PCM1

Pericentriolar material 1, also known as PCM1, is a is_associated_with::protein which in humans is encoded by the PCM1 is_associated_with::gene.

Function
The PCM1 protein was originally identified by virtue of its distinct is_associated_with::cell cycle-dependent association with the is_associated_with::centrosome complex and is_associated_with::microtubules. The protein appears to associate with the centrosome complex during the cell cycle. Dissociation occurs during mitosis when PCM1 is dispersed throughout the cell. is_associated_with::Immunolabeling studies performed found that PCM1 was present in centriolar satellites and in electron dense granules between 70 and 100 nm in diameter. These were originally thought to be scattered only around the centrosomes, but further studies proved that PCM1 was also found throughout the cytoplasm.

PCM1 was shown to be essential for cell division because PCM1 antibodies cause cell-cycle arrest when microinjected into fertilized murine eggs. Targeting of is_associated_with::centrin, pericentrin and ninein was also dramatically reduced after PCM1 depletion using siRNA, overexpression of PCM1 deletion mutants and PCM1 antibody microinjection. As a result of this depletion, the radial organization of the microtubules was found to be disrupted, but did not appear to effect microtubule nucleation.

Structure
PCM1 has four known transcripts, the longest of which has 39 exons. The open reading frame of PCM1 encodes a protein of 2024 amino acids. The protein contains is_associated_with::coiled coil regions between areas of low complexity as well as an is_associated_with::adenosine triphosphate (ATP) / is_associated_with::GTPase domain, a nuclear localization domain and a eukaryotic molybdopterin domain. The eukaryotic molybdopterin binding domain is currently found in only five other human genes, is_associated_with::xanthine dehydrogenase, is_associated_with::sulfite oxidase (mitochondrial precursor), is_associated_with::aldehyde oxidase, is_associated_with::erythropoietin receptor precursor and the ATPbinding cassette, sub-family A, member 2 (is_associated_with::ABCA2).

Tissue distribution
PCM1 mRNA expression in the mouse brain has been found to be highest in the is_associated_with::hippocampus. In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.

Clinical significance
Mutations in the PCM1 gene have been shown to cause genetic susceptibility to is_associated_with::schizophrenia. If an isoleucine amino acid change in PCM1 is inherited the risk of developing schizophrenia was found to be 68% in two independent samples from south England and Scotland. This means that it may now be possible to offer very limited is_associated_with::genetic counselling to a small proportion of people with schizophrenia who are also carriers of this mutation.

PCM1 forms a complex at the is_associated_with::centrosome with disrupted-in-schizophrenia 1 (is_associated_with::DISC1) and Bardet-Biedl syndrome 4 protein (is_associated_with::BBS4), which provides a link between aberrant PCM1 and the abnormal cortical development associated with the pathology of schizophrenia.

Interactions
PCM1 has been shown to interact with is_associated_with::PCNT.