InterPro domain: IPR033897

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 [ 1 ], 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 [ 2 ]. 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 alpha-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 beta-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 ( IPR002487 ).

SRF-like/Type I subfamily of MADS (MCM1, Agamous, Deficiens, and SRF (serum response factor)) box family of eukaryotic transcriptional regulators [ 3 ]. Binds DNA and exists as hetero- and homo-dimers [ 4 , 5 ]. 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 [ 5 ]. Also found in fungi [ 6 , 7 ].

1. Structure of serum response factor core bound to DNA. Nature 376, 490-8
2. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 55, 989-1003
3. The MADS-box family of transcription factors. Eur. J. Biochem. 229, 1-13
4. Crystal structure of a ternary SAP-1/SRF/c-fos SRE DNA complex. J. Mol. Biol. 314, 495-506
5. An ancestral MADS-box gene duplication occurred before the divergence of plants and animals. Proc. Natl. Acad. Sci. U.S.A. 97, 5328-33
6. Classification and phylogeny of the MADS-box multigene family suggest defined roles of MADS-box gene subfamilies in the morphological evolution of eukaryotes. J. Mol. Evol. 43, 484-516
7. Function and evolution of the plant MADS-box gene family. Nat. Rev. Genet. 2, 186-95