4WLR | pdb_00004wlr

Crystal Structure of mUCH37-hRPN13 CTD-hUb complex

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
C	d4wlrc_	Alpha and beta proteins (a+b)	beta-Grasp (ubiquitin-like)	Ubiquitin-like	Ubiquitin-related	Ubiquitin	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2 Family	RPN13 C-terminal domain-like	8045758	4004665	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	Deubiquitinase adaptor domain (DEUBAD)-like	8091996	3002549	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Ubiquitin-like	8101457	3000157	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	KOG2778	e4wlrA2	A: alpha duplicates or obligate multimers	X: L27 domain (From Topology)	H: L27 domain (From Topology)	T: L27 domain	F: KOG2778	ECOD (1.6)
A	Peptidase_C12	e4wlrA1	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: Peptidase_C12	ECOD (1.6)
B	RPN13_C	e4wlrB1	A: alpha arrays	X: C-terminal domain of hRpn13 (From Topology)	H: C-terminal domain of hRpn13 (From Topology)	T: C-terminal domain of hRpn13	F: RPN13_C	ECOD (1.6)
C	ubiquitin_1	e4wlrC1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.40.532.10	Alpha Beta	3-Layer(aba) Sandwich	Ubiquitin C-terminal Hydrolase UCH-l3	Peptidase C12, ubiquitin carboxyl-terminal hydrolase	CATH (utative)
A	1.20.58.860	Mainly Alpha	Up-down Bundle	Methane Monooxygenase Hydroxylase	Chain G, domain 1	CATH (utative)
B	1.10.2020.20	Mainly Alpha	Orthogonal Bundle	uronate isomerase, domain 2, chain A		CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF18031	Ubiquitin carboxyl-terminal hydrolases (UCH_C)	Ubiquitin carboxyl-terminal hydrolases	This is the C-terminal domain found in eukaryotic UCH37 proteins (also known as Ubiquitin carboxyl-terminal hydrolase isozyme L5, UCHL5). UCH37 is a subunit of two complexes: INO80, which performs ATP-dependent sliding of nucleosomes for transcriptio ...	This is the C-terminal domain found in eukaryotic UCH37 proteins (also known as Ubiquitin carboxyl-terminal hydrolase isozyme L5, UCHL5). UCH37 is a subunit of two complexes: INO80, which performs ATP-dependent sliding of nucleosomes for transcriptional regulation and DNA repair, and the 26S proteasome, which performs ATP-dependent proteolysis of polyubiquitylated proteins in the cytosol and nucleus. Recruitment to the proteasome is mediated by the C-terminal domain of RPN13 (also known as ADRM1). Recruitment to INO80 is mediated by the N-terminal domain of NFRKB. Structural and biochemical analysis reveal that RPN13 and NFRKB make similar interactions with the UCH37 C-terminal domain but have very different interactions with the catalytic UCH domain that are activating in the case of RPN13 and highly inhibitory in the case of NFRKB [3].	Domain
A	PF01088	Ubiquitin carboxyl-terminal hydrolase, family 1 (Peptidase_C12)	Ubiquitin carboxyl-terminal hydrolase, family 1		Domain
C	PF00240	Ubiquitin family (ubiquitin)	Ubiquitin family	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry ...	This family contains a number of ubiquitin-like proteins: SUMO (smt3 homologue) (see Swiss:Q02724), Nedd8 (see Swiss:P29595), Elongin B (see Swiss:Q15370), Rub1 (see Swiss:Q9SHE7), and Parkin (see Swiss:O60260). A number of them are thought to carry a distinctive five-residue motif termed the proteasome-interacting motif (PIM), which may have a biologically significant role in protein delivery to proteasomes and recruitment of proteasomes to transcription sites [5].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Ubiquitin carboxyl-terminal hydrolase isozyme L5	enzyme regulator activity peptidase activity peptidase regulator activity catalytic activity, acting on a protein hydrolase activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity molecular function inhibitor activity molecular function regulator activity catalytic activity endopeptidase activity cysteine-type peptidase activity enzyme regulator activity peptidase activity peptidase regulator activity catalytic activity, acting on a protein hydrolase activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity endopeptidase inhibitor activity molecular function inhibitor activity molecular function regulator activity catalytic activity endopeptidase activity cysteine-type peptidase activity ubiquitin-like protein peptidase activity cysteine-type deubiquitinase activity deubiquitinase activity protein-containing complex binding binding proteasome binding	developmental process multicellular organismal process head development animal organ development brain development nervous system development multicellular organism development central nervous system development midbrain development anatomical structure development system development regulation of biological process regulation of cellular component organization regulation of cellular process developmental process multicellular organismal process head development animal organ development brain development nervous system development multicellular organism development central nervous system development midbrain development anatomical structure development system development