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MGP004792

UniProt Annotations

Entry Information
Gene Nameunc-51 like kinase 3
Protein EntryULK3_HUMAN
UniProt IDQ6PHR2
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; IsoId=Q6PHR2-1; Sequence=Displayed; Name=2; IsoId=Q6PHR2-2; Sequence=VSP_038147, VSP_038148; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.; Name=3; IsoId=Q6PHR2-3; Sequence=VSP_039925; Note=May be due to competing donor splice site. No experimental confirmation available.; Name=4; IsoId=Q6PHR2-4; Sequence=VSP_057411; Note=No experimental confirmation available.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
FunctionSerine/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:0000269|PubMed:19279323, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20643644}.
InductionUp-regulated during senescence. {ECO:0000269|PubMed:19279323}.
PtmAutophosphorylated. Autophosphorylation is blocked by interaction with SUFU. {ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:20643644}.
Sequence CautionSequence=CAB55955.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 2 MIT domains. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:19279323, ECO:0000269|PubMed:19878745}. Note=Localizes to pre-autophagosomal structure during cellular senescence.
SubunitInteracts (via protein kinase domain) with SUFU. {ECO:0000269|PubMed:20643644}.
Tissue SpecificityWidely 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:0000269|PubMed:19878745}.
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