INCENP

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} {{Infobox protein family | Symbol = INCENP_N | Name = Chromosome passenger complex (CPC) protein INCENP N terminal | image = | width = | caption = crystal structure of a survivin-borealin-incenp core complex | Pfam = PF12178 | Pfam_clan = | InterPro = IPR022006 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} {{Infobox protein family | Symbol = INCENP_ARK-bind | Name = Inner centromere protein, ARK binding region | image = | width = | caption = crystal structure of aurora b kinase in complex with a aminothiazole inhibitor | Pfam = PF03941 | Pfam_clan = | InterPro = IPR005635 | SMART = | PROSITE = | MEROPS = | SCOP = | TCDB = | OPM family = | OPM protein = | CAZy = | CDD = }} '''Inner centromere protein''' is a protein that in humans is encoded by the ''INCENP'' gene.<ref name="pmid1860899">{{cite journal |vauthors=Earnshaw WC, Cooke CA | title = 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 | journal = J Cell Sci | volume = 98 | issue = 4| pages = 443–61 |date=Sep 1991 | doi = 10.1242/jcs.98.4.443 | pmid = 1860899 }}</ref><ref name="pmid11453556">{{cite journal |vauthors=Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, Svingen PA, Kaufmann SH, Earnshaw WC | title = Human INCENP colocalizes with the Aurora-B/AIRK2 kinase on chromosomes and is overexpressed in tumour cells | journal = Chromosoma | volume = 110 | issue = 2 | pages = 65–74 |date=Jul 2001 | pmid = 11453556 | doi =10.1007/s004120100130 | s2cid = 13778759 }}</ref><ref name="entrez">{{Cite web| title = Entrez Gene: INCENP inner centromere protein antigens 135/155kDa| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=3619}}</ref> It is a regulatory protein in the chromosome passenger complex (CPC).<ref>{{cite journal | last1=Dietz | first1=Anne | last2=Subedi | first2=Prabal | last3=Azimzadeh | first3=Omid | last4=Duchrow | first4=Lukas | last5=Kaestle | first5=Felix | last6=Paetzold | first6=Juliane | last7=Katharina Payer | first7=Sarah | last8=Hornhardt | first8=Sabine | last9=von Toerne | first9=Christine | last10=Hauck | first10=Stefanie M. | last11=Kempkes | first11=Bettina | last12=Kuklik-Roos | first12=Cornelia | last13=Brandes | first13=Danielle | last14=Borkhardt | first14=Arndt | last15=Moertl | first15=Simone | last16=Gomolka | first16=Maria | title=The Chromosome Passenger Complex (CPC) Components and Its Associated Pathways Are Promising Candidates to Differentiate Between Normosensitive and Radiosensitive ATM-Mutated Cells | journal=Biomarker Insights | date=2024 | volume=19 | doi=10.1177/11772719241274017 | url=https://journals.sagepub.com/doi/full/10.1177/11772719241274017 | pmc=11528597 }}</ref> It is involved in regulation of the catalytic proteins Aurora B and Aurora C.<ref>{{Cite journal |last1=Sasai |first1=Kaori |last2=Katayama |first2=Hiroshi |last3=Hawke |first3=David H |last4=Sen |first4=Subrata |date=2016-01-01 |title=Aurora-C Interactions with Survivin and INCENP Reveal Shared and Distinct Features Compared with Aurora-B Chromosome Passenger Protein Complex |journal=PLOS ONE |volume=11 |issue=6 |article-number=e0157305 |doi=10.1371/journal.pone.0157305 |issn=1932-6203 |pmc=4917241 |pmid=27332895 |bibcode=2016PLoSO..1157305S |doi-access=free }}</ref><ref>{{Cite journal |last1=Li |first1=Xiangyu |last2=Sakashita |first2=Gyosuke |last3=Matsuzaki |first3=Hideki |last4=Sugimoto |first4=Kenji |last5=Kimura |first5=Keiji |last6=Hanaoka |first6=Fumio |last7=Taniguchi |first7=Hisaaki |last8=Furukawa |first8=Koichi |last9=Urano |first9=Takeshi |date=2004-11-01 |title=Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C |journal=The Journal of Biological Chemistry |volume=279 |issue=45 |pages=47201–47211 |doi=10.1074/jbc.m403029200 |issn=1083-351X |pmid=15316025 |doi-access=free }}</ref><ref name="ReferenceA">{{Cite journal |last1=Honda |first1=Reiko |last2=Körner |first2=Roman |last3=Nigg |first3=Erich A |date=2003-08-01 |title=Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis |journal=Molecular Biology of the Cell |volume=14 |issue=8 |pages=3325–3341 |doi=10.1091/mbc.e02-11-0769 |issn=1939-4586 |pmid=12925766|pmc=181570 }}</ref> 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.<ref>{{Cite journal |last1=Jeyaprakash |first1=A. Arockia |last2=Klein |first2=Ulf R. |last3=Lindner |first3=Doris |last4=Ebert |first4=Judith |last5=Nigg |first5=Erich A. |last6=Conti |first6=Elena |date=2007-10-19 |title=Structure of a Survivin–Borealin–INCENP Core Complex Reveals How Chromosomal Passengers Travel Together |journal=Cell |language=en |volume=131 |issue=2 |pages=271–285 |doi=10.1016/j.cell.2007.07.045 |pmid=17956729 |s2cid=15199822 |issn=0092-8674|doi-access=free }}</ref><ref name="ReferenceA"/>

