KIF11

General Information

Full gene name:kinesin family member 11
Entrez Gene ID:3832
Location:10q24.1
Synonyms:MCLMR, HKSP, TRIP5, KNSL1, EG5
Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP Distance (bp) Direction
rs1111875 47730 downstream

NCBI Summary

This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

OMIM

OMIM ID:`OMIM ID 148760 `_

Allelic Variants (Selected Examples)

.0001 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In 4 patients from 2 unrelated families with microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (152950), Ostergaard et al. (2012) identified heterozygosity for a 1159C-T transition in exon 10 of the KIF11 gene, resulting in an arg387-to-ter (R387X) substitution. The mutation segregated with disease in the first family but was found to have arisen de novo in the second family, and was not found in dbSNP, the 1000 Genomes Project, or in 250 controls. The 2 patients from the first family had microcephaly without eye abnormalities, and both had congenital edema: the male patient had minimal edema and mild learning difficulties (LD), whereas the female patient had congenital bilateral lower limb edema, mild LD, and dysmorphic features. The 2 patients from the second family had microcephaly with eye abnormalities but without congenital edema; the female patient had chorioretinopathy and mild LD, whereas the male patient had hypermetropic astigmatism, chorioretinopathy, and moderate LD.

.0002 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In a male and a female patient from a family with microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (152950), Ostergaard et al. (2012) identified heterozygosity for a 2-bp deletion (1039delCT) in exon 9 of the KIF11 gene, predicted to cause a frameshift and premature termination codon. The mutation segregated with disease in the family and was not found in dbSNP, the 1000 Genomes Project, or in 250 controls. Both patients had microcephaly. Whereas the male patient had only mild learning difficulties (LD) without lymphedema or eye abnormalities, the female patient, who had more severe microcephaly, had congenital bilateral lower limb edema and pleural effusions, hypermetropic astigmatism and chorioretinopathy, and LD.

.0003 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In a male patient with microcephaly, bilateral chorioretinopathy, congenital bilateral lymphedema of the lower limbs, and mild learning difficulties (152950), originally reported by Vasudevan et al. (2005), Ostergaard et al. (2012) identified heterozygosity for a de novo 2830C-T transition in exon 3 of the KIF11 gene, resulting in an arg944-to-cys (R944C) substitution at a highly conserved residue within the bimC box in the C-terminal tail. The mutation was not found in dbSNP, the 1000 Genomes Project, or in 250 controls.

.0004 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In 2 related patients who had microcephaly without mental retardation but with variable presence of chorioretinopathy and lymphedema (152950), Ostergaard et al. (2012) identified heterozygosity for a 1-bp deletion (1592delA) in exon 13 of the KIF11 gene, predicted to cause a frameshift and premature termination codon. The mutation segregated with disease in the family and was not found in dbSNP, the 1000 Genomes Project, or in 250 controls. Neither patient had learning difficulties. Whereas the female patient exhibited only microcephaly, the male patient also had congenital bilateral lower limb edema, bilateral chorioretinopathy, atrial septal defect, and dysmorphic features.

.0005 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In 3 sibs, their mother, and their maternal grandfather, who had microcephaly without eye abnormalities but with variable presence of congenital lymphedema and/or mental retardation (152950), Ostergaard et al. (2012) identified heterozygosity for a 2547+2T-C transition in intron 18 of the KIF11 gene, predicted to cause premature truncation. The mutation segregated with disease in the family and was not found in dbSNP, the 1000 Genomes Project, or in 250 controls. Two of the patients had mild lymphedema of the hands in addition to congenital bilateral lymphedema of the lower extremities.

.0006 MICROCEPHALY WITH OR WITHOUT CHORIORETINOPATHY, LYMPHEDEMA, OR MENTAL RETARDATION

In 2 related female patients with microcephaly and bilateral chorioretinopathy (152950), Ostergaard et al. (2012) identified heterozygosity for a 704C-G transversion in exon 7 of the KIF11 gene, resulting in a ser235-to-cys (S235C) substitution at a highly conserved residue within the motor domain. The mutation segregated with disease in the family and was not found in dbSNP, the 1000 Genomes Project, or in 250 controls. Neither patient had lymphedema, and only 1 of them had learning difficulties.

