6WCW

Structure of human Rubicon RH domain in complex with GTP-bound Rab7

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 [auth B]	d6wcwb_	Alpha and beta proteins (a/b)	P-loop containing nucleoside triphosphate hydrolases	P-loop containing nucleoside triphosphate hydrolases	G proteins	automated matches	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 [auth B]	SCOP2B Superfamily	Ras-like P-loop GTPases	8057260	3002022	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 [auth B]	PF00071	e6wcwB1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: PF00071	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth B]	3.40.50.300	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	P-loop containing nucleotide triphosphate hydrolases	CATH (utative)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth B]	PF00071	Ras family (Ras)	Ras family	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motil ...	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices [1].	Domain
B [auth A]	PF13901	Rubicon Homology Domain (RH_dom)	Rubicon Homology Domain	This is the Rubicon homology domain (RH) characterised at the C-terminal of Rubicon, PLEKHM1 and Pacer, proteins that modulate late steps in autophagy [1,2]. Rubicon (RUBCN) negatively regulates autophagy and endolysosomal trafficking by inhibiting P ...	This is the Rubicon homology domain (RH) characterised at the C-terminal of Rubicon, PLEKHM1 and Pacer, proteins that modulate late steps in autophagy [1,2]. Rubicon (RUBCN) negatively regulates autophagy and endolysosomal trafficking by inhibiting PI3K complex II (PI3KC3-C2), which impairs autophagosome maturation process. PLEKHM1 is an adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways [3,4]. On the other hand, Pacer positively regulates autophagy, promoting autophagosome maturation by facilitating the biogenesis of phosphatidylinositol 3-phosphate (PtdIns3P) in late steps of autophagy; it antagonises RUBCN [5]. This domain contains nine conserved cysteines and one conserved histidine, which have been predicted to bind divalent zinc cations being required for Rubicon and PLEKHM1 to interact with Rab7.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth B]	Ras-related protein Rab-7a	small GTPase binding protein binding binding enzyme binding GTPase binding pyrophosphatase activity GTPase 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 protein-containing complex binding retromer complex binding small GTPase binding protein binding binding enzyme binding GTPase binding pyrophosphatase activity GTPase 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 protein-containing complex binding retromer complex binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding GDP binding G protein activity molecular function regulator activity	cellular component organization organelle organization cellular process cellular component organization or biogenesis phagosome maturation homeostatic process biological regulation intracellular pH reduction regulation of intracellular pH phagosome acidification cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis regulation of pH cellular component organization organelle organization cellular process cellular component organization or biogenesis phagosome maturation homeostatic process biological regulation intracellular pH reduction regulation of intracellular pH phagosome acidification cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis regulation of pH monoatomic ion homeostasis intracellular chemical homeostasis regulation of biological quality monoatomic cation homeostasis regulation of cellular pH intracellular monoatomic ion homeostasis cellular localization transport intracellular transport establishment of localization vesicle-mediated transport endosomal transport localization cytosolic transport retrograde transport, endosome to Golgi establishment of localization in cell vesicle localization establishment of organelle localization organelle localization establishment of vesicle localization protein localization establishment of protein localization nitrogen compound transport establishment of protein localization to plasma membrane endocytic recycling cellular macromolecule localization protein localization to cell periphery establishment of protein localization to membrane protein localization to plasma membrane organic substance transport localization within membrane protein localization to membrane vesicle-mediated transport to the plasma membrane endosome to plasma membrane protein transport protein transport macromolecule localization intracellular protein transport multicellular organismal process multicellular organismal-level homeostasis tissue remodeling bone remodeling anatomical structure homeostasis tissue homeostasis bone resorption cellular catabolic process catabolic process lipophagy macroautophagy cellular metabolic process autophagy metabolic process process utilizing autophagic mechanism membrane docking protein to membrane docking import into cell membrane fusion organelle membrane fusion vesicle organization cellular component biogenesis lysosome organization cellular component assembly phagolysosome assembly phagocytosis membrane organization vacuole organization organelle