Centromere protein F (CENPF)

The protein contains 3210 amino acids for an estimated molecular weight of 367764 Da.

 

Required for kinetochore function and chromosome segregation in mitosis. Required for kinetochore localization of dynein, LIS1, NDE1 and NDEL1. Regulates recycling of the plasma membrane by acting as a link between recycling vesicles and the microtubule network though its association with STX4 and SNAP25. Acts as a potential inhibitor of pocket protein-mediated cellular processes during development by regulating the activity of RB proteins during cell division and proliferation. May play a regulatory or permissive role in the normal embryonic cardiomyocyte cell cycle and in promoting continued mitosis in transformed, abnormally dividing neonatal cardiomyocytes. Interaction with RB directs embryonic stem cells toward a cardiac lineage. Involved in the regulation of DNA synthesis and hence cell cycle progression, via its C-terminus. Has a potential role regulating skeletal myogenesis and in cell differentiation in embryogenesis. Involved in dendritic cell regulation of T-cell immunity against chlamydia. (updated: March 4, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

(right-click above to access to more options from the contextual menu)

VariantDescription
dbSNP:rs1050065
dbSNP:rs1050066
dbSNP:rs17023281
dbSNP:rs2070065
dbSNP:rs3795524
dbSNP:rs3795523
dbSNP:rs3795522
dbSNP:rs3795519
dbSNP:rs3795518
dbSNP:rs12067133
dbSNP:rs3795517
dbSNP:rs2666839
dbSNP:rs3795514
dbSNP:rs3748692
dbSNP:rs3790647
dbSNP:rs7289

The reference OMIM entry for this protein is 600236

Centromeric protein f; cenpf

DESCRIPTION

The CENPF gene encodes a protein that is dynamically expressed throughout the cell cycle and is associated with the kinetochore and mitotic spindles (summary by Waters et al., 2015).

CLONING

Rattner et al. (1993) identified a human kinetochore protein with a molecular weight of approximately 400 kD. Designated centromeric protein F, it was only transiently associated with kinetochores from the onset of mitosis to metaphase. Liao et al. (1995) reported the cDNA sequence of CENPF. The predicted structure of the 367-kD CENPF protein consists of two 1,600-amino acid-long coil domains that flank a central flexible core. Waters et al. (2015) found that CENPF localized to the basal body in ciliated fibroblasts and at the subdistal appendages of the motor centriole in mouse inner medullary collecting duct cells.

GENE STRUCTURE

Waters et al. (2015) stated that the CENPF gene consists of 20 coding exons that encode at least 2 protein-coding transcripts.

MAPPING

Using CENPF cDNA in fluorescence in situ hybridization, Testa et al. (1994) mapped the CENPF gene to chromosome 1q32-q41. By interspecific backcross analysis, Fowler et al. (1998) mapped the mouse Cenpf gene to the distal region of chromosome 1.

GENE FUNCTION

Liao et al. (1995) reported the expression and localization patterns of CENPF at different stages of the HeLa cell cycle. CENPF is a protein of the nuclear matrix that gradually accumulates during the cell cycle until it reaches peak levels in G2- and M-phase cells and is rapidly degraded upon completion of mitosis. CENPF is first detected at the prekinetochore complex during late G2, and by prophase is clearly detectable as paired foci that correspond to all the centromeres. During mitosis, CENPF is associated with kinetochores from prometaphase until early anaphase and then is detected at the spindle midzone throughout the remainder of anaphase. By telophase, CENPF is concentrated within the intracellular bridge at either side of the midbody. Waters et al. (2015) found that CENPF colocalized with IFT88 (600595) and KIF3B (603754) at the centrosome and along ciliary axonemes. The findings indicated that CENPF has a role in ciliogenesis.

MOLECULAR GENETICS

In 4 affected fetuses from a nonconsanguineous Caucasian family with primary ciliary dyskinesia-31 (CILD31; 616369), Waters et al. (2015) identified compound heterozygous mutations in the CENPF gene (600236.0001 and 600236.0002). The mutations were found by whole-exome sequencing. Exome sequencing of the CENPF gene in 1,000 patients with microcephaly further identified 1 patient who was compound heterozygous for 2 truncating mutations (600236.0001 and 600236.0003).

ANIMAL MODEL

Waters et al. (2015) found that morpholino knockdown of cenpf in zebrafish embryos resulted in decreased survival and a ciliopathy phenotype, including axis curvature defects, abnormal heart looping, hydrocephalus, and pronephric cysts. Mutant zebrafish also showed left-right patterning defects and shortened Kupffer vesicle cilia compared to controls. ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600236 was added.