5IFW

Quantitative interaction mapping reveals an extended ubiquitin regulatory domain in ASPL that disrupts functional p97 hexamers and induces cell death

External Resource: Annotation

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

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	CDC48_N	e5ifwB5	A: beta barrels	X: cradle loop barrel	H: RIFT-related	T: double psi	F: CDC48_N	ECOD (1.6)
B	CDC48	e5ifwB4	A: alpha arrays	X: Histone-like	H: Histone-related	T: AAA+ ATPase lid domain	F: CDC48	ECOD (1.6)
B	Vps4_C_C	e5ifwB6	A: alpha arrays	X: Histone-like	H: Histone-related	T: AAA+ ATPase lid domain	F: Vps4_C_C	ECOD (1.6)
B	CDC48_2	e5ifwB3	A: a+b two layers	X: Cdc48 domain 2-like (From Topology)	H: Cdc48 domain 2-like (From Topology)	T: Cdc48 domain 2-like	F: CDC48_2	ECOD (1.6)
B	Sigma54_activat	e5ifwB2	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Sigma54_activat	ECOD (1.6)
B	Sigma54_activat,Vps4_C_C	e5ifwB1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Sigma54_activat,Vps4_C_C	ECOD (1.6)
A	UBX	e5ifwA1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: UBX	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	2.40.40.20	Mainly Beta	Beta Barrel	Barwin-like endoglucanases		CATH (4.3.0)
B	3.10.330.10	Alpha Beta	Roll	Vcp-like ATPase	Chain A, domain 2	CATH (4.3.0)
B	3.40.50.300	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	P-loop containing nucleotide triphosphate hydrolases	CATH (4.3.0)
B	1.10.8.60	Mainly Alpha	Orthogonal Bundle	Helicase, Ruva Protein	domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B	PF02933	Cell division protein 48 (CDC48), domain 2 (CDC48_2)	Cell division protein 48 (CDC48), domain 2	This domain has a double psi-beta barrel fold and includes VCP-like ATPase and N-ethylmaleimide sensitive fusion protein N-terminal domains. Both the VAT and NSF N-terminal functional domains consist of two structural domains of which this is at t ...	This domain has a double psi-beta barrel fold and includes VCP-like ATPase and N-ethylmaleimide sensitive fusion protein N-terminal domains. Both the VAT and NSF N-terminal functional domains consist of two structural domains of which this is at the C-terminus. The VAT-N domain found in AAA ATPases Pfam:PF00004 is a substrate 185-residue recognition domain [1].	Domain
B	PF17862	AAA+ lid domain (AAA_lid_3)	AAA+ lid domain	This entry represents the alpha helical AAA+ lid domain that is found to the C-terminus of AAA domains.	Domain
B	PF00004	ATPase family associated with various cellular activities (AAA) (AAA)	ATPase family associated with various cellular activities (AAA)	AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes [2].	Domain
B	PF02359	Cell division protein 48 (CDC48), N-terminal domain (CDC48_N)	Cell division protein 48 (CDC48), N-terminal domain	This domain has a double psi-beta barrel fold and includes VCP-like ATPase and N-ethylmaleimide sensitive fusion protein N-terminal domains. Both the VAT and NSF N-terminal functional domains consist of two structural domains of which this is at t ...	This domain has a double psi-beta barrel fold and includes VCP-like ATPase and N-ethylmaleimide sensitive fusion protein N-terminal domains. Both the VAT and NSF N-terminal functional domains consist of two structural domains of which this is at the N-terminus. The VAT-N domain found in AAA ATPases Pfam:PF00004 is a substrate 185-residue recognition domain [1].	Domain
A	PF00789	UBX domain (UBX)	UBX domain	This domain is present in ubiquitin-regulatory proteins and is a general Cdc48-interacting module [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B	Transitional endoplasmic reticulum ATPase	protein phosphatase binding phosphatase binding protein binding binding enzyme binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding protein phosphatase binding phosphatase binding protein binding binding enzyme binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding ubiquitin-modified protein reader activity modification-dependent protein binding protein-macromolecule adaptor activity ubiquitin-like protein reader activity molecular adaptor activity ubiquitin protein ligase binding ubiquitin-like protein ligase binding protein domain specific binding lipid binding enzyme regulator activity enzyme activator activity peptidase regulator activity molecular function activator activity molecular function regulator activity deubiquitinase activator activity peptidase activator activity pyrophosphatase activity ATP hydrolysis activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity ATP-dependent activity MHC class I protein binding signaling receptor binding MHC protein binding polyubiquitin modification-dependent protein binding K48-linked polyubiquitin modification-dependent protein binding ubiquitin-specific protease binding protease binding ADP binding identical protein binding protein-containing complex binding BAT3 complex binding RNA binding nucleic acid binding	catabolic process autophagy cellular process metabolic process process utilizing autophagic mechanism cellular response to stimulus cellular response to heat response to stimulus cellular response to stress response to stress response to heat response to abiotic stimulus response to temperature stimulus protein deubiquitination catabolic process autophagy cellular process metabolic process process utilizing autophagic mechanism cellular response to stimulus cellular response to heat response to stimulus cellular response to stress response to stress response to heat response to abiotic stimulus response to temperature stimulus protein deubiquitination regulation of cellular process regulation of protein modification process positive regulation of protein metabolic process positive regulation of biological process positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process protein modification by