PCM1

PCM1
Identifiers
Aliases	PCM1, PTC4, RET/PCM-1, pericentriolar material 1
External IDs	OMIM: 600299; MGI: 1277958; HomoloGene: 4518; GeneCards: PCM1; OMA:PCM1 - orthologs
Gene location (Mouse) Chr. Chromosome 8 (mouse)[1] Band 8 A4|8 23.89 cM Start 41,239,752 bp[1] End 41,332,344 bp[1]
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in spermatocyte saccule spermatid otic placode ascending aorta aortic valve median eminence dorsomedial hypothalamic nucleus supraoptic nucleus secondary oocyte BioGPS More reference expression data
Gene ontology Molecular function protein binding identical protein binding Cellular component ciliary basal body cell projection nuclear membrane membrane microtubule organizing center centriole cytoskeleton ciliary transition zone centrosome centriolar satellite pericentriolar material cytoplasm cytosol apical part of cell non-motile cilium protein-containing complex Biological process positive regulation of intracellular protein transport neuron migration neuronal stem cell population maintenance intraciliary transport involved in cilium assembly cell projection organization G2/M transition of mitotic cell cycle cytoplasmic microtubule organization negative regulation of neurogenesis interkinetic nuclear migration microtubule anchoring at centrosome protein localization to centrosome microtubule anchoring social behavior cilium assembly ciliary basal body-plasma membrane docking non-motile cilium assembly centrosome cycle regulation of G2/M transition of mitotic cell cycle protein localization to organelle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5108 18536 Ensembl ENSG00000078674 ENSMUSG00000031592 UniProt Q15154 Q9R0L6 RefSeq (mRNA) NM_006197 NM_001315507 NM_001315508 NM_023662 RefSeq (protein) NP_001302436 NP_001302437 NP_006188 NP_001339561 NP_001339562 NP_001339563 NP_001339564 NP_001339565 NP_001339566 NP_001339567 NP_001339568 NP_001339569 NP_001339570 NP_001339571 NP_001339572 NP_001339573 NP_001339574 NP_001339575 NP_001339576 NP_001339577 NP_001339578 NP_001339579 NP_001339580 NP_001339581 NP_001339582 NP_001339583 NP_001339584 NP_001339585 NP_001339586 NP_001339587 NP_001339588 NP_001339589 NP_001302436.1 NP_076151 NP_001390746 NP_001390748 NP_001390749 NP_001390752 NP_001390753 NP_001390754 Location (UCSC) n/a Chr 8: 41.24 – 41.33 Mb PubMed search [2] [3]
Wikidata
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Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene.^[4][5][6]

Function

The PCM1 protein was originally identified by virtue of its distinct cell cycle-dependent association with the centrosome complex and 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. 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 centrin, pericentrin and ninein was also dramatically reduced after PCM1 depletion using siRNA, overexpression of PCM1 deletion mutants and PCM1 antibody microinjection.^[7] As a result of this depletion, the radial organization of the microtubules was found to be disrupted, but did not appear to affect microtubule nucleation.

Gene 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 coiled coil regions between areas of low complexity as well as an adenosine triphosphate (ATP) / 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, xanthine dehydrogenase, sulfite oxidase (mitochondrial precursor), aldehyde oxidase, erythropoietin receptor precursor and the ATPbinding cassette, sub-family A, member 2 (ABCA2).

Tissue distribution

PCM1 mRNA expression in the mouse brain has been found to be highest in the hippocampus.^[8] In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.^[9]

Clinical significance

Mutations in the PCM1 gene have been shown to cause genetic susceptibility to 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 genetic counselling to a small proportion of people with schizophrenia who are also carriers of this mutation.^[10][11]

PCM1 forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a link between aberrant PCM1 and the abnormal cortical development associated with the pathology of schizophrenia.^[12]

Interactions

PCM1 has been shown to interact with PCNT.^[13]

References

Further reading