CENPF (centromere protein F, 350/400ka (mitosin))

Identity

Other names	AH antigen
	CENF
	hcp-1
	Mitosin
	PRO1779
HGNC	CENPF
Location	1q41
Local_order	Chromosome 1, 61,381 bases, 5'- 212,843,155 - 212,904,535 -3': strand (+)

DNA/RNA

	A schematic diagram of the CENPF gene. The exon numbers are labeled.
Description	The CENPF gene structure consists of twenty exons, ranging from 92 to 3,404 bp, and nineteen introns, ranging from approximately 1 to approximately 10 kb.
Transcription	10,294 bp mRNA; 9630 bp open reading frame.
Pseudogene	No pseudogene.

Protein

	A schematics representing the domain structure of full length CENPF. NLS, nuclear localization signal.

Description	The gene encodes a protein associated with the centromere-kinetochore complex, 3210 amino acids (aa), 367594 Da, containing internal repeats, coiled-coil (potential) and NLS (potential).
Expression	Breast, eye, gastro-intestinal tract, heart, liver, lymph node, ovary, placenta, skin, stomach, testis.
Localisation	Nucleus matrix, but not in the nucleolus, reorganization to the kinetochore/centromere (coronal surface of the outer plate) and the spindle during mitosis.
Function	CenpF is recruited to kinetochore early in mitosis after recruitment of Bub1 and modulates kinetochore association of certain mitotic proteins including BubR1 for kinetochore assembly. CenpF that has a CAAX motif in their C-terminal is target for farnesylation. This modification changes is necessary for CenpF function at the G2/M transition. CenpE and CenpF have a significant role in the antitumor activity of farnesyl transferase inhibitors due to their importance in normal cell division.
Homology	no

Implicated in

Entity	Head and neck squamous cell carcinoma
Disease	CENPF gene amplification and overexpression were observed in head and neck squamous cell carcinoma (HNSCC). Up-regulation of CenpF, especially by gene amplification, suggests the possibility that increased CenpF protein levels could influence tumorigenesis particularly at early stages of tumor development. In addition, over-expression of CenpF is significantly correlated with poor prognosis of HNSCC. CenpF expression is able to use clinically as a proliferation marker in oral epithelia.
Entity	Breast cancer
Disease	Over-expression of CENPF mRNA was associated with larger tumor size as well as estrogen receptor (ER) - negative, high grade tumors. CENPF mRNA expression correlated significantly with worse overall survival and a decreased probability of remaining metastasis-free. CenpF expression was also correlated with telomerase activity, cyclin E over-expression, c-Myc amplification and nuclear expression of surviving, indicating that CenpF is a good biomarker for proliferation of breast cancer. ver-expressing In addition, a significant proportion of brest cancer cells over-expressing CENPF were aneuploid, supporting evidence for the relation between CenpF expression and chromosomal instability.
Entity	Astrocytic gliomas
Disease	In microarray and real-time RT-PCR analyses, CENPF mRNA levels significantly increased in primary astrocytic gliomas. Interestingly, secondary glioblastomas demonstrated higher CENPF mRNA levels than primary glioblastomas. However, amplification of the gene was not found.
Entity	Salivary gland tumor
Disease	CenpF expression was significantly correlated with Ki-67 labeling index in primary malignant salivary gland tumor by immunohistochemical study. In addition, CENPF mRNA level was associated with clinical stage. The data suggests that CenpF expression is a candidate for biomarker of proliferation of salivary tumor.

