Myomegalin, also known asphosphodiesterase 4D-interacting protein orcardiomyopathy-associated protein 2, is aprotein that in humans is encoded by thePDE4DIPgene.[5][6][7] It has roles in theformation ofmicrotubules from thecentrosome.[8] Its name derives from the fact that it is highly expressed in units of tubularmyofibrils known assarcomeres and is a large protein, at 2,324 amino acids.[9] It was first characterised in 2000.[9]
Myomegalin is necessary for the sufficientgrowth ofmicrotubules from thecentrosomes. The CM-MMG isoform binds at the centrosome withγ-tubulin in anAKAP9-dependent manner and on the near side of theGolgi apparatus, while the EB-MMG isoform binds withMAPRE1 at the Golgi apparatus and increases MAPRE1's effects on microtubule growth.[8]
Myomegalin, specifically the CM-MMG isoform, is aparalogue ofCDK5RAP2.[8][10][11] Myomegalin depletion in cells does not lead to decreases in γ-tubulin or CDK5RAP2, unlike CDK5RAP2 depletion, and does not appear to affectmitosis through variousspindle anchoring and orientation defects, unlike CDK5RAP2. This indicates that CDK5RAP2 can somewhat serve to compensate for the absence of myomegalin. However, myomegalin-depleted cells have slowermigration, since microtubules are crucial for cell motility.[8]
Orthologues of myomegalin are seen invertebrates as far back asbony fish, around 450 million years ago. Inmammals, around 200 million years ago, myomegalin gained anOlduvai domain. Olduvai domains have so far only elsewhere been found inNBPF genes inplacental mammals, many of which are adjacent to myomegalin on chromosome 1, so it is believed that these genes originated from a duplication of myomegalin.[12] Increased NPBF Olduvai domain duplications in humans have been implicated in human brain size evolution.[13]
The protein was discovered in 2000 and was so named because it was highly expressed in ratheart musclesarcomeres (units of tubularmyofibrils) and is a large protein, at 2,324 amino acids.[9]
Soejima H, Kawamoto S, Akai J, Miyoshi O, Arai Y, Morohka T, et al. (May 2001). "Isolation of novel heart-specific genes using the BodyMap database".Genomics.74 (1):115–20.doi:10.1006/geno.2001.6527.PMID11374908.
