1NBF

Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde

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
Structure Motif: Primary M-CSA Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1nbfb_	Alpha and beta proteins (a+b)	Cysteine proteinases	Cysteine proteinases	Ubiquitin carboxyl-terminal hydrolase, UCH	Ubiquitin carboxyl-terminal hydrolase 7 (USP7, HAUSP)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E	d1nbfe_	Alpha and beta proteins (a+b)	Cysteine proteinases	Cysteine proteinases	Ubiquitin carboxyl-terminal hydrolase, UCH	Ubiquitin carboxyl-terminal hydrolase 7 (USP7, HAUSP)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1nbfa_	Alpha and beta proteins (a+b)	Cysteine proteinases	Cysteine proteinases	Ubiquitin carboxyl-terminal hydrolase, UCH	Ubiquitin carboxyl-terminal hydrolase 7 (USP7, HAUSP)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1nbfc_	Alpha and beta proteins (a+b)	beta-Grasp (ubiquitin-like)	Ubiquitin-like	Ubiquitin-related	Ubiquitin	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d1nbfd_	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	SCOP2B Superfamily	Cysteine proteinases	8043739	3001808	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Cysteine proteinases	8043739	3001808	SCOP2B (2022-06-29)
A	SCOP2 Family	USP domain-like	8031361	4003158	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Cysteine proteinases	8043739	3001808	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Ubiquitin-like	8043829	3000157	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Ubiquitin-like	8043829	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)
B	UCH	e1nbfB1	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: UCH	ECOD (1.6)
E	UCH	e1nbfE1	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: UCH	ECOD (1.6)
A	UCH	e1nbfA1	A: a+b complex topology	X: Cysteine proteinases-like	H: Cysteine proteinases (From Topology)	T: Cysteine proteinases	F: UCH	ECOD (1.6)
C	ubiquitin_1	e1nbfC1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_1	ECOD (1.6)
D	ubiquitin_1	e1nbfD1	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)
B	2.20.210.10	Mainly Beta	Single Sheet	ubp-family deubiquitinating enzyme fold	ubp-family deubiquitinating enzyme superfamily	CATH (4.3.0)
E	2.20.210.10	Mainly Beta	Single Sheet	ubp-family deubiquitinating enzyme fold	ubp-family deubiquitinating enzyme superfamily	CATH (4.3.0)
A	2.20.210.10	Mainly Beta	Single Sheet	ubp-family deubiquitinating enzyme fold	ubp-family deubiquitinating enzyme superfamily	CATH (4.3.0)
C	3.10.20.90	Alpha Beta	Roll	Ubiquitin-like (UB roll)	Phosphatidylinositol 3-kinase Catalytic Subunit	CATH (4.3.0)
D	3.10.20.90	Alpha Beta	Roll	Ubiquitin-like (UB roll)	Phosphatidylinositol 3-kinase Catalytic Subunit	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, E	PF00443	Ubiquitin carboxyl-terminal hydrolase (UCH)	Ubiquitin carboxyl-terminal hydrolase	-	Family
C, D	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, B, E	Ubiquitin carboxyl-terminal hydrolase 7	p53 binding protein binding binding ubiquitin-like protein peptidase activity peptidase activity catalytic activity, acting on a protein hydrolase activity K48-linked deubiquitinase activity catalytic activity deubiquitinase activity cysteine-type peptidase activity cysteine-type endopeptidase activity endopeptidase activity cysteine-type deubiquitinase activity	regulation of cellular process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of biological process biological regulation primary metabolic process regulation of cellular process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of biological process biological regulation primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression regulation of molecular function biosynthetic process regulation of DNA-binding transcription factor activity metabolic process cellular process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription macromolecule metabolic process regulation of metabolic process regulation of protein stability regulation of biological quality protein stabilization negative regulation of biological process negative regulation of gene expression via chromosomal CpG island methylation cellular component organization chromatin organization negative regulation of cellular process chromatin remodeling cellular component organization or biogenesis negative regulation of macromolecule metabolic process epigenetic regulation of gene expression negative regulation of metabolic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of gene expression, epigenetic rhythmic process circadian rhythm regulation of circadian rhythm regulation of localization cellular localization regulation of transport transport intracellular transport regulation of vesicle-mediated transport establishment of localization vesicle-mediated transport endosomal transport localization regulation of cellular localization cytosolic transport establishment of localization in cell retrograde transport, endosome to Golgi regulation of retrograde transport, endosome to Golgi regulation of intracellular transport protein ubiquitination macromolecule modification protein metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal protein deubiquitination monoubiquitinated protein deubiquitination protein modification by small protein removal cellular response to stimulus response to stimulus DNA metabolic process DNA alkylation repair cellular response to stress DNA damage response response to stress DNA repair transcription-coupled nucleotide-excision repair nucleotide-excision repair negative regulation of DNA-binding transcription factor activity negative regulation of NF-kappaB transcription factor activity negative regulation of molecular function catabolic process negative regulation of proteolysis negative regulation of proteolysis involved in 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 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 protein 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 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 establishment of protein localization to telomere protein localization establishment of protein localization regulation of protein localization regulation of protein localization to chromosome, telomeric region cellular macromolecule localization establishment of protein localization to chromosome regulation of establishment of protein localization to chromosome regulation of establishment of protein