assembly lytic vacuole organization phagosome-lysosome fusion organelle fusion endocytosis vesicle fusion endosome to lysosome transport lysosomal transport vacuolar transport autophagosome assembly autophagosome organization exosomal secretion regulation of localization regulation of cellular process negative regulation of biological process negative regulation of transport secretion by cell regulation of secretion by cell negative regulation of secretion negative regulation of exocytosis negative regulation of exosomal secretion negative regulation of cellular process negative regulation of secretion by cell regulation of biological process secretion regulation of transport regulation of exosomal secretion export from cell regulation of vesicle-mediated transport extracellular exosome biogenesis regulation of secretion exocytosis extracellular vesicle biogenesis regulation of exocytosis positive regulation of protein metabolic process positive regulation of biological process macromolecule catabolic process regulation of primary metabolic process positive regulation of metabolic process organic substance metabolic process positive regulation of macromolecule metabolic process protein metabolic process organonitrogen compound catabolic process organonitrogen compound metabolic process regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process macromolecule metabolic process regulation of metabolic process organic substance catabolic process regulation of protein catabolic process vesicle budding from membrane regulation of cellular component organization regulation of endosome organization endosome organization endomembrane system organization negative regulation of cellular component organization negative regulation of intralumenal vesicle formation intralumenal vesicle formation regulation of organelle organization negative regulation of organelle organization negative regulation of endosome organization regulation of intralumenal vesicle formation lipid catabolic process lipid metabolic process biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to bacterium response to external stimulus response to external biotic stimulus response to biotic stimulus exit from host cell viral process viral release from host cell viral life cycle biological process involved in interaction with host biological process involved in symbiotic interaction positive regulation of secretion by cell positive regulation of exosomal secretion positive regulation of exocytosis positive regulation of secretion positive regulation of cellular process positive regulation of cellular component biogenesis regulation of cellular component biogenesis positive regulation of transport cellular response to stimulus signaling negative regulation of signaling negative regulation of ERBB signaling pathway regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway negative regulation of cell communication cell communication regulation of epidermal growth factor receptor signaling pathway epidermal growth factor receptor signaling pathway epidermal growth factor catabolic process signal transduction enzyme-linked receptor protein signaling pathway regulation of signaling regulation of ERBB signaling pathway cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus negative regulation of epidermal growth factor receptor signaling pathway ERBB signaling pathway regulation of cell communication protein targeting establishment of protein localization to vacuole protein targeting to lysosome protein targeting to vacuole protein localization to vacuole protein localization to lysosome establishment of protein localization to organelle protein localization to organelle vesicle-mediated transport between endosomal compartments early endosome to late endosome transport regulation of viral process positive regulation of viral process	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle mitochondrial membrane intracellular anatomical structure mitochondrion membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle mitochondrial membrane intracellular anatomical structure mitochondrion membrane intracellular membrane-bounded organelle intracellular organelle organelle envelope mitochondrial envelope cytoplasm organelle membrane cytosol endosome membrane endosome intracellular vesicle late endosome membrane endomembrane system cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane late endosome vacuolar membrane autophagosome membrane vacuole autophagosome phagocytic vesicle phagocytic vesicle membrane endocytic vesicle membrane endocytic vesicle lytic vacuole lytic vacuole membrane lysosomal membrane lysosome Golgi apparatus synapse transport vesicle membrane presynapse synaptic vesicle synaptic vesicle membrane cell junction transport vesicle exocytic vesicle membrane secretory vesicle exocytic vesicle pigment granule chitosome melanosome melanosome membrane pigment granule membrane lamellar body secretory granule alveolar lamellar body cell periphery plasma membrane phagophore assembly site membrane phagophore assembly site secretory granule membrane lipid droplet intracellular non-membrane-bounded organelle non-membrane-bounded organelle
