Details for: KIF14

Gene ID: 9928

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: KIF14

Ensembl ID: ENSG00000118193

Description: kinesin family member 14

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 4.83
    rCSI 5.58%
    PRS 96.96
  • neural crest cell CL0011012
    CSI 4.54
    rCSI 3.59%
    PRS 98.23
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 3.6
    rCSI 4.62%
    PRS 97.93
  • glioblast CL0000030
    CSI 3.17
    rCSI 5.06%
    PRS 96.85
  • erythrocyte CL0000232
    CSI 2.72
    rCSI 6.16%
    PRS 97.85
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 2.69
    rCSI 2.43%
    PRS 98.91
  • placental villous trophoblast CL2000060
    CSI 2.39
    rCSI 3.69%
    PRS 98.23
  • promonocyte CL0000559
    CSI 2.32
    rCSI 3.97%
    PRS 99.34
  • transit amplifying cell of small intestine CL0009012
    CSI 2.26
    rCSI 9.9%
    PRS 99.21
  • erythroblast CL0000765
    CSI 2.25
    rCSI 5.98%
    PRS 98.47
  • GABAergic neuron CL0000617
    CSI 2.07
    rCSI 6.93%
    PRS 93.85
  • large pre-B-II cell CL0000957
    CSI 2.05
    rCSI 5.86%
    PRS 98.34

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [KIF14](/details-gene/9928) (Kinesin Family Member 14) is a protein-coding gene located on chromosome 1q32.1. It encodes a plus-end-directed microtubule motor protein that plays a crucial role in cell division, particularly in the process of cytokinesis. As a member of the kinesin superfamily, [KIF14](/details-gene/9928) utilizes ATP hydrolysis to move along microtubules, which is essential for chromosomal alignment and the physical separation of daughter cells. Its expression is strongly associated with highly proliferative cell populations, including various neural progenitors such as '[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)' and hematopoietic precursors like '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)'. Its involvement in regulating cell cycle progression has implicated it in both normal development and oncogenesis. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [KIF14](/details-gene/9928) underscores its fundamental role in cell proliferation across multiple tissues. It is most significantly expressed in cells undergoing rapid division and differentiation. The highest significance scores are observed in neural progenitor populations, including '[neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338)' (CSI: 4.83), '[neural crest cell](/details-cell/CL0011012)' (CSI: 4.54), and '[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)' (CSI: 3.60). This suggests a critical function in nervous system development. High expression in '[glioblast](/details-cell/CL0000030)' (CSI: 3.17) is also notable, pointing towards its role in the pathology of brain tumors. Beyond the nervous system, [KIF14](/details-gene/9928) shows significant expression in the hematopoietic lineage, particularly in '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' (CSI: 2.69), '[promonocyte](/details-cell/CL0000559)' (CSI: 2.32), and '[erythroblast](/details-cell/CL0000765)' (CSI: 2.25). This pattern is consistent with its function in replenishing blood and immune cells. Additionally, its high CSI in other proliferative tissues, such as '[placental villous trophoblast](/details-cell/CL2000060)' (CSI: 2.39) and '[transit amplifying cell of small intestine](/details-cell/CL0009012)' (CSI: 2.26), further establishes [KIF14](/details-gene/9928) as a key regulator of cell division in tissues with high turnover rates. ## Pathways and Molecular Function The molecular functions of [KIF14](/details-gene/9928) are centered on its identity as a motor protein. Its primary activities include '[microtubule motor activity](/details-cell/GO:0003777)', '[ATP binding](/details-cell/GO:0005524)', and '[ATP hydrolysis activity](/details-cell/GO:0016887)', which collectively enable its movement along microtubules. Functionally, this motor activity is indispensable for '[cell division](/details-cell/GO:0051301)'. It localizes to critical mitotic structures such as the '[spindle midzone](/details-cell/GO:0051233)' and the '[midbody](/details-cell/GO:0030496)', where it facilitates the '[positive regulation of cytokinesis](/details-cell/GO:0032467)'. Research has confirmed that [KIF14](/details-gene/9928) acts in concert with citron kinase to ensure the successful completion of cell division, and its silencing leads to cytokinesis failure ([Link](https://doi.org/10.1083/jcb.200511061); [Link](https://doi.org/10.1128/mcb.26.10.3853-3863.2006)). In addition to its canonical role in mitosis, [KIF14](/details-gene/9928) is involved in signaling pathways that control cell growth and adhesion. It participates in the '[Signaling by rho gtpases](/details-pathway/R-HSA-194315)' pathway, a central hub for cytoskeletal regulation. Moreover, it is implicated in the '[regulation of rap protein signal transduction](/details-cell/GO:0032487)', with studies showing it negatively regulates Rap1a-Radil signaling, a pathway involved in controlling cell adhesion and migration during breast cancer progression ([Link](https://doi.org/10.1083/jcb.201206051)). This dual role in both cytokinesis and cell adhesion signaling highlights its importance in coordinating cell proliferation with tissue architecture. ## Research Directions The established role of [KIF14](/details-gene/9928) as a critical mitotic regulator, combined with its high expression in progenitor and cancer cells, opens several avenues for future investigation. **Proposed Hypotheses:** 1. Given its high expression in various '[neuroblast](/details-cell/CL0000031)' populations and its annotation in processes like '[cerebellar cortex development](/details-cell/GO:0021695)', it is hypothesized that [KIF14](/details-gene/9928) is essential for maintaining the fidelity of asymmetric cell division in neural stem cells. Dysregulation of [KIF14](/details-gene/9928) may disrupt mitotic spindle orientation, leading to aberrant cell fate decisions and contributing to neurodevelopmental disorders or the formation of pediatric brain tumors. 2. The high significance of [KIF14](/details-gene/9928) in '[megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050)' and '[erythroblast](/details-cell/CL0000765)' suggests a critical, non-redundant function in hematopoiesis. It is hypothesized that partial loss-of-function mutations in [KIF14](/details-gene/9928) could be an underlying cause of certain congenital dyserythropoietic anemias, where failed cytokinesis in erythroblasts leads to binucleated cells and ineffective red blood cell production. **Experimental Approach:** To test the role of [KIF14](/details-gene/9928) in neurogenesis (Hypothesis 1), a conditional knockout mouse model could be generated using a Nestin-Cre driver to specifically delete [KIF14](/details-gene/9928) in neural progenitor cells. The developing brains of these mice could be analyzed at different embryonic stages via immunohistochemistry for markers of proliferation (Ki67), apoptosis (cleaved Caspase-3), and neural differentiation (e.g., Tuj1, Satb2, Ctip2) to assess defects in cell cycle exit, cell survival, and cortical layering. Furthermore, live-cell imaging of cultured neurospheres derived from these animals would allow direct visualization of mitotic progression, spindle dynamics, and the outcomes of cell division. **Therapeutic Potential:** [KIF14](/details-gene/9928) represents a promising therapeutic target for oncology. Its function is essential for the rapid proliferation that characterizes cancer, and its overexpression is linked to poor outcomes in several cancers, including hepatocellular carcinoma ([Link](https://doi.org/10.1038/emm.2014.23)) and breast cancer ([Link](https://doi.org/10.1083/jcb.201206051)). The therapeutic strategy would involve **inhibition** of its function. As an intracellular motor protein with a druggable ATPase domain, [KIF14](/details-gene/9928) is an attractive candidate for the development of specific small molecule inhibitors. Such compounds could act as potent anti-mitotic agents, selectively targeting rapidly dividing cancer cells while potentially sparing quiescent, non-cancerous cells.

