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

2008-04-01   Hideo Shigeishi , Koichiro Higashikawa , Nobuyuki Kamata 

Department of Oral, Maxillofacial Surgery, Hiroshima University, Kasumi, Hiroshima 734-855, Japan




Atlas Image
A schematic diagram of the CENPF gene. The exon numbers are labeled.


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.


10,294 bp mRNA; 9630 bp open reading frame.


No pseudogene.


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


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).


Breast, eye, gastro-intestinal tract, heart, liver, lymph node, ovary, placenta, skin, stomach, testis.


Nucleus matrix, but not in the nucleolus, reorganization to the kinetochore/centromere (coronal surface of the outer plate) and the spindle during mitosis.


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.



Implicated in

Entity name
Head and neck squamous cell carcinoma
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 name
Breast cancer
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 name
Astrocytic gliomas
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 name
Salivary gland tumor
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.


Pubmed IDLast YearTitleAuthors
113028612001Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.Abu-Shakra M et al
108529152000Farnesyl transferase inhibitors block the farnesylation of CENP-E and CENP-F and alter the association of CENP-E with the microtubules.Ashar HR et al
116408912001A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines.Blajeski AL et al
162520092005Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.Bomont P et al
173892282007Bub1 is essential for assembly of the functional inner centromere.Boyarchuk Y et al
97634201998Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1.Chan GK et al
111546882001The farnesyltransferase inhibitor, FTI-2153, blocks bipolar spindle formation and chromosome alignment and causes prometaphase accumulation during mitosis of human lung cancer cells.Crespo NC et al
94994201998Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres.Faulkner NE et al
162196942005Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint.Holt SV et al
174854872007Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments.Huang H et al
99143701998The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.Jablonski SA et al
150206842004Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression.Johnson VL et al
150621032004The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo.Joseph J et al
88750581996Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies.Landberg G et al
156543312005FoxM1 is required for execution of the mitotic programme and chromosome stability.Laoukili J et al
75426571995CENP-F is a protein of the nuclear matrix that assembles onto kinetochores at late G2 and is rapidly degraded after mitosis.Liao H et al
107451662000Markers of proliferation in normal and leukoplakic oral epithelia.Liu SC et al
126404632003Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis.Liu ST et al
88443951996Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle.Mancini MA et al
172055172007CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer.O'Brien SL et al
162303622005Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors.Pan J et al
93366561997High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F.Rattner JB et al
106078282000Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins.Saffery R et al
153396622004Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.Salic A et al
174311102007Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function.Schafer-Hales K et al
159275222005Correlation of CENP-F gene expression with tumor-proliferating activity in human salivary gland tumors.Shigeishi H et al
110036572000Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.Sorensen CS et al
151334822004Sgt1 is required for human kinetochore assembly.Steensgaard P et al
165658622006Cenp-F (mitosin) is more than a mitotic marker.Varis A et al
176007102007Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.Vergnolle MA et al
158702782005Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death.Yang Z et al
154943742004GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation.Yang Z et al
162339752005The kinetochore and cancer: what's the connection?Yuen KW et al
76426391995The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization.Zhu X et al
113036272001CENP-F gene amplification and overexpression in head and neck squamous cell carcinomas.de la Guardia C et al
129371442003Characterization 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 et al

Other Information

Locus ID:

NCBI: 1063
MIM: 600236
HGNC: 1857
Ensembl: ENSG00000117724


dbSNP: 1063
ClinVar: 1063
TCGA: ENSG00000117724


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Signal TransductionREACTOMER-HSA-162582
Signaling by Rho GTPasesREACTOMER-HSA-194315
RHO GTPase EffectorsREACTOMER-HSA-195258
RHO GTPases Activate ForminsREACTOMER-HSA-5663220
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G2-G2/M phasesREACTOMER-HSA-453274
G2/M TransitionREACTOMER-HSA-69275
Polo-like kinase mediated eventsREACTOMER-HSA-156711
Mitotic PrometaphaseREACTOMER-HSA-68877
Resolution of Sister Chromatid CohesionREACTOMER-HSA-2500257
Mitotic Metaphase and AnaphaseREACTOMER-HSA-2555396
Mitotic AnaphaseREACTOMER-HSA-68882
Separation of Sister ChromatidsREACTOMER-HSA-2467813

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
248236402014Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.126
176007102007Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.81
162196942005Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint.50
162520092005Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.48
158702782005Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death.47
121540712002Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis.46
166019782006CENP-F is a novel microtubule-binding protein that is essential for kinetochore attachments and affects the duration of the mitotic checkpoint delay.43
206601912010Bub1 and CENP-F can contribute to Kaposi's sarcoma-associated herpesvirus genome persistence by targeting LANA to kinetochores.40
172055172007CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer.37
203982472010Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma.30


Hideo Shigeishi ; Koichiro Higashikawa ; Nobuyuki Kamata

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

Atlas Genet Cytogenet Oncol Haematol. 2008-04-01

Online version: http://atlasgeneticsoncology.org/gene/40057/cenpf-(centromere-protein-f-350-400ka-(mitosin))