INCENP

INCENP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2QFA, 4AF3
Identifiers
Aliases	INCENP , inner centromere protein
External IDs	OMIM: 604411; MGI: 1313288; HomoloGene: 9624; GeneCards: INCENP; OMA:INCENP - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q12.3 Start 62,123,998 bp [1] End 62,153,169 bp [1]
Gene location (Mouse) Chr. Chromosome 19 (mouse) [2] Band 19 A|19 6.1 cM Start 9,849,660 bp [2] End 9,876,915 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence sural nerve bone marrow cells mucosa of esophagus cerebellar hemisphere right hemisphere of cerebellum stromal cell of endometrium testicle prefrontal cortex Top expressed in Paneth cell condyle fossa ureter primitive streak fetal liver hematopoietic progenitor cell renal corpuscle Rostral migratory stream primary oocyte internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component cytoplasm central element pericentric heterochromatin spindle nucleoplasm lateral element chromosome chromocenter synaptonemal complex chromosome, centromeric region microtubule cytoskeleton kinetochore nucleus cytosol nuclear body midbody protein-containing complex Biological process chromosome segregation cell division cell cycle mitotic cytokinesis mitotic sister chromatid segregation regulation of mitotic cytokinesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3619 16319 Ensembl ENSG00000149503 ENSMUSG00000024660 UniProt Q9NQS7 Q9WU62 RefSeq (mRNA) NM_001040694 NM_020238 NM_016692 NM_001369356 RefSeq (protein) NP_001035784 NP_064623 NP_057901 Location (UCSC) Chr 11: 62.12 – 62.15 Mb Chr 19: 9.85 – 9.88 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Chromosome passenger complex (CPC) protein INCENP N terminal
Identifiers
Symbol	INCENP_N
Pfam	PF12178
InterPro	IPR022006
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Inner centromere protein, ARK binding region
Identifiers
Symbol	INCENP_ARK-bind
Pfam	PF03941
InterPro	IPR005635
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Inner centromere protein is a protein that in humans is encoded by the INCENP gene. ^{[5] [6] [7]} It is a regulatory protein in the chromosome passenger complex (CPC). ^[8] It is involved in regulation of the catalytic proteins Aurora B and Aurora C. ^{[9] [10] [11]} It acts in association with two other proteins - Survivin and Borealin. These proteins form a tight three-helical bundle. The N-terminal domain of INCENP is the domain involved in formation of this three-helical bundle while its C-terminal domain is responsible for the interaction with Aurora B. ^{[12] [11]}

In mammalian cells, two broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger' (or transiently interacting) proteins. ^[13] The constitutive proteins include CENPA (centromere protein A), CENPB, CENPC1, and CENPD.

The term 'passenger proteins' encompasses a broad collection of proteins that localize to the centromere during specific stages of the cell cycle. ^[14] These include CENPE; MCAK; KID; cytoplasmic dynein (e.g., DYNC1H1); CliPs (e.g. CLIP1); and CENPF/mitosin (CENPF). The inner centromere proteins (INCENPs), ^[5] the initial members of the passenger protein group, display a broad localization along chromosomes in the early stages of mitosis but gradually become concentrated at centromeres as the cell cycle progresses into mid-metaphase. During telophase, the proteins are located within the midbody in the intercellular bridge, where they are discarded after cytokinesis. ^{[7] [15]}

Interactions

INCENP has been shown to interact with H2AFZ, ^[16] Survivin ^[17] and CDCA8. ^[18] The ARK binding region has been found to be necessary and sufficient for binding to aurora-related kinase. This interaction has been implicated in the coordination of chromosome segregation with cell division in yeast. ^[19]