External links

	Nomenclature
HGNC	CENPF   1857
Entrez_Gene	CENPF  1063  centromere protein F, 350/400ka (mitosin)
	Cards
Atlas	CENPFID40057ch1q41
GeneCards	CENPF
Ensembl	CENPF [Search_View]   ENSG00000117724 [Gene_View]
Genatlas	CENPF
GeneLynx	CENPF
eGenome	CENPF
euGene	1063
	Genomic and cartography
GoldenPath	CENPF  -  1q41   chr1:212843155-212904537 +  1q32-q41   [Description]    (hg18-Mar_2006)
Ensembl	CENPF - 1q32-q41 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	CENPF
	Gene and transcription
Genbank	AK307690 [ ENTREZ ]
Genbank	BG680819 [ ENTREZ ]
Genbank	BQ774943 [ ENTREZ ]
Genbank	BU155312 [ ENTREZ ]
Genbank	BU662228 [ ENTREZ ]
RefSeq	NM_016343 [ SRS ]    NM_016343 [ ENTREZ ]
RefSeq	AC_000044 [ SRS ]    AC_000044 [ ENTREZ ]
RefSeq	AC_000133 [ SRS ]    AC_000133 [ ENTREZ ]
RefSeq	NC_000001 [ SRS ]    NC_000001 [ ENTREZ ]
RefSeq	NT_021877 [ SRS ]    NT_021877 [ ENTREZ ]
RefSeq	NW_001838537 [ SRS ]    NW_001838537 [ ENTREZ ]
RefSeq	NW_926794 [ SRS ]    NW_926794 [ ENTREZ ]
AceView	CENPF AceView - NCBI
Unigene	Hs.497741 [ SRS ]    Hs.497741 [ NCBI ]     HS497741 [ spliceNest ]
Fast-db	17830 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P49454 [ SRS]    P49454 [ EXPASY ]     P49454 [ INTERPRO ]     P49454 [ UNIPROT ]
CluSTr	P49454
Blocks	P49454
HPRD	02582
	Protein Interaction databases
DIP	P49454
IntAct	P49454
	Polymorphism : SNP, mutations, diseases
OMIM	600236    [ map ]
GENECLINICS	600236
SNP	CENPF [dbSNP-NCBI]
SNP	NM_016343 [SNP-NCI]
SNP	CENPF [GeneSNPs - Utah]  CENPF] [HGBASE - SRS]
HAPMAP	CENPF [HAPMAP]
HGMD	CENPF
	General knowledge
Family Browser	CENPF [UCSC Family Browser]
SOURCE	NM_016343
SMD	Hs.497741
SAGE	Hs.497741
GO	G2 phase of mitotic cell cycle [Amigo]  G2 phase of mitotic cell cycle
GO	kinetochore [Amigo]  kinetochore
GO	chromatin [Amigo]  chromatin
GO	spindle pole [Amigo]  spindle pole
GO	outer kinetochore of condensed chromosome [Amigo]  outer kinetochore of condensed chromosome
GO	outer kinetochore of condensed chromosome [Amigo]  outer kinetochore of condensed chromosome
GO	chromatin binding [Amigo]  chromatin binding
GO	nucleus [Amigo]  nucleus
GO	nuclear envelope [Amigo]  nuclear envelope
GO	chromosome [Amigo]  chromosome
GO	cytoplasm [Amigo]  cytoplasm
GO	mitosis [Amigo]  mitosis
GO	mitotic cell cycle spindle assembly checkpoint [Amigo]  mitotic cell cycle spindle assembly checkpoint
GO	protein C-terminus binding [Amigo]  protein C-terminus binding
GO	transcription factor binding [Amigo]  transcription factor binding
GO	cell proliferation [Amigo]  cell proliferation
GO	regulation of striated muscle development [Amigo]  regulation of striated muscle development
GO	nuclear matrix [Amigo]  nuclear matrix
GO	negative regulation of transcription [Amigo]  negative regulation of transcription
GO	response to drug [Amigo]  response to drug
GO	protein homodimerization activity [Amigo]  protein homodimerization activity
GO	dynein binding [Amigo]  dynein binding
GO	protein heterodimerization activity [Amigo]  protein heterodimerization activity
GO	cell division [Amigo]  cell division
GO	metaphase plate congression [Amigo]  metaphase plate congression
GO	kinetochore assembly [Amigo]  kinetochore assembly
PubGene	CENPF
TreeFam	CENPF
CTD	1063 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	CENPF Related clones (RZPD - Berlin)
	PubMed
PubMed	31 Pubmed reference(s) in LocusLink

Bibliography

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PMID 7904902

CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis.

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PMID 7542657

The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization.

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PMID 7642639

Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies.

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PMID 8875058

Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle.

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J Cell Biochem 1996; 62: 158-164. (REVIEW)

PMID 8844395

High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F.

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PMID 9336656

Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1.

Chan GK, Schaar BT, Yen TJ.

J Cell Biol 1998; 143: 49-63.

PMID 9763420

Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres.

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PMID 9499420

The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.

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Chromosoma 1998; 107: 386-396.

PMID 9914370

Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.

Ashar HR, James L, Gray K, Carr D, Black S, Armstrong L, Bishop WR, Kirschmeier P.

J Biol Chem 2000; 275: 30451-30457.

PMID 10852915

Markers of proliferation in normal and leukoplakic oral epithelia.

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Oral Oncol 2000; 36: 145-151. (REVIEW)

PMID 10745166

Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins.

Saffery R, Irvine DV, Griffiths B, Kalitsis P, Wordeman L, Choo KH.

Hum Mol Genet 2000; 9: 175-185.

PMID 10607828

Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.

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Mol Cell Biol 2000; 20: 7613-7623.

PMID 11003657

Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.

Abu-Shakra M, Buskila D, Ehrenfeld M, Conrad K, Shoenfeld Y.

Ann Rheum Dis 2001; 60: 433-441. (REVIEW)

PMID 11302861

CENP-F gene amplification and overexpression in head and neck squamous cell carcinomas.

de la Guardia C, Casiano CA, Trinidad-Pinedo J, Báez A.

Head Neck 2001; 23: 104-112.

PMID 11303627

A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines.

Blajeski AL, Kottke TJ, Kaufmann SH.

Exp Cell Res 2001; 270: 277-288.

