Kinetokoriproteiinien geenejä (Kinetochore Assembly) CENP-A,-B,-C,-E,-T,-W ,..

 Poikkeuksellinen on CENP-E. Siitä erikseen.

Assemly of the Kinetochore. the formation of nucleosomes containig  an H3 isoform at centromeric chromatin (Kinetokori toimii interfaasipintana kromosomin sentrosomin ja mikrotubulusten välillä. )
.https://www.youtube.com/watch?v=0JpOJ4F4984
Genes
CENP-A (2p33.2) CenH3, centromeric specific histone
CENP-B (20p13), major centromeric autoantigen B, binds to alfa-satellite DNA
CENP-C  (4q13.1) , MIF-2, bcp-4, CENPC1, located on inner kinetochore plate.
CENP-N  (16q23.2) BM039, ICEN32, C16orf60, recruits other proteins; absent in M and G1 phases, bound to kinetochore in S and G2 phases).
CENP-T (16q22.1), interphase centromeric complex protein 22, centromeric protein T.
CENP-W  (6q22.32) C6orf, CUG2 (cancer upregualted gene 2 protein)

( 17.5. 2019. Hain näiden geenien tiedot tänään ja minulla on de omalla tietokoneella  muistiinkirjoitettuna.  Asetan joksikin aikaa listan tähän ja siten poistan myöhemmin tekstit, kun olen käynyt ne läpi  jä jätän vain yhden linkin  jokaisesta. Tästä  blogista on nopeampi klikata tekstejä esiin kuin omasta tietokoneesta. Kromosomien sentromeeristä kinetokoriproteiinien geenejä)

• KINETOCHORE Assembly proteines, Genes

• CENP-A (2p33.2) 140 a.a.

https://www.ncbi.nlm.nih.gov/gene/1058

Also known as

CenH3; CENP-A

Summary

Centromeres are the differentiated chromosomal domains that specify the mitotic behavior of chromosomes. This gene encodes a centromere protein which contains a histone H3 related histone fold domain that is required for targeting to the centromere. Centromere protein A is proposed to be a component of a modified nucleosome or nucleosome-like structure in which it replaces 1 or both copies of conventional histone H3 in the (H3-H4)2 tetrameric core of the nucleosome particle. The protein is a replication-independent histone that is a member of the histone H3 family. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Nov 2015]

Expression

Broad expression in lymph node (RPKM 4.5), appendix (RPKM 2.5) and 14 other tissues See more

Orthologs

mouse all

Preferred Names

histone H3-like centromeric protein A

Names

centromere autoantigen A

centromere protein A, 17kDa

centromere-specific histone

Related articles in PubMed

1. Phosphorylation of CENP-A on serine 7 does not control centromere function. Barra V, et al. Nat Commun, 2019 Jan 11. PMID 30635586, Free PMC Article
2. Mislocalization of centromeric histone H3 variant CENP-A contributes to chromosomal instability (CIN) in human cells. Shrestha RL, et al. Oncotarget, 2017 Jul 18. PMID 28596481, Free PMC Article
3. Motifs in the amino-terminus of CENP-A are required for its accumulation within the nucleus and at the centromere. Jing R, et al. Oncotarget, 2017 Jun 20. PMID 28489565, Free PMC Article
4. CENP-A Modifications on Ser68 and Lys124 Are Dispensable for Establishment, Maintenance, and Long-Term Function of Human Centromeres. Fachinetti D, et al. Dev Cell, 2017 Jan 9. PMID 28073008, Free PMC Article
5. A Dual Inhibitory Mechanism Sufficient to Maintain Cell-Cycle-Restricted CENP-A Assembly. Stankovic A, et al. Mol Cell, 2017 Jan 19. PMID 28017591, Free PMC Article