NCBI Phenotypes

  • Gene Reviews
  • Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.
  • OMIM
  • GTR
  • Chorioretinal dysplasia-microcephaly-mental retardation syndrome
  • NHGRI GWA Catalog

Gene Ontology

  • kinesin complex
  • spindle assembly involved in mitosis
  • microtubule-based movement
  • protein kinase binding
  • microtubule
  • cell division
  • cytoplasm
  • mitotic spindle organization
  • chromatin remodeling complex
  • cytosol
  • spindle microtubule
  • mitosis
  • microtubule motor activity
  • mitotic centrosome separation
  • blood coagulation
  • spindle organization
  • microtubule binding
  • spindle
  • spindle pole
  • ATP binding

KEGG Pathways

No pathways found linked to this gene.

GeneRIFs

  • Eg5 kinesin has a role in ATP hydrolysis and structural transitions [PMID 20154092]
  • For the first time at a cellular level, the propensity of selected Eg5 point mutants to confer drug resistance confirms the target specificity of monastrol and S-trityl-L-cysteine for Eg5. [PMID 19896928]
  • Data show that 4-oxo-4-HPR inhibited tubulin polymerization and modulated gene expression of spindle aberration associated genes Kif 1C, Kif 2A, Eg5, Tara, tankyrase-1, centractin, and TOGp. [PMID 19996280]
  • Affinity Capture-MS [PMID 16969126]
  • analysis of a genome-wide siRNA screen for enhancers and suppressors of a Kinesin-5 inhibitor in human cells to elucidate cellular responses [PMID 19802393]
  • ATPase pathway for monomeric Eg5 is more similar to conventional kinesin than the spindle motors Ncd and Kar3, where ADP product release is rate-limiting for steady-state turnover [PMID 15247293]
  • the rotational pitch of microtubule sliding conveniently reports on the processivity of the driving motors, confirming that two-headed Eg5 is much less processive than two-headed kinesin-1 [PMID 18806799]
  • B23 regulates microtubule dynamics by directly inhibiting Eg5 ATPase activity [PMID 20404347]
  • Two-hybrid [PMID 9235942]
  • Reconstituted Complex; Two-hybrid [PMID 9235942]
  • Crystal structure (2.7A) of the complex between human Eg5 and a new keto derivative of monastrol (named mon-97), a potent antimitotic inhibitor. [PMID 17251189]
  • Eg5 is downstream of and regulated by Bcr-Abl tyrosine kinase in Philadelphia chromosome positive cells. Inhibition of Eg5 expression or its activity blocks cell cycle progression and induces cell death independent of the cellular response to Imatinib [PMID 16969080]
  • model of movement of the mitotic motor Eg5 [PMID 16115880]
  • The Eg5 gene, a member of the kinesin-5 family, plays critical roles in proper mitotic spindle function, and is a potential microtubule-related target for proliferating cancer cells. [PMID 18512732]
  • Data show that the Eg5-513 dimer binds microtubules with both heads to two adjacent tubulin heterodimers along the same microtubule protofilament, and that this binding is inhibited by monastrol. [PMID 16642039]
  • Observational study of gene-disease association. (HuGE Navigator) [PMID 20508983]
  • Monastrol causes aberrant interactions with the microtubule, and reversals at the ATP hydrolysis step which alter the ability of Eg5 to generate force, thereby yielding a nonproductive Mt.Eg5 complex that cannot establish or maintain the bipolar spindle [PMID 15665380]
  • Single-nucleotide polymorphisms in the KIF11 gene are associated with susceptibility to type 2 diabetes across the boundary of race. [PMID 17971426]
  • Loop L5 acts as a conformational latch in the mitotic kinesin Eg5. [PMID 21148480]
  • Data indicate that EMD534085 is a potent and selective compound which inhibits ATPase activity of Kinesin-5. [PMID 21782324]
  • Allosteric drug discrimination is coupled to mechanochemical changes in the kinesin-5 motor core [PMID 20299460]
  • correlates with poor differentiation of bladder cancer and represents an independent prognostic factor in predicting early intravesical recurrence in non-muscle invasive bladder carcinoma patients [PMID 21449971]
  • Affinity Capture-MS [PMID 17643375]
  • Affinity Capture-MS [PMID 17643375]
  • L5 may be an element in the pathway that links the state of the nucleotide-binding site to the neck linker in Eg5 kinesin motors [PMID 16434397]
