MKL1 Antibody - #AF5302

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.

Phosphorylation at Ser-6 by Erk inhibits binding of globular actin (G-actin), unmasking the nuclear localization signal (NLS) and promoting nuclear import.

Cytoplasm. Nucleus.
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 (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).

Ubiquitously expressed, has been detected in lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, muscle, heart and brain.

Interacts with SRF, forming the SRF-MRTFA nuclear complex which binds the 5'-CArG-3' consensus motif (CArG box) on DNA via SRF. Interacts (via RPEL repeats) with globular actin (G-actin), thereby regulating its subcellular location and activity of the complex formed with SRF. Either forms a trivalent (by binding three G-actin monomers) or pentavalent (by binding five G-actin monomers) complex with G-actin (By similarity). Forms a nuclear ternary complex with SCAI and SRF, leading to suppress MRTFA-induced SRF transcriptional activity. Interacts with beta-actin (ACTB); interaction with ACTB prevents interaction with SCAI (By similarity). Interacts with MRTFB.

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.