5AQH

Fragment-based screening of HSP70 sheds light on the functional role of ATP-binding site residues

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	d5aqha1	Alpha and beta proteins (a/b)	Ribonuclease H-like motif	Actin-like ATPase domain	Actin/HSP70	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)
B	SCOP2B Superfamily	BAG domain	8033373	3001951	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	HSP70_1st	e5aqhA2	A: mixed a+b and a/b	X: Ribonuclease H-like	H: Ribonuclease H-like (From Topology)	T: Ribonuclease H-like	F: HSP70_1st	ECOD (1.6)
A	MreB_Mbl_C	e5aqhA1	A: mixed a+b and a/b	X: Ribonuclease H-like	H: Ribonuclease H-like (From Topology)	T: Ribonuclease H-like	F: MreB_Mbl_C	ECOD (1.6)
B	BAG	e5aqhB1	A: alpha bundles	X: Spectrin repeat-like	H: BAG domain (From Topology)	T: BAG domain	F: BAG	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.420.40	Alpha Beta	2-Layer Sandwich	Nucleotidyltransferase	domain 5	CATH (4.3.0)
A	3.30.30.30	Alpha Beta	2-Layer Sandwich	Defensin A-like		CATH (4.3.0)
A	3.90.640.10	Alpha Beta	Alpha-Beta Complex	Actin	Chain A, domain 4	CATH (4.3.0)
B	1.20.58.120	Mainly Alpha	Up-down Bundle	Methane Monooxygenase Hydroxylase	Chain G, domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00012	Hsp70 protein (HSP70)	Hsp70 protein	-	Family
B	PF02179	BAG domain (BAG)	BAG domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	HEAT SHOCK COGNATE 71 KDA PROTEIN	protein carrier chaperone molecular carrier activity protein-containing complex destabilizing activity ATP-dependent protein disaggregase activity ATP-dependent activity protein binding binding heat shock protein binding A1 adenosine receptor binding signaling receptor binding G protein-coupled receptor binding adenosine receptor binding protein-folding chaperone binding adenyl ribonucleotide binding protein carrier chaperone molecular carrier activity protein-containing complex destabilizing activity ATP-dependent protein disaggregase activity ATP-dependent activity protein binding binding heat shock protein binding A1 adenosine receptor binding signaling receptor binding G protein-coupled receptor binding adenosine receptor binding protein-folding chaperone 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 cell adhesion molecule binding cadherin binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding enzyme binding clathrin-uncoating ATPase 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 C3HC4-type RING finger domain binding protein domain specific binding protein-containing complex binding MHC protein complex binding MHC class II protein complex binding protein-macromolecule adaptor activity molecular adaptor activity ADP binding modified amino acid binding phospholipid binding lipid binding phosphatidylserine binding RNA binding nucleic acid binding ATP-dependent protein folding chaperone protein folding chaperone unfolded protein binding prostaglandin binding fatty acid derivative binding peptide binding	response to stimulus response to chemical response to xenobiotic stimulus cellular response to stimulus positive regulation of response to biotic stimulus regulation of cellular process pattern recognition receptor signaling pathway regulation of NLRP3 inflammasome complex assembly negative regulation of biological process regulation of signal transduction response to biotic stimulus intracellular signal transduction cell communication cellular component biogenesis response to stimulus response to chemical response to xenobiotic stimulus cellular response to stimulus positive regulation of response to biotic stimulus regulation of cellular process pattern recognition receptor signaling pathway regulation of NLRP3 inflammasome complex assembly negative regulation of biological process regulation of signal transduction response to biotic stimulus intracellular signal transduction cell communication cellular component biogenesis immune response-activating signaling pathway cellular component assembly inflammasome-mediated signaling pathway positive regulation of immune response canonical inflammasome complex assembly regulation of immune system process signal transduction negative regulation of NLRP3 inflammasome complex assembly positive regulation of immune system process innate immune response-activating signaling pathway regulation of biological process negative regulation of cellular component organization immune response response to other organism regulation of innate immune response response to external stimulus regulation of inflammasome-mediated signaling pathway negative regulation of protein-containing complex assembly regulation of response to stimulus defense response to other organism regulation of pattern recognition receptor signaling pathway NLRP3 inflammasome complex assembly positive regulation of defense response activation of innate immune response regulation of immune response inflammatory response activation of immune response cytoplasmic pattern recognition receptor signaling pathway regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of cellular component organization regulation of response to external stimulus intracellular receptor signaling pathway signaling negative regulation of signaling negative regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of intracellular signal transduction positive regulation of biological process regulation of cytoplasmic pattern recognition receptor signaling pathway negative regulation of cell communication positive regulation of response to stimulus cellular component organization regulation of protein-containing complex assembly positive regulation of response to external stimulus immune response-regulating signaling pathway regulation of intracellular signal transduction regulation of response to stress response to stress innate immune response negative regulation of cellular process protein-containing complex assembly response to external biotic stimulus cellular component organization or biogenesis regulation of signaling positive regulation of innate immune response defense response negative regulation of response to stimulus protein-containing complex organization biological regulation defense response to symbiont regulation of cellular component biogenesis negative regulation of signal transduction negative regulation of immune system process immune system process regulation of cell communication cellular process negative regulation of inflammasome-mediated signaling pathway response to topologically incorrect protein response to unfolded protein cellular response to heat cellular response to stress response to heat response