Alternative titles; symbols
HGNC Approved Gene Symbol: ULK2
Cytogenetic location: 17p11.2 Genomic coordinates (GRCh38) : 17:19,770,830-19,867,936 (from NCBI)
By sequencing clones obtained from a size-fractionated brain cDNA library, Ishikawa et al. (1998) cloned ULK2, which they designated KIAA0623. The ULK2 transcript contains a 3-prime Alu sequence, and the deduced protein contains 1,036 amino acids. RT-PCR detected highest ULK2 expression in ovary and testis, followed by brain, kidney, lung, heart, skeletal muscle, and liver. Little to no expression was detected in spleen.
Yan et al. (1999) cloned mouse Ulk2, which contains several polyadenylation sites. The deduced 1,037-amino acid protein has an N-terminal kinase domain characteristic of serine/threonine kinases, as well as a proline/serine-rich domain. Northern blot analysis detected several transcripts between 3.5 and 5.5 kb in all mouse tissues examined. The longest transcript was most abundant in skeletal muscle, and the shortest transcript was most abundant in testis. In situ hybridization of mouse embryos detected Ulk2 in several regions of the developing brain and spinal cord.
Yan et al. (1999) found that mouse Ulk2 was phosphorylated following transfection into COS-7 cells, primarily due to autophosphorylation within the kinase domain.
Using yeast 2-hybrid assays, Tomoda et al. (2004) determined that the C terminus of mouse Unc51.2 binds the C terminus of SynGAP (603384), a negative regulator of Ras (190020) that is associated with neural development.
Chan et al. (2009) found that murine Ulk1 (603168) and Ulk2 associated with different large molecular mass complexes. Mutation analysis showed that both kinase activity and the C-terminal domain of Ulk1 regulated its association with these complexes. Independent motifs within the C-terminal domains of Ulk1 and Ulk2 regulated autophosphorylation, membrane association, and binding and phosphorylation of human ATG13 (615088), an autophagosome protein. The isolated C-terminal domains of Ulk1 and Ulk2 functioned as dominant-negative inhibitors of starvation-induced autophagosome formation and protein degradation. Kinase-inactivated forms of Ulk1 and Ulk2 in HEK293 cells inhibited starvation-induced autophagy. Ulk1 associated with lipid raft markers in detergent-resistant membranes, and its membrane association was not altered following amino acid starvation. In contrast, Ulk2 became partially dephosphorylated and more strongly associated with autophagosomal membranes following amino acid starvation.
By radiation hybrid analysis, Ishikawa et al. (1998) mapped the ULK2 gene to chromosome 17.
Hartz (2013) mapped the ULK2 gene to chromosome 17p11.2 based on an alignment of the ULK2 sequence (GenBank AB014523) with the genomic sequence (GRCh37).
Using FISH, Yan et al. (1999) mapped the mouse Ulk2 gene to chromosome 11B1.3.
Chan, E. Y. W., Longatti, A., McKnight, N. C., Tooze, S. A. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Molec. Cell. Biol. 29: 157-171, 2009. [PubMed: 18936157] [Full Text: https://doi.org/10.1128/MCB.01082-08]
Hartz, P. A. Personal Communication. Baltimore, Md. 2/20/2013.
Ishikawa, K., Nagase, T., Suyama, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 5: 169-176, 1998. [PubMed: 9734811] [Full Text: https://doi.org/10.1093/dnares/5.3.169]
Tomoda, T., Kim, J. H., Zhan, C., Hatten, M. E. Role of Unc51.1 and its binding partners in CNS axon outgrowth. Genes Dev. 18: 541-558, 2004. [PubMed: 15014045] [Full Text: https://doi.org/10.1101/gad.1151204]
Yan, J., Kuroyanagi, H., Tomemori, T., Okazaki, N., Asato, K., Matsuda, Y., Suzuki, Y., Ohshima, Y., Mitani, S., Masuho, Y., Shirasawa, T., Muramatsu, M. Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains. Oncogene 18: 5850-5859, 1999. [PubMed: 10557072] [Full Text: https://doi.org/10.1038/sj.onc.1202988]