2kw9

Structural highlights

Disease

MRTFA_HUMAN Megakaryoblastic acute myeloid leukemia with t(1;22)(p13;q13);Immune deficiency due to impaired neutrophil phagocytosis and migration. A chromosomal aberration involving MRTFA may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with RBM15 (PubMed:11431691, PubMed:11344311). Although both reciprocal fusion transcripts are detected in acute megakaryoblastic leukemia (AMKL, FAB-M7), the RBM15-MRTFA chimeric protein has all the putative functional domains encoded by each gene and is the candidate oncogene (PubMed:11431691, PubMed:11344311).^{[1] [2]} The disease is caused by variants affecting the gene represented in this entry.

Function

MRTFA_HUMAN Transcription coactivator that associates with the serum response factor (SRF) transcription factor to control expression of genes regulating the cytoskeleton during development, morphogenesis and cell migration (PubMed:26224645). The SRF-MRTFA complex activity responds to Rho GTPase-induced changes in cellular globular actin (G-actin) concentration, thereby coupling cytoskeletal gene expression to cytoskeletal dynamics. MRTFA binds G-actin via its RPEL repeats, regulating activity of the MRTFA-SRF complex. Activity is also regulated by filamentous actin (F-actin) in the nucleus.[UniProtKB:Q8K4J6]^[3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA. Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proc Natl Acad Sci U S A. 2001 May 8;98(10):5776-9. doi: 10.1073/pnas.101001498. PMID:11344311 doi:http://dx.doi.org/10.1073/pnas.101001498
2. ↑ 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. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet. 2001 Jul;28(3):220-1. doi: 10.1038/90054. PMID:11431691 doi:http://dx.doi.org/10.1038/90054
3. ↑ Record J, Malinova D, Zenner HL, Plagnol V, Nowak K, Syed F, Bouma G, Curtis J, Gilmour K, Cale C, Hackett S, Charras G, Moulding D, Nejentsev S, Thrasher AJ, Burns SO. Immunodeficiency and severe susceptibility to bacterial infection associated with a loss-of-function homozygous mutation of MKL1. Blood. 2015 Sep 24;126(13):1527-35. PMID:26224645 doi:10.1182/blood-2014-12-611012