PCM1

Pericentriolar material 1
Identifiers
Symbols	PCM1; PTC4
External IDs	OMIM: 600299 MGI: 1277958 HomoloGene: 4518 GeneCards: PCM1 Gene
Gene Ontology Molecular function • protein binding • identical protein binding Cellular component • pericentriolar material • cytoplasm • cytoplasm • centrosome • centrosome • cytosol • cytoskeleton • nonmotile primary cilium • nuclear membrane • centriolar satellite Biological process • G2/M transition of mitotic cell cycle • mitotic cell cycle • interkinetic nuclear migration • cell projection organization • microtubule anchoring • cilium assembly • negative regulation of neurogenesis • centrosome organization • protein localization to centrosome Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5108	18536
Ensembl	ENSG00000078674	ENSMUSG00000031592
UniProt	Q15154	Q9R0L6
RefSeq (mRNA)	NM_006197	NM_023662.3
RefSeq (protein)	NP_006188	NP_076151.2
Location (UCSC)	Chr 8: 17.78 – 17.89 Mb	Chr 8: 42.33 – 42.42 Mb
PubMed search	[1]	[2]

Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene.^[1][2][3]

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.

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.^[4] In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.^[5] 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 effect 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.^[6][7]

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.^[8]

Interactions

PCM1 has been shown to interact with PCNT.^[9]

References

1. ^ "Entrez Gene: PCM1 pericentriolar material 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5108. 
2. ^ Balczon R, Bao L, Zimmer WE (March 1994). "PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution". J. Cell Biol. 124 (5): 783–93. doi:10.1083/jcb.124.5.783. PMC 2119948. PMID 8120099. http://www.jcb.org/cgi/pmidlookup?view=long&pmid=8120099. 
3. ^ Hames RS, Crookes RE, Straatman KR, Merdes A, Hayes MJ, Faragher AJ, Fry AM (April 2005). "Dynamic Recruitment of Nek2 Kinase to the Centrosome Involves Microtubules, PCM-1, and Localized Proteasomal Degradation". Mol. Biol. Cell 16 (4): 1711–24. doi:10.1091/mbc.E04-08-0688. PMC 1073654. PMID 15659651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1073654. 
4. ^ "Gene Expression Summary for Pcm1; pericentriolar material 1". Allen Institute for Brain Science. http://mouse.brain-map.org/brain/Pcm1.html?ispopup=1. Retrieved 2009-04-30. 
5. ^ "PCM1, Probe set 202174_s_at". BioGPS - your Gene Portal System. http://biogps.gnf.org/?referer=symatlas#goto=genereport&id=5108. Retrieved 2009-04-30. 
6. ^ Datta SR, McQuillin A, Rizig M, Blaveri E, Thirumalai S, Kalsi G, Lawrence J, Bass NJ, Puri V, Choudhury K, Pimm J, Crombie C, Fraser G, Walker N, Curtis D, Zvelebil M, Pereira A, Kandaswamy R, St Clair D, Gurling HM (December 2008). "A threonine to isoleucine missense mutation in the pericentriolar material 1 gene is strongly associated with schizophrenia". Mol. Psychiatry 15 (6): 615–28. doi:10.1038/mp.2008.128. PMID 19048012. 
7. ^ Gurling HM, Critchley H, Datta SR, McQuillin A, Blaveri E, Thirumalai S, Pimm J, Krasucki R, Kalsi G, Quested D, Lawrence J, Bass N, Choudhury K, Puri V, O'Daly O, Curtis D, Blackwood D, Muir W, Malhotra AK, Buchanan RW, Good CD, Frackowiak RS, Dolan RJ (August 2006). "Genetic Association and Brain Morphology Studies and the Chromosome 8p22 Pericentriolar Material 1 (PCM1) Gene in Susceptibility to Schizophrenia". Arch. Gen. Psychiatry 63 (8): 844–54. doi:10.1001/archpsyc.63.8.844. PMC 2634866. PMID 16894060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2634866. 
8. ^ Kamiya A, Tan PL, Kubo K, Engelhard C, Ishizuka K, Kubo A, Tsukita S, Pulver AE, Nakajima K, Cascella NG, Katsanis N, Sawa A (September 2008). "PCM1 is recruited to the centrosome by the cooperative action of DISC1 and BBS4 and is a candidate for psychiatric illness". Arch. Gen. Psychiatry 65 (9): 996–1006. doi:10.1001/archpsyc.65.9.996. PMC 2727928. PMID 18762586. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2727928. 
9. ^ Li, Q; Hansen D, Killilea A, Joshi H C, Palazzo R E, Balczon R (February 2001). "Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1". J. Cell. Sci. (England) 114 (Pt 4): 797–809. ISSN 0021-9533. PMID 11171385. 