In mammalian cells, two broad groups of centromere-interacting proteins have been described: constitutively binding centromere proteins and 'passenger' (or transiently interacting) proteins.<ref name="isbn0-19-857780-X">{{Cite book | author = Choo, K. H. Andy | title = The centromere | publisher = Oxford University Press | location = Oxford [Oxfordshire] | year = 1997 | isbn = 978-0-19-857780-5 | url = https://archive.org/details/centromere0000choo | url-access = registration }}</ref> 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.<ref name="pmid8088460">{{cite journal |vauthors=Earnshaw WC, Mackay AM | title = Role of nonhistone proteins in the chromosomal events of mitosis | journal = FASEB J. | volume = 8 | issue = 12 | pages = 947–56 |date=September 1994 | pmid = 8088460 | doi = 10.1096/fasebj.8.12.8088460| doi-access = free | s2cid = 14062246 }}</ref> These include CENPE; MCAK; KID; cytoplasmic dynein (e.g., DYNC1H1); CliPs (e.g. CLIP1); and CENPF/mitosin (CENPF). The inner centromere proteins (INCENPs),<ref name="pmid1860899" /> 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.<ref name="entrez"/><ref name="pmid10369859">{{cite journal |vauthors=Cutts SM, Fowler KJ, Kile BT, Hii LL, O'Dowd RA, Hudson DF, Saffery R, Kalitsis P, Earle E, Choo KH | title = Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice | journal = Hum. Mol. Genet. | volume = 8 | issue = 7 | pages = 1145–55 |date=July 1999 | pmid= 10369859 | doi = 10.1093/hmg/8.7.1145| doi-access = free }}</ref>

==Interactions== INCENP has been shown to interact with H2AFZ,<ref name="pmid12660166">{{cite journal |vauthors=Rangasamy D, Berven L, Ridgway P, Tremethick DJ | title = Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development | journal = EMBO J. | volume = 22 | issue = 7 | pages = 1599–607 |date=April 2003 | pmid = 12660166 | pmc = 152904 | doi = 10.1093/emboj/cdg160 }}</ref> Survivin<ref name="pmid11516652">{{cite journal |vauthors=Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC | title = INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis | journal = Curr. Biol. | volume = 11 | issue = 11 | pages = 886–90 |date=June 2001 | pmid = 11516652 | doi = 10.1016/S0960-9822(01)00238-X| doi-access = free | bibcode = 2001CBio...11..886W }}</ref> and CDCA8.<ref name="pmid15249581">{{cite journal |vauthors=Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, Nigg EA, Gerloff DL, Earnshaw WC | title = Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle | journal = J. Cell Biol. | volume = 166 | issue = 2 | pages = 179–91 |date=July 2004 | pmid = 15249581 | pmc = 2172304 | doi = 10.1083/jcb.200404001 }}</ref> 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.<ref name="pmid11950927">{{cite journal |vauthors=Leverson JD, Huang HK, Forsburg SL, Hunter T | title = The Schizosaccharomyces pombe aurora-related kinase Ark1 interacts with the inner centromere protein Pic1 and mediates chromosome segregation and cytokinesis | journal = Mol. Biol. Cell | volume = 13 | issue = 4 | pages = 1132–43 |date=April 2002 | pmid = 11950927 | pmc = 102257 | doi = 10.1091/mbc.01-07-0330 }}</ref>

