InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ULK3

Summary

InnateDB Protein

IDBP-377894.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ULK3

Protein Name

unc-51-like kinase 3 (C. elegans)

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000400312

InnateDB Gene

IDBG-22723 (ULK3)

Protein Structure

UniProt Annotation

Function

Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy. {ECO:0000269PubMed:19279323, ECO:0000269PubMed:19878745, ECO:0000269PubMed:20643644}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:19279323, ECO:0000269PubMed:19878745}. Note=Localizes to pre-autophagosomal structure during cellular senescence.

Disease Associations

Tissue Specificity

Widely expressed. Highest levels observed in fetal brain. In adult tissues, high levels in brain, liver and kidney, moderate levels in testis and adrenal gland and low levels in heart, lung, stomach, thymus, prostate and placenta. In the brain, highest expression in the hippocampus, high levels also detected in the cerebellum, olfactory bulb and optic nerve. In the central nervous system, lowest levels in the spinal cord. {ECO:0000269PubMed:19878745}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor

Biological Process

GO:0000045	autophagic vacuole assembly
GO:0006468	protein phosphorylation
GO:0006914	autophagy
GO:0009103	lipopolysaccharide biosynthetic process
GO:0010506	regulation of autophagy
GO:0045879	negative regulation of smoothened signaling pathway
GO:0045880	positive regulation of smoothened signaling pathway
GO:0046777	protein autophosphorylation
GO:0090398	cellular senescence

Cellular Component

GO:0000407	pre-autophagosomal structure
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane
GO:0034273	ATG1/UKL1 signaling complex

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR007330 MIT
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF04212
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00745
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt