Inner centromere protein

Available protein structures:
PDB	IPR022006 PF12178 (ECOD; PDBsum)
AlphaFold	IPR022006; PF12178;

Chromosome passenger complex (CPC) protein INCENP N terminal
Chromosome passenger complex (CPC) protein INCENP N terminal
Identifiers
Symbol	INCENP_N
Pfam	PF12178
InterPro	IPR022006
PDB
Available protein structures:
PDB	IPR022006 PF12178 (ECOD; PDBsum)
AlphaFold	IPR022006; PF12178;

INCENP
Identifiers
Aliases	INCENP, inner centromere protein
External IDs	OMIM: 604411; MGI: 1313288; GeneCards: INCENP
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2QFA, 4AF3
Gene location (Human)
Chr.	Chromosome 11 (human)
End	62,153,169 bp
Gene location (Mouse)
Chr.	Chromosome 19 (mouse)
End	9,876,915 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; ganglionic eminence; ; sural nerve; ; bone marrow cell; ; 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
	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
Databases	NCBI: entry; OMA: entry
	3619
	16319
	ENSG00000149503
	ENSMUSG00000024660
	Q9NQS7
	Q9WU62
	NM_001040694; NM_020238
	NM_016692; NM_001369356
	NP_001035784; NP_064623
	NP_057901
	Wikidata
View/Edit Human	View/Edit Mouse

Inner centromere protein, ARK binding region

Identifiers

Symbol

INCENP_ARK-bind

Available protein structures:
PDB	IPR005635 PF03941 (ECOD; PDBsum)
AlphaFold	IPR005635 PF03941

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 2 3 GRCh38: Ensembl release 89: ENSG00000149503 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024660 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
1 2 Earnshaw WC, Cooke CA (September 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". Journal of Cell Science. 98 (4): 443–461. doi:10.1242/jcs.98.4.443. PMID 1860899.
↑ Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, et al. (July 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.
1 2 "Entrez Gene: INCENP inner centromere protein antigens 135/155kDa".
↑ Dietz A, Subedi P, Azimzadeh O, Duchrow L, Kaestle F, Paetzold J, et al. (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 11772719241274017. doi:10.1177/11772719241274017. PMC 11528597. PMID 39493730.
↑ Sasai K, Katayama H, Hawke DH, Sen S (2016). "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. PMC 4917241. PMID 27332895.
↑ Li X, Sakashita G, Matsuzaki H, Sugimoto K, Kimura K, Hanaoka F, et al. (November 2004). "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. PMID 15316025.
1 2 Honda R, Körner R, Nigg EA (August 2003). "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. PMC 181570. PMID 12925766.
↑ Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E (October 2007). "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. PMID 17956729. S2CID 15199822.
↑ Choo, K. H. Andy (1997). The centromere. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-857780-5.
↑ Earnshaw WC, Mackay AM (September 1994). "Role of nonhistone proteins in the chromosomal events of mitosis". FASEB Journal. 8 (12): 947–956. doi:10.1096/fasebj.8.12.8088460. PMID 8088460. S2CID 14062246.
↑ Cutts SM, Fowler KJ, Kile BT, Hii LL, O'Dowd RA, Hudson DF, et al. (July 1999). "Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice". Human Molecular Genetics. 8 (7): 1145–1155. doi:10.1093/hmg/8.7.1145. PMID 10369859.
↑ Rangasamy D, Berven L, Ridgway P, Tremethick DJ (April 2003). "Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development". The EMBO Journal. 22 (7): 1599–1607. doi:10.1093/emboj/cdg160. PMC 152904. PMID 12660166.
↑ 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". Current Biology. 11 (11): 886–890. Bibcode:2001CBio...11..886W. doi:10.1016/S0960-9822(01)00238-X. PMID 11516652.
↑ Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, et al. (July 2004). "Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle". The Journal of Cell Biology. 166 (2): 179–191. doi:10.1083/jcb.200404001. PMC 2172304. PMID 15249581.
↑ 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". Molecular Biology of the Cell. 13 (4): 1132–1143. doi:10.1091/mbc.01-07-0330. PMC 102257. PMID 11950927.

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". The Journal of Cell Biology. 143 (7): 1763–1774. 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): 461–470. doi:10.1007/s004120050330. PMID 9914378. S2CID 24935187.
Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, et al. (March 2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3491–3496. Bibcode:2000PNAS...97.3491D. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800.
Wheatley SP, Kandels-Lewis SE, Adams RR, Ainsztein AM, Earnshaw WC (January 2001). "INCENP binds directly to tubulin and requires dynamic microtubules to target to the cleavage furrow". Experimental Cell Research. 262 (2): 122–127. doi:10.1006/excr.2000.5088. PMID 11139336.
Parra MT, Viera A, Gómez R, Page J, Carmena M, Earnshaw WC, et al. (March 2003). "Dynamic relocalization of the chromosomal passenger complex proteins inner centromere protein (INCENP) and aurora-B kinase during male mouse meiosis". Journal of Cell Science. 116 (Pt 6): 961–974. doi:10.1242/jcs.00330. PMID 12584241.
Wheatley SP, Henzing AJ, Dodson H, Khaled W, Earnshaw WC (February 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". The Journal of Biological Chemistry. 279 (7): 5655–5660. doi:10.1074/jbc.M311299200. PMID 14610074.
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". The Biochemical Journal. 389 (Pt 2): 373–381. 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". Journal of Biomedical Science. 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 Reports. 7 (1): 85–92. doi:10.1038/sj.embor.7400562. PMC 1369225. PMID 16239925.
Goto H, Kiyono T, Tomono Y, Kawajiri A, Urano T, Furukawa K, et al. (February 2006). "Complex formation of Plk1 and INCENP required for metaphase-anaphase transition". Nature Cell Biology. 8 (2): 180–187. 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

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000149503 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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.

[Earnshaw_1991-5] 1 2 Earnshaw WC, Cooke CA (September 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". Journal of Cell Science. 98 (4): 443–461. doi:10.1242/jcs.98.4.443. PMID 1860899.

[Adams_2001-6] Adams RR, Eckley DM, Vagnarelli P, Wheatley SP, Gerloff DL, Mackay AM, et al. (July 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.

[entrez-7] 1 2 "Entrez Gene: INCENP inner centromere protein antigens 135/155kDa".

[8] Dietz A, Subedi P, Azimzadeh O, Duchrow L, Kaestle F, Paetzold J, et al. (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 11772719241274017. doi:10.1177/11772719241274017. PMC 11528597. PMID 39493730.

[9] Sasai K, Katayama H, Hawke DH, Sen S (2016). "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. PMC 4917241. PMID 27332895.

[10] Li X, Sakashita G, Matsuzaki H, Sugimoto K, Kimura K, Hanaoka F, et al. (November 2004). "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. PMID 15316025.

[Honda_2003-11] 1 2 Honda R, Körner R, Nigg EA (August 2003). "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. PMC 181570. PMID 12925766.

[12] Jeyaprakash AA, Klein UR, Lindner D, Ebert J, Nigg EA, Conti E (October 2007). "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. PMID 17956729. S2CID 15199822.

[isbn0-19-857780-X-13] Choo, K. H. Andy (1997). The centromere. Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-857780-5.

[Earnshaw_1994-14] Earnshaw WC, Mackay AM (September 1994). "Role of nonhistone proteins in the chromosomal events of mitosis". FASEB Journal. 8 (12): 947–956. doi:10.1096/fasebj.8.12.8088460. PMID 8088460. S2CID 14062246.

[Cutts_1999-15] Cutts SM, Fowler KJ, Kile BT, Hii LL, O'Dowd RA, Hudson DF, et al. (July 1999). "Defective chromosome segregation, microtubule bundling and nuclear bridging in inner centromere protein gene (Incenp)-disrupted mice". Human Molecular Genetics. 8 (7): 1145–1155. doi:10.1093/hmg/8.7.1145. PMID 10369859.

[Rangasamy_2003-16] Rangasamy D, Berven L, Ridgway P, Tremethick DJ (April 2003). "Pericentric heterochromatin becomes enriched with H2A.Z during early mammalian development". The EMBO Journal. 22 (7): 1599–1607. doi:10.1093/emboj/cdg160. PMC 152904. PMID 12660166.

[Wheatley_2001-17] 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". Current Biology. 11 (11): 886–890. Bibcode:2001CBio...11..886W. doi:10.1016/S0960-9822(01)00238-X. PMID 11516652.

[Gassmann_2004-18] Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, et al. (July 2004). "Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle". The Journal of Cell Biology. 166 (2): 179–191. doi:10.1083/jcb.200404001. PMC 2172304. PMID 15249581.

[Leverson_2002-19] 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". Molecular Biology of the Cell. 13 (4): 1132–1143. doi:10.1091/mbc.01-07-0330. PMC 102257. PMID 11950927.

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Inner centromere protein

Interactions

References

Further reading