Alternative titles; symbols
HGNC Approved Gene Symbol: KIFAP3
Cytogenetic location: 1q24.2 Genomic coordinates (GRCh38) : 1:169,921,329-170,085,184 (from NCBI)
Using a yeast 2-hybrid system, Shimizu et al. (1996) isolated the gene encoding a protein which interacts with smg GDS (see 179502) and named it SMAP, for 'smg GDS-associated protein.' The cDNA encodes a 792-amino acid polypeptide containing 9 Armadillo repeats, found in the Drosophila 'Armadillo' protein and implicated in protein-protein interactions. SMAP protein is phosphorylated by v-src (SRC; 190090), and this phosphorylation reduces the affinity of SMAP for smg GDS. Northern blot and tissue distribution analyses revealed that SMAP is expressed ubiquitously and is highly concentrated in the endoplasmic reticulum. Shimizu et al. (1996) also noted that SMAP is homologous to the sea urchin gene SpKAP115, an accessory subunit of sea urchin kinesin.
Stumpf (2024) mapped the KIFAP3 gene to chromosome 1q24.2 based on an alignment of the KIFAP3 sequence (GenBank BC028679) with the genomic sequence (GRCh38).
For discussion of a possible association between variation in the KIFAP3 gene and survival in amyotrophic lateral sclerosis (ALS), see 105400.
Mutations in the superoxide dismutase-1 (SOD1; 147450) gene cause familial amyotrophic lateral sclerosis (ALS1; 105400), likely due to the toxic properties of misfolded mutant SOD1 protein. Tateno et al. (2009) demonstrated that, starting from the pre-onset stage of ALS, misfolded SOD1 species associated specifically with Kifap3 in the ventral white matter of SOD1G93A-transgenic mouse spinal cord. KIFAP3 is responsible for binding to cargoes including choline acetyltransferase (CHAT; 118490) as a component of the kinesin-2 motor complex. Motor axons in SOD1G93A-Tg mice also showed a reduction in ChAT transport from the pre-onset stage. Using a purified hybrid mouse neuroblastoma/rat glioma cell line NG108-15 transfected with SOD1 mutations, the authors showed that microtubule-dependent release of acetylcholine was significantly impaired by misfolded SOD1 species and that impairment was normalized by KIFAP3 overexpression. KIFAP3 was incorporated into SOD1 aggregates in spinal motor neurons from human ALS patients as well. Tateno et al. (2009) suggested that KIFAP3 sequestration by misfolded SOD1 species and the resultant inhibition of ChAT transport play a role in the pathophysiology of ALS.
Shimizu, K., Kawabe, H., Minimi, S., Honda, T., Takaishi, K., Shirataki, H., Takai, Y. SMAP, an Smg GDS-associating protein having arm repeats and phosphorylated by Src tyrosine kinase. J. Biol. Chem. 271: 27013-27017, 1996. [PubMed: 8900189] [Full Text: https://doi.org/10.1074/jbc.271.43.27013]
Stumpf, A. M. Personal Communication. Baltimore, Md. 04/03/2024.
Tateno, M., Kato, S., Sakurai, T., Nukina, N., Takahashi, R., Araki, T. Mutant SOD1 impairs axonal transport of choline acetyltransferase and acetylcholine release by sequestering KAP3. Hum. Molec. Genet. 18: 942-955, 2009. [PubMed: 19088126] [Full Text: https://doi.org/10.1093/hmg/ddn422]