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

Written2008-04Hideo Shigeishi, Koichiro Higashikawa, Nobuyuki Kamata
Department of Oral, Maxillofacial Surgery, Hiroshima University, Kasumi, Hiroshima 734-855, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_namescentromere protein F, 350/400kDa (mitosin)
centromere protein F, 350/400kDa
Alias_symbol (synonym)hcp-1
Other aliasAH antigen
CENF
Mitosin
PRO1779
HGNC (Hugo) CENPF
LocusID (NCBI) 1063
Atlas_Id 40057
Location 1q41  [Link to chromosome band 1q41]
Location_base_pair Starts at 214603189 and ends at 214664571 bp from pter ( according to hg19-Feb_2009)  [Mapping CENPF.png]
Local_order Chromosome 1, 61,381 bases, 5'- 212,843,155 - 212,904,535 -3': strand (+)
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CENPF (1q41) / CENPF (1q41)CENPF (1q41) / HS2ST1 (1p22.3)CENPF (1q41) / SUSD4 (1q41)
GALT (9p13.3) / CENPF (1q41)PDE3A (12p12.2) / CENPF (1q41)PPP1CC (12q24.11) / CENPF (1q41)
RPL23 (17q12) / CENPF (1q41)

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

Note
  
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.
  

Bibliography

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PMID 11302861
 
Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.
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A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines.
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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
 
Bub1 is essential for assembly of the functional inner centromere.
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PMID 17389228
 
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
 
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
 
Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres.
Faulkner NE, Vig B, Echeverri CJ, Wordeman L, Vallee RB.
Hum Mol Genet 1998; 7: 671-677.
PMID 9499420
 
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
 
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
 
The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.
Jablonski SA, Chan GK, Cooke CA, Earnshaw WC, Yen TJ.
Chromosoma 1998; 107: 386-396.
PMID 9914370
 
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
 
Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies.
Landberg G, Erlanson M, Roos G, Tan EM, Casiano CA.
Cytometry 1996; 25: 90-98.
PMID 8875058
 
FoxM1 is required for execution of the mitotic programme and chromosome stability.
Laoukili J, Kooistra MR, Brás A, Kauw J, Kerkhoven RM, Morrison A, Clevers H, Medema RH.
Nat Cell Biol 2005; 7: 126-136.
PMID 15654331
 
CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis.
Liao H, Winkfein RJ, Mack G, Rattner JB, Yen TJ.
J Cell Biol 1995; 130: 507-518.
PMID 7542657
 
Markers of proliferation in normal and leukoplakic oral epithelia.
Liu SC, Klein-Szanto AJ.
Oral Oncol 2000; 36: 145-151. (REVIEW)
PMID 10745166
 
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
 
Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle.
Mancini MA, He D, Ouspenski II, Brinkley BR.
J Cell Biochem 1996; 62: 158-164. (REVIEW)
PMID 8844395
 
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
 
Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors.
Pan J, Yeung SC.
Cancer Res 2005; 65: 9109-9112. (REVIEW)
PMID 16230362
 
High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F.
Rattner JB, Rees J, Whitehead CM, Casiano CA, Tan EM, Humbel RL, Conrad K, Fritzler MJ.
Clin Invest Med 1997; 20: 308-319.
PMID 9336656
 
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
 
Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.
Salic A, Waters JC, Mitchison TJ.
Cell 2004; 118: 567 578.
PMID 15339662
 
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
 
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
 
Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.
Sorensen CS, Lukas C, Kramer ER, Peters JM, Bartek J, Lukas J.
Mol Cell Biol 2000; 20: 7613-7623.
PMID 11003657
 
Sgt1 is required for human kinetochore assembly.
Steensgaard P, Garr M, Muradore I, Transidico P, Nigg EA, Kitagawa K, Earnshaw WC, Faretta M, Musacchio A.
EMBO Rep 2004; 5: 626-631.
PMID 15133482
 
Cenp-F (mitosin) is more than a mitotic marker.
Varis A, Salmela AL, Kallio MJ.
Chromosoma 2006; 115:288-295. (REVIEW)
PMID 16565862
 
Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.
Vergnolle MA, Taylor SS.
Curr Biol 2007; 17: 1173-1179.
PMID 17600710
 
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
 
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
 
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
 
The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization.
Zhu X, Chang KH, He D, Mancini MA, Brinkley WR, Lee WH.
J Biol Chem 1995; 270: 19545-19550.
PMID 7642639
 
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
 
Characterization of gene expression profiles associated with glioma progression using oligonucleotide-based microarray analysis and real-time reverse transcription-polymerase chain reaction.
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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. 2009;13(2):106-109.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CENPFID40057ch1q41.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(5;16)(q32;p13) NDE1/PDGFRB


External links

Nomenclature
HGNC (Hugo)CENPF   1857
Cards
AtlasCENPFID40057ch1q41
Entrez_Gene (NCBI)CENPF  1063  centromere protein F
AliasesCENF; CILD31; PRO1779; STROMS; 
hcp-1
GeneCards (Weizmann)CENPF
Ensembl hg19 (Hinxton)ENSG00000117724 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000117724 [Gene_View]  chr1:214603189-214664571 [Contig_View]  CENPF [Vega]
ICGC DataPortalENSG00000117724
TCGA cBioPortalCENPF
AceView (NCBI)CENPF
Genatlas (Paris)CENPF
WikiGenes1063
SOURCE (Princeton)CENPF
Genetics Home Reference (NIH)CENPF
Genomic and cartography
GoldenPath hg38 (UCSC)CENPF  -     chr1:214603189-214664571 +  1q41   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CENPF  -     1q41   [Description]    (hg19-Feb_2009)
EnsemblCENPF - 1q41 [CytoView hg19]  CENPF - 1q41 [CytoView hg38]
Mapping of homologs : NCBICENPF [Mapview hg19]  CENPF [Mapview hg38]
OMIM243605   600236   616369   
Gene and transcription
Genbank (Entrez)AK307690 BC172232 BG680819 BQ774943 BU155312
RefSeq transcript (Entrez)NM_016343
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CENPF
Cluster EST : UnigeneHs.497741 [ NCBI ]
CGAP (NCI)Hs.497741
Alternative Splicing GalleryENSG00000117724
Gene ExpressionCENPF [ NCBI-GEO ]   CENPF [ EBI - ARRAY_EXPRESS ]   CENPF [ SEEK ]   CENPF [ MEM ]
Gene Expression Viewer (FireBrowse)CENPF [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1063
GTEX Portal (Tissue expression)CENPF
Human Protein AtlasENSG00000117724-CENPF [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP49454   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP49454  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP49454
Splice isoforms : SwissVarP49454
PhosPhoSitePlusP49454
Domains : Interpro (EBI)CenpF/LEK1_Rb-prot-bd    Centromere_CenpF_leu-rich_rpt    Centromere_CenpF_N   
Domain families : Pfam (Sanger)CENP-F_C_Rb_bdg (PF10490)    CENP-F_leu_zip (PF10473)    CENP-F_N (PF10481)   
Domain families : Pfam (NCBI)pfam10490    pfam10473    pfam10481   
Conserved Domain (NCBI)CENPF
DMDM Disease mutations1063
Blocks (Seattle)CENPF
SuperfamilyP49454
Human Protein Atlas [tissue]ENSG00000117724-CENPF [tissue]
Peptide AtlasP49454
HPRD02582
IPIIPI00855998   IPI00384044   
Protein Interaction databases
DIP (DOE-UCLA)P49454
IntAct (EBI)P49454
FunCoupENSG00000117724
BioGRIDCENPF
STRING (EMBL)CENPF
ZODIACCENPF
Ontologies - Pathways
QuickGOP49454
