Kinase Family ULK

Kinase Classification: Group Other: Family ULK

ULK (Unc-51-Like Kinases) kinases found in almost all eukaryotes, involved in autophagy.

Classification and Evolution

ULK kinases are found in all eukaryotes examined. There are four main subfamilies: Fused, ULK1, ULK3 and ULK4. ULK4 may be the oldest, though it is a pseudokinase.

ULK1 subfamily are characterized by a C-terminal DUF3543 domain. The kinase domain of animal ULK3 is somewhat closer to protist ULK1s, so the subfamily definition also incorporates the DUF3543 domain.

ULK1 has the strongest link to autophagy in yeast (Atg1) and human (ULK1 and ULK3).

ULK3 and Fused are involved in hedgehog signaling

ULK4 is an ancient and conserved pseudokinase. Human ULK4 has been genetically linked to multiple myeloma by GWAS, and may be linked to hydrocephalus and blood pressure. The Arabidopsis homolog, RUK, is involved in cytokinesis (http://www.ncbi.nlm.nih.gov/gene/831988).

Domain Structure

All ULK kinases have an N-terminal kinase domain and most have C-terminal extensions. ULK1 have a C-terminal DUF3543 domain, Fused proteins have HEAT repeats, and ULK3 often have MIT domains

References

1. Asensio CS, Sirkis DW, and Edwards RH. RNAi screen identifies a role for adaptor protein AP-3 in sorting to the regulated secretory pathway. J Cell Biol. 2010 Dec 13;191(6):1173-87. DOI:10.1083/jcb.201006131 |
2. Zhao Y, Zheng J, Ling Y, Hou L, and Zhang B. Transcriptional upregulation of DNA polymerase beta by TEIF. Biochem Biophys Res Commun. 2005 Aug 5;333(3):908-16. DOI:10.1016/j.bbrc.2005.05.172 |

Unlinked References

1. Bjorklund pmid=16496002
2. Lim pmid=16713569