==References== {{Reflist}}

==Further reading== {{Refbegin| 2}} *{{Cite journal |vauthors=Ainsztein AM, Kandels-Lewis SE, Mackay AM, Earnshaw WC |title=INCENP centromere and spindle targeting: identification of essential conserved motifs and involvement of heterochromatin protein HP1. |journal=J. Cell Biol. |volume=143 |issue= 7 |pages= 1763–74 |year= 1999 |pmid= 9864353 |doi=10.1083/jcb.143.7.1763 | pmc=2175214 }} *{{Cite journal |vauthors=Martineau-Thuillier S, Andreassen PR, Margolis RL |title=Colocalization of TD-60 and INCENP throughout G2 and mitosis: evidence for their possible interaction in signalling cytokinesis. |journal=Chromosoma |volume=107 |issue= 6–7 |pages= 461–70 |year= 1999 |pmid= 9914378 |doi=10.1007/s004120050330 |s2cid=24935187 }} *{{Cite journal |vauthors=Dias Neto E, Correa RG, Verjovski-Almeida S, etal |title=Shotgun sequencing of the human transcriptome with ORF expressed sequence tags. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=97 |issue= 7 |pages= 3491–6 |year= 2000 |pmid= 10737800 |doi=10.1073/pnas.97.7.3491 | pmc=16267 |bibcode=2000PNAS...97.3491D |doi-access=free }} *{{Cite journal |vauthors=Wheatley SP, Kandels-Lewis SE, Adams RR, etal |title=INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow. |journal=Exp. Cell Res. |volume=262 |issue= 2 |pages= 122–7 |year= 2001 |pmid= 11139336 |doi= 10.1006/excr.2000.5088 }} *{{Cite journal |vauthors=Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC |title=INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. |journal=Curr. Biol. |volume=11 |issue= 11 |pages= 886–90 |year= 2001 |pmid= 11516652 |doi=10.1016/S0960-9822(01)00238-X |doi-access=free |bibcode=2001CBio...11..886W }} *{{Cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }} *{{Cite journal |vauthors=Parra MT, Viera A, Gómez R, etal |title=Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis. |journal=J. Cell Sci. |volume=116 |issue= Pt 6 |pages= 961–74 |year= 2003 |pmid= 12584241 |doi=10.1242/jcs.00330 |doi-access=free }} *{{Cite journal |vauthors=Rangasamy D, Berven L, Ridgway P, Tremethick DJ |title=Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development. |journal=EMBO J. |volume=22 |issue= 7 |pages= 1599–607 |year= 2003 |pmid= 12660166 |doi= 10.1093/emboj/cdg160 | pmc=152904 }} *{{Cite journal |vauthors=Honda R, Körner R, Nigg EA |title=Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. |journal=Mol. Biol. Cell |volume=14 |issue= 8 |pages= 3325–41 |year= 2004 |pmid= 12925766 |doi= 10.1091/mbc.E02-11-0769 | pmc=181570 }} *{{Cite journal |vauthors=Wheatley SP, Henzing AJ, Dodson H, etal |title=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. |journal=J. Biol. Chem. |volume=279 |issue= 7 |pages= 5655–60 |year= 2004 |pmid= 14610074 |doi= 10.1074/jbc.M311299200 |doi-access= free }} *{{Cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |doi-access= free }} *{{Cite journal |vauthors=Gassmann R, Carvalho A, Henzing AJ, etal |title=Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. |journal=J. Cell Biol. |volume=166 |issue= 2 |pages= 179–91 |year= 2004 |pmid= 15249581 |doi= 10.1083/jcb.200404001 | pmc=2172304 }} *{{Cite journal |vauthors=Li X, Sakashita G, Matsuzaki H, etal |title=Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. |journal=J. Biol. Chem. |volume=279 |issue= 45 |pages= 47201–11 |year= 2004 |pmid= 15316025 |doi= 10.1074/jbc.M403029200 |doi-access= free }} *{{Cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }} *{{Cite journal |vauthors=Zhu C, Bossy-Wetzel E, Jiang W |title=Recruitment of MKLP1 to the spindle midzone/midbody by INCENP is essential for midbody formation and completion of cytokinesis in human cells. |journal=Biochem. J. |volume=389 |issue= Pt 2 |pages= 373–81 |year= 2005 |pmid= 15796717 |doi= 10.1042/BJ20050097 | pmc=1175114 }} *{{Cite journal |vauthors=Chen HL, Tang CJ, Chen CY, Tang TK |title=Overexpression of an Aurora-C kinase-deficient mutant disrupts the Aurora-B/INCENP complex and induces polyploidy. |journal=J. Biomed. Sci. |volume=12 |issue= 2 |pages= 297–310 |year= 2005 |pmid= 15917996 |doi= 10.1007/s11373-005-0980-0 }} *{{Cite journal |vauthors=Vader G, Kauw JJ, Medema RH, Lens SM |title=Survivin mediates targeting of the chromosomal passenger complex to the centromere and midbody. |journal=EMBO Rep. |volume=7 |issue= 1 |pages= 85–92 |year= 2006 |pmid= 16239925 |doi= 10.1038/sj.embor.7400562 | pmc=1369225 }} *{{Cite journal |vauthors=Goto H, Kiyono T, Tomono Y, etal |title=Complex formation of Plk1 and INCENP required for metaphase-anaphase transition. |journal=Nat. Cell Biol. |volume=8 |issue= 2 |pages= 180–7 |year= 2006 |pmid= 16378098 |doi= 10.1038/ncb1350 |s2cid=11583385 }} {{Refend}}

Category:Protein families