens
MRTFA
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2KVU, 2KW9

Identifiers
AliasesMRTFA, BSAC, MAL, MRTF-A, megakaryoblastic leukemia (translocation) 1, MKL, MKL1, myocardin related transcription factor A
External IDsOMIM: 606078; MGI: 2384495; HomoloGene: 32487; GeneCards: MRTFA; OMA:MRTFA - orthologs
Gene location (Human)
Chromosome 22 (human)
Chr.Chromosome 22 (human)[1]
Chromosome 22 (human)
Genomic location for MRTFA
Genomic location for MRTFA
Band22q13.1-q13.2Start40,410,281 bp[1]
End40,636,719 bp[1]
Gene location (Mouse)
Chromosome 15 (mouse)
Chr.Chromosome 15 (mouse)[2]
Chromosome 15 (mouse)
Genomic location for MRTFA
Genomic location for MRTFA
Band15|15 E1Start80,896,482 bp[2]
End81,074,958 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • monocyte

  • granulocyte

  • popliteal artery

  • tibial arteries

  • right testis

  • bone marrow cells

  • 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
SpeciesHumanMouse
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 MbChr 15: 80.9 – 81.07 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196588 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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.
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