regulation of biological process regulation of cellular component organization regulation of cellular process biological regulation chromosome organization regulation of chromosome organization regulation of organelle organization cellular component organization organelle organization cellular process cellular component organization or biogenesis primary metabolic process DNA metabolic process regulation of macromolecule metabolic process nucleic acid metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process DNA replication metabolic process macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of metabolic process regulation of DNA replication regulation of DNA metabolic process lateral ventricle development forebrain development ventricular system development telencephalon development cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction cell communication positive regulation of response to stimulus positive regulation of smoothened signaling pathway signal transduction positive regulation of cellular process regulation of smoothened signaling pathway regulation of signaling cell surface receptor signaling pathway smoothened signaling pathway regulation of response to stimulus regulation of cell communication positive regulation of signaling regulation of cellular response to stress positive regulation of metabolic process positive regulation of DNA repair cellular response to stress response to stress regulation of response to stress positive regulation of macromolecule metabolic process DNA repair positive regulation of nucleobase-containing compound metabolic process regulation of DNA repair positive regulation of DNA metabolic process DNA damage response DNA recombination telomere organization telomere maintenance catabolic process negative regulation of proteolysis negative regulation of proteolysis involved in protein catabolic process proteolysis involved in protein catabolic process negative regulation of biological process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process regulation of ubiquitin-dependent protein catabolic process negative regulation of protein catabolic process regulation of proteolysis involved in protein catabolic process regulation of proteolysis modification-dependent macromolecule catabolic process proteolysis negative regulation of cellular process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of ubiquitin-dependent protein catabolic process negative regulation of catabolic process negative regulation of proteasomal ubiquitin-dependent protein catabolic process regulation of protein metabolic process negative regulation of metabolic process proteasomal protein catabolic process protein catabolic process regulation of catabolic process regulation of proteasomal ubiquitin-dependent protein catabolic process modification-dependent protein catabolic process negative regulation of proteasomal protein catabolic process regulation of proteasomal protein catabolic process ubiquitin-dependent protein catabolic process regulation of protein catabolic process brain morphogenesis forebrain morphogenesis anatomical structure morphogenesis animal organ morphogenesis positive regulation of DNA-templated transcription RNA metabolic process positive regulation of macromolecule biosynthetic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process positive regulation of RNA metabolic process regulation of gene expression biosynthetic process positive regulation of RNA biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription protein deubiquitination protein modification by small protein removal macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation or removal regulation of embryonic development regulation of multicellular organismal development regulation of developmental process embryo development regulation of multicellular organismal process cell cycle regulation of cell cycle positive regulation of organelle organization telomere maintenance in response to DNA damage positive regulation of telomere maintenance positive regulation of chromosome organization regulation of telomere maintenance positive regulation of cellular component organization positive regulation of telomere maintenance in response to DNA damage regulation of telomere maintenance in response to DNA damage regulation of DNA strand elongation DNA strand elongation chromatin organization chromatin remodeling	membrane-bounded organelle ATPase complex protein-containing complex intracellular anatomical structure nucleus membrane-enclosed lumen nuclear protein-containing complex nuclear chromosome chromosome intracellular organelle lumen intracellular organelle cellular anatomical structure membraneless organelle SWI/SNF superfamily-type complex membrane-bounded organelle ATPase complex protein-containing complex intracellular anatomical structure nucleus membrane-enclosed lumen nuclear protein-containing complex nuclear chromosome chromosome intracellular organelle lumen intracellular organelle cellular anatomical structure membraneless organelle SWI/SNF superfamily-type complex INO80-type complex catalytic complex intracellular membraneless organelle chromatin intracellular membrane-bounded organelle Ino80 complex organelle lumen organelle nuclear lumen nucleolus cytoplasm cytosol nucleoplasm peptidase complex cytosolic proteasome complex proteasome complex endopeptidase complex intracellular protein-containing complex
