8SOI | pdb_00008soi

Structure of human ULK1 complex core (2:1:1 stoichiometry)

External Resource: Annotation

Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C	PF12063	Atg1-like, MIT domain 1 (ATG1-like_MIT1)	Atg1-like, MIT domain 1	Members of this entry are serine/threonine-protein kinases and includes ATG1 from yeasts, Unc-51 from C. elegans and ULK1-2 from humans. ATG1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway [1,2]. U ...	Members of this entry are serine/threonine-protein kinases and includes ATG1 from yeasts, Unc-51 from C. elegans and ULK1-2 from humans. ATG1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway [1,2]. Unc-51 is important for axonal elongation and axonal guidance [4] and ULK1-2 are involved in autophagy in response to starvation [3]. They consist of a kinase domain at the N-terminal (Pfam:PF00069) and two tandem microtubule interacting and transport (MIT) domains (tMIT) at the C-terminal. MIT domains are known to mediate protein-protein interactions. In ATG1, MIT domains mediate the interaction with ATG13 [1]. In ULK1-2, MIT domains control the regulatory function and localization of the proteins and also mediate interactions with additional autophagy proteins [3]. This is the C-terminal MIT domain (MIT2).	Domain
C	PF21127	ATG1-like, MIT domain 2 (ATG1-like_MIT2)	ATG1-like, MIT domain 2	Members of this entry are serine/threonine-protein kinases and includes Atg1 from yeasts, Unc-51 from C. elegans and ULK1-2 from humans. Atg1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway [1,2]. ...	Members of this entry are serine/threonine-protein kinases and includes Atg1 from yeasts, Unc-51 from C. elegans and ULK1-2 from humans. Atg1 is required for vesicle formation in autophagy and the cytoplasm-to-vacuole targeting (Cvt) pathway [1,2]. Unc-51 is important for axonal elongation and axonal guidance [4,5] and ULK1-2 are involved in autophagy in response to starvation [3]. They consist of a kinase domain at the N-terminal (Pfam:PF00069) and two tandem microtubule interacting and transport (MIT) domains (tMIT) at the C-terminal which, in ATG1, mediates the interaction with ATG13 [1]. In ULK1-2, MIT domain control the regulatory function and localization of the proteins and also mediate interactions with additional autophagy proteins [3]. This is the C-terminal MIT domain (MIT2).	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	RB1-inducible coiled-coil protein 1	protein-membrane adaptor activity protein-macromolecule adaptor activity molecular adaptor activity protein binding binding kinase binding enzyme binding protein kinase binding	carbohydrate metabolic process catabolic process glucan catabolic process energy derivation by oxidation of organic compounds macroautophagy glycogen metabolic process carbohydrate catabolic process autophagy primary metabolic process generation of precursor metabolites and energy macromolecule catabolic process polysaccharide metabolic process glucan metabolic process glycogen catabolic process glycophagy carbohydrate metabolic process catabolic process glucan catabolic process energy derivation by oxidation of organic compounds macroautophagy glycogen metabolic process carbohydrate catabolic process autophagy primary metabolic process generation of precursor metabolites and energy macromolecule catabolic process polysaccharide metabolic process glucan metabolic process glycogen catabolic process glycophagy polysaccharide catabolic process metabolic process cellular process energy reserve metabolic process macromolecule metabolic process process utilizing autophagic mechanism developmental process multicellular organism development multicellular organismal process hepaticobiliary system development gland development animal organ development anatomical structure development liver development system development heart development circulatory system development autophagosome assembly organelle assembly vacuole organization autophagosome organization cellular component biogenesis cellular component organization organelle organization cellular component assembly cellular component organization or biogenesis piecemeal microautophagy of the nucleus microautophagy nucleophagy biological process involved in interspecies interaction between organisms response to stimulus immune response response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus immune system process defense response to other organism response to stress innate immune response response to external biotic stimulus cellular response to stimulus regulation of biological process regulation of cellular process cell surface receptor signaling pathway signaling biological regulation cell death extrinsic apoptotic signaling pathway cell communication apoptotic signaling pathway signal transduction apoptotic process programmed cell death autophagy of peroxisome pexophagy ribophagy positive regulation of cell communication positive regulation of signal transduction positive regulation of biological process regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus positive regulation of JNK cascade regulation of intracellular signal transduction JNK cascade intracellular signaling cassette positive regulation of cellular process regulation of signaling positive regulation of MAPK cascade regulation of JNK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication positive regulation of signaling autophagy of mitochondrion negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation negative regulation of cellular process negative regulation of biological process negative regulation of signaling regulation of programmed cell death negative regulation of cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway negative regulation of response to stimulus negative regulation of programmed cell death regulation of apoptotic process negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic process regulation of apoptotic signaling pathway positive regulation of cell size regulation of cellular component size regulation of biological quality regulation of cell size regulation of anatomical structure size regulation of protein modification process lipoprotein biosynthetic process lipoprotein metabolic process regulation of primary metabolic process protein lipidation regulation of lipoprotein metabolic process protein metabolic process protein modification process regulation of biosynthetic process regulation of protein lipidation regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule biosynthetic process biosynthetic process macromolecule modification regulation of macromolecule biosynthetic process regulation of metabolic process defense response to virus response to virus positive regulation of autophagy regulation of catabolic process regulation of autophagy positive regulation of catabolic process positive regulation of metabolic process reticulophagy	membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope cellular anatomical structure organelle nuclear envelope organelle membrane protein kinase complex membrane-bounded organelle intracellular anatomical structure nuclear membrane membrane nucleus intracellular membrane-bounded organelle endomembrane system intracellular organelle organelle envelope cellular anatomical structure organelle nuclear envelope organelle membrane protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex catalytic complex serine/threonine protein kinase complex Atg1/ULK1 kinase complex cytoplasm transferase complex cytosol phagophore assembly site membrane phagophore assembly site lytic vacuole vacuole lysosome organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane vacuolar membrane autophagosome membrane autophagosome bounding membrane of organelle
C	Serine/threonine-protein kinase ULK1	small GTPase binding protein binding binding enzyme binding GTPase binding protein serine/threonine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups histone H2AS121 kinase activity histone modifying activity small GTPase binding protein binding binding enzyme binding GTPase binding protein serine/threonine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups histone H2AS121 kinase activity histone modifying activity histone H2A kinase activity catalytic activity histone kinase activity AMP-activated protein kinase activity DNA-dependent protein kinase activity histone H3T45 kinase activity histone H3 kinase activity eukaryotic translation initiation factor 2alpha kinase activity adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding protein-containing complex binding histone H3T6 kinase activity histone H3T3 kinase activity histone H2BS14 kinase activity histone H2B kinase activity identical protein binding histone H3S57 kinase activity Rho-dependent protein serine/threonine kinase activity histone H2AT120 kinase activity histone H2AXS139 kinase activity histone H2AX kinase activity histone H4S1 kinase activity histone H4 kinase activity protein serine kinase activity histone H3T11 kinase activity histone H3S28 kinase activity 3-phosphoinositide-dependent protein kinase activity histone H2BS36 kinase activity histone H2AS1 kinase activity ribosomal protein S6 kinase activity histone H3S10 kinase activity	multicellular organismal process regulation of growth regulation of cellular process axonogenesis regulation of cellular component size cell projection organization developmental growth negative regulation of biological process regulation of cell differentiation regulation of neurogenesis neuron projection development regulation of cell development multicellular organism development cell projection morphogenesis neuron differentiation multicellular organismal process regulation of growth regulation of cellular process axonogenesis regulation of cellular component size cell projection organization developmental growth negative regulation of biological process regulation of cell differentiation regulation of neurogenesis neuron projection development regulation of cell development multicellular organism development cell projection morphogenesis neuron differentiation negative regulation of growth neuron projection morphogenesis cell differentiation anatomical structure development regulation of biological quality system development developmental process regulation of biological process negative regulation of cellular component organization regulation of cell projection organization negative regulation of cell growth nervous system development developmental growth involved in morphogenesis generation of neurons negative regulation of axonogenesis negative regulation of developmental growth negative regulation of multicellular organismal process regulation of neuron projection development regulation of collateral sprouting regulation of cellular component organization cellular developmental process regulation of developmental process plasma membrane bounded cell projection morphogenesis cell development cell growth cell morphogenesis cellular component organization regulation of nervous system development neurogenesis negative regulation of neurogenesis regulation of extent of cell growth regulation of axonogenesis negative regulation of cellular process negative regulation of nervous system development regulation of multicellular organismal process negative regulation of cell differentiation cellular component organization or biogenesis negative regulation of cell projection organization