Human Gene CENPF (uc001hkm.3) Description and Page Index
  Description: Homo sapiens centromere protein F, 350/400kDa (CENPF), mRNA.
RefSeq Summary (NM_016343): This gene encodes a protein that associates with the centromere-kinetochore complex. The protein is a component of the nuclear matrix during the G2 phase of interphase. In late G2 the protein associates with the kinetochore and maintains this association through early anaphase. It localizes to the spindle midzone and the intracellular bridge in late anaphase and telophase, respectively, and is thought to be subsequently degraded. The localization of this protein suggests that it may play a role in chromosome segregation during mitotis. It is thought to form either a homodimer or heterodimer. Autoantibodies against this protein have been found in patients with cancer or graft versus host disease. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: U30872.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000366955.8/ ENSP00000355922.3 RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr1:214,776,532-214,837,914 Size: 61,383 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg19 chr1:214,787,098-214,837,137 Size: 50,040 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:214,776,532-214,837,914)mRNA (may differ from genome)Protein (3114 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: CENPF_HUMAN
DESCRIPTION: RecName: Full=Centromere protein F; Short=CENP-F; AltName: Full=AH antigen; AltName: Full=Kinetochore protein CENPF; AltName: Full=Mitosin; Flags: Precursor;
FUNCTION: 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.
SUBUNIT: Interacts with and STX4 (via C-terminus) (By similarity). Interacts (via N-terminus) with RBL1, RBL2 and SNAP25 (By similarity). Self-associates. Interacts with CENP-E and BUBR1 (via C-terminus). Interacts (via C-terminus) with NDE1, NDEL1 and RB1.
INTERACTION: Q9GZM8:NDEL1; NbExp=5; IntAct=EBI-968343, EBI-928842;
SUBCELLULAR LOCATION: Cytoplasm, perinuclear region. Nucleus matrix. Chromosome, centromere, kinetochore. Cytoplasm, cytoskeleton, spindle. Note=Relocalizes to the kinetochore/centromere (coronal surface of the outer plate) and the spindle during mitosis. Observed in nucleus during interphase but not in the nucleolus. At metaphase becomes localized to areas including kinetochore and mitotic apparatus as well as cytoplasm. By telophase, is concentrated within the intracellular bridge at either side of the mid-body.
DEVELOPMENTAL STAGE: Gradually accumulates during the cell cycle, reaching peak levels in G2 and M phase, and is rapidly degraded upon completion of mitosis.
PTM: Hyperphosphorylated during mitosis. Phosphorylated upon DNA damage, probably by ATM or ATR.
SIMILARITY: Belongs to the centromere protein F family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/CENPFID40057ch1q41.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): CENPF
CDC HuGE Published Literature: CENPF
Positive Disease Associations: Leukemia, Lymphocytic, Chronic, B-Cell , Lipoproteins, VLDL , Stroke
Related Studies:
  1. Leukemia, Lymphocytic, Chronic, B-Cell
    Rachel Wade et al. Haematologica 2011, Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial., Haematologica. [PubMed 21659360]
    Our findings provide evidence that genetic variation is a determinant of progression-free survival of patients with chronic lymphocytic leukemia. Specific associations warrant further analyses.
  2. Lipoproteins, VLDL
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
  3. Lipoproteins, VLDL
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: CENPF
Diseases sorted by gene-association score: stromme syndrome* (926), moved to 243605* (750), intestinal atresia (17), ciliopathy (10), microcephaly (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 13.73 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 35.97 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -51.50174-0.296 Picture PostScript Text
3' UTR -199.54777-0.257 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR019513 - Centromere_CenpF_leu-rich_rpt
IPR018463 - Centromere_CenpF_N
IPR018302 - Centromere_CenpF_Rb-prot-bd

Pfam Domains:
PF10473 - Leucine-rich repeats of kinetochore protein Cenp-F/LEK1
PF10481 - Cenp-F N-terminal domain
PF10490 - Rb-binding domain of kinetochore protein Cenp-F/LEK1

ModBase Predicted Comparative 3D Structure on P49454
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003682 chromatin binding
GO:0005515 protein binding
GO:0008022 protein C-terminus binding
GO:0008134 transcription factor binding
GO:0042803 protein homodimerization activity
GO:0070840 dynein complex binding