B	Proteasomal ubiquitin receptor ADRM1	molecular function inhibitor activity molecular function regulator activity protein binding binding enzyme binding protease binding protein-containing complex binding proteasome binding enzyme regulator activity peptidase activity peptidase regulator activity catalytic activity, acting on a protein molecular function activator activity hydrolase activity molecular function inhibitor activity molecular function regulator activity protein binding binding enzyme binding protease binding protein-containing complex binding proteasome binding enzyme regulator activity peptidase activity peptidase regulator activity catalytic activity, acting on a protein molecular function activator activity hydrolase activity peptidase activator activity endopeptidase regulator activity endopeptidase activator activity enzyme activator activity catalytic activity endopeptidase activity	cellular component organization cellular component biogenesis proteasome assembly cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis transcription elongation by RNA polymerase II RNA metabolic process primary metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process cellular component organization cellular component biogenesis proteasome assembly cellular component assembly protein-containing complex organization protein-containing complex assembly cellular process cellular component organization or biogenesis transcription elongation by RNA polymerase II RNA metabolic process primary metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process DNA-templated transcription elongation transcription by RNA polymerase II biosynthetic process metabolic process macromolecule metabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process protein metabolic process	protein-containing complex catalytic complex peptidase complex proteasome complex endopeptidase complex intracellular protein-containing complex cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane proteasome regulatory particle protein-containing complex catalytic complex peptidase complex proteasome complex endopeptidase complex intracellular protein-containing complex cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane proteasome regulatory particle proteasome regulatory particle, lid subcomplex proteasome accessory complex membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen
C	Polyubiquitin-B	protein tag activity molecular tag activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding	developmental process multicellular organismal process reproductive system development gonad development tube development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics seminiferous tubule development developmental process multicellular organismal process reproductive system development gonad development tube development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics seminiferous tubule development anatomical structure development reproductive structure development system development regulation of mitochondrial membrane potential biological regulation regulation of biological quality regulation of membrane potential catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis metabolic process cellular process macromolecule metabolic process protein metabolic process regulation of biological process neuron apoptotic process regulation of cellular process regulation of apoptotic process regulation of programmed cell death cell death apoptotic process programmed cell death regulation of neuron apoptotic process multicellular organismal-level homeostasis homeostatic process energy homeostasis regulation of protein modification process positive regulation of protein metabolic process positive regulation of biological process regulation of protein ubiquitination positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process protein ubiquitination positive regulation of macromolecule metabolic process regulation of protein modification by small protein conjugation or removal protein modification process positive regulation of cellular process positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination regulation of post-translational protein modification regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule modification post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator regulation of signal transduction regulation of intrinsic apoptotic signaling pathway intracellular signal transduction cell communication positive regulation of apoptotic signaling pathway positive regulation of response to stimulus regulation of intracellular signal transduction regulation of signal transduction by p53 class mediator positive regulation of signal transduction by p53 class mediator signal transduction intrinsic apoptotic signaling pathway regulation of signaling positive regulation of programmed cell death positive regulation of intracellular signal transduction signal transduction by p53 class mediator positive regulation of apoptotic process apoptotic signaling pathway regulation of response to stimulus regulation of cell communication intrinsic apoptotic signaling pathway by p53 class mediator positive regulation of intrinsic apoptotic signaling pathway regulation of intrinsic apoptotic signaling pathway by p53 class mediator regulation of apoptotic signaling pathway positive regulation of signaling cellular developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis cellular component organization neurogenesis cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation cellular component organization or biogenesis plasma membrane bounded cell projection organization nervous system development generation of neurons anatomical structure morphogenesis neuron development hypothalamus development forebrain development central nervous system neuron development central nervous system neuron differentiation hypothalamus cell differentiation hypothalamus gonadotrophin-releasing hormone neuron development limbic system development head development forebrain generation of neurons hypothalamus gonadotrophin-releasing hormone neuron differentiation brain development diencephalon development forebrain neuron development central nervous system development forebrain neuron differentiation sexual reproduction organelle fission meiotic cell cycle multicellular organismal reproductive process female gamete generation meiotic cell cycle process gamete generation nuclear division organelle organization meiosis I meiosis I cell cycle process female meiosis I female meiotic nuclear division meiotic nuclear division cell cycle cell cycle process positive regulation of protein monoubiquitination protein monoubiquitination regulation of protein monoubiquitination regulation of proteolysis involved in protein catabolic process regulation of proteolysis proteasomal protein catabolic process regulation of catabolic process regulation of proteasomal protein catabolic process regulation of protein catabolic process male meiosis I male meiotic nuclear division male gamete generation connective tissue development adipose tissue development fat pad development tissue development female gonad development female sex differentiation development of primary female sexual characteristics establishment of organelle localization cellular localization organelle transport along microtubule transport establishment of mitochondrion localization intracellular transport establishment of localization localization mitochondrion localization establishment of mitochondrion localization, microtubule-mediated mitochondrion transport along microtubule organelle localization establishment of localization in cell microtubule-based transport transport along microtubule cytoskeleton-dependent intracellular transport microtubule-based movement microtubule-based process	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cytosol cell periphery plasma membrane membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen organelle subcompartment endomembrane system endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane cell projection neuron projection plasma membrane bounded cell projection intracellular vesicle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane endocytic vesicle membrane endocytic vesicle endosome membrane endosome mitochondrial membrane organelle outer membrane organelle envelope mitochondrial envelope mitochondrial outer membrane outer membrane somatodendritic compartment cell body neuronal cell body

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR033837	Ubiquitinyl hydrolase-L5	Domain
A	IPR038765	Papain-like cysteine peptidase superfamily	Homologous Superfamily
A	IPR017390	Ubiquitinyl hydrolase, UCH37 type	Family
A	IPR001578	Peptidase C12, ubiquitin carboxyl-terminal hydrolase	Domain
A	IPR041507	Peptidase C12, C-terminal domain	Domain
A	IPR036959	Peptidase C12, ubiquitin carboxyl-terminal hydrolase superfamily	Homologous Superfamily
B	IPR044868	Rpn13/ADRM1, Pru domain	Domain
B	IPR038108	RPN13, DEUBAD domain superfamily	Homologous Superfamily
B	IPR032368	RPN13, DEUBAD domain	Domain
B	IPR006773	Proteasomal ubiquitin receptor Rpn13/ADRM1	Family
B	IPR038633	Proteasomal ubiquitin receptor Rpn13/ADRM1, Pru domain superfamily	Homologous Superfamily
B	IPR044867	DEUBAD domain	Domain
C	IPR019954	Ubiquitin conserved site	Conserved Site
C	IPR050158	Ubiquitin and ubiquitin-like	Family
C	IPR000626	Ubiquitin-like domain	Domain
C	IPR019956	Ubiquitin domain	Domain
C	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: Q16186	colorectal adenoma ovarian cancer colorectal cancer diabetes mellitus
C	Pharos: P0CG47	astrocytic tumor cleft soft palate lung cancer Cleft of hard palate ovarian cancer isolated cleft palate

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.