Protein: Myocardin-related transcription factor A (MRTF-A) (Basic SAP coiled-coil transcription activator) (MKL/myocardin-like protein 1) (Megakaryoblastic leukemia 1 protein homolog) (Megakaryocytic acute leukemia protein homolog) (Q8K4J6)
Organism: Mus musculus (Mouse)
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. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:12732141, ECO:0000269|PubMed:17588931, ECO:0000269|PubMed:19008859, ECO:0000269|PubMed:21673315, ECO:0000269|PubMed:25759381, ECO:0000269|PubMed:27304076}. Nucleus {ECO:0000269|PubMed:12019265, ECO:0000269|PubMed:12732141, ECO:0000269|PubMed:17588931, ECO:0000269|PubMed:19008859, ECO:0000269|PubMed:20818336, ECO:0000269|PubMed:21673315, ECO:0000269|PubMed:25759381, ECO:0000269|PubMed:27304076}. Note=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 (PubMed:17588931, PubMed:21673315). G-actin-binding in the cytoplasm inhibits nuclear import by masking the nuclear localization signal (NLS) (PubMed:17588931, PubMed:20818336, PubMed:21673315). In contrast, binding to nuclear globular actin (G-actin) promotes nuclear export to the cytoplasm (PubMed:17588931). 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 (By similarity). Nuclear import is mediated by importins KPNA4 and KPNB1 (PubMed:20818336). {ECO:0000250|UniProtKB:Q969V6, ECO:0000269|PubMed:17588931, ECO:0000269|PubMed:20818336, ECO:0000269|PubMed:21673315}.
Interaction partners:
- Serum response factor
- Importin subunit alpha-1
- Transforming protein RhoA
- Protein diaphanous homolog 1
- Mothers against decapentaplegic homolog 3
Sequence:
MTLLEPEMLMMAVQSVLQLKLQQRRTREELVSQGIMPPLKSPAAFHEQRRSLERARTEDYLKRKIRSRPERAELVRMHILEETSAEPSLQAKQLKLKRARLADDLNEKIAQRPGPMELVEKNILPVESSLKEAIIVGQVNYPKVADSSSFDEDSSDALSPEQPASHESQGSVPSPLESRVSDPLPSATSISPTQVLSQLPMAPDPGETLFLAEQPPLPPAPLLPPSLANGSIVPTAKPAPTLIKQSQPKSASEKSQRSKKAKELKPKVKKLKYHQYIPPDQKQDKGAPAMDSSYAKILQQQQLFLQLQILNQQQQQQQQQHYNYQAILPAPPKPSAETPGSSAPTPSRSLSTSSSPSSGTPGPSGLARQSSTALAAKPGALPANLDDMKVAELKQELKLRSLPVSGTKTELIERLRAYQDQVSPAPGAPKAPATTSVLSKAGEVVVAFPAALLSTGSALVTAGLAPAEMVVATVTSNGMVKFGSTGSTPPVSPTPSERSLLSTGDENSTPGDAFGEMVTSPLTQLTLQASPLQIVKEEGARAASCCLSPGARAELEGLDKDQMLQEKDKQIEELTRMLQQKQQLVELLRLQLEQQKRAQQPAPASSPVKRESGFSSCQLSCQPQGSAHAFGSGLVVPTTNHGDTQAPAPESPPVVVKQEAGPPEPDLAPSSQLLLGSQGTSFLKRVSPPTLVTDSTGTHLILTVTNKSADGPGLPAGSPQQPLSQPGSPAPGPPAQMDLEHPPQPPFATPTSLLKKEPPGYEETVTQQPKQQENGSSSQHMDDLFDILIQSGEISADFKEPPSLPGKEKSPPAAAAYGPPLTPQPSPLSELPQAAPPPGSPTLPGRLEDFLESSTGLPLLTSGHEGPEPLSLIDDLHSQMLSSSAILDHPPSPMDTSELHFAPEPSSGMGLDLAVGHLDSMDWLELSSGGPVLSLAPLSTAAPSLFSMDFLDGHDLQLHWDSCL