Alternative titles; symbols
HGNC Approved Gene Symbol: UHMK1
Cytogenetic location: 1q23.3 Genomic coordinates (GRCh38) : 1:162,497,174-162,529,631 (from NCBI)
By use of a yeast 2-hybrid analysis with a human B-cell library, Boehm et al. (2002) identified a cDNA, designated kinase-interacting stathmin (KIS), that interacts with the cyclin-dependent kinase inhibitor p27Kip1 (CDKN1B; 600778). KIS encodes a 49-kD protein with 98% homology to rat KIS. The protein contains an N-terminal serine/threonine kinase consensus region and a C-terminal region with homology to U2AF65 (191318), a subunit of the mRNA splicing factor U2AF. Northern blot analysis detected ubiquitous expression of a 9.4-kb transcript, with highest expression in skeletal muscle, kidney, placenta, and peripheral blood leukocytes.
Bieche et al. (2003) reported that KIS encodes a predicted 419-amino acid protein, with only 4 divergent amino acids from rat and mouse Kis. Quantitative real-time RT-PCR assays detected ubiquitous expression of rat and human KIS, with highest expression in brain. In rat brain, high KIS expression was seen in the substantia nigra and sensory and motor nuclei of the brainstem. KIS was expressed during brain development, with a large increase in expression after birth through the first postnatal month. Quantitative RT-PCR on human tumor samples showed KIS overexpression in NF1 (613113)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors.
Using a variety of assays, Boehm et al. (2002) found that KIS binds to the C-terminal region of p27Kip1 and phosphorylates it on serine-10, both in vitro and in vivo. Immunofluorescence and confocal microscopy showed that KIS localizes to the nucleus and that its expression is reduced during serum starvation. During serum stimulation, KIS protein levels and kinase activity on p27Kip1 ser10 increased. Pulse-chase analysis showed that p27Kip1 protein expression was stabilized by KIS phosphorylation. Subcellular localization of p27Kip1 was dependent on KIS phosphorylation, and p27Kip1 was redistributed to the cytoplasm during serum stimulation. Expression of KIS small interfering RNA blocked p27Kip1 ser10 phosphorylation and cell cycle progression, as measured by an accumulation of cells at G0/G1.
Bieche et al. (2003) determined that the KIS gene contains 8 exons and spans approximately 31.7 kb.
By radiation hybrid analysis, Boehm et al. (2002) mapped the KIS gene to chromosome 1q23.1.
Bieche, I., Manceau, V., Curmi, P. A., Laurendeau, I., Lachkar, S., Leroy, K., Vidaud, D., Sobel, A., Maucuer, A. Quantitative RT-PCR reveals a ubiquitous but preferentially neural expression of the KIS gene in rat and human. Molec. Brain Res. 114: 55-64, 2003. [PubMed: 12782393] [Full Text: https://doi.org/10.1016/s0169-328x(03)00132-3]
Boehm, M., Yoshimoto, T., Crook, M. F., Nallamshetty, S., True, A., Nabel, G. J., Nabel, E. G. A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J. 21: 3390-3401, 2002. [PubMed: 12093740] [Full Text: https://doi.org/10.1093/emboj/cdf343]