See all (136) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. H3.3 chaperones HIRA and DAXX promote ectopic CENP-A deposition.
2. phosphorylation of CENP-A on serine 7 dispensable to correct centromere dynamics and function
3. CENP-N stabilizes CENP-A nucleosomes alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP-N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of CENP-A nucleosomes in chromatin does not arise solely from its interactions with CENP-C or CENP-N.
4. Aurora A-dependent phosphorylation of CENP-A at the inner centromere protects chromosomes against tension-induced cohesion fatigue until the last kinetochore is attached to spindle microtubules.
5. CENP-A undergoes alpha-amino trimethylation by the enzyme NRMT in vivo.
6. H4K5ac and H4K12ac, mediated by RbAp46/48, facilitates efficient CENP-A deposition into centromeres.
7. Collectively, these studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.
8. the SGT1-HSP90 complex contributes to the E3 ligase activity of the CUL4A complex that is necessary for CENP-A ubiquitylation and CENP-A deposition at the centromere.
9. during the CENP-A/H4 deposition process, the chaperone HJURP protects various substructures of the dimer, serving both as a folding and binding chaperone
10. This study provides insights into how overexpression of CENP-A may contribute to CIN in cancers and underscore the importance of understanding the pathways that prevent CENP-A mislocalization for genome stability.

Submit: New GeneRIF Correction See all GeneRIFs (91)

• CENP-C (4q13.1)

Also known as

MIF2; hcp-4; CENP-C; CENPC1

Summary

Centromere protein C 1 is a centromere autoantigen and a component of the inner kinetochore plate. The protein is required for maintaining proper kinetochore size and a timely transition to anaphase. A putative pseudogene exists on chromosome 12. [provided by RefSeq, Jul 2008]

Expression

Ubiquitous expression in bone marrow (RPKM 7.9), testis (RPKM 4.6) and 25 other tissues See more

Orthologs

mouse all

Related articles in PubMed

1. CENP-C is a blueprint for constitutive centromere-associated network assembly within human kinetochores. Klare K, et al. J Cell Biol, 2015 Jul 6. PMID 26124289, Free PMC Article
2. Death receptor-induced apoptosis reveals a novel interplay between the chromosomal passenger complex and CENP-C during interphase. Faragher AJ, et al. Mol Biol Cell, 2007 Apr. PMID 17287400, Free PMC Article
3. CENP-C binds the alpha-satellite DNA in vivo at specific centromere domains. Politi V, et al. J Cell Sci, 2002 Jun 1. PMID 12006616
4. Mutational analysis of the central centromere targeting domain of human centromere protein C, (CENP-C). Song K, et al. Exp Cell Res, 2002 Apr 15. PMID 11925107
5. Human chromosome pellicle antibody recognizing centromere protein-C (CENP-C), the main component of the kinetochore. Xie Y, et al. Cell Res, 1997 Jun. PMID 9261558

See all (59) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. CENP-N stabilizes CENP-A nucleosomes alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP-N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of CENP-A nucleosomes in chromatin does not arise solely from its interactions with CENP-C or CENP-N.
2. Collectively, these studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.
3. Levels of centromere aberrations increase upon depletion of CENP-A, CENP-C, and CENP-T/W, during replicative senescence, and in cancer cells.
4. Upon cross-linking, the entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an alpha-satellite dimer that comprises the fundamental unit of centromeric chromatin. We conclude that CENPA/CENPC and CENPT pathways for kinetochore assembly are physically integrated over young alpha-satellite dimers.
5. Whereas CENP-C recruits a single MIS12:NDC80 complex, the authors show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites.
6. CENP-C specifically binds alpha satellite non-coding RNAs.
7. CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly.
8. A nonhistone centromere protein, CENP-C, binds and reshapes the nucleosome, sliding the DNA gyres back to positions similar to those in canonical nucleosomes containing conventional histone H3.
9. HPV18 E7 inhibited the binding of CENP-C to alpha-satellite DNAs.
10. We used a synthetic system to dissect how CenH3(CENP-A) contributes to the accumulation of CENP-C and CENP-T, two key components that are necessary for the formation of functional kinetochores