  • characterization of selective ATP competitive inhibitors of the human mitotic kinesin KSP [PMID 17999913]
  • Affinity Capture-MS [PMID 17707232]
  • Affinity Capture-Western [PMID 17707232]
  • The cocrystal structure of the motor domain of HsEg5 in complex with CK0238273 at a 2.15 A resolution was reported. [PMID 18503753]
  • The neck linker and the neck are involved not only in motility generation in general and in determination of movement direction, but also in velocity regulation. [PMID 18640125]
  • Heterozygous KIF11 mutations in three individuals with a combination of microcephaly and lymphedema from a microcephaly-lymphedema-chorioretinal-dysplasia cohort. [PMID 22284827]
  • Data show the crystal structure of the Eg5 motor domain complexed with a potent antimitotic inhibitor STLC (S-trityl-L-cysteine) to 2.0 A resolution. [PMID 19793049]
  • KIF11 inhibitor, ARRY-520, as a substitute for Paclitaxel in type I ovarian cancer cells is reported. [PMID 19619321]
  • In a series of 428 psoriatic patients anti-hsEG5 (NuMA-2) autoantibodies were found only in a patient, at a titer of 1:640, without any apparent clinical relevance. [PMID 19951065]
  • Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 17293876]
  • a novel function for Parkin in modulating the expression of Eg5 through the Hsp70-JNK-c-Jun signaling pathway. [PMID 18845538]
  • The thermodynamic aspects of nucleotide and inhibitor (ispinesib and monastrol) binding to the motor domain of wild-type Eg5 and its D130V and A133D mutants were studied. [PMID 19824700]
  • A critical element of Eg5, loop 5 (L5), accelerates ADP release during the initial microtubule-binding event. [PMID 22261065]
  • Dimeric Eg5 appears to undergo a conformational change shortly after collision with the microtubule that primes the motor for its characteristically short processive runs [PMID 18037705]
  • The results define the energy landscape of a kinesin ATPase cycle in the absence and presence of microtubules and shed light on the role of molecular motor mechanochemistry in cellular microtubule dynamics. [PMID 20558732]
  • Affinity Capture-MS [PMID 14527417]
  • Affinity Capture-MS [PMID 19615732]
  • the molecular motor Eg5 associates with ribosomes and enhances the efficiency of translation [PMID 21795388]
  • The Eg5-513-5His velocity data were described by a minimal, three-state model where a force-dependent transition follows nucleotide binding. [PMID 16604065]
  • KIF11 is critical for proper spindle assembly in the area of cell cycle inhibition [PMID 19545421]
  • The authors report that in G2 phase polo-like kinase 1 (Plk1) can trigger centrosome separation independently of Cdk1 by phosphorylating the motor protein Eg5. [PMID 21522128]
  • Inhibition of KSP induces apoptosis independently of p53 and that p53 is dispensable for spindle checkpoint function. Thus, KSP inhibitors should be active in p53-deficient tumors. [PMID 17101792]
  • ATP hydrolysis in Eg5 kinesin involves a catalytic two-water mechanism. [PMID 20018897]
  • Binding to kinesin I ensures properly assembled and functioning Kv3.1 channels are transported into axons. [PMID 21106837]
  • there is an association between PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 and type 2 diabetes in the Chinese population [PMID 19862325]
  • these results suggest that the interaction between XPF and Eg5 plays a role in mitosis and DNA repair and offer new insights into the pathogenesis of XP-F and XFE. [PMID 22353549]
  • These results suggest possible involvement of XB-S in the function of Eg5. [PMID 18679583]
  • Affinity Capture-MS [PMID 21906983]
  • microtubule-Eg5 complex binds MgATP tightly, followed by rapid ATP hydrolysis with a subsequent slow step that limits steady-state turnover. [PMID 17014086]
  • Abeta impairs the assembly and maintenance of the mitotic spindle. Mechanistically, these defects result from Abeta’s inhibition of mitotic motor kinesins, including Eg5, KIF4A and MCAK. [PMID 21566458]
  • Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. [PMID 21642957]
  • dimeric Eg5 is the first kinesin motor identified to have a rate-limiting ATP hydrolysis step [PMID 17062577]
  • Two-hybrid [PMID 7776974]

