PCM1

PCM1
Identifiers
AliasesPCM1, PTC4, RET/PCM-1, pericentriolar material 1
External IDsMGI: 1277958 HomoloGene: 4518 GeneCards: PCM1
Gene location (Human)
Chr.Chromosome 8 (human)[1]
BandNo data availableStart17,922,840 bp[1]
End18,029,944 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

5108

18536

Ensembl

ENSG00000078674

ENSMUSG00000031592

UniProt

Q15154

Q9R0L6

RefSeq (mRNA)

NM_006197
NM_001315507
NM_001315508

NM_023662

RefSeq (protein)

NP_076151

Location (UCSC)Chr 8: 17.92 – 18.03 MbChr 8: 41.24 – 41.33 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Pericentriolar material 1, also known as PCM1, is a protein which in humans is encoded by the PCM1 gene.[5][6][7]

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.[8] 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 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.[9] In humans it is expressed above the median level of central nervous system (CNS) expression in most parts of the brain.[10]

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.[11][12]

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.[13]

Interactions

PCM1 has been shown to interact with PCNT.[14]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000078674 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031592 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ "Entrez Gene: PCM1 pericentriolar material 1".
  6. ↑ 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. PMC 2119948 Freely accessible. PMID 8120099. doi:10.1083/jcb.124.5.783.
  7. ↑ 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. PMC 1073654 Freely accessible. PMID 15659651. doi:10.1091/mbc.E04-08-0688.
  8. ↑ Dammermann, A.; Merdes, A. (2002). "Assembly of centrosomal proteins and microtubule organization depends on PCM-1". The Journal of Cell Biology. 159 (2): 255–266. PMC 2173044 Freely accessible. PMID 12403812. doi:10.1083/jcb.200204023.
  9. ↑ "Gene Expression Summary for Pcm1; pericentriolar material 1". Allen Institute for Brain Science. Retrieved 2009-04-30.
  10. ↑ "PCM1, Probe set 202174_s_at". BioGPS - your Gene Portal System. Retrieved 2009-04-30.
  11. ↑ 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. PMID 19048012. doi:10.1038/mp.2008.128.
  12. ↑ 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. PMC 2634866 Freely accessible. PMID 16894060. doi:10.1001/archpsyc.63.8.844.
  13. ↑ 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. PMC 2727928 Freely accessible. PMID 18762586. doi:10.1001/archpsyc.65.9.996.
  14. ↑ 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

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