Biological Process:
GO:0000278 mitotic cell cycle
GO:0001822 kidney development
GO:0007049 cell cycle
GO:0007059 chromosome segregation
GO:0007094 mitotic spindle assembly checkpoint
GO:0007275 multicellular organism development
GO:0007517 muscle organ development
GO:0008283 cell proliferation
GO:0010389 regulation of G2/M transition of mitotic cell cycle
GO:0015031 protein transport
GO:0016202 regulation of striated muscle tissue development
GO:0021591 ventricular system development
GO:0030154 cell differentiation
GO:0042493 response to drug
GO:0045892 negative regulation of transcription, DNA-templated
GO:0051301 cell division
GO:0051310 metaphase plate congression
GO:0051382 kinetochore assembly
GO:0051726 regulation of cell cycle
GO:0071897 DNA biosynthetic process

Cellular Component:
GO:0000775 chromosome, centromeric region
GO:0000776 kinetochore
GO:0000777 condensed chromosome kinetochore
GO:0000922 spindle pole
GO:0000940 condensed chromosome outer kinetochore
GO:0005634 nucleus
GO:0005635 nuclear envelope
GO:0005654 nucleoplasm
GO:0005694 chromosome
GO:0005737 cytoplasm
GO:0005813 centrosome
GO:0005819 spindle
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005930 axoneme
GO:0016363 nuclear matrix
GO:0030496 midbody
GO:0036064 ciliary basal body
GO:0045120 pronucleus
GO:0048471 perinuclear region of cytoplasm
GO:0097539 ciliary transition fiber
GO:0000785 chromatin


-  Descriptions from all associated GenBank mRNAs
  U19769 - Human CENP-F kinetochore protein mRNA, complete cds.
U30872 - Human mitosin mRNA, complete cds.
BC172232 - Synthetic construct Homo sapiens clone IMAGE:9036759; MGC:198937 centromere protein F, 350/400ka (mitosin) (CENPF) gene, encodes complete protein.
U25725 - Human AH antigen mRNA, partial cds.
AF118076 - Homo sapiens PRO1779 mRNA, complete cds.
AK307690 - Homo sapiens cDNA, FLJ97638.
JD130261 - Sequence 111285 from Patent EP1572962.
JD040093 - Sequence 21117 from Patent EP1572962.
JD298269 - Sequence 279293 from Patent EP1572962.
JD090374 - Sequence 71398 from Patent EP1572962.
JD136012 - Sequence 117036 from Patent EP1572962.
JD239159 - Sequence 220183 from Patent EP1572962.
JD350282 - Sequence 331306 from Patent EP1572962.
JD538440 - Sequence 519464 from Patent EP1572962.
JD268011 - Sequence 249035 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P49454 (Reactome details) participates in the following event(s):

R-HSA-141409 Mad1 binds kinetochore
R-HSA-375302 Kinetochore capture of astral microtubules
R-HSA-5666129 CDC42:GTP recruits DIAPH2-2 to kinetochores
R-HSA-5666169 Kinetochore capture of astral microtubules is positively regulated by CDC42:GTP:p-S196-DIAPH2-2
R-HSA-141431 MAD2 associates with the Mad1 kinetochore complex
R-HSA-141439 Release of activated MAD2 from kinetochores
R-HSA-2467811 Separation of sister chromatids
R-HSA-2467809 ESPL1 (Separase) cleaves centromeric cohesin
R-HSA-5666160 AURKB phosphorylates DIAPH2-2 at kinetochores
R-HSA-141422 MAD2 converted to an inhibitory state via interaction with Mad1
R-HSA-1638821 PP2A-B56 dephosphorylates centromeric cohesin
R-HSA-1638803 Phosphorylation of cohesin by PLK1 at centromeres
R-HSA-2468287 CDK1 phosphorylates CDCA5 (Sororin) at centromeres
R-HSA-156711 Polo-like kinase mediated events
R-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-68877 Mitotic Prometaphase
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-69275 G2/M Transition
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-141424 Amplification of signal from the kinetochores
R-HSA-68886 M Phase
R-HSA-195258 RHO GTPase Effectors
R-HSA-453274 Mitotic G2-G2/M phases
R-HSA-68882 Mitotic Anaphase
R-HSA-69618 Mitotic Spindle Checkpoint
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-194315 Signaling by Rho GTPases
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-1640170 Cell Cycle
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: CENPF_HUMAN, NM_016343, NP_057427, P49454, Q13171, Q13246, Q5VVM7
UCSC ID: uc001hkm.3
RefSeq Accession: NM_016343
Protein: P49454 (aka CENPF_HUMAN or CENF_HUMAN)
CCDS: CCDS31023.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_016343.3
exon count: 20CDS single in 3' UTR: no RNA size: 10316
ORF size: 9345CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 18839.00frame shift in genome: no % Coverage: 99.81
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.