MRTFA
Domain
The N-terminal region is required for nuclear localization and the C-terminal region mediates transcriptional activity.
The RPEL repeats mediate binding to globular actin (G-actin); each RPEL repeat-binding to one G-actin monomer. In addition, each intervening spacer sequence region can bind one G-actin monomer, to reach a pentavalent complex.
Function
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.
Involvement in disease
A chromosomal aberration involving MRTFA may be a cause of acute megakaryoblastic leukemia. Translocation t(1;22)(p13;q13) with RBM15 (PubMed:11344311, PubMed:11431691). 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:11344311, PubMed:11431691).
Immunodeficiency 66
IMD66
An autosomal recessive primary immunologic disorder characterized by recurrent viral infections from infancy, associated with impaired neutrophil migration due to defects in cytoskeletal actin dynamics.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylation at Ser-6 by Erk inhibits binding of globular actin (G-actin), unmasking the nuclear localization signal (NLS) and promoting nuclear import.
Tissue Specificity
Ubiquitously expressed, has been detected in lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, muscle, heart and brain (PubMed:11344311). Expressed in peripheral blood mononuclear cells (at protein level) (PubMed:26224645).
Cellular localization
- Cytoplasm
- Nucleus
- Subcellular location is tightly regulated by actin both in cytoplasm and nucleus: high levels of G-actin in the nucleus observed during serum deprivation lead to low levels of nuclear MRTFA, while reduced levels of nuclear G-actin result in accumulation of MRTFA in the nucleus (By similarity). G-actin-binding in the cytoplasm inhibits nuclear import by masking the nuclear localization signal (NLS) (By similarity). In contrast, binding to nuclear globular actin (G-actin) promotes nuclear export to the cytoplasm (By similarity). Nuclear localization is regulated by MICAL2, which mediates depolymerization of nuclear actin, which decreases nuclear G-actin pool, thereby promoting retention of MRTFA in the nucleus and subsequent formation of an active complex with SRF (PubMed:24440334). Nuclear import is mediated by importins KPNA4 and KPNB1 (By similarity).
Alternative names
KIAA1438, MAL, MKL1, MRTFA, Myocardin-related transcription factor A, MRTF-A, MKL/myocardin-like protein 1, Megakaryoblastic leukemia 1 protein, Megakaryocytic acute leukemia protein