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KIF14 (kinesin family member 14)

Identity

Other namesKIAA0042
HUMORFW
MGC142302
HGNC (Hugo) KIF14
LocusID (NCBI) 9928
Location 1q32.1
Location_base_pair Starts at 200520625 and ends at 200589862 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Genes flanking KIF14 at 1q32.1 are (centromeric to telomeric): ZNF281 (zinc finger protein 281), KIF14, DDX59 (DEAD (Asp-Glu-Ala-Asp) box polypeptide 59).

DNA/RNA

Description Gene spans 68.5 kbp on the minus strand at 1q32.1.
Transcription One known 6586 base transcript, 30 exons. The KIF14 promoter is bound by p130/ E2F4 under growth arrest conditions; further details of transcriptional regulation are currently lacking.

Protein

 
  Schematic representation of the KIF14 protein (not to scale). KIF14 contains two major effector domains. The first is a highly conserved 274 aa kinesin motor domain containing an ATP-binding site (aa 447-454) which is involved in microtubule-dependent ATPase activity, and a microtubule binding site (aa 455-628) involved in ATP-dependent protein transport. The second is a 67 aa forkhead-associated (FHA) domain (aa 825-891) which has similarity to the SMAD Mad Homology 2 (MH2) domain, and is involved in mediating protein-protein interactions with phosphoproteins, although no such interactions have been documented for KIF14. In addition to the highly conserved N-type neck region (N) adjacent to the motor domain, KIF14 also contains 4 other C-terminal regions predicted to form coiled-coil structures (1-4). Phosphorylation sites have been identified on Tyr-196, Ser-1200 and Ser-1292 (P), and a ubiquitination site identified on Lys-275 (U). The kinesin motor and FHA domains are flanked by a 354 aa N-terminal extension, and a 758 aa C-terminal stalk and tail region. The N-terminal extension is involved in the binding of PRC1 (protein-regulating cytokinesis 1), a protein crucial for the proper formation of the central spindle structure during cytokinesis. Citron kinase has been shown to interact with the C-terminal stalk and tail of KIF14, and this interaction is required for proper localization of KIF14 to the mitotic spindle.
Description KIF14 is a 186 kDa, 1648 aa protein, containing kinesin motor and forkhead-associated (FHA) domains. It is a member of the N-3 family of kinesins. High-throughput studies have identified phosphorylations on Tyr-196; Ser-1200 and Ser-1292, and ubiquitination on Lys-275.
Expression KIF14 was cloned from an immature myeloid cell line, KG-1. By qRT-PCR, KIF14 is expressed at low levels in normal adult tissues and at higher levels in placenta and fetal tissues; highest expression is in fetal thymus and liver. KIF14 expression varies with the cell cycle, with highest expression at G2-M.
Localisation In HeLa cells, KIF14 is localized to the cytoplasm during interphase, and becomes tightly localized to the midbody and central spindle during cytokinesis.
Function KIF14 is a mitotic kinesin motor protein with ATPase activity. It interacts with protein regulator of cytokinesis 1 (PRC1) and is essential for localizing citron kinase to the mitotic spindle. KIF14 knockdown results in failure of cytokinesis, leading to multinucleation and/or apoptosis, but no chromosome segregation defects.
Homology There are KIF14 orthologs in several mammalian species. The closest Drosophila melanogaster gene, with 40% amino acid identity, is nebbish/tiovivo, encoding Klp38B (kinesin-like protein 38B). Klp38B is a mitotic kinesin that binds to chromatin and microtubules in the formation of the bipolar spindle and attachment of chromosomes to the spindle, and/or acts in cytokinesis.

Mutations

Germinal None yet identified.
Somatic None yet identified.

Implicated in

Entity Retinoblastoma
Prognosis KIF14 mRNA and protein expression is greatly increased in tumors versus normal adult and fetal retina. mRNA expression is higher in older patients' tumors than younger.
Cytogenetics KIF14 lies in a "hotspot" of genomic gain at 1q31.3-1q32.1. Low-level genomic gain (3-5 copies) of the gene is observed in 50% of tumors. High-level amplification has been observed in one tumor (along with, but independent of, MYCN amplification).
  
Entity Breast carcinoma
Prognosis mRNA expression increases with grade, and is higher in ductal than lobular carcinoma, and in estrogen receptor (ER) negative over ER positive tumors. Expression correlates with proliferation, and overexpression is prognostic for poor overall and disease-free survival.
Cytogenetics KIF14 lies in a "hotspot" of genomic gain at 1q31.3-1q32.1. Low-level genomic gain of the gene is observed in 50% of breast cancer cell lines.
  