Submit: New GeneRIF Correction See all GeneRIFs (26)

• CENP-N (16q23.2)

Also known as

BM039; CENP-N; ICEN32; C16orf60

Summary

The protein encoded by this gene forms part of the nucleosome-associated complex and is important for kinetochore assembly. It is bound to kinetochores during S phase and G2 and recruits other proteins to the centromere. Pseudogenes of this gene are located on chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

Expression

Ubiquitous expression in prostate (RPKM 4.4), bone marrow (RPKM 3.9) and 25 other tissues See more

Orthologs

mouse all

Preferred Names

centromere protein N

Names

interphase centromere complex protein 32

Related articles in PubMed

1. Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N. Chittori S, et al. Science, 2018 Jan 19. PMID 29269420, Free PMC Article
2. Dynamics of CENP-N kinetochore binding during the cell cycle. Hellwig D, et al. J Cell Sci, 2011 Nov 15. PMID 22100916, Free PMC Article
3. The CENP-L-N Complex Forms a Critical Node in an Integrated Meshwork of Interactions at the Centromere-Kinetochore Interface. McKinley KL, et al. Mol Cell, 2015 Dec 17. PMID 26698661, Free PMC Article
4. Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Carroll CW, et al. Nat Cell Biol, 2009 Jul. PMID 19543270, Free PMC Article
5. Constitutive centromere-associated network contacts confer differential stability on CENP-A nucleosomes in vitro and in the cell. Cao S, et al. Mol Biol Cell, 2018 Mar 15. PMID 29343552, Free PMC Article

See all (18) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. CENP-N stabilizes CENP-A nucleosomes alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP-N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of CENP-A nucleosomes in chromatin does not arise solely from its interactions with CENP-C or CENP-N.
2. Collectively, these studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.
3. this study reports cryo-electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N.
4. Study demonstrate that the CENP-L-N complex plays a crucial role at the core of the 16-subunit Constitutive Centromere-Associated Network through interactions with CENP-C and CENP-H-I-KM.
5. CENP-N is bound to kinetochores during S phase and G2, but is absent from kinetochores during mitosis and G1.
6. Data suggest that CENP-N interprets the information encoded within CENP-A nucleosomes and recruits other proteins to centromeric chromatin that are required for centromere function and propagation.

• CENP-T (16q22.1)

Also known as

CENP-T; C16orf56

Preferred Names

centromere protein T

Names

interphase centromere complex protein 22

Summary

The centromere is a specialized chromatin domain, present throughout the cell cycle, that acts as a platform on which the transient assembly of the kinetochore occurs during mitosis. All active centromeres are characterized by the presence of long arrays of nucleosomes in which CENPA (MIM 117139) replaces histone H3 (see MIM 601128). CENPT is an additional factor required for centromere assembly (Foltz et al., 2006 [PubMed 16622419]).[supplied by OMIM, Mar 2008]

Expression

Ubiquitous expression in skin (RPKM 26.3), testis (RPKM 20.1) and 25 other tissues See more

Related articles in PubMed

1. A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. Hung CY, et al. PLoS One, 2017. PMID 29228025, Free PMC Article
2. CENP-T provides a structural platform for outer kinetochore assembly. Nishino T, et al. EMBO J, 2013 Feb 6. PMID 23334297, Free PMC Article
3. Holliday junction recognition protein interacts with and specifies the centromeric assembly of CENP-T. Ding M, et al. J Biol Chem, 2019 Jan 18. PMID 30459232,
4. Distinct organization and regulation of the outer kinetochore KMN network downstream of CENP-C and CENP-T. Rago F, et al. Curr Biol, 2015 Mar 2. PMID 25660545, Free PMC Article
5. Integrity of the human centromere DNA repeats is protected by CENP-A, CENP-C, and CENP-T. Giunta S, et al. Proc Natl Acad Sci U S A, 2017 Feb 21. PMID 28167779, Free PMC Article

See all (36) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. these data define a novel molecular mechanism underlying the assembly of CENP-T onto the centromere by a temporally regulated HJURP-CENP-T interaction.
2. Levels of centromere aberrations increase upon depletion of CENP-A, CENP-C, and CENP-T/W, during replicative senescence, and in cancer cells.
3. report a novel disease gene encoding the constitutive inner kinetochore member CENPT, which is involved in kinetochore targeting and assembly, resulting in severe growth failure in two siblings of a consanguineous family
4. Upon cross-linking, the entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an alpha-satellite dimer that comprises the fundamental unit of centromeric chromatin. We conclude that CENPA/CENPC and CENPT pathways for kinetochore assembly are physically integrated over young alpha-satellite dimers.
5. Whereas CENP-C recruits a single MIS12:NDC80 complex, the authors show here that CENP-T binds one MIS12:NDC80 and two NDC80 complexes upon phosphorylation by the mitotic CDK1:Cyclin B complex at three distinct CENP-T sites.
6. FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres.
7. We used a synthetic system to dissect how CenH3(CENP-A) contributes to the accumulation of CENP-C and CENP-T, two key components that are necessary for the formation of functional kinetochores
8. CENP-T directly interacts with Ndc80, which in turn promotes KNL1/Mis12 complex recruitment at kinetochores during chromosome segregation.
9. CSN5 regulates the stability of the inner kinetochore components CENP-T and CENP-W, providing the first direct link between CSN5 and the mitotic apparatus, highlighting the role of CSN5 as a multifunctional cell cycle regulator.
10. CENP-T provides a structural platform for outer kinetochore assembly.

• CENP-B (20p13)

https://www.ncbi.nlm.nih.gov/gene/1059

Summary

This gene product is a highly conserved protein that facilitates centromere formation. It is a DNA-binding protein that is derived from transposases of the pogo DNA transposon family. It contains a helix-loop-helix DNA binding motif at the N-terminus, and a dimerization domain at the C-terminus. The DNA binding domain recognizes and binds a 17-bp sequence (CENP-B box) in the centromeric alpha satellite DNA. This protein is proposed to play an important role in the assembly of specific centromere structures in interphase nuclei and on mitotic chromosomes. It is also considered a major centromere autoantigen recognized by sera from patients with anti-centromere antibodies. [provided by RefSeq, Jul 2008]

Orthologs

mouse all

Preferred Names

major centromere autoantigen B

Names

CENP-B

centromere autoantigen B

centromere protein B, 80kDa

Related articles in PubMed

1. Mutational spectrum of CENP-B box and α-satellite DNA on chromosome 21 in Down syndrome children. Chen Q, et al. Mol Med Rep, 2017 Apr. PMID 28259924
2. Stable complex formation of CENP-B with the CENP-A nucleosome. Fujita R, et al. Nucleic Acids Res, 2015 May 26. PMID 25916850, Free PMC Article
3. HTLV-1 bZIP factor suppresses the centromere protein B (CENP-B)-mediated trimethylation of histone H3K9 through the abrogation of DNA-binding ability of CENP-B. Mukai R, et al. J Gen Virol, 2015 Jan. PMID 25281565
4. Identification of novel α-n-methylation of CENP-B that regulates its binding to the centromeric DNA. Dai X, et al. J Proteome Res, 2013 Sep 6. PMID 23978223, Free PMC Article
5. Anti-CENP-B antibodies are associated with prolonged survival in breast cancer. Atalay C, et al. Future Oncol, 2010 Mar. PMID 20222802