Ontology : AmiGOmitotic cell cycle  chromosome, centromeric region  kinetochore  chromatin  spindle pole  condensed chromosome outer kinetochore  condensed chromosome outer kinetochore  kidney development  chromatin binding  protein binding  nucleus  nuclear envelope  nucleoplasm  cytoplasm  centrosome  spindle  cytosol  axoneme  chromosome segregation  chromosome segregation  sister chromatid cohesion  mitotic spindle assembly checkpoint  muscle organ development  protein C-terminus binding  transcription factor binding  cell proliferation  regulation of G2/M transition of mitotic cell cycle  protein transport  protein transport  regulation of striated muscle tissue development  nuclear matrix  ventricular system development  cell differentiation  midbody  ciliary basal body  response to drug  protein homodimerization activity  pronucleus  negative regulation of transcription, DNA-templated  perinuclear region of cytoplasm  cell division  metaphase plate congression  kinetochore assembly  regulation of cell cycle  dynein complex binding  DNA biosynthetic process  ciliary transition fiber  
Ontology : EGO-EBImitotic cell cycle  chromosome, centromeric region  kinetochore  chromatin  spindle pole  condensed chromosome outer kinetochore  condensed chromosome outer kinetochore  kidney development  chromatin binding  protein binding  nucleus  nuclear envelope  nucleoplasm  cytoplasm  centrosome  spindle  cytosol  axoneme  chromosome segregation  chromosome segregation  sister chromatid cohesion  mitotic spindle assembly checkpoint  muscle organ development  protein C-terminus binding  transcription factor binding  cell proliferation  regulation of G2/M transition of mitotic cell cycle  protein transport  protein transport  regulation of striated muscle tissue development  nuclear matrix  ventricular system development  cell differentiation  midbody  ciliary basal body  response to drug  protein homodimerization activity8/A>&lbcp; pronucleus  negative regulation of transcription, DNA-templated  perinuclear region of cytoplasm  cell division  metaphase plate congression  kinetochore assembly  regulation of cell cycle  dynein complex binding  DNA biosynthetic process  ciliary transition fiber  
REACTOMEP49454 [protein]
REACTOME PathwaysR-HSA-68877 [pathway]   
NDEx NetworkCENPF
Atlas of Cancer Signalling NetworkCENPF
Wikipedia pathwaysCENPF
Orthology - Evolution
OrthoDB1063
GeneTree (enSembl)ENSG00000117724
Phylogenetic Trees/Animal Genes : TreeFamCENPF
HOVERGENP49454
HOGENOMP49454
Homologs : HomoloGeneCENPF
Homology/Alignments : Family Browser (UCSC)CENPF
Gene fusions - Rearrangements
Fusion: TCGACENPF 1q41 SUSD4 1q41 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCENPF [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CENPF
dbVarCENPF
ClinVarCENPF
1000_GenomesCENPF 
Exome Variant ServerCENPF
ExAC (Exome Aggregation Consortium)ENSG00000117724
GNOMAD BrowserENSG00000117724
Genetic variants : HAPMAP1063
Genomic Variants (DGV)CENPF [DGVbeta]
DECIPHERCENPF [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCENPF 
Mutations
ICGC Data PortalCENPF 
TCGA Data PortalCENPF 
Broad Tumor PortalCENPF
OASIS PortalCENPF [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCENPF  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCENPF
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CENPF
DgiDB (Drug Gene Interaction Database)CENPF
DoCM (Curated mutations)CENPF (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CENPF (select a term)
intoGenCENPF
NCG5 (London)CENPF
Cancer3DCENPF(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM243605    600236    616369   
Orphanet23477   
MedgenCENPF
Genetic Testing Registry CENPF
NextProtP49454 [Medical]
TSGene1063
GENETestsCENPF
Target ValidationCENPF
Huge Navigator CENPF [HugePedia]
snp3D : Map Gene to Disease1063
BioCentury BCIQCENPF
ClinGenCENPF
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1063
Chemical/Pharm GKB GenePA26401
Clinical trialCENPF
Miscellaneous
canSAR (ICR)CENPF (select the gene name)
Probes
Litterature
PubMed74 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCENPF
EVEXCENPF
GoPubMedCENPF
iHOPCENPF
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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