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) Band 8 A4|8 23.89 cM Start 41,239,752 bp End 41,332,344 bp
RNA expression pattern Bgee Human Mouse (ortholog) n/a Top expressed in spermatocyte genital tubercle tail of embryo saccule ventricular zone spermatid otic placode ascending aorta zygote otic vesicle 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
Wikidata
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Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene.

Gene

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. In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.

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. 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.

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.

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.

Interactions

PCM1 has been shown to interact with PCNT.

Further reading

• Tollenaere MA, Mailand N, Bekker-Jensen S (January 2015). "Centriolar satellites: key mediators of centrosome functions". Cellular and Molecular Life Sciences. 72 (1): 11–23. doi:10.1007/s00018-014-1711-3. PMC 11114028. PMID 25173771. S2CID 2243856.
• Ohata H, Fujiwara Y, Koyama K, Nakamura Y (1995). "Mapping of the human autoantigen pericentriolar material 1 (PCM1) gene to chromosome 8p21.3-p22". Genomics. 24 (2): 404–406. doi:10.1006/geno.1994.1640. PMID 7698772.
• Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA, Engelender S, et al. (December 1997). "Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin". Human Molecular Genetics. 6 (13): 2205–2212. doi:10.1093/hmg/6.13.2205. PMID 9361024.
• Briones MR, Nagai MA, Da Silva Jr W, Zago MA, Bordin S, Costa FF, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
• Corvi R, Berger N, Balczon R, Romeo G (2000). "RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma". Oncogene. 19 (37): 4236–4242. doi:10.1038/sj.onc.1203772. PMID 10980597.
• Halsey W, Van Horn M, Mao J, Sathe G, Mui P, Agarwal P, et al. (October 2001). "Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries". Osteoarthritis and Cartilage. 9 (7): 641–653. doi:10.1053/joca.2001.0421. PMID 11597177.
• Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Hill J, Hoskins BE, Leitch CC, Chul Kim J, Ross AJ, Eichers ER, et al. (October 2003). "Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome". Nature. 425 (6958): 628–633. Bibcode:2003Natur.425..628A. doi:10.1038/nature02030. PMID 14520415. S2CID 4310157.
• Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
• Esmail MA, Hill J, Hoskins BE, Leitch CC, Venner K, Ansley SJ, et al. (May 2004). "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression". Nature Genetics. 36 (5): 462–470. doi:10.1038/ng1352. PMID 15107855.
• Mukherji M, Stettler-Gill M, Peters EC, Brill LM, Salomon AR, Ficarro SB (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–2772. doi:10.1021/ac035352d. PMID 15144186.
• Ciciulla J, Ramus SJ, Soo WK, Mahoney A, Yarovaya N, Henderson MA, et al. (July 2004). "Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers". Oncogene. 23 (33): 5697–5702. doi:10.1038/sj.onc.1207740. PMID 15184884.
• Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP, et al. (August 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–12135. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Schwartz D, Gygi SP, Ballif BA, Villén J, Beausoleil SA (November 2004). "Phosphoproteomic analysis of the developing mouse brain". Molecular & Cellular Proteomics. 3 (11): 1093–1101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
• Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, et al. (October 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, et al. (April 2005). "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2". Cancer Research. 65 (7): 2662–2667. doi:10.1158/0008-5472.CAN-04-4263. PMID 15805263.
• Perot C, Talmant P, Giraudier S, Lodé L, Letessier A, Delaval B, et al. (September 2005). "PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation". Leukemia. 19 (9): 1692–1696. doi:10.1038/sj.leu.2403879. PMID 16034466.