KIF5A explained

Kinesin family member 5A is a protein that in humans is encoded by the KIF5A gene. It is part of the kinesin family of motor proteins.^{[1] [2] [3]}

This gene encodes a member of the kinesin family of proteins. Members of this family are part of a multi-subunit complex that functions as a microtubule motor in intracellular organelle transport. Mutations in this gene cause autosomal dominant spastic paraplegia 10.^[3]

Interactions

KIF5A has been shown to interact with KLC1.^{[4] [5]}

Clinical significance

Mutations in KIF5A have been reported to cause hereditary spastic paraplegia type 10 (SPG1).^[6]

Mutations in KIF5A have also been found to cause amyotrophic lateral sclerosis.^[7]

KIF5A has been shown to play a role in Alzheimer's disease by modulating the toxic effect of beta-amyloid on axonal transport of mitochondria.^[8]

Further reading

• Fichera M, Lo Giudice M, Falco M, Sturnio M, Amata S, Calabrese O, Bigoni S, Calzolari E, Neri M . 6 . Evidence of kinesin heavy chain (KIF5A) involvement in pure hereditary spastic paraplegia . Neurology . 63 . 6 . 1108–10 . September 2004 . 15452312 . 10.1212/01.wnl.0000138731.60693.d2 . 10854107 .
• Niclas J, Navone F, Hom-Booher N, Vale RD . Cloning and localization of a conventional kinesin motor expressed exclusively in neurons . Neuron . 12 . 5 . 1059–72 . May 1994 . 7514426 . 10.1016/0896-6273(94)90314-X . 32927183 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Rahman A, Friedman DS, Goldstein LS . Two kinesin light chain genes in mice. Identification and characterization of the encoded proteins . The Journal of Biological Chemistry . 273 . 25 . 15395–403 . June 1998 . 9624122 . 10.1074/jbc.273.25.15395 . free .
• Rahman A, Kamal A, Roberts EA, Goldstein LS . Defective kinesin heavy chain behavior in mouse kinesin light chain mutants . The Journal of Cell Biology . 146 . 6 . 1277–88 . September 1999 . 10491391 . 2156125 . 10.1083/jcb.146.6.1277 .
• Kanai Y, Okada Y, Tanaka Y, Harada A, Terada S, Hirokawa N . KIF5C, a novel neuronal kinesin enriched in motor neurons . The Journal of Neuroscience . 20 . 17 . 6374–84 . September 2000 . 10964943 . 6772948 . 10.1523/JNEUROSCI.20-17-06374.2000.
• Setou M, Seog DH, Tanaka Y, Kanai Y, Takei Y, Kawagishi M, Hirokawa N . Glutamate-receptor-interacting protein GRIP1 directly steers kinesin to dendrites . Nature . 417 . 6884 . 83–7 . May 2002 . 11986669 . 10.1038/nature743 . 2002Natur.417...83S . 4400494 .
• Macioce P, Gambara G, Bernassola M, Gaddini L, Torreri P, Macchia G, Ramoni C, Ceccarini M, Petrucci TC . 6 . Beta-dystrobrevin interacts directly with kinesin heavy chain in brain . Journal of Cell Science . 116 . Pt 23 . 4847–56 . December 2003 . 14600269 . 10.1242/jcs.00805 . 27097248 .
• Amit I, Yakir L, Katz M, Zwang Y, Marmor MD, Citri A, Shtiegman K, Alroy I, Tuvia S, Reiss Y, Roubini E, Cohen M, Wides R, Bacharach E, Schubert U, Yarden Y . 6 . Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis and retrovirus budding . Genes & Development . 18 . 14 . 1737–52 . July 2004 . 15256501 . 478194 . 10.1101/gad.294904 .
• Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE . 6 . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• Blair MA, Ma S, Hedera P . Mutation in KIF5A can also cause adult-onset hereditary spastic paraplegia . Neurogenetics . 7 . 1 . 47–50 . March 2006 . 16489470 . 10.1007/s10048-005-0027-8 . 24405076 .

Notes and References

1. Hamlin PJ, Jones PF, Leek JP, Bransfield K, Lench NJ, Aldersley MA, Howdle PD, Markham AF, Robinson PA . 6 . Assignment of GALGT encoding beta-1, 4N-acetylgalactosaminyl-transferase (GalNAc-T) and KIF5A encoding neuronal kinesin (D12S1889) to human chromosome band 12q13 by assignment to ICI YAC 26EG10 and in situ hybridization. [e-mail] . Cytogenetics and Cell Genetics . 82 . 3–4 . 267–8 . Feb 1999 . 9858832 . 10.1159/000015115 . 84466204 .
2. Reid E, Dearlove AM, Rhodes M, Rubinsztein DC . A new locus for autosomal dominant "pure" hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity . American Journal of Human Genetics . 65 . 3 . 757–63 . September 1999 . 10441583 . 1377983 . 10.1086/302555 .
3. Web site: Entrez Gene: KIF5A kinesin family member 5A.
4. Rahman A, Friedman DS, Goldstein LS . Two kinesin light chain genes in mice. Identification and characterization of the encoded proteins . The Journal of Biological Chemistry . 273 . 25 . 15395–403 . June 1998 . 9624122 . 10.1074/jbc.273.25.15395 . free .
5. Rahman A, Kamal A, Roberts EA, Goldstein LS . Defective kinesin heavy chain behavior in mouse kinesin light chain mutants . The Journal of Cell Biology . 146 . 6 . 1277–88 . September 1999 . 10491391 . 2156125 . 10.1083/jcb.146.6.1277 .
6. Reid E, Kloos M, Ashley-Koch A, Hughes L, Bevan S, Svenson IK, Graham FL, Gaskell PC, Dearlove A, Pericak-Vance MA, Rubinsztein DC, Marchuk DA . 6 . A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10) . American Journal of Human Genetics . 71 . 5 . 1189–94 . November 2002 . 12355402 . 385095 . 10.1086/344210 .
7. Nicolas A, Kenna KP, Renton AE, Ticozzi N, Faghri F, Chia R, etal . Genome-wide Analyses Identify KIF5A as a Novel ALS Gene . Neuron . 97 . 6 . 1268–1283.e6 . March 2018 . 29566793 . 5867896 . 10.1016/j.neuron.2018.02.027 .
8. Wang Q, Tian J, Chen H, Du H, Guo L . Amyloid beta-mediated KIF5A deficiency disrupts anterograde axonal mitochondrial movement . Neurobiology of Disease . 127 . 410–418 . July 2019 . 30923004 . 10.1016/j.nbd.2019.03.021 . 85496004 .