Genular Protein ID: 324407666

Symbol: KIF14_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q15058 Q14CI8 Q4G0A5 Q5T1W3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 ChEBI 1 ChEMBL 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 2 GO 45 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MIM 5 MINT 1 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PRINTS 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 3 RefSeq 5 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7584044

Title: 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.

PubMed ID: 7584044

DOI: 10.1093/dnares/1.5.223

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15843429

Title: Functional analysis of human microtubule-based motor proteins, the kinesins and dyneins, in mitosis/cytokinesis using RNA interference.

PubMed ID: 15843429

DOI: 10.1091/mbc.e05-02-0167

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 16431929

Title: KIF14 and citron kinase act together to promote efficient cytokinesis.

PubMed ID: 16431929

DOI: 10.1083/jcb.200511061

PubMed ID: 16820410

Title: Novel function of beta-arrestin2 in the nucleus of mature spermatozoa.

PubMed ID: 16820410

DOI: 10.1242/jcs.03046

PubMed ID: 16648480

Title: RNA interference-mediated silencing of mitotic kinesin KIF14 disrupts cell cycle progression and induces cytokinesis failure.

PubMed ID: 16648480

DOI: 10.1128/mcb.26.10.3853-3863.2006

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 20309963

Title: Novel interactors and a role for supervillin in early cytokinesis.

PubMed ID: 20309963

DOI: 10.1002/cm.20449

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23209302

Title: KIF14 negatively regulates Rap1a-Radil signaling during breast cancer progression.

PubMed ID: 23209302

DOI: 10.1083/jcb.201206051

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24854087

Title: Silencing of KIF14 interferes with cell cycle progression and cytokinesis by blocking the p27(Kip1) ubiquitination pathway in hepatocellular carcinoma.

PubMed ID: 24854087

DOI: 10.1038/emm.2014.23

PubMed ID: 24784001

Title: KIF14 promotes AKT phosphorylation and contributes to chemoresistance in triple-negative breast cancer.

