A microprotein (miP) is a small protein encoded from a small open reading frame (sORF), [1] also known as sORF-encoded protein (SEP). They are a class of protein with a single protein domain that are related to multidomain proteins. [2] Microproteins regulate larger multidomain proteins at the post-translational level. [3] Microproteins are analogous to microRNAs (miRNAs) and heterodimerize with their targets causing dominant and negative effects. [4] In animals and plants, microproteins have been found to greatly influence biological processes. [2] Because of microproteins' dominant effects on their targets, microproteins are currently being studied for potential applications in biotechnology. [2]
The first microprotein (miP) discovered was during a research in the early 1990s on genes for basic helix–loop–helix (bHLH) transcription factors from a murine erythroleukaemia cell cDNA library. [3] The protein was found to be an inhibitor of DNA binding (ID protein), and it negatively regulated the transcription factor complex. [3] The ID protein was 16 kDa and consisted of a helix-loop-helix (HLH) domain. [2] The microprotein formed bHLH/HLH heterodimers which disrupted the functional basic helix–loop–helix (bHLH) homodimers. [2]
The first microprotein discovered in plants was the LITTLE ZIPPER (ZPR) protein. [2] The LITTLE ZIPPER protein contains a leucine zipper domain but does not have the domains required for DNA binding and transcription activation. [2] Thus, LITTLE ZIPPER protein is analogous to the ID protein. [2] Despite not all proteins being small, in 2011, this class of protein was given the name microproteins because their negative regulatory actions are similar to those of miRNAs. [3]
Evolutionarily, the ID protein or proteins similar to ID found in all animals. [3] In plants, microproteins are only found in higher order. [3] However, the homeodomain transcription factors that belong to the three-amino-acid loop-extension (TALE) family are targets of microproteins, and these homeodomain proteins are conserved in animals, plants, and fungi. [3]
Microproteins are generally small proteins with a single protein domain. [2] [4] The active form of microproteins are translated from smORF. [1] The smORF codons which microproteins are translated from can be less than 100 codons. [1] However, not all microproteins are small, and the name was given because their actions are analogous to miRNAs. [3]
The function of microproteins is post-translational regulators. [3] Microproteins disrupt the formation of heterodimeric, homodimeric, or multimeric complexes. [4] Furthermore, microproteins can interact with any protein that require functional dimers to function normally. [3] The primary targets of microproteins are transcription factors that bind to DNA as dimers. [5] [3] Microproteins regulate these complexes by creating homotypic dimers with the targets and inhibit protein complex function. [3] There are two types of miP inhibitions: homotypic miP inhibition and heterotypic miP inhibition. [4] In homotypic miP inhibition, microproteins interact with proteins with similar protein-protein interaction (PPI) domain. [4] In heterotypic miP inhibition, microproteins interact with proteins with different but compatible PPI domain. [4] In both types of inhibition, microproteins interfere and prevent the PPI domains from interacting with their normal proteins. [4]