KIF18A

KIF18A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3LRE
Identifiers
Aliases	KIF18A , MS-PPP1R99, kinesin family member 18A
External IDs	OMIM: 611271; MGI: 2446977; HomoloGene: 41820; GeneCards: KIF18A; OMA:KIF18A - orthologs
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11p14.1 Start 28,020,619 bp [1] End 28,108,156 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2|2 E3 Start 109,111,083 bp [2] End 109,172,092 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone gonad testicle secondary oocyte ganglionic eminence sperm left testis right testis stromal cell of endometrium bone marrow Top expressed in zygote secondary oocyte primary oocyte spermatid fetal liver hematopoietic progenitor cell ventricular zone genital tubercle spermatocyte epiblast tail of embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding microtubule motor activity tubulin-dependent ATPase activity microtubule binding microtubule plus-end binding protein binding actin binding plus-end-directed microtubule motor activity ATP binding ATPase activity Cellular component cytoplasm cytosol cell projection kinetochore microtubule kinesin complex ruffle microtubule cytoskeleton microtubule organizing center mitotic spindle midzone caveola microtubule cytoskeleton nucleus kinetochore mitotic spindle astral microtubule Biological process antigen processing and presentation of exogenous peptide antigen via MHC class II male meiotic nuclear division regulation of microtubule cytoskeleton organization microtubule-based movement seminiferous tubule development protein transport microtubule depolymerization mitotic metaphase plate congression retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum cellular response to estradiol stimulus mitotic sister chromatid segregation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 81930 228421 Ensembl ENSG00000121621 ENSMUSG00000027115 UniProt Q8NI77 Q91WD7 RefSeq (mRNA) NM_031217 NM_139303 RefSeq (protein) NP_112494 NP_647464 Location (UCSC) Chr 11: 28.02 – 28.11 Mb Chr 2: 109.11 – 109.17 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Kinesin family member KIF18A is a human protein encoded by the KIF18A gene. ^{[5] [6]} It is part of the kinesin family of motor proteins.

Function

KIF18A is a plus-end directed motor protein, and migrates to the plus ends of the spindle during early mitosis. It first accumulates there during prophase and metaphase, and is depleted during anaphase. ^[7]

KIF18a(-/-) knockout in mice results in complete sterility in males, but not females, due to abnormal development of the seminiferous tubules. ^[8] The mice were otherwise normal, suggesting KIF18a is not essential for cell divisions in non-germ cells.

Therapeutic Target

KIF18A has been considered as a cancer target because it is overexpressed in many cancer types and mouse studies suggest it is dispensable in somatic cells. ^[9] As such, small molecule inhibitors of KIF18A have been developed to block its activity. ^[9]

References

1. GRCh38: Ensembl release 89: ENSG00000121621 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027115 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–435. doi:10.1101/gr.GR1547R. PMC   311072 . PMID   11230166.
6. "Entrez Gene: KIF18A kinesin family member 18A".
7. Mayr MI, Hümmer S, Bormann J, Grüner T, Adio S, Woehlke G, et al. (March 2007). "The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression". Current Biology. 17 (6): 488–498. Bibcode:2007CBio...17..488M. doi: 10.1016/j.cub.2007.02.036 . PMID   17346968.
8. Liu XS, Zhao XD, Wang X, Yao YX, Zhang LL, Shu RZ, et al. (January 2010). "Germinal Cell Aplasia in Kif18a Mutant Male Mice Due to Impaired Chromosome Congression and Dysregulated BubR1 and CENP-E". Genes & Cancer. 1 (1): 26–39. doi:10.1177/1947601909358184. PMC   2963078 . PMID   20981276.
9. Payton M, Belmontes B, Hanestad K, Moriguchi J, Chen K, McCarter JD, et al. (January 2024). "Small-molecule inhibition of kinesin KIF18A reveals a mitotic vulnerability enriched in chromosomally unstable cancers". Nature Cancer. 5 (1): 66–84. doi:10.1038/s43018-023-00699-5. PMC   10824666 . PMID   38151625.

Further reading

• Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–1795. doi:10.1101/gr.143000. PMC   310948 . PMID   11076863.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi: 10.1038/ng1285 . PMID   14702039.
• Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID   14743216. S2CID   11683986.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, et al. (July 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–1332. doi:10.1101/gr.2334104. PMC   442148 . PMID   15231748.
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (October 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, et al. (October 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–2144. doi:10.1101/gr.2576704. PMC   528930 . PMID   15489336.
• Luboshits G, Benayahu D (May 2005). "MS-KIF18A, new kinesin; structure and cellular expression". Gene. 351: 19–28. doi:10.1016/j.gene.2005.02.009. PMID   15878648.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, et al. (January 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC   1356129 . PMID   16344560.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, et al. (January 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415 –D418. doi:10.1093/nar/gkj139. PMC   1347501 . PMID   16381901.
• Nousiainen M, Silljé HH, Sauer G, Nigg EA, Körner R (April 2006). "Phosphoproteome analysis of the human mitotic spindle". Proceedings of the National Academy of Sciences of the United States of America. 103 (14): 5391–5396. Bibcode:2006PNAS..103.5391N. doi: 10.1073/pnas.0507066103 . PMC   1459365 . PMID   16565220.

External links

• PDBe-KB provides an overview of all the structure information available in the PDB for Human Kinesin-like protein KIF18A