PubMed Articles

Recent articles:

  • Tan LJ et al. “Xeroderma pigmentosum group F protein binds to Eg5 and is required for proper mitosis: implications for XP-F and XFE.” Genes Cells. 2012 Mar;17(3):173-85. PMID 22353549
  • Ostergaard P et al. “Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy.” Am J Hum Genet. 2012 Feb 10;90(2):356-62. PMID 22284827
  • Waitzman JS et al. “The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5.” Biophys J. 2011 Dec 7;101(11):2760-9. PMID 22261065
  • Tang Y et al. “Rapid induction of apoptosis during Kinesin-5 inhibitor-induced mitotic arrest in HL60 cells.” Cancer Lett. 2011 Nov 1;310(1):15-24. PMID 21782324
  • Kim W et al. “Systematic and quantitative assessment of the ubiquitin-modified proteome.” Mol Cell. 2011 Oct 21;44(2):325-40. PMID 21906983
  • Bartoli KM et al. “Kinesin molecular motor Eg5 functions during polypeptide synthesis.” Mol Biol Cell. 2011 Sep;22(18):3420-30. PMID 21795388
  • Bertran MT et al. “Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5.” EMBO J. 2011 Jun 3;30(13):2634-47. PMID 21642957
  • Smith E et al. “Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1.” EMBO J. 2011 Jun 1;30(11):2233-45. PMID 21522128
  • Borysov SI et al. “Alzheimer Aβ disrupts the mitotic spindle and directly inhibits mitotic microtubule motors.” Cell Cycle. 2011 May 1;10(9):1397-410. PMID 21566458
  • Sim X et al. “Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.” PLoS Genet. 2011 Apr;7(4):e1001363. PMID 21490949

Top Pubmed articles linked to gene KIF11 matching any search term:

  • Qian Y et al. “Genetic variants of IDE-KIF11-HHEX at 10q23.33 associated with type 2 diabetes risk: a fine-mapping study in Chinese population.” PLoS One. 2012;7(4):e35060. PMID 22506066
  • Sim X et al. “Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.” PLoS Genet. 2011 Apr;7(4):e1001363. PMID 21490949
  • Cui J et al. “Targeted inactivation of kinesin-1 in pancreatic β-cells in vivo leads to insulin secretory deficiency.” Diabetes. 2011 Jan;60(1):320-30. PMID 20870970
  • Hu C et al. “PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.” PLoS One. 2009 Oct 28;4(10):e7643. PMID 19862325
  • Lewis JP et al. “Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies.” Diabetes. 2008 Aug;57(8):2220-5. PMID 18443202
  • Lindgren CM et al. “Mechanisms of disease: genetic insights into the etiology of type 2 diabetes and obesity.” Nat Clin Pract Endocrinol Metab. 2008 Mar;4(3):156-63. PMID 18212765
  • Furukawa Y et al. “Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population.” J Clin Endocrinol Metab. 2008 Jan;93(1):310-4. PMID 17971426
  • Grarup N et al. “Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies.” Diabetes. 2007 Dec;56(12):3105-11. PMID 17827400
  • Sladek R et al. “A genome-wide association study identifies novel risk loci for type 2 diabetes.” Nature. 2007 Feb 22;445(7130):881-5. PMID 17293876
  • Feuk L et al. “Mutation screening of a haplotype block around the insulin degrading enzyme gene and association with Alzheimer’s disease.” Am J Med Genet B Neuropsychiatr Genet. 2005 Jul 5;136B(1):69-71. PMID 15858821
  • Prince JA et al. “Genetic variation in a haplotype block spanning IDE influences Alzheimer disease.” Hum Mutat. 2003 Nov;22(5):363-71. PMID 14517947

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