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Gene Review

ULK1  -  unc-51 like autophagy activating kinase 1

Homo sapiens

Synonyms: ATG1, ATG1A, Autophagy-related protein 1 homolog, KIAA0722, Serine/threonine-protein kinase ULK1, ...
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High impact information on ULK1

  • Previous studies showed that the serine/threonine kinase Unc51.1 is one of the earliest genes in neuronal differentiation and is required for granule cell axon formation [1].
  • Transient expression of the six ATG-1-translated 4.1R isoforms tagged with a c-Myc epitope revealed that all of them predominantly distributed to the plasma membrane and the endoplasmic reticulum [2].
  • In contrast to findings in yeast, induction of autophagy by Atg1 is dependent on its kinase activity [3].
  • CONCLUSIONS: Our results reveal a central role for Atg1 in mounting a coordinated autophagic response and demonstrate that autophagy has the capacity to induce cell death [3].
  • Direct induction of autophagy by atg1 inhibits cell growth and induces apoptotic cell death [3].

Biological context of ULK1

  • Both FISH and RH mapping confirmed the regional localization of ULK1 to human chromosome 12q24.3 [4].
  • Sequence analysis of the human ULK1 cDNA showed that an open reading frame is composed of 1050 amino acids with a calculated MW of 112.6 kDa and a pI of 8.80 [4].
  • Southern blot analyses suggested that the ULK1 gene spans 30-40 kb in the human genome as a single-copy gene [4].
  • Amino acid starvation or rapamycin treatment, which upregulates autophagy, causes a redistribution of mAtg9 from the TGN to peripheral, endosomal membranes, which are positive for the autophagosomal marker GFP-LC3. siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution [5].
  • Theses findings indicated that ULK2 is involved in apoptosis through p53 pathway [6].

Anatomical context of ULK1

  • In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized [7].
  • Northern blot analysis revealed that ULK1 is ubiquitously expressed in adult human tissues such as skeletal muscle, heart, pancreas, brain, placenta, liver, kidney, and lung, whereas UNC-51 is specifically detected in the nervous system of C. elegans [4].
  • We identified two mammalian ULK1 (Unc-51-like kinase involved in neurite extension) binding proteins by yeast two-hybrid screening [7].
  • Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes [5].
  • In control experiments, the patterns of the biologic effects of preimmune rIgG or hIgG preparations were similar to those of rATG and hATG, indicating a nonspecific nature of the effects of ATG on progenitor cells [8].

Associations of ULK1 with chemical compounds


Other interactions of ULK1

  • Mouse ULK2 cDNA encodes a putative polypeptide of 1033 aa which has an overall 52% and 33% amino acid identity to ULK1 and UNC-51, respectively [9].

Analytical, diagnostic and therapeutic context of ULK1


  1. Role of Unc51.1 and its binding partners in CNS axon outgrowth. Tomoda, T., Kim, J.H., Zhan, C., Hatten, M.E. Genes Dev. (2004) [Pubmed]
  2. The N-terminal 209-aa domain of high molecular-weight 4.1R isoforms abrogates 4.1R targeting to the nucleus. Luque, C.M., Lallena, M.J., Pérez-Ferreiro, C.M., de Isidro, Y., De Cárcer, G., Alonso, M.A., Correas, I. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Direct induction of autophagy by atg1 inhibits cell growth and induces apoptotic cell death. Scott, R.C., Juh??sz, G., Neufeld, T.P. Curr. Biol. (2007) [Pubmed]
  4. Human ULK1, a novel serine/threonine kinase related to UNC-51 kinase of Caenorhabditis elegans: cDNA cloning, expression, and chromosomal assignment. Kuroyanagi, H., Yan, J., Seki, N., Yamanouchi, Y., Suzuki, Y., Takano, T., Muramatsu, M., Shirasawa, T. Genomics (1998) [Pubmed]
  5. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. Young, A.R., Chan, E.Y., Hu, X.W., Köchl, R., Crawshaw, S.G., High, S., Hailey, D.W., Lippincott-Schwartz, J., Tooze, S.A. J. Cell. Sci. (2006) [Pubmed]
  6. The Gene Expression Profiling in Murine Cortical Cells Undergoing Programmed Cell Death (PCD) Induced by Serum Deprivation. Yang, M.H., Yoo, K.H., Yook, Y.J., Park, E.Y., Jeon, J.O., Choi, S.H., Park, S.Y., Woo, Y.M., Lee, M.J., Park, J.H. J. Biochem. Mol. Biol. (2007) [Pubmed]
  7. Interaction of the Unc-51-like kinase and microtubule-associated protein light chain 3 related proteins in the brain: possible role of vesicular transport in axonal elongation. Okazaki, N., Yan, J., Yuasa, S., Ueno, T., Kominami, E., Masuho, Y., Koga, H., Muramatsu, M. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  8. Is there a direct effect of antithymocyte globulin on hematopoiesis? Chen, G., Kook, H., Zeng, W., Young, N.S., Maciejewski, J.P. Hematol. J. (2004) [Pubmed]
  9. Mouse ULK2, a novel member of the UNC-51-like protein kinases: unique features of functional domains. Yan, J., Kuroyanagi, H., Tomemori, T., Okazaki, N., Asato, K., Matsuda, Y., Suzuki, Y., Ohshima, Y., Mitani, S., Masuho, Y., Shirasawa, T., Muramatsu, M. Oncogene (1999) [Pubmed]
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