Entity Non-small-cell lung carcinoma
Prognosis mRNA expression decreases with differentiation, and is higher in squamous cell than adenocarcinoma. Overexpression is independently prognostic for poor disease-free survival, and prognostic for poor overall survival.
Oncogenesis Knockdown of KIF14 decreases proliferation of H1299 NSCLC cells, and decreases their ability to form colonies in soft agar.
  
Entity Hepatocellular carcinoma
Cytogenetics Low-level gain of the KIF14 locus is seen in 58% tumors.
  

To be noted

Numerous microarray studies indexed in Oncomine document overexpression of KIF14 in other cancers, including brain tumors, seminoma, prostate and tongue cancers.

External links

Nomenclature
HGNC (Hugo)KIF14   19181
Entrez_Gene (NCBI)KIF14  9928  kinesin family member 14
Cards
AtlasKIF14ID44138ch1q32
GeneCards (Weizmann)KIF14
Ensembl (Hinxton)ENSG00000118193 [Gene_View]  chr1:200520625-200589862 [Contig_View]  KIF14 [Vega]
AceView (NCBI)KIF14
Genatlas (Paris)KIF14
euGene (Indiana)9928
SOURCE (Stanford)NM_014875
Genomic and cartography
GoldenPath (UCSC)KIF14  -  1q32.1   chr1:200520625-200589862 -  1q32.1   [Description]    (hg19-Feb_2009)
EnsemblKIF14 - 1q32.1 [CytoView]
Mapping of homologs : NCBIKIF14 [Mapview]
OMIM611279   
Gene and transcription
Genbank (Entrez)BC098582 BC113742 BC144068 D26361 HQ258545
RefSeq transcript (SRS)NM_014875
RefSeq transcript (Entrez)NM_014875
RefSeq genomic (SRS)AC_000133 NC_000001 NT_004487 NW_001838533
RefSeq genomic (Entrez)AC_000133 NC_000001 NT_004487 NW_001838533
Consensus coding sequences : CCDS (NCBI)KIF14
Cluster EST : UnigeneHs.3104 [ SRS ] Hs.3104 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17688
Alternative Splicing GalleryENSG00000118193
Gene ExpressionKIF14 [ NCBI-GEO ]   KIF14 [ EBI - ARRAY_EXPRESS ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ15058 (SRS) Q15058 (Uniprot)
With graphics : InterProQ15058
Splice isoforms : SwissVarQ15058(Swissvar)
Domaine pattern : Prosite (SRS)FHA_DOMAIN (PS50006)    KINESIN_MOTOR_DOMAIN1 (PS00411)    KINESIN_MOTOR_DOMAIN2 (PS50067)   
Domaine pattern : Prosite (Expaxy)FHA_DOMAIN (PS50006)    KINESIN_MOTOR_DOMAIN1 (PS00411)    KINESIN_MOTOR_DOMAIN2 (PS50067)   
Domains : Interpro (SRS)FHA_dom    Kinesin_motor_CS    Kinesin_motor_dom    SMAD_FHA_domain   
Domains : Interpro (EBI)FHA_dom    Kinesin_motor_CS    Kinesin_motor_dom    SMAD_FHA_domain   
Related proteins : CluSTrQ15058
Domain families : Pfam (SRS)FHA (PF00498)    Kinesin (PF00225)   
Domain families : Pfam (Sanger)FHA (PF00498)    Kinesin (PF00225)   
Domain families : Pfam (NCBI)pfam00498    pfam00225   
Domain families : Smart (EMBL)FHA (SM00240)  KISc (SM00129)  
Blocks (Seattle)Q15058
Human Protein AtlasENSG00000118193
HPRD06605
IPIIPI00299554   
Protein Interaction databases
DIP (DOE-UCLA)Q15058
IntAct (EBI)Q15058
FunCoupENSG00000118193
REACTOMEKIF14
BioGRIDKIF14
InParanoidQ15058
Interologous Interaction database Q15058
Polymorphism : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)KIF14
SNP (GeneSNP Utah)KIF14
SNP : HGBaseKIF14
Genetic variants : HAPMAPKIF14
Somatic Mutations in Cancer : COSMICKIF14 
CONAN: Copy Number AnalysisKIF14 
Mutations and Diseases : HGMDKIF14
OMIM611279   
GENETests611279   
Disease Genetic AssociationKIF14
Huge Navigator KIF14 [HugePedia]  KIF14 [HugeCancerGEM]
Genomic VariantsKIF14
snp3D : Map Gene to Disease9928
General knowledge
Homologs : HomoloGeneKIF14
Homology/Alignments : Family Browser (UCSC)KIF14
Phylogenetic Trees/Animal Genes : TreeFamKIF14
Chemical/Protein Interactions : CTD9928
Chemical/Pharm GKB GenePA38820
Clinical trialKIF14
Cancer Resource (Charite)ENSG00000118193
Ontology : AmiGOnucleotide binding  microtubule motor activity  protein binding  ATP binding  nucleus  cytoplasm  spindle  cytoskeleton  microtubule  microtubule-based movement  
Ontology : EGO-EBInucleotide binding  microtubule motor activity  protein binding  ATP binding  nucleus  cytoplasm  spindle  cytoskeleton  microtubule  microtubule-based movement  
Other databases
Probes
Probes : ImagenesKIF14 Related clones (RZPD - Berlin)
Litterature
PubMed23 Pubmed reference(s) in Entrez
PubGeneKIF14
iHOPKIF14