small protein removal positive regulation of macromolecule metabolic process protein metabolic process protein modification process regulation of protein modification by small protein conjugation or removal regulation of protein K63-linked deubiquitination positive regulation of cellular process positive regulation of protein K63-linked deubiquitination positive regulation of protein modification by small protein conjugation or removal regulation of biological process regulation of post-translational protein modification protein K63-linked deubiquitination regulation of protein metabolic process positive regulation of protein deubiquitination biological regulation primary metabolic process regulation of macromolecule metabolic process regulation of protein deubiquitination macromolecule modification macromolecule metabolic process post-translational protein modification regulation of metabolic process protein modification by small protein conjugation or removal DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process DNA damage response interstrand cross-link repair DNA repair translesion synthesis postreplication repair nucleobase-containing compound biosynthetic process DNA synthesis involved in DNA repair macromolecule biosynthetic process nucleic acid biosynthetic process biosynthetic process DNA biosynthetic process positive regulation of proteasomal protein catabolic process proteolysis involved in protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process positive regulation of ubiquitin-dependent protein catabolic process regulation of proteolysis regulation of proteolysis involved in protein catabolic process modification-dependent macromolecule catabolic process proteolysis proteasomal protein catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of proteolysis involved in protein catabolic process positive regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process positive regulation of proteolysis regulation of proteasomal protein catabolic process positive regulation of proteasomal ubiquitin-dependent protein catabolic process ubiquitin-dependent protein catabolic process regulation of protein catabolic process localization cellular localization transport establishment of localization in cell intracellular transport endoplasmic reticulum to Golgi vesicle-mediated transport establishment of localization Golgi vesicle transport vesicle-mediated transport cytoplasm protein quality control protein quality control for misfolded or incompletely synthesized proteins cellular component biogenesis cellular component organization cellular component assembly aggresome assembly inclusion body assembly cellular component organization or biogenesis cellular response to misfolded protein response to misfolded protein cellular response to topologically incorrect protein response to topologically incorrect protein signaling endoplasmic reticulum unfolded protein response cellular response to unfolded protein response to unfolded protein intracellular signal transduction cell communication signal transduction response to endoplasmic reticulum stress protein localization establishment of protein localization cellular macromolecule localization macromolecule localization regulation of localization protein localization to chromatin regulation of protein localization protein localization to chromosome regulation of cellular localization protein localization to organelle regulation of protein localization to chromatin regulation of cellular component organization regulation of synapse organization cell junction organization regulation of synapse structure or activity synapse organization regulation of biological quality regulation of mitochondrial membrane potential positive regulation of mitochondrial membrane potential positive regulation of membrane potential regulation of membrane potential protein exit from endoplasmic reticulum nitrogen compound transport ERAD pathway endoplasmic reticulum to cytosol transport response to nitrogen compound protein transport response to chemical retrograde protein transport, ER to cytosol intracellular protein transport macroautophagy positive regulation of Lys63-specific deubiquitinase activity regulation of catalytic activity positive regulation of peptidase activity positive regulation of molecular function regulation of peptidase activity positive regulation of catalytic activity regulation of molecular function positive regulation of hydrolase activity regulation of hydrolase activity positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction regulation of non-canonical NF-kappaB signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of signaling non-canonical NF-kappaB signal transduction positive regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication positive regulation of non-canonical NF-kappaB signal transduction positive regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway positive regulation of Wnt signaling pathway Wnt signaling pathway positive regulation of canonical Wnt signaling pathway cell surface receptor signaling pathway regulation of Wnt signaling pathway protein-DNA covalent cross-linking repair cellular component disassembly protein-containing complex organization protein-containing complex disassembly autophagosome maturation spindle disassembly microtubule cytoskeleton organization mitotic cell cycle mitotic spindle organization organelle organization mitotic cell cycle process organelle disassembly mitotic spindle disassembly microtubule-based process cell cycle cytoskeleton organization microtubule cytoskeleton organization involved in mitosis spindle organization cell cycle process positive regulation of cellular component organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis positive regulation of protein-containing complex assembly regulation of