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

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

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

Identity

HGNC

CENPF

LOCATION

1q41

LOCUSID

1063

ALIAS

CENF,CILD31,PRO1779,STROMS,hcp-1

FUSION GENES

Show Gene Fusions

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.

Proteins

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

Implicated in

Entity name

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 name

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 name

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 name

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.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
11302861	2001	Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies.	Abu-Shakra M et al
10852915	2000	Farnesyl 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
11640891	2001	A multistep model for paclitaxel-induced apoptosis in human breast cancer cell lines.	Blajeski AL et al
16252009	2005	Unstable microtubule capture at kinetochores depleted of the centromere-associated protein CENP-F.	Bomont P et al
17389228	2007	Bub1 is essential for assembly of the functional inner centromere.	Boyarchuk Y et al
9763420	1998	Characterization of the kinetochore binding domain of CENP-E reveals interactions with the kinetochore proteins CENP-F and hBUBR1.	Chan GK et al
11154688	2001	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 et al
9499420	1998	Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres.	Faulkner NE et al
16219694	2005	Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint.	Holt SV et al
17485487	2007	Tripin/hSgo2 recruits MCAK to the inner centromere to correct defective kinetochore attachments.	Huang H et al
9914370	1998	The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis.	Jablonski SA et al
15020684	2004	Bub1 is required for kinetochore localization of BubR1, Cenp-E, Cenp-F and Mad2, and chromosome congression.	Johnson VL et al
15062103	2004	The RanGAP1-RanBP2 complex is essential for microtubule-kinetochore interactions in vivo.	Joseph J et al
8875058	1996	Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies.	Landberg G et al
15654331	2005	FoxM1 is required for execution of the mitotic programme and chromosome stability.	Laoukili J et al
7542657	1995	CENP-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
10745166	2000	Markers of proliferation in normal and leukoplakic oral epithelia.	Liu SC et al
12640463	2003	Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis.	Liu ST et al
8844395	1996	Dynamic continuity of nuclear and mitotic matrix proteins in the cell cycle.	Mancini MA et al
17205517	2007	CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer.	O'Brien SL et al
16230362	2005	Recent advances in understanding the antineoplastic mechanisms of farnesyltransferase inhibitors.	Pan J et al
9336656	1997	High frequency of neoplasia in patients with autoantibodies to centromere protein CENP-F.	Rattner JB et al
10607828	2000	Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins.	Saffery R et al
15339662	2004	Vertebrate shugoshin links sister centromere cohesion and kinetochore microtubule stability in mitosis.	Salic A et al
17431110	2007	Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and human tumors by compromising CENP-E and CENP-F function.	Schafer-Hales K et al
15927522	2005	Correlation of CENP-F gene expression with tumor-proliferating activity in human salivary gland tumors.	Shigeishi H et al
11003657	2000	Nonperiodic activity of the human anaphase-promoting complex-Cdh1 ubiquitin ligase results in continuous DNA synthesis uncoupled from mitosis.	Sorensen CS et al
15133482	2004	Sgt1 is required for human kinetochore assembly.	Steensgaard P et al
16565862	2006	Cenp-F (mitosin) is more than a mitotic marker.	Varis A et al
17600710	2007	Cenp-F links kinetochores to Ndel1/Nde1/Lis1/dynein microtubule motor complexes.	Vergnolle MA et al
15870278	2005	Silencing mitosin induces misaligned chromosomes, premature chromosome decondensation before anaphase onset, and mitotic cell death.	Yang Z et al
15494374	2004	GW182 is critical for the stability of GW bodies expressed during the cell cycle and cell proliferation.	Yang Z et al
16233975	2005	The kinetochore and cancer: what's the connection?	Yuen KW et al
7642639	1995	The C terminus of mitosin is essential for its nuclear localization, centromere/kinetochore targeting, and dimerization.	Zhu X et al
11303627	2001	CENP-F gene amplification and overexpression in head and neck squamous cell carcinomas.	de la Guardia C et al
12937144	2003	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 et al

Other Information

Locus ID:

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

Variants:

dbSNP: 1063
ClinVar: 1063
TCGA: ENSG00000117724
COSMIC: CENPF

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000117724	ENST00000366955	P49454
ENSG00000117724	ENST00000614578	A0A087WTY4

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Signal Transduction	REACTOME	R-HSA-162582
Signaling by Rho GTPases	REACTOME	R-HSA-194315
RHO GTPase Effectors	REACTOME	R-HSA-195258
RHO GTPases Activate Formins	REACTOME	R-HSA-5663220
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle, Mitotic	REACTOME	R-HSA-69278
Mitotic G2-G2/M phases	REACTOME	R-HSA-453274
G2/M Transition	REACTOME	R-HSA-69275
Polo-like kinase mediated events	REACTOME	R-HSA-156711
M Phase	REACTOME	R-HSA-68886
Mitotic Prometaphase	REACTOME	R-HSA-68877
Resolution of Sister Chromatid Cohesion	REACTOME	R-HSA-2500257
Mitotic Metaphase and Anaphase	REACTOME	R-HSA-2555396
Mitotic Anaphase	REACTOME	R-HSA-68882
Separation of Sister Chromatids	REACTOME	R-HSA-2467813

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
37287300	2024	CENPF Upregulation is Associated with Immunosuppressive Status and Poor Clinical Outcomes in Lung Adenocarcinoma Validated by qRT-PCR.	0
37287300	2024	CENPF Upregulation is Associated with Immunosuppressive Status and Poor Clinical Outcomes in Lung Adenocarcinoma Validated by qRT-PCR.	0
36720923	2023	CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis.	0
36899270	2023	Long Non-Coding RNA Small Nucleolar RNA Host Gene 4 Induced by Transcription Factor SP1 Promoted the Progression of Nasopharyngeal Carcinoma Through Modulating microRNA-510-5p/Centromere Protein F Axis.	1
37247093	2023	Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma.	0
37814871	2023	[Heterogeneity analysis of pancreatic cancer and identification of molecular subtypes of tumor cells based on CEACAM5, LGALS1 and CENPF gene expression].	0
38002928	2023	Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome.	0
36720923	2023	CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis.	0
36899270	2023	Long Non-Coding RNA Small Nucleolar RNA Host Gene 4 Induced by Transcription Factor SP1 Promoted the Progression of Nasopharyngeal Carcinoma Through Modulating microRNA-510-5p/Centromere Protein F Axis.	1
37247093	2023	Integrated pan-cancer analysis of centromere protein F and experimental verification of its role and clinical significance in cholangiocarcinoma.	0
37814871	2023	[Heterogeneity analysis of pancreatic cancer and identification of molecular subtypes of tumor cells based on CEACAM5, LGALS1 and CENPF gene expression].	0
38002928	2023	Novel Loss of Function Variants in CENPF Including a Large Intragenic Deletion in Patients with Strømme Syndrome.	0
34857915	2022	Centromere protein F promotes progression of hepatocellular carcinoma through ERK and cell cycle-associated pathways.	8
35123514	2022	CENPF/CDK1 signaling pathway enhances the progression of adrenocortical carcinoma by regulating the G2/M-phase cell cycle.	13
35189004	2022	CENPF as an independent prognostic and metastasis biomarker corresponding to CD4+ memory T cells in cutaneous melanoma.	15

Citation

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))