SCAI is a transcriptional cofactor and tumour suppressor that suppresses MKL1-induced SRF transcriptional activity. It may function in the RHOA-DIAPH1 signal transduction pathway and regulate cell migration through transcriptional regulation of ITGB1 [].
This entry represents protein SCAI from metazoans and plants. SCAI is a transcriptional cofactor and tumour suppressor that suppresses MKL1-induced SRF transcriptional activity. It may function in the RHOA-DIAPH1 signal transduction pathway and regulate cell migration through transcriptional regulation of ITGB1 [].
Myocardin-related transcription factor A (MRTFA, also known MKL1) is an actin-binding transcriptional coactivator whose localisation is regulated by its interaction with monomeric actin (G-actin) []. Its N-terminal domain consists of three tandem RPEL repeats, where the G-actin binding site and the nuclear localisation signal can be found [, ]. In the nucleus MAL associates with SRF (serum response factor) and activates transcription of SRF:MAL-dependent target genes []. It has been implicated in human diseases, such as acute megakaryocytic leukemia []and other cancers [].
Myocardial zonula adherens protein (Myozap) plays a role in cellular signaling via Rho-related GTP-binding proteins and activation of transcription factor SRF []. It localises to the intercalated disk in cardiomyocytes and colocalises with GRIN1 in postsynaptic neurites [, ]. It also colocalises with cortical actin at the intercalated disc in the cardiomyocytes []. In cortical neurons, it may play a role in glutaminergic signal transduction through interaction with the NMDA receptor subunit GRIN1 [].
This entry represents the MEF2 (myocyte enhancer factor 2)-like/Type II subfamily of MADS (MCM1, Agamous, Deficiens, and SRF (serum response factor)) box family of eukaryotic transcriptional regulators []. Binds DNA and exists as hetero and homo-dimers. Differs from SRF-like/Type I subgroup mainly in position of the alpha helix responsible for the dimerization interface []. Important in homeotic regulation in plants and in immediate-early development in animals []. Also found in fungi [].
RPEL repeat (RPxxxEL) containing proteins are found in a wide range ofmetazoan organisms. RPEL repeats have been shown to be required forunpolymerised actin binding and proteins containing RPEL repeats are able tomodify cell shape and/or are important in the regulation of gene expression bythe actin cytoskeleton. RPEL repeats can be found in association with the SAPmotif, which could be involved in DNA binding [, ].Some proteins known to containRPEL repeats are listed below:Mammalian myocardin, heart-specific serum response factor (SRF) co-activator.Vertebrate myocardin-related transcription factor A (MRTF-A or MAL), asignal-regulated SRF co-activator.Vertebrate myocardin-related transcription factor B (MRTF-B).Mammalian phosphatase and actin regulator 1 to 3.
Myocardin (Myocd) is a coactivator of serum response factor (SRF), which is a key regulator of the expression of smooth and cardiac muscle genes. Myocardin plays a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage (myogenesis) [, ]. It contains the RPEL repeats, which are monomeric globular actin (G-actin) binding elements. However, it binds to actin-related protein 5 (Arp5) instead of conventional actin, resulting in a significant suppression of Myocd activity [].Myocardin-related transcription factor A (MRTFA, also known MKL1) is an actin-binding transcriptional coactivator whose localisation is regulated by its interaction with monomeric actin (G-actin) []. Its N-terminal domain consists of three tandem RPEL repeats, where the G-actin binding site and the nuclear localisation signal can be found [, ]. In the nucleus MAL associates with SRF (serum response factor) and activates transcription of SRF:MAL-dependent target genes []. It has been implicated in human diseases, such as acute megakaryocytic leukemia []and other cancers [].MKL2 binds to and activates SRF (serum response factor) similar to myocardin and MKL1 [].This entry includes Myocardin and MKL/myocardin-like protein 1/2 (MKL1/2).
SRF-like/Type I subfamily of MADS (MCM1, Agamous, Deficiens, and SRF (serum response factor)) box family of eukaryotic transcriptional regulators []. Binds DNA and exists as hetero- and homo-dimers [, ]. Differs from the MEF-like/Type II subgroup mainly in position of the alpha 2 helix responsible for the dimerization interface. Important in homeotic regulation in plants and in immediate-early development in animals []. Also found in fungi [, ].Human serum response factor (SRF) is a ubiquitous nuclear protein important for cell proliferation and differentiation. SRF function is essential for transcriptional regulation of numerous growth-factor-inducible genes, such as c-fos oncogene and muscle-specific actin genes. A core domain of around 90 amino acids is sufficient for the activities of DNA-binding, dimerisation and interaction with accessory factors. Within the core is a DNA-binding region, designated the MADS box [], that is highly similar to many eukaryotic regulatory proteins: among these are MCM1, the regulator of cell type-specific genes in fission yeast; DSRF, a Drosophila trachea development factor; the MEF2 family of myocyte-specific enhancer factors; and the Agamous and Deficiens families of plant homeotic proteins.In SRF, the MADS box has been shown to be involved in DNA-binding and dimerisation []. Proteins belonging to the MADS family function as dimers, the primary DNA-binding element of which is an anti-parallel coiled coil of two amphipathic α-helices, one from each subunit. The DNA wraps around the coiled coil allowing the basic N-termini of the helices to fit into the DNA major groove. The chain extending from the helix N-termini reaches over the DNA backbone and penetrates into the minor groove. A 4-stranded, anti-parallel β-sheet packs against the coiled-coil face opposite the DNA and is the central element of the dimerisation interface. The MADS-box domain is commonly found associated with K-box region see ().
