Alternative titles; symbols
HGNC Approved Gene Symbol: SNRK
Cytogenetic location: 3p22.1 Genomic coordinates (GRCh38) : 3:43,286,540-43,351,143 (from NCBI)
SNRK is a member of the sucrose nonfermenting (SNF)-related kinase family of serine/threonine kinases (Kertesz et al., 2002).
By sequencing clones obtained from a size-fractionated KG-1 immature myeloid cell line cDNA library, Nagase et al. (1995) obtained a partial SNRK clone, which they designated KIAA0096. The deduced protein has a prenylation site. Northern blot analysis detected SNRK expression in all tissues and cell lines examined, with highest expression in peripheral blood leukocytes.
Using the partial cDNA clone KIAA0096 isolated by Nagase et al. (1995) and the corresponding rat Snrk cDNA for 5-prime RACE, Kertesz et al. (2002) cloned full-length human SNRK from KG-1 cell RNA. The deduced 766-amino acid protein has a calculated molecular mass of 84.27 kD and shares 88% identity with mouse Snrk. Human, rat, and mouse SNRK proteins share a conserved serine/threonine kinase catalytic domain, a bipartite nuclear targeting signal, and an SNF1 homology domain (SNH), the latter being characteristic of some SNF1-related proteins and also found within a ubiquitin-associated (UBA) domain in ubiquitin pathway enzymes.
By RT-PCR of CD34+ cell subsets sorted by FACS analysis, Kertesz et al. (2002) detected significantly lower SNRK expression in quiescent CD34+/CD38- cells compared to highly proliferating CD34+/CD38+ cells and suggested that SNRK may be involved in hematopoietic proliferation. In addition, they detected SNRK expression in numerous leukemic cell lines with the exception of TF-1 cells. Whole-mount in situ hybridization of mouse embryos detected Snrk expression at 8-8.5 days postcoitum extending dorsally along the epithelium of the differentiating neural tube. After 12.5 days postcoitum, Snrk expression became more restricted to the caudal neurotube and neuropore. Snrk expression was also detected in developing primitive gut endoderm, and pericardium of the developing heart, aorta, and endothelial and hematopoietic cells of the yolk-sac blood islands and vessels. Later in development, 12.5-14.5 days postcoitum, Snrk expression persisted in the endocardium and heart septum with decreased neural tube and gut expression. RT-PCR of adult mouse tissues detected strong Snrk expression in kidney, liver, testis, thymus, lymph node, and spleen with lower expression in brain, heart, and lung.
Of 9 rat tissues studied by immunoprecipitation, immunoblot, and activity assay, Jaleel et al. (2005) detected Snrk protein and enzymatic activity only in testis.
By in vitro kinase assay of recombinant SNRK, Kertesz et al. (2002) demonstrated that SNRK acts as a kinase and displays autophosphorylation activity.
Jaleel et al. (2005) identified SNRK as a substrate for the LKB1 tumor suppressor (STK11; 602216), which phosphorylated SNRK at residue thr173. LKB1 is required for phosphorylation and activation of SNRK in HeLa cells and required STRAD (608626) and MO25 (see CAB39, 612174) LKB1 complex-associated subunits.
Using morpholino-mediated gene knockdown in zebrafish, Pramanik et al. (2009) showed that Dusp5 (603069) and Snrk1 targeted a common signaling pathway and coordinately functioned in controlling angioblast numbers at the lateral plate mesoderm.
Using gain- and loss-of-function studies, Chun et al. (2009) showed that Snrk1 played an essential role in the migration, maintenance, and differentiation of angioblasts in zebrafish. The kinase function of Snrk1 was critical for migration and maintenance, but not for differentiation of angioblasts. In vitro, Snrk1-knockdown endothelial cells showed only defects in migration. Snrk1 acted downstream or parallel to Notch (NOTCH1; 190198) and upstream of gridlock (HEY2; 604674) during artery-vein specification. The human SNRK gene compensated for zebrafish Snrk1 knockdown, suggesting conservation of function.
Kertesz et al. (2002) determined that the SNRK gene contains 6 exons spanning 39.8 kb.
By radiation hybrid analysis, Nagase et al. (1995) mapped the SNRK gene to chromosome 3. By genomic sequence analysis, Kertesz et al. (2002) mapped the SNRK gene to chromosome 3p21.
Somatic Mutations
Pramanik et al. (2009) identified a somatic arg248-to-gln (R248Q) mutation in the SNRK gene in 8 of 24 vascular anomaly samples, including venous and lymphatic malformations, but not infantile hemangiomas (602089). Six of the 8 samples also carried a somatic ser147-to-pro (S147P) mutation in the DUSP5 gene. Since studies in zebrafish implicated a role for the Dusp5/Snrk signaling pathway in vascular development, the findings suggested that variation in these genes may provide susceptibility to the development of vascular anomalies in humans.
Chun, C. Z., Kaur, S., Samant, G. V., Wang, L., Pramanik, K., Garnaas, M. K., Li, K., Field, L., Mukhopadhyay, D., Ramchandran, R. Snrk-1 is involved in multiple steps of angioblast development and acts via notch signaling pathway in artery-vein-specification in vertebrates. Blood 113: 1192-1199, 2009. [PubMed: 18723694] [Full Text: https://doi.org/10.1182/blood-2008-06-162156]
Jaleel, M., McBride, A., Lizcano, J. M., Deak, M., Toth, R., Morrice, N. A., Alessi, D. R. Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate. FEBS Lett. 579: 1417-1423, 2005. [PubMed: 15733851] [Full Text: https://doi.org/10.1016/j.febslet.2005.01.042]
Kertesz, N., Samson, J., Debacker, C., Wu, H., Labastie, M.-C. Cloning and characterization of human and mouse SNRK sucrose non-fermenting protein (SNF-1)-related kinases. Gene 294: 13-24, 2002. [PubMed: 12234663] [Full Text: https://doi.org/10.1016/s0378-1119(02)00829-6]
Nagase, T, Miyajima, N, Tanaka, A., Sazuka, T., Seki, N., Sato, S., Tabata, S., Ishikawa, K., Kawarabayashi, Y., Kotani, H., Nomura, N. Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. DNA Res. 2: 37-43, 1995. [PubMed: 7788527] [Full Text: https://doi.org/10.1093/dnares/2.1.37]
Pramanik, K., Chun, C. Z., Garnaas, M. K., Samant, G. V., Li, K., Horswill, M. A., North, P. E., Ramchandran, R. Dusp-5 and Snrk-1 coordinately function during vascular development and disease. Blood 113: 1184-1191, 2009. [PubMed: 18927432] [Full Text: https://doi.org/10.1182/blood-2008-06-162180]