2HTH

Structural basis for ubiquitin recognition by the human EAP45/ESCRT-II GLUE domain

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)
A	d2htha_	Alpha and beta proteins (a+b)	beta-Grasp (ubiquitin-like)	Ubiquitin-like	Ubiquitin-related	Ubiquitin	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2hthb1	All beta proteins	PH domain-like barrel	PH domain-like	VPS36 N-terminal domain-like	Vacuolar protein sorting protein 36, VPS36	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)
A	SCOP2B Superfamily	Ubiquitin-like	8043829	3000157	SCOP2B (2022-06-29)
B	SCOP2 Family	VPS36 N-terminal domain-like	8030044	4000344	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	PH domain-like	8042423	3000134	SCOP2 (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	ubiquitin_1	e2hthA1	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: ubiquitin_1	ECOD (1.6)
B	Vps36_ESCRT-II	e2hthB1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: Vps36_ESCRT-II	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.10.20.90	Alpha Beta	Roll	Ubiquitin-like (UB roll)	Phosphatidylinositol 3-kinase Catalytic Subunit	CATH (4.3.0)
B	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	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
B	PF11605	Vacuolar protein sorting protein 36 Vps36 (Vps36_ESCRT-II)	Vacuolar protein sorting protein 36 Vps36	Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is criti ...	Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Ubiquitin	protein binding binding enzyme binding protease binding protein tag activity molecular tag activity ubiquitin protein ligase binding ubiquitin-like protein ligase binding RNA binding organic cyclic compound binding nucleic acid binding	organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis metabolic process protein metabolic process macromolecule metabolic process organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic 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 cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle 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 cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle 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
B	Vacuolar protein sorting protein 36	protein binding binding ubiquitin binding ubiquitin-like protein binding phospholipid binding lipid binding phosphatidylinositol-3-phosphate binding phosphatidylinositol phosphate binding phosphatidylinositol binding	membrane organization cellular component organization membrane fission cellular process cellular component organization or biogenesis cellular catabolic process catabolic process macroautophagy cellular metabolic process autophagy metabolic process process utilizing autophagic mechanism organelle assembly multivesicular body assembly membrane organization cellular component organization membrane fission cellular process cellular component organization or biogenesis cellular catabolic process catabolic process macroautophagy cellular metabolic process autophagy metabolic process process utilizing autophagic mechanism organelle assembly multivesicular body assembly vesicle organization cellular component biogenesis organelle organization cellular component assembly multivesicular body organization endosome organization endomembrane system organization protein localization establishment of protein localization cellular localization nitrogen compound transport transport proteolysis involved in protein catabolic process establishment of protein localization to vacuole macromolecule catabolic process vesicle-mediated transport localization organic substance metabolic process late endosome to vacuole transport modification-dependent macromolecule catabolic process late endosome to vacuole transport via multivesicular body sorting pathway proteolysis cellular macromolecule localization establishment of localization in cell protein metabolic process endosome transport via multivesicular body sorting pathway organonitrogen compound catabolic process organonitrogen compound metabolic process organic substance transport protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway primary metabolic process protein localization to vacuole intracellular transport protein catabolic process establishment of localization endosomal transport establishment of protein localization to organelle protein transport modification-dependent protein catabolic process multivesicular body sorting pathway macromolecule localization protein localization to organelle ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway ubiquitin-dependent protein catabolic process vacuolar transport macromolecule metabolic process organic substance catabolic process intracellular protein transport	membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm vesicle extracellular exosome extracellular vesicle membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cytosol endosome membrane protein-containing complex ESCRT complex membrane membrane protein complex cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane organelle membrane ESCRT II complex late endosome membrane late endosome lytic vacuole vacuole lysosome nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR019954	Ubiquitin conserved site	Conserved Site
A	IPR000626	Ubiquitin-like domain	Domain
A	IPR019956	Ubiquitin domain	Domain
A	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
B	IPR036388	Winged helix-like DNA-binding domain superfamily	Homologous Superfamily
B	IPR036390	Winged helix DNA-binding domain superfamily	Homologous Superfamily
B	IPR040608	Snf8/Vps36 family	Family
B	IPR011993	PH-like domain superfamily	Homologous Superfamily
B	IPR021648	Vacuolar protein sorting protein 36, GLUE domain	Domain
B	IPR037855	Vacuolar protein sorting protein 36	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	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
B	Pharos: Q86VN1	astrocytic tumor glioblastoma non-small cell lung carcinoma atypical teratoid rhabdoid tumor malignant ependymoma ovarian cancer breast cancer malignant glioma Pick disease

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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 R01GM133198.