B [auth A]	Run domain Beclin-1-interacting and cysteine-rich domain-containing protein	binding phospholipid binding lipid binding phosphatidylinositol phosphate binding phosphatidylinositol binding enzyme regulator activity molecular function regulator activity phosphatidylinositol 3-kinase inhibitor activity phosphatidylinositol 3-kinase regulator activity kinase regulator activity	immune system process localization transport multivesicular body sorting pathway cellular process establishment of localization vesicle-mediated transport negative regulation of cellular catabolic process catabolic process regulation of cellular component organization regulation of cellular process regulation of autophagosome maturation macroautophagy autophagy immune system process localization transport multivesicular body sorting pathway cellular process establishment of localization vesicle-mediated transport negative regulation of cellular catabolic process catabolic process regulation of cellular component organization regulation of cellular process regulation of autophagosome maturation macroautophagy autophagy negative regulation of biological process protein-containing complex disassembly regulation of autophagy regulation of protein-containing complex disassembly negative regulation of cellular metabolic process cellular catabolic process cellular component organization autophagosome maturation negative regulation of protein-containing complex disassembly negative regulation of cellular process cellular component organization or biogenesis process utilizing autophagic mechanism cellular component disassembly negative regulation of catabolic process regulation of biological process negative regulation of cellular component organization protein-containing complex organization cellular metabolic process negative regulation of metabolic process biological regulation regulation of cellular metabolic process regulation of catabolic process negative regulation of autophagosome maturation regulation of organelle organization negative regulation of macroautophagy organelle organization regulation of macroautophagy negative regulation of autophagy regulation of cellular catabolic process metabolic process regulation of metabolic process cellular response to stimulus regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction import into cell phagocytosis endocytosis regulation of localization regulation of transport negative regulation of transport negative regulation of endocytosis regulation of vesicle-mediated transport regulation of endocytosis	membrane-bounded organelle intracellular anatomical structure early endosome endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm vesicle cytosol membrane-bounded organelle intracellular anatomical structure early endosome endosome intracellular vesicle cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm vesicle cytosol late endosome nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen lytic vacuole vacuole lysosome

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth B]	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A [auth B]	IPR001806	Small GTPase	Family
A [auth B]	IPR005225	Small GTP-binding protein domain	Domain
B [auth A]	IPR037213	RUN domain superfamily	Homologous Superfamily
B [auth A]	IPR025258	Rubicon Homology Domain	Domain
B [auth A]	IPR004012	RUN domain	Domain
B [auth A]	IPR048569	Rubicon, PI3K-binding domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth B]	Pharos: P51149	Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease type 2B peripheral neuropathy astrocytic tumor coronary artery disease motor peripheral neuropathy ovarian cancer peripheral nervous system disease attention deficit hyperactivity disorder, inattentive type glioblastoma myocardial ischemia Pain Disorder breast carcinoma chronic kidney disease malignant glioma Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease type 2B peripheral neuropathy astrocytic tumor coronary artery disease motor peripheral neuropathy ovarian cancer peripheral nervous system disease attention deficit hyperactivity disorder, inattentive type glioblastoma myocardial ischemia Pain Disorder breast carcinoma chronic kidney disease malignant glioma neurodegenerative disease pancreatic intraductal papillary-mucinous neoplasm pilocytic astrocytoma
B [auth A]	Pharos: Q92622	autosomal recessive spinocerebellar ataxia 15 astrocytic tumor juvenile dermatomyositis malignant ependymoma osteosarcoma spinocerebellar ataxia type 2 spinocerebellar ataxia type 6 Ataxias, Hereditary cerebellar ataxia large cell medulloblastoma malignant mesothelioma ovarian cancer spinocerebellar ataxia type 4 spinocerebellar ataxia type 7 autosomal dominant cerebellar ataxia autosomal recessive spinocerebellar ataxia 15 astrocytic tumor juvenile dermatomyositis malignant ependymoma osteosarcoma spinocerebellar ataxia type 2 spinocerebellar ataxia type 6 Ataxias, Hereditary cerebellar ataxia large cell medulloblastoma malignant mesothelioma ovarian cancer spinocerebellar ataxia type 4 spinocerebellar ataxia type 7 autosomal dominant cerebellar ataxia intellectual disability lung cancer neurodegenerative disease spinocerebellar ataxia type 1 spinocerebellar ataxia type 5

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.