Microprotein

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]