protein-containing complex assembly protein-containing complex assembly regulation of apoptotic process apoptotic process regulation of programmed cell death cell death programmed cell death protein ubiquitination protein modification by small protein conjugation cellular response to arsenic-containing substance response to oxygen-containing compound response to arsenic-containing substance cellular response to oxygen-containing compound cellular response to chemical stimulus response to arsenite ion cellular response to arsenite ion hippo signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process negative regulation of cell communication negative regulation of cellular process negative regulation of response to stimulus negative regulation of hippo signaling negative regulation of signal transduction regulation of hippo signaling nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process nucleotide metabolic process NAD metabolic process NADH metabolic process purine-containing compound metabolic process purine nucleotide metabolic process organophosphate metabolic process nucleobase-containing small molecule metabolic process phosphate-containing compound metabolic process pyridine-containing compound metabolic process small molecule metabolic process phosphorus metabolic process pyridine nucleotide metabolic process nucleotide biosynthetic process carbohydrate derivative metabolic process purine ribonucleotide biosynthetic process positive regulation of phosphate metabolic process purine ribonucleoside triphosphate biosynthetic process positive regulation of nucleotide biosynthetic process regulation of nucleotide biosynthetic process regulation of ATP metabolic process ribonucleotide biosynthetic process purine nucleoside triphosphate biosynthetic process regulation of small molecule metabolic process positive regulation of purine nucleotide biosynthetic process regulation of phosphate metabolic process regulation of nucleotide metabolic process regulation of nucleobase-containing compound metabolic process ribose phosphate biosynthetic process positive regulation of nucleobase-containing compound metabolic process positive regulation of phosphorus metabolic process regulation of purine nucleotide metabolic process ribonucleoside triphosphate biosynthetic process positive regulation of ATP metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process regulation of phosphorus metabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process purine nucleotide biosynthetic process ribose phosphate metabolic process ATP metabolic process ATP biosynthetic process positive regulation of nucleotide metabolic process ribonucleotide metabolic process positive regulation of biosynthetic process purine ribonucleoside triphosphate metabolic process purine-containing compound biosynthetic process ribonucleoside triphosphate metabolic process purine nucleoside triphosphate metabolic process regulation of biosynthetic process carbohydrate derivative biosynthetic process regulation of purine nucleotide biosynthetic process nucleoside triphosphate biosynthetic process positive regulation of purine nucleotide metabolic process positive regulation of ATP biosynthetic process regulation of ATP biosynthetic process positive regulation of small molecule metabolic process aerobic respiration cellular respiration energy derivation by oxidation of organic compounds regulation of generation of precursor metabolites and energy generation of precursor metabolites and energy regulation of cellular respiration regulation of aerobic respiration oxidative phosphorylation positive regulation of oxidative phosphorylation positive regulation of cellular respiration regulation of oxidative phosphorylation protein-RNA complex disassembly protein-RNA complex organization stress granule disassembly flavin-containing compound metabolic process flavin adenine dinucleotide catabolic process organophosphate catabolic process flavin adenine dinucleotide metabolic process nucleoside phosphate catabolic process nucleobase-containing compound catabolic process flavin-containing compound catabolic process nucleotide catabolic process viral genome replication viral process viral life cycle negative regulation of smoothened signaling pathway regulation of smoothened signaling pathway smoothened signaling pathway negative regulation of protein localization to chromatin negative regulation of protein localization endoplasmic reticulum stress-induced pre-emptive quality control double-strand break repair endosome to lysosome transport lysosomal transport endosomal transport endosome to lysosome transport via multivesicular body sorting pathway multivesicular body sorting pathway vacuolar transport endosome transport via multivesicular body sorting pathway	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle protein-containing complex organelle subcompartment membrane membrane protein complex intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle Derlin-1 retrotranslocation complex cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle protein-containing complex organelle subcompartment membrane membrane protein complex intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle Derlin-1 retrotranslocation complex organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum protein-containing complex endoplasmic reticulum membrane catalytic complex peptidase complex proteasome complex endopeptidase complex intracellular protein-containing complex extracellular region vesicle lumen intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen secretory granule lumen intracellular organelle lumen cytoplasmic vesicle organelle lumen secretory granule secretory vesicle vesicle site of double-strand break membraneless organelle site of DNA damage intracellular membraneless organelle chromosome extracellular exosome extracellular vesicle extracellular organelle extracellular space extracellular membrane-bounded organelle synapse cell junction glutamatergic synapse perinuclear region of cytoplasm VCP-NPL4-UFD1 AAA ATPase complex cytoplasmic ribonucleoprotein granule ribonucleoprotein granule supramolecular complex cytoplasmic stress granule lytic vacuole vacuolar lumen lysosome azurophil granule vacuole azurophil granule lumen primary lysosome ficolin-1-rich granule ficolin-1-rich granule lumen nucleus nucleoplasm nuclear lumen ATPase complex VCP-NSFL1C complex lipid droplet