Bibliography

Prediction of the coding sequences of unidentified human genes. II. The coding sequences of 40 new genes (KIAA0041-KIAA0080) deduced by analysis of cDNA clones from human cell line KG-1.
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PMID 7584044
 
A chromatin-associated kinesin-related protein required for normal mitotic chromosome segregation in Drosophila.
Molina I, Baars S, Brill JA, Hales KG, Fuller MT, Ripoll P
The Journal of cell biology. 1997 ; 139 (6) : 1361-1371.
PMID 9396743
 
Mutation of a gene for a Drosophila kinesin-like protein, Klp38B, leads to failure of cytokinesis.
Ohkura H, Trk T, Tick G, Hoheisel J, Kiss I, Glover DM
Journal of cell science. 1997 ; 110 ( Pt 8) : 945-954.
PMID 9152020
 
The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.
Durocher D, Taylor IA, Sarbassova D, Haire LF, Westcott SL, Jackson SP, Smerdon SJ, Yaffe MB
Molecular cell. 2000 ; 6 (5) : 1169-1182.
PMID 11106755
 
The molecular basis of FHA domain:phosphopeptide binding specificity and implications for phospho-dependent signaling mechanisms.
Durocher D, Taylor IA, Sarbassova D, Haire LF, Westcott SL, Jackson SP, Smerdon SJ, Yaffe MB
Molecular cell. 2000 ; 6 (5) : 1169-1182.
PMID 11106755
 
KIF14 is a candidate oncogene in the 1q minimal region of genomic gain in multiple cancers.
Corson TW, Huang A, Tsao MS, Gallie BL
Oncogene. 2005 ; 24 (30) : 4741-4753.
PMID 15897902
 
Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference.
Zhu C, Zhao J, Bibikova M, Leverson JD, Bossy-Wetzel E, Fan JB, Abraham RT, Jiang W
Molecular biology of the cell. 2005 ; 16 (7) : 3187-3199.
PMID 15843429
 
RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.
Carleton M, Mao M, Biery M, Warrener P, Kim S, Buser C, Marshall CG, Fernandes C, Annis J, Linsley PS
Molecular and cellular biology. 2006 ; 26 (10) : 3853-3863.
PMID 16648480
 
KIF14 mRNA expression is a predictor of grade and outcome in breast cancer.
Corson TW, Gallie BL
International journal of cancer. Journal international du cancer. 2006 ; 119 (5) : 1088-1094.
PMID 16570270
 
KIF14 and citron kinase act together to promote efficient cytokinesis.
Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, Barr FA
The Journal of cell biology. 2006 ; 172 (3) : 363-372.
PMID 16431929
 
Profiling genomic copy number changes in retinoblastoma beyond loss of RB1.
Bowles E, Corson TW, Bayani J, Squire JA, Wong N, Lai PB, Gallie BL
Genes, chromosomes & cancer. 2007 ; 46 (2) : 118-129.
PMID 17099872
 
KIF14 messenger RNA expression is independently prognostic for outcome in lung cancer.
Corson TW, Zhu CQ, Lau SK, Shepherd FA, Tsao MS, Gallie BL
Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 ; 13 (11) : 3229-3234.
PMID 17545527
 
High expression of KIF14 in retinoblastoma: association with older age at diagnosis.
Madhavan J, Coral K, Mallikarjuna K, Corson TW, Amit N, Khetan V, George R, Biswas J, Gallie BL, Kumaramanickavel G
Investigative ophthalmology & visual science. 2007 ; 48 (11) : 4901-4906.
PMID 17962437
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2007Brigitte L Thériault, Timothy W Corson
Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, ON, Canada (BLT); Department of Molecular, Cellular and Developmental Biology, Yale (TWC)

Citation

This paper should be referenced as such :
Thériault BL, Corson TW . KIF14 (kinesin family member 14). Atlas Genet Cytogenet Oncol Haematol. December 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/KIF14ID44138ch1q32.html

This paper is referenced by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38552/1/12-2007-KIF14ID44138ch1q32.pdf   [ Bibliographic record ]

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indexed on : Sat Apr 28 15:09:21 CEST 2012

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