References

1. GRCh38: Ensembl release 89: ENSG00000149503 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000024660 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Earnshaw WC, Cooke CA (Sep 1991). "Analysis of the distribution of the INCENPs throughout mitosis reveals the existence of a pathway of structural changes in the chromosomes during metaphase and early events in cleavage furrow formation". J Cell Sci. 98 (4): 443–61. doi:10.1242/jcs.98.4.443. PMID   1860899.
6. Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, Svingen PA, Kaufmann SH, Earnshaw WC (Jul 2001). "Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells". Chromosoma. 110 (2): 65–74. doi:10.1007/s004120100130. PMID   11453556. S2CID   13778759.
7. "Entrez Gene: INCENP inner centromere protein antigens 135/155kDa".
8. Dietz, Anne; Subedi, Prabal; Azimzadeh, Omid; Duchrow, Lukas; Kaestle, Felix; Paetzold, Juliane; Katharina Payer, Sarah; Hornhardt, Sabine; von Toerne, Christine; Hauck, Stefanie M.; Kempkes, Bettina; Kuklik-Roos, Cornelia; Brandes, Danielle; Borkhardt, Arndt; Moertl, Simone; Gomolka, Maria (2024). "The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells". Biomarker Insights. 19. doi:10.1177/11772719241274017.
9. Sasai, Kaori; Katayama, Hiroshi; Hawke, David H; Sen, Subrata (2016-01-01). "Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex". PLOS ONE. 11 (6): e0157305. Bibcode:2016PLoSO..1157305S. doi: 10.1371/journal.pone.0157305 . ISSN   1932-6203. PMC   4917241 . PMID   27332895.
10. Li, Xiangyu; Sakashita, Gyosuke; Matsuzaki, Hideki; Sugimoto, Kenji; Kimura, Keiji; Hanaoka, Fumio; Taniguchi, Hisaaki; Furukawa, Koichi; Urano, Takeshi (2004-11-01). "Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C". The Journal of Biological Chemistry. 279 (45): 47201–47211. doi: 10.1074/jbc.m403029200 . ISSN   1083-351X. PMID   15316025.
11. Honda, Reiko; Körner, Roman; Nigg, Erich A (2003-08-01). "Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis". Molecular Biology of the Cell. 14 (8): 3325–3341. doi:10.1091/mbc.e02-11-0769. ISSN   1939-4586. PMC   181570 . PMID   12925766.
12. Jeyaprakash, A. Arockia; Klein, Ulf R.; Lindner, Doris; Ebert, Judith; Nigg, Erich A.; Conti, Elena (2007-10-19). "Structure of a Survivin–Borealin–INCENP Core Complex Reveals How Chromosomal Passengers Travel Together". Cell. 131 (2): 271–285. doi: 10.1016/j.cell.2007.07.045 . ISSN   0092-8674. PMID   17956729. S2CID   15199822.
13. Choo, K. H. Andy (1997). The centromere . Oxford [Oxfordshire]: Oxford University Press. ISBN   978-0-19-857780-5.
14. Earnshaw WC, Mackay AM (September 1994). "Role of nonhistone proteins in the chromosomal events of mitosis". FASEB J. 8 (12): 947–56. doi: 10.1096/fasebj.8.12.8088460 . PMID   8088460. S2CID   14062246.
15. Cutts SM, Fowler KJ, Kile BT, Hii LL, O'Dowd RA, Hudson DF, Saffery R, Kalitsis P, Earle E, Choo KH (July 1999). "Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice". Hum. Mol. Genet. 8 (7): 1145–55. doi: 10.1093/hmg/8.7.1145 . PMID   10369859.
16. Rangasamy D, Berven L, Ridgway P, Tremethick DJ (April 2003). "Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development". EMBO J. 22 (7): 1599–607. doi:10.1093/emboj/cdg160. PMC   152904 . PMID   12660166.
17. Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC (June 2001). "INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis". Curr. Biol. 11 (11): 886–90. Bibcode:2001CBio...11..886W. doi: 10.1016/S0960-9822(01)00238-X . PMID   11516652.
18. Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, Nigg EA, Gerloff DL, Earnshaw WC (July 2004). "Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle". J. Cell Biol. 166 (2): 179–91. doi:10.1083/jcb.200404001. PMC   2172304 . PMID   15249581.
19. Leverson JD, Huang HK, Forsburg SL, Hunter T (April 2002). "The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis". Mol. Biol. Cell. 13 (4): 1132–43. doi:10.1091/mbc.01-07-0330. PMC   102257 . PMID   11950927.