Further reading

• 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): 404–6. doi:10.1006/geno.1994.1640. PMID 7698772. 
• Balczon R, Bao L, Zimmer WE (1994). "PCM-1, A 228-kD centrosome autoantigen with a distinct cell cycle distribution". J. Cell Biol. 124 (5): 783–93. doi:10.1083/jcb.124.5.783. PMC 2119948. PMID 8120099. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2119948. 
• Engelender S, Sharp AH, Colomer V et al. (1998). "Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin". Hum. Mol. Genet. 6 (13): 2205–12. doi:10.1093/hmg/6.13.2205. PMID 9361024. 
• Dias Neto E, Correa RG, Verjovski-Almeida S et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16267. 
• Corvi R, Berger N, Balczon R, Romeo G (2000). "RET/PCM-1: a novel fusion gene in papillary thyroid carcinoma". Oncogene 19 (37): 4236–42. doi:10.1038/sj.onc.1203772. PMID 10980597. 
• Li Q, Hansen D, Killilea A et al. (2001). "Kendrin/pericentrin-B, a centrosome protein with homology to pericentrin that complexes with PCM-1". J. Cell. Sci. 114 (Pt 4): 797–809. PMID 11171385. 
• Kumar S, Connor JR, Dodds RA et al. (2001). "Identification and initial characterization of 5000 expressed sequenced tags (ESTs) each from adult human normal and osteoarthritic cartilage cDNA libraries". Osteoarthr. Cartil. 9 (7): 641–53. doi:10.1053/joca.2001.0421. PMID 11597177. 
• Dammermann A, Merdes A (2002). "Assembly of centrosomal proteins and microtubule organization depends on PCM-1". J. Cell Biol. 159 (2): 255–66. doi:10.1083/jcb.200204023. PMC 2173044. PMID 12403812. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2173044. 
• Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Ansley SJ, Badano JL, Blacque OE et al. (2003). "Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome". Nature 425 (6958): 628–33. doi:10.1038/nature02030. PMID 14520415. 
• Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. 
• Kim JC, Badano JL, Sibold S et al. (2004). "The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression". Nat. Genet. 36 (5): 462–70. doi:10.1038/ng1352. PMID 15107855. 
• Brill LM, Salomon AR, Ficarro SB et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186. 
• Armes JE, Hammet F, de Silva M et al. (2004). "Candidate tumor-suppressor genes on chromosome arm 8p in early-onset and high-grade breast cancers". Oncogene 23 (33): 5697–702. doi:10.1038/sj.onc.1207740. PMID 15184884. 
• Beausoleil SA, Jedrychowski M, Schwartz D et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=514446. 
• Ballif BA, Villén J, Beausoleil SA et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747. 
• Gerhard DS, Wagner L, Feingold EA et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=528928. 
• Hames RS, Crookes RE, Straatman KR et al. (2005). "Dynamic Recruitment of Nek2 Kinase to the Centrosome Involves Microtubules, PCM-1, and Localized Proteasomal Degradation". Mol. Biol. Cell 16 (4): 1711–24. doi:10.1091/mbc.E04-08-0688. PMC 1073654. PMID 15659651. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1073654. 
• Reiter A, Walz C, Watmore A et al. (2005). "The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2". Cancer Res. 65 (7): 2662–7. doi:10.1158/0008-5472.CAN-04-4263. PMID 15805263. 
• Murati A, Gelsi-Boyer V, Adélaïde J et al. (2005). "PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation". Leukemia 19 (9): 1692–6. doi:10.1038/sj.leu.2403879. PMID 16034466.