regulation of anatomical structure morphogenesis regulation of cell size regulation of multicellular organismal development collateral sprouting regulation of developmental growth plasma membrane bounded cell projection organization developmental cell growth negative regulation of developmental process biological regulation growth axon development regulation of cell growth cell morphogenesis involved in neuron differentiation negative regulation of neuron projection development anatomical structure morphogenesis negative regulation of cell development neuron development cellular process negative regulation of collateral sprouting regulation of plasma membrane bounded cell projection organization regulation of anatomical structure size protein localization localization cellular localization cellular macromolecule localization macromolecule localization catabolic process macroautophagy autophagy regulation of catabolic process regulation of autophagy regulation of macroautophagy metabolic process process utilizing autophagic mechanism regulation of metabolic process cellular response to stimulus cellular response to nutrient levels response to nutrient levels response to stimulus piecemeal microautophagy of the nucleus microautophagy nucleophagy protein-containing complex organization regulation of cellular component biogenesis negative regulation of protein-containing complex assembly cellular component biogenesis regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly protein phosphorylation protein autophosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process peptidyl-serine modification peptidyl-serine phosphorylation peptidyl-amino acid modification axon extension neuron projection extension regulation of protein modification process lipoprotein biosynthetic process lipoprotein metabolic process regulation of primary metabolic process protein lipidation regulation of lipoprotein metabolic process regulation of biosynthetic process regulation of protein lipidation regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule biosynthetic process biosynthetic process regulation of macromolecule biosynthetic process positive regulation of organelle organization positive regulation of cellular component organization positive regulation of vacuole organization positive regulation of biological process autophagosome organization positive regulation of metabolic process positive regulation of autophagosome assembly positive regulation of macroautophagy positive regulation of cellular process positive regulation of autophagy autophagosome assembly organelle assembly vacuole organization positive regulation of cellular component biogenesis regulation of autophagosome assembly regulation of vacuole organization regulation of organelle organization positive regulation of catabolic process organelle organization regulation of organelle assembly positive regulation of organelle assembly signaling response to cytokine regulation of signal transduction cytokine-mediated signaling pathway cell communication cellular response to tumor necrosis factor tumor necrosis factor-mediated signaling pathway cellular response to cytokine stimulus signal transduction regulation of signaling regulation of tumor necrosis factor-mediated signaling pathway cell surface receptor signaling pathway regulation of cytokine-mediated signaling pathway response to peptide regulation of response to cytokine stimulus regulation of response to stimulus response to chemical regulation of cell communication response to tumor necrosis factor regeneration neuron projection regeneration cellular response to stress response to stress response to starvation negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation mitophagy autophagy of mitochondrion reticulophagy	protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex cellular anatomical structure intracellular anatomical structure catalytic complex serine/threonine protein kinase complex Atg1/ULK1 kinase complex cytoplasm transferase complex cytosol membrane-bounded organelle intracellular organelle organelle protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex cellular anatomical structure intracellular anatomical structure catalytic complex serine/threonine protein kinase complex Atg1/ULK1 kinase complex cytoplasm transferase complex cytosol membrane-bounded organelle intracellular organelle organelle vacuole autophagosome intracellular membrane-bounded organelle vacuolar membrane autophagosome membrane membrane bounding membrane of organelle organelle membrane endosome intracellular vesicle recycling endosome endomembrane system cytoplasmic vesicle vesicle mitochondrial membrane mitochondrion organelle outer membrane organelle envelope mitochondrial envelope mitochondrial outer membrane outer membrane axon cell projection neuron projection plasma membrane bounded cell projection phagophore assembly site phagophore assembly site membrane organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane omegasome membrane omegasome