Human serum response factor (SRF) is a ubiquitous nuclear protein important for cell proliferation and differentiation. SRF function is essential for transcriptional regulation of numerous growth-factor-inducible genes, such as c-fos oncogene and muscle-specific actin genes. A core domain of around 90 amino acids is sufficient for the activities of DNA-binding, dimerisation and interaction with accessory factors. Within the core is a DNA-binding region, designated the MADS box [], that is highly similar to many eukaryotic regulatory proteins: among these are MCM1, the regulator of cell type-specific genes in fission yeast; DSRF, a Drosophila trachea development factor; the MEF2 family of myocyte-specific enhancer factors; and the Agamous and Deficiens families of plant homeotic proteins.In SRF, the MADS box has been shown to be involved in DNA-binding and dimerisation []. Proteins belonging to the MADS family function as dimers, the primary DNA-binding element of which is an anti-parallel coiled coil of two amphipathic α-helices, one from each subunit. The DNA wraps around the coiled coil allowing the basic N-termini of the helices to fit into the DNA major groove. The chain extending from the helix N-termini reaches over the DNA backbone and penetrates into the minor groove. A 4-stranded, anti-parallel β-sheet packs against the coiled-coil face opposite the DNA and is the central element of the dimerisation interface. The MADS-box domain is commonly found associated with K-box region see ().
Human serum response factor (SRF) is a ubiquitous nuclear protein important for cell proliferation and differentiation. SRF function is essential for transcriptional regulation of numerous growth-factor-inducible genes, such as c-fos oncogene and muscle-specific actin genes. A core domain of around 90 amino acids is sufficient for the activities of DNA-binding, dimerisation and interaction with accessory factors. Within the core is a DNA-binding region, designated the MADS box [], that is highly similar to many eukaryotic regulatory proteins: among these are MCM1, the regulator of cell type-specific genes in fission yeast; DSRF, a Drosophila trachea development factor; the MEF2 family of myocyte-specific enhancer factors; and the Agamous and Deficiens families of plant homeotic proteins.In SRF, the MADS box has been shown to be involved in DNA-binding and dimerisation []. Proteins belonging to the MADS family function as dimers, the primary DNA-binding element of which is an anti-parallel coiled coil of two amphipathic α-helices, one from each subunit. The DNA wraps around the coiled coil allowing the basic N-termini of the helices to fit into the DNA major groove. The chain extending from the helix N-termini reaches over the DNA backbone and penetrates into the minor groove. A 4-stranded, anti-parallel β-sheet packs against the coiled-coil face opposite the DNA and is the central element of the dimerisation interface. The MADS-box domain is commonly found associated with K-box region see ().
MICAL (molecule Interacting with CasL) family is a group of multifunctional proteins that contain the calponin homology (CH), a LIM and a coiled-coil (CC) domains []. They interact with receptors on the target cells, help recruiting other proteins, and promote the modulation of their activity with respect to the downstream events []. There is only one MICAL protein found in Drosophila [], while there are 5 MICAL (MICAL1/2/3, MICAL-like1/2) isoforms found in vertebrates []. Drosophila MICAL and vertebrate MICAL1/2/3 contain an extra N-terminal FAD (flavin adenine dinucleotide binding monooxygenase) domain, whose structure resembles that of a flavo-enzyme, p-hydroxybenzoate hydroxylase []. Drosophila MICAL has an NADPH-dependent actin depolymerising activity []. Vertebrate MICALs are also shown to be effectors of small Rab GTPases, which play important roles in vesicular trafficking []. MICAL2 is a nuclear monooxygenase that promotes depolymerisation of F-actin. Its substrate is the sulfur of a methionine of actin. The FAD domain of MICAL2 could regulate NADPH reduction in the presence of F-actin []. MICAL2 can also regulate SRF (serum response factor) signalling through redox modification of nuclear actin []. Its overexpression has been linked to prostate cancer progression [].