PubMed ID: 24784001

DOI: 10.1016/j.neo.2014.03.008

PubMed ID: 24128419

Title: Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype.

PubMed ID: 24128419

DOI: 10.1111/cge.12301

PubMed ID: 28892560

Title: Mutations of KIF14 cause primary microcephaly by impairing cytokinesis.

PubMed ID: 28892560

DOI: 10.1002/ana.25044

PubMed ID: 29343805

Title: Biallelic variants in KIF14 cause intellectual disability with microcephaly.

PubMed ID: 29343805

DOI: 10.1038/s41431-017-0088-9

Sequence Information:

  • Length: 1648
  • Mass: 186492
  • Checksum: FB1423668A7B79D7
  • Sequence:
    • MSLHSTHNRN NSGDILDIPS SQNSSSLNAL THSSRLKLHL KSDMSECEND DPLLRSAGKV 
RDINRTYVIS ASRKTADMPL TPNPVGRLAL QRRTTRNKES SLLVSELEDT TEKTAETRLT 
LQRRAKTDSA EKWKTAEIDS VKMTLNVGGE TENNGVSKES RTNVRIVNNA KNSFVASSVP 
LDEDPQVIEM MADKKYKETF SAPSRANENV ALKYSSNRPP IASLSQTEVV RSGHLTTKPT 
QSKLDIKVLG TGNLYHRSIG KEIAKTSNKF GSLEKRTPTK CTTEHKLTTK CSLPQLKSPA 
PSILKNRMSN LQVKQRPKSS FLANKQERSA ENTILPEEET VVQNTSAGKD PLKVENSQVT 
VAVRVRPFTK REKIEKASQV VFMSGKEITV EHPDTKQVYN FIYDVSFWSF DECHPHYASQ 
TTVYEKLAAP LLERAFEGFN TCLFAYGQTG SGKSYTMMGF SEEPGIIPRF CEDLFSQVAR 
KQTQEVSYHI EMSFFEVYNE KIHDLLVCKD ENGQRKQPLR VREHPVYGPY VEALSMNIVS 
SYADIQSWLE LGNKQRATAA TGMNDKSSRS HSVFTLVMTQ TKTEFVEGEE HDHRITSRIN 
LIDLAGSERC STAHTNGDRL KEGVSINKSL LTLGKVISAL SEQANQRSVF IPYRESVLTW 
LLKESLGGNS KTAMIATISP AASNIEETLS TLRYANQARL IVNIAKVNED MNAKLIRELK 
AEIAKLKAAQ RNSRNIDPER YRLCRQEITS LRMKLHQQER DMAEMQRVWK EKFEQAEKRK 
LQETKELQKA GIMFQMDNHL PNLVNLNEDP QLSEMLLYMI KEGTTTVGKY KPNSSHDIQL 
SGVLIADDHC TIKNFGGTVS IIPVGEAKTY VNGKHILEIT VLRHGDRVIL GGDHYFRFNH 
PVEVQKGKRP SGRDTPISEG PKDFEFAKNE LLMAQRSQLE AEIKEAQLKA KEEMMQGIQI 
AKEMAQQELS SQKAAYESKI KALEAELREE SQRKKMQEIN NQKANHKIEE LEKAKQHLEQ 
EIYVNKKRLE METLATKQAL EDHSIRHARI LEALETEKQK IAKEVQILQQ NRNNRDKTFT 
VQTTWSSMKL SMMIQEANAI SSKLKTYYVF GRHDISDKSS SDTSIRVRNL KLGISTFWSL 
EKFESKLAAM KELYESNGSN RGEDAFCDPE DEWEPDITDA PVSSLSRRRS RSLMKNRRIS 
GCLHDIQVHP IKNLHSSHSS GLMDKSSTIY SNSAESFLPG ICKELIGSSL DFFGQSYDEE 
RTIADSLINS FLKIYNGLFA ISKAHEEQDE ESQDNLFSSD RAIQSLTIQT ACAFEQLVVL 
MKHWLSDLLP CTNIARLEDE LRQEVKKLGG YLQLFLQGCC LDISSMIKEA QKNAIQIVQQ 
AVKYVGQLAV LKGSKLHFLE NGNNKAASVQ EEFMDAVCDG VGLGMKILLD SGLEKAKELQ 
HELFRQCTKN EVTKEMKTNA MGLIRSLENI FAESKIKSFR RQVQEENFEY QDFKRMVNRA 
PEFLKLKHCL EKAIEIIISA LKGCHSDINL LQTCVESIRN LASDFYSDFS VPSTSVGSYE 
SRVTHIVHQE LESLAKSLLF CFESEESPDL LKPWETYNQN TKEEHQQSKS SGIDGSKNKG 
VPKRVYELHG SSPAVSSEEC TPSRIQWV