A	Tether containing UBX domain for GLUT4	-	protein localization cellular localization establishment of protein localization nitrogen compound transport transport intracellular transport establishment of localization localization protein transport establishment of localization in cell cellular macromolecule localization macromolecule localization cellular process intracellular protein transport protein localization cellular localization establishment of protein localization nitrogen compound transport transport intracellular transport establishment of localization localization protein transport establishment of localization in cell cellular macromolecule localization macromolecule localization cellular process intracellular protein transport regulation of biological process regulation of cellular process regulation of protein modification process positive regulation of protein metabolic process regulation of protein metabolic process biological regulation positive regulation of biological process primary metabolic process regulation of macromolecule metabolic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process macromolecule modification metabolic process positive regulation of macromolecule metabolic process protein metabolic process macromolecule metabolic process protein modification process regulation of metabolic process positive regulation of cellular process regulation of localization hexose transmembrane transport D-glucose import regulation of transport carbohydrate transport transmembrane transport regulation of transmembrane transport D-glucose transmembrane transport regulation of D-glucose transmembrane transport monosaccharide transmembrane transport carbohydrate transmembrane transport regulation of D-glucose import chemical homeostasis homeostatic process glucose homeostasis carbohydrate homeostasis	cellular anatomical structure endomembrane system membrane-bounded organelle intracellular anatomical structure membrane intracellular membrane-bounded organelle intracellular organelle bounding membrane of organelle organelle endoplasmic reticulum-Golgi intermediate compartment membrane endoplasmic reticulum-Golgi intermediate compartment cytoplasm organelle membrane cytosol cellular anatomical structure endomembrane system membrane-bounded organelle intracellular anatomical structure membrane intracellular membrane-bounded organelle intracellular organelle bounding membrane of organelle organelle endoplasmic reticulum-Golgi intermediate compartment membrane endoplasmic reticulum-Golgi intermediate compartment cytoplasm organelle membrane cytosol perinuclear region of cytoplasm cell periphery plasma membrane vesicle membrane vesicle cytoplasmic side of plasma membrane cytoplasmic side of membrane side of membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B	IPR003959	ATPase, AAA-type, core	Domain
B	IPR005938	AAA ATPase, CDC48 family	Family
B	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
B	IPR029067	CDC48 domain 2-like superfamily	Homologous Superfamily
B	IPR003338	CDC48, N-terminal subdomain	Domain
B	IPR004201	CDC48, domain 2	Domain
B	IPR009010	Aspartate decarboxylase-like domain superfamily	Homologous Superfamily
B	IPR003593	AAA+ ATPase domain	Domain
B	IPR041569	AAA ATPase, AAA+ lid domain	Domain
B	IPR050168	AAA ATPase domain-containing protein	Family
B	IPR003960	ATPase, AAA-type, conserved site	Conserved Site
A	IPR021569	TUG ubiquitin-like domain	Domain
A	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
A	IPR001012	UBX domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P55072	amyotrophic lateral sclerosis Charcot-Marie-Tooth disease type 2Y inclusion body myopathy with Paget disease of bone and frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Charcot-Marie-Tooth disease Stevens-Johnson syndrome inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 behavioral variant of frontotemporal dementia peripheral neuropathy neurodegenerative disease Mycoplasma-Induced Stevens-Johnson Syndrome osteosarcoma peripheral nervous system disease plasma cell myeloma prostate cancer amyotrophic lateral sclerosis Charcot-Marie-Tooth disease type 2Y inclusion body myopathy with Paget disease of bone and frontotemporal dementia frontotemporal dementia and/or amyotrophic lateral sclerosis 6 Charcot-Marie-Tooth disease Stevens-Johnson syndrome inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1 behavioral variant of frontotemporal dementia peripheral neuropathy neurodegenerative disease Mycoplasma-Induced Stevens-Johnson Syndrome osteosarcoma peripheral nervous system disease plasma cell myeloma prostate cancer dementia lymphoplasmacytic lymphoma myopathy ovarian cancer arthrogryposis psoriasis bone Paget disease motor peripheral neuropathy pancreatic ductal adenocarcinoma Pick disease progressive non-fluent aphasia astrocytic tumor spastic paraplegia-Paget disease of bone syndrome toxic epidermal necrolysis cytomegalovirus infection distal myopathy frontotemporal dementia with motor neuron disease limb-girdle muscular dystrophy
A	Pharos: Q9BZE9	alveolar soft part sarcoma MIT family translocation renal cell carcinoma attention deficit hyperactivity disorder, inattentive type cancer

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.