PMID 11640891

The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells.

Crespo NC, Ohkanda J, Yen TJ, Hamilton AD, Sebti SM.

J Biol Chem 2001; 276: 16161-16167

PMID 11154688

Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis.

Liu ST, Hittle JC, Jablonski SA, Campbell MS, Yoda K, Yen TJ.

Nat Cell Biol 2003; 5: 341-345.

PMID 12640463

Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.

van den Boom J, Wolter M, Kuick R, Misek DE, Youkilis AS, Wechsler DS, Sommer C, Reifenberger G, Hanash SM.

Am J Pathol 2003; 163: 1033-1043.

PMID 12937144

Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression.

Johnson VL, Scott MI, Holt SV, Hussein D, Taylor SS.

J Cell Sci 2004; 117: 1577-1589.

PMID 15020684

The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo.

Joseph J, Liu ST, Jablonski SA, Yen TJ, Dasso M.

Curr Biol 2004; 14: 611-617.

PMID 15062103

Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.

Salic A, Waters JC, Mitchison TJ.

Cell 2004; 118: 567­578.

PMID 15339662

Sgt1 is required for human kinetochore assembly.

Steensgaard P, Garrč M, Muradore I, Transidico P, Nigg EA, Kitagawa K, Earnshaw WC, Faretta M, Musacchio A.

EMBO Rep 2004; 5: 626-631.

PMID 15133482

GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation.

Yang Z, Jakymiw A, Wood MR, Eystathioy T, Rubin RL, Fritzler MJ, Chan EK.

J Cell Sci 2004; 117: 5567-5578.

PMID 15494374

Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.

Bomont P, Maddox P, Shah JV, Desai AB, Cleveland DW.

EMBO J 2005; 24: 3927-3939.

PMID 16252009

Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint.

Holt SV, Vergnolle MA, Hussein D, Wozniak MJ, Allan VJ, Taylor SS.

J Cell Sci 2005; 118:4889-4900.

PMID 16219694

FoxM1 is required for execution of the mitotic programme and chromosome stability.

Laoukili J, Kooistra MR, Brįs A, Kauw J, Kerkhoven RM, Morrison A, Clevers H, Medema RH.

Nat Cell Biol 2005; 7: 126-136.

PMID 15654331

Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors.

Pan J, Yeung SC.

Cancer Res 2005; 65: 9109-9112. (REVIEW)

Correlation of CENP-F gene expression with tumor-proliferating activity in human salivary gland tumors.

Shigeishi H, Mizuta K, Higashikawa K, Yoneda S, Ono S, Kamata N.

Oral Oncol 2005;41: 716-722.

PMID 15927522

Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death.

Yang Z, Guo J, Chen Q, Ding C, Du J, Zhu X.

Mol Cell Biol 2005; 25: 4062-4074.

PMID 15870278

The kinetochore and cancer: what's the connection?

Yuen KW, Montpetit B, Hieter P.

Curr Opin Cell Biol 2005; 17: 576-82. (REVIEW)

PMID 16233975

Cenp-F (mitosin) is more than a mitotic marker.

Varis A, Salmela AL, Kallio MJ.

Chromosoma 2006; 115:288-295. (REVIEW)

Bub1 is essential for assembly of the functional inner centromere.

Boyarchuk Y, Salic A, Dasso M, Arnaoutov A.

J Cell Biol 2007; 176: 919-928.

PMID 17389228

Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments.

Huang H, Feng J, Famulski J, Rattner JB, Liu ST, Kao GD, Muschel R, Chan GK, Yen TJ.

J Cell Biol 2007; 177: 413-424.

PMID 17485487

CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer.

O'Brien SL, Fagan A, Fox EJ, Millikan RC, Culhane AC, Brennan DJ, McCann AH, Hegarty S, Moyna S, Duffy MJ, Higgins DG, Jirström K, Landberg G, Gallagher WM.

Int J Cancer 2007; 120: 1434-1443.

PMID 17205517

Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function.

Schafer-Hales K, Iaconelli J, Snyder JP, Prussia A, Nettles JH, El-Naggar A, Khuri FR, Giannakakou P, Marcus AI.

Mol Cancer Ther 2007; 6: 1317-1328.

PMID 17431110

Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.

Vergnolle MA, Taylor SS.

Curr Biol 2007; 17: 1173-1179.

PMID 17600710

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Contributor(s)

Written	04-2008	Hideo Shigeishi, Koichiro Higashikawa, Nobuyuki Kamata
		Department of Oral and Maxillofacial Surgery, Hiroshima University, Kasumi, Hiroshima 734-855, Japan

Citation

This paper should be referenced as such :

Shigeishi H, Higashikawa K, Kamata N . CENPF (centromere protein F, 350/400ka (mitosin)). Atlas Genet Cytogenet Oncol Haematol. April 2008 . URL : http://AtlasGeneticsOncology.org/Genes/CENPFID40057ch1q41.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:12:57 2008