D	Autophagy-related protein 13	protein binding binding kinase binding enzyme binding protein kinase binding enzyme regulator activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity protein kinase regulator activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups molecular function regulator activity protein binding binding kinase binding enzyme binding protein kinase binding enzyme regulator activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity protein kinase regulator activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups molecular function regulator activity catalytic activity kinase regulator activity protein serine/threonine kinase activity protein serine/threonine kinase activator activity molecular function activator activity kinase activator activity enzyme activator activity protein kinase activator activity	negative regulation of cell population proliferation regulation of biological process cell population proliferation regulation of cellular process regulation of cell population proliferation negative regulation of cellular process biological regulation negative regulation of biological process cellular process autophagosome assembly catabolic process organelle assembly vacuole organization macroautophagy negative regulation of cell population proliferation regulation of biological process cell population proliferation regulation of cellular process regulation of cell population proliferation negative regulation of cellular process biological regulation negative regulation of biological process cellular process autophagosome assembly catabolic process organelle assembly vacuole organization macroautophagy autophagy autophagosome organization cellular component biogenesis cellular component organization organelle organization cellular component assembly metabolic process cellular component organization or biogenesis process utilizing autophagic mechanism piecemeal microautophagy of the nucleus microautophagy nucleophagy regulation of protein modification process lipoprotein biosynthetic process lipoprotein metabolic process regulation of primary metabolic process protein lipidation regulation of lipoprotein metabolic process protein metabolic process protein modification process regulation of biosynthetic process regulation of protein lipidation regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process macromolecule biosynthetic process biosynthetic process macromolecule modification regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process cellular response to stimulus cellular response to stress response to stimulus response to mitochondrial depolarisation response to stress mitophagy autophagy of mitochondrion positive regulation of autophagy positive regulation of biological process regulation of catabolic process regulation of autophagy positive regulation of catabolic process positive regulation of metabolic process positive regulation of cellular process protein localization regulation of localization establishment of protein localization cellular localization regulation of protein localization protein targeting regulation of protein targeting to mitochondrion positive regulation of establishment of protein localization localization cellular macromolecule localization positive regulation of protein targeting to mitochondrion regulation of establishment of protein localization establishment of localization regulation of establishment of protein localization to mitochondrion establishment of protein localization to organelle regulation of protein targeting regulation of cellular localization macromolecule localization protein localization to organelle protein localization to mitochondrion positive regulation of protein localization protein targeting to mitochondrion establishment of protein localization to mitochondrion positive regulation of establishment of protein localization to mitochondrion protein localization to phagophore assembly site	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle vacuole autophagosome protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex catalytic complex membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle vacuole autophagosome protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex catalytic complex serine/threonine protein kinase complex Atg1/ULK1 kinase complex transferase complex cytosol phagophore assembly site membrane membrane phagophore assembly site organelle subcompartment endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR019460	Autophagy-related protein 11, C-terminal	Domain
A, B	IPR040040	Autophagy-related protein 11	Family
C	IPR045269	Serine/threonine-protein kinase Atg1-like	Family
C	IPR000719	Protein kinase domain	Domain
C	IPR048941	ATG1-like, MIT domain 2	Domain
C	IPR016237	Serine/threonine-protein kinase, Ulk1/Ulk2	Family
C	IPR017441	Protein kinase, ATP binding site	Binding Site
C	IPR022708	Serine/threonine-protein kinase Atg1-like, tMIT domain	Domain
C	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
C	IPR008271	Serine/threonine-protein kinase, active site	Active Site
D	IPR036570	HORMA domain superfamily	Homologous Superfamily
D	IPR040182	Autophagy-related protein 13	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q8TDY2	schizophrenia breast carcinoma Alzheimer disease breast adenocarcinoma glioblastoma limb-girdle muscular dystrophy Malignant neoplasm of breast ovarian cancer astrocytic tumor breast cancer hereditary breast carcinoma malignant glioma plasma cell myeloma spina bifida atypical teratoid rhabdoid tumor schizophrenia breast carcinoma Alzheimer disease breast adenocarcinoma glioblastoma limb-girdle muscular dystrophy Malignant neoplasm of breast ovarian cancer astrocytic tumor breast cancer hereditary breast carcinoma malignant glioma plasma cell myeloma spina bifida atypical teratoid rhabdoid tumor hereditary spastic paraplegia malignant mesothelioma sarcoidosis
C	Pharos: O75385	gastrointestinal stromal tumor malignant glioma Pancreatic Neuroendocrine Tumor subependymal giant cell astrocytoma lung adenocarcinoma osteosarcoma pilocytic astrocytoma thrombocytopenia due to immune destruction malignant ependymoma ovarian mucinous adenocarcinoma renal cell carcinoma
D	Pharos: O75143	atypical teratoid rhabdoid tumor lung cancer psoriasis autism spectrum disorder osteoarthritis vascular disease large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.