localization protein localization to chromosome, telomeric region establishment of protein localization to organelle protein localization to chromosome regulation of establishment of protein localization to telomere macromolecule localization protein localization to organelle symbiont-mediated disruption of host anatomical structure biological process involved in interspecies interaction between organisms symbiont-mediated disruption of host cell PML body disruption of anatomical structure in another organism symbiont-mediated disruption of host cellular anatomical structure regulation of telomere maintenance regulation of cellular component organization telomere organization chromosome organization regulation of chromosome organization regulation of organelle organization telomere maintenance organelle organization telomere capping regulation of telomere capping regulation of DNA metabolic process signaling negative regulation of signaling negative regulation of intracellular signal transduction regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication negative regulation of TORC1 signaling regulation of intracellular signal transduction negative regulation of TOR signaling signal transduction regulation of TORC1 signaling TOR signaling regulation of signaling regulation of TOR signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus regulation of cell communication TORC1 signaling monosaccharide metabolic process negative regulation of small molecule metabolic process gluconeogenesis negative regulation of gluconeogenesis regulation of small molecule metabolic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process negative regulation of carbohydrate metabolic process carbohydrate metabolic process small molecule biosynthetic process carbohydrate biosynthetic process hexose metabolic process monosaccharide biosynthetic process hexose biosynthetic process regulation of gluconeogenesis regulation of carbohydrate biosynthetic process glucose metabolic process signal transduction by p53 class mediator regulation of signal transduction by p53 class mediator	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen cellular anatomical structure intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen protein-containing complex membraneless organelle intracellular membraneless organelle chromosome nuclear body PML body
C, D	Ubiquitin aldehyde	protein tag activity molecular tag activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding RNA binding organic cyclic compound binding nucleic acid binding	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 protein metabolic process macromolecule metabolic process protein ubiquitination macromolecule modification 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 protein metabolic process macromolecule metabolic process protein ubiquitination macromolecule modification post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal	membrane-bounded organelle intracellular anatomical structure membrane intracellular vesicle intracellular membrane-bounded organelle intracellular organelle cellular anatomical structure cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane organelle endocytic vesicle membrane cytoplasm membrane-bounded organelle intracellular anatomical structure membrane intracellular vesicle intracellular membrane-bounded organelle intracellular organelle cellular anatomical structure cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane organelle endocytic vesicle membrane cytoplasm vesicle organelle membrane endocytic vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cytosol endosome membrane endosome endomembrane system mitochondrial membrane mitochondrion organelle outer membrane organelle envelope mitochondrial envelope mitochondrial outer membrane outer membrane cell periphery plasma membrane nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum endoplasmic reticulum membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, E	IPR028889	Ubiquitin specific protease domain	Domain
A, B, E	IPR018200	Ubiquitin specific protease, conserved site	Conserved Site
A, B, E	IPR024729	Ubiquitin carboxyl-terminal hydrolase 7, ICP0-binding domain	Domain
A, B, E	IPR038765	Papain-like cysteine peptidase superfamily	Homologous Superfamily
A, B, E	IPR002083	MATH/TRAF domain	Domain
A, B, E	IPR029346	Ubiquitin carboxyl-terminal hydrolase, C-terminal	Domain
A, B, E	IPR050164	Ubiquitin carboxyl-terminal hydrolases	Family
A, B, E	IPR001394	Peptidase C19, ubiquitin carboxyl-terminal hydrolase	Domain
A, B, E	IPR008974	TRAF-like	Homologous Superfamily
C, D	IPR019954	Ubiquitin conserved site	Conserved Site
C, D	IPR000626	Ubiquitin-like domain	Domain
C, D	IPR019956	Ubiquitin domain	Domain
C, D	IPR050158	Ubiquitin and ubiquitin-like	Family
C, D	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, E	Pharos: Q93009	urinary bladder cancer prostate cancer Hao-Fountain syndrome Prostatic Neoplasms intellectual disability urinary bladder neoplasm
C, D	Pharos: P0CG48	acute myeloid leukemia heart disease myocardial infarction pancreatic ductal adenocarcinoma astrocytic tumor lung cancer osteosarcoma renal cell carcinoma glioblastoma malignant pancreatic neoplasm ovarian cancer

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	ubiquitinyl hydrolase 1 (peptidase C19 type) M-CSA #789	Deubiquinylation is a vital process in eukaryotic cells because it protects proteins from degradation. It involves the hydrolysis of the peptide bond that joins the C terminal residue of ubiquitin to the lysine residue in the protein, and is catalysed by DUPs (Deubiquinylating proteins) such as HAUSP, described here. This family of enzymes is one of the largest in the human genome, reflecting their importance in the cell. For example, the tumour suppressing protein p53 relies on HAUSP action in order to prevent it from being degraded; thus malfunctions in the expression or activity of HAUSP can lead to cancer. HAUSP, along with the rest of the homologous family, is a cysteine protease, and displays structural and sequence homology to other cysteine proteases with different roles in the cell.	Defined by 4 residues: ASN:A-11 [auth A-218]CYS:A-16 [auth A-223]HIS:A-257 [auth A-464]ASP:A-274 [auth A-481] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 3.1.2.15 (PDB Primary Data) Search M-CSA Motif + EC 3.1.2.15 EC: 3.4.19.12 (UniProt) Search M-CSA Motif + EC 3.4.19.12

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.