Further reading

• Ainsztein AM, Kandels-Lewis SE, Mackay AM, Earnshaw WC (1999). "INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1". J. Cell Biol. 143 (7): 1763–74. doi:10.1083/jcb.143.7.1763. PMC   2175214 . PMID   9864353.
• Martineau-Thuillier S, Andreassen PR, Margolis RL (1999). "Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis". Chromosoma. 107 (6–7): 461–70. doi:10.1007/s004120050330. PMID   9914378. S2CID   24935187.
• 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. Bibcode:2000PNAS...97.3491D. doi: 10.1073/pnas.97.7.3491 . PMC   16267 . PMID   10737800.
• Wheatley SP, Kandels-Lewis SE, Adams RR, et al. (2001). "INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow". Exp. Cell Res. 262 (2): 122–7. doi:10.1006/excr.2000.5088. PMID   11139336.
• Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC (2001). "INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis". Curr. Biol. 11 (11): 886–90. Bibcode:2001CBio...11..886W. doi: 10.1016/S0960-9822(01)00238-X . PMID   11516652.
• 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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Parra MT, Viera A, Gómez R, et al. (2003). "Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis". J. Cell Sci. 116 (Pt 6): 961–74. doi: 10.1242/jcs.00330 . PMID   12584241.
• Rangasamy D, Berven L, Ridgway P, Tremethick DJ (2003). "Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development". EMBO J. 22 (7): 1599–607. doi:10.1093/emboj/cdg160. PMC   152904 . PMID   12660166.
• Honda R, Körner R, Nigg EA (2004). "Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis". Mol. Biol. Cell. 14 (8): 3325–41. doi:10.1091/mbc.E02-11-0769. PMC   181570 . PMID   12925766.
• Wheatley SP, Henzing AJ, Dodson H, et al. (2004). "Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo". J. Biol. Chem. 279 (7): 5655–60. doi: 10.1074/jbc.M311299200 . PMID   14610074.
• 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.
• Gassmann R, Carvalho A, Henzing AJ, et al. (2004). "Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle". J. Cell Biol. 166 (2): 179–91. doi:10.1083/jcb.200404001. PMC   2172304 . PMID   15249581.
• Li X, Sakashita G, Matsuzaki H, et al. (2004). "Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C". J. Biol. Chem. 279 (45): 47201–11. doi: 10.1074/jbc.M403029200 . PMID   15316025.
• 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.
• Zhu C, Bossy-Wetzel E, Jiang W (2005). "Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells". Biochem. J. 389 (Pt 2): 373–81. doi:10.1042/BJ20050097. PMC   1175114 . PMID   15796717.
• Chen HL, Tang CJ, Chen CY, Tang TK (2005). "Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy". J. Biomed. Sci. 12 (2): 297–310. doi:10.1007/s11373-005-0980-0. PMID   15917996.
• Vader G, Kauw JJ, Medema RH, Lens SM (2006). "Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody". EMBO Rep. 7 (1): 85–92. doi:10.1038/sj.embor.7400562. PMC   1369225 . PMID   16239925.
• Goto H, Kiyono T, Tomono Y, et al. (2006). "Complex formation of Plk1 and INCENP required for metaphase-anaphase transition". Nat. Cell Biol. 8 (2): 180–7. doi:10.1038/ncb1350. PMID   16378098. S2CID   11583385.

This article incorporates text from the public domain Pfam and InterPro: IPR005635

This article incorporates text from the public domain Pfam and InterPro: IPR022006