See all (67) citations in PubMed

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Given that CENP-B is the only centromere protein that binds centromere-specific DNA elements, our study provides a new link between centromere DNA and unique epigenetic landscape of centromere chromatin
2. Upon cross-linking, the entire CENPA/CENPB/CENPC/CENPT complex is nuclease-protected over an alpha-satellite dimer that comprises the fundamental unit of centromeric chromatin. We conclude that CENPA/CENPC and CENPT pathways for kinetochore assembly are physically integrated over young alpha-satellite dimers.
3. Findings indicate that expression of the scleroderma autoantigens IFI-16 and CENPs, which are associated with severe vascular disease, is increased in vascular progenitors and mature endothelial cells. High level, lineage-enriched expression of autoantigens may explain the striking association between clinical phenotypes and the immune targeting of specific autoantigens.
4. The results indicated that CENPB boxes are highly conserved in Down syndrome (DS) patients and may not be responsible for Chr21 nondisjunction events. However, alphasatDNA in Chr21 is variable and deoxynucleotide deletions, mutations and polymorphisms may act as potential molecular diagnostic markers of DS.
5. CENP-B directly binds both CENP-A's amino-terminal tail and CENP-C, a key nucleator of kinetochore assembly
6. The results revealed that CENP-B binding in the vicinity of the CENP-A nucleosome substantially stabilizes the CENP-A nucleosome on alphoid DNA in human cells.
7. Centromere protein B (CENP-B) as a novel interacting partner of HBZ.
8. INMAP as a model regulator of CENP-B
9. N-terminal methylation is required for CENP-B's binding to the CENP-B box.
10. Human Nap1, an acidic histone chaperone, inhibited the non-specific binding of CENP-B to nucleosomes and apparently stimulated CENP-B binding to its cognate CENP-B box DNA.

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• CENP-W, (6q22.32) C6Orf, CUG2.

https://www.ncbi.nlm.nih.gov/gene/387103

Expr. Bone marrow, testis.

Preferred Names

centromere protein W

Names

cancer-up-regulated gene 2 protein

cancer-upregulated gene 2

Related articles in PubMed

1. Cancer upregulated gene 2 induces epithelial-mesenchymal transition of human lung cancer cells via TGF-β signaling. Kaowinn S, et al. Oncotarget, 2017 Jan 17. PMID 27974707, Free PMC Article
2. CENP-W plays a role in maintaining bipolar spindle structure. Kaczmarczyk A, et al. PLoS One, 2014. PMID 25329824, Free PMC Article
3. Cancer-upregulated gene 2 (CUG2) overexpression induces apoptosis in SKOV-3 cells. Lee S, et al. Cell Biochem Funct, 2010 Aug. PMID 20648695
4. CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway. Park EH, et al. Cancer Gene Ther, 2010 May. PMID 20075984
5. Centromere Protein (CENP)-W Interacts with Heterogeneous Nuclear Ribonucleoprotein (hnRNP) U and May Contribute to Kinetochore-Microtubule Attachment in Mitotic Cells. Chun Y, et al. PLoS One, 2016. PMID 26881882, Free PMC Article

See all (42) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. CENP-W showed a higher affinity toward the beta-TrCP1 b isoform.
2. we suggest that STAT1HDAC4 signaling induces malignant tumor features such as EMT and sphere formation in CUG2overexpressing cancer cells.
3. Report provides evidence that CUG2 induces the EMT in human lung cancer cells via enhancement of TGF-beta signaling and that that TGF-beta signaling is a potential target for CUG2-mediated oncogenesis.
4. It has been proposed that CENP-W may function as a booster of beta-TrCP1 nuclear import to increase the oncogenicity of beta-TrCP1.
5. FACT chaperone stabilizes the soluble CENP-T/-W complex in the cell and promotes dynamics of exchange, enabling CENP-T/-W deposition at centromeres.
6. CENP-W interacts with hnRNPU and may contribute to kinetochore-microtubule attachment in mitotic cells.
7. CENP-W is a novel kinetochore component that may be involved in the EZH2-mediated silencing machinery.
8. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction forces exerted by motor proteins during chromosome congression
9. CUG2-mediated antiviral activity can be reduced by ISG15 deficiency in A549 cells, which eventually enhances sensitivity of the cells to vesicular stomatitis virus infection.
10. our results suggest that CUG2 enhances metastasis and drug resistance through STAT1 activation, which eventually contributes to tumor progression

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