to abiotic stimulus response to temperature stimulus regulation of localization import into cell positive regulation of cellular component organization transport vesicle-mediated transport localization positive regulation of endocytosis phagocytosis positive regulation of cellular process regulation of endocytosis regulation of transport regulation of phagocytosis regulation of vesicle-mediated transport establishment of localization positive regulation of phagocytosis positive regulation of transport endocytosis developmental process multicellular organismal process head development animal organ development brain development nervous system development multicellular organism development cerebellum development central nervous system development metencephalon development anatomical structure development hindbrain development system development cellular component disassembly clathrin coat disassembly protein-containing complex disassembly vesicle uncoating protein depolymerization regulation of supramolecular fiber organization negative regulation of supramolecular fiber organization supramolecular fiber organization cellular response to nutrient levels response to nutrient levels response to starvation cellular response to starvation protein localization establishment of protein localization cellular localization catabolic process nitrogen compound transport protein targeting to vacuole involved in autophagy protein targeting autophagy establishment of protein localization to vacuole protein targeting to lysosome involved in chaperone-mediated autophagy lysosomal transport macromolecule catabolic process cellular catabolic process chaperone-mediated autophagy protein targeting to lysosome cellular macromolecule localization establishment of localization in cell protein metabolic process process utilizing autophagic mechanism protein targeting to vacuole cellular metabolic process primary metabolic process protein localization to vacuole intracellular transport protein catabolic process protein localization to lysosome establishment of protein localization to organelle protein transport macromolecule localization protein localization to organelle metabolic process vacuolar transport macromolecule metabolic process intracellular protein transport negative regulation of cardiac muscle cell apoptotic process muscle cell apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of cardiac muscle cell apoptotic process regulation of muscle cell apoptotic process regulation of programmed cell death cell death cardiac muscle cell apoptotic process negative regulation of apoptotic process regulation of striated muscle cell apoptotic process striated muscle cell apoptotic process negative regulation of muscle cell apoptotic process negative regulation of striated muscle cell apoptotic process apoptotic process programmed cell death postsynapse organization regulation of postsynapse organization regulation of synapse organization cell junction organization regulation of synapse structure or activity synapse organization regulation of biological quality cellular biosynthetic process RNA metabolic process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of DNA-templated transcription negative regulation of metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process negative regulation of cellular biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process response to odorant protein import regulation of protein localization regulation of establishment of protein localization regulation of protein transport regulation of protein import regulation of cellular localization response to activity forebrain development membrane organization chaperone-mediated autophagy translocation complex disassembly synaptic vesicle uncoating synaptic vesicle cycle presynaptic endocytosis vesicle-mediated transport in synapse synaptic vesicle recycling synaptic vesicle endocytosis maintenance of synapse structure cellular component maintenance cell junction maintenance organelle organization maintenance of postsynaptic specialization structure postsynaptic density organization postsynaptic specialization organization regulation of mRNA splicing, via spliceosome mRNA processing positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process RNA processing positive regulation of nucleobase-containing compound metabolic process positive regulation of mRNA metabolic process positive regulation of RNA metabolic process positive regulation of mRNA processing positive regulation of mRNA splicing, via spliceosome positive regulation of cellular metabolic process positive regulation of biosynthetic process regulation of mRNA processing RNA splicing regulation of RNA splicing mRNA metabolic process RNA splicing, via transesterification reactions positive regulation of gene expression mRNA splicing, via spliceosome RNA splicing, via transesterification reactions with bulged adenosine as nucleophile regulation of mRNA metabolic process positive regulation of RNA splicing positive regulation of cellular biosynthetic process response to lipid response to estradiol response to oxygen-containing compound response to organic cyclic compound protein refolding protein maturation protein folding modulation by host of symbiont process viral life cycle modulation by host of viral genome replication biological process involved in symbiotic interaction modulation by host of viral process viral genome replication viral process positive regulation by host of viral process biological process involved in interaction with symbiont positive regulation by host of viral genome replication ovulation cycle rhythmic process estrous cycle reproductive process multicellular organismal reproductive process response to ketone response to hormone response to steroid hormone response to endogenous stimulus response to progesterone regulation of protein complex stability cellular response to organic cyclic compound cellular response to endogenous stimulus cellular response to chemical stimulus cellular response to lipid cellular response to steroid hormone stimulus cellular response to hormone stimulus regulation of protein refolding positive regulation of protein folding regulation of protein folding positive regulation of protein refolding nucleocytoplasmic transport nuclear transport protein localization to nucleus import into nucleus protein import into nucleus positive regulation of protein metabolic process regulation of protein metabolic process regulation of proteolysis proteolysis positive regulation of proteolysis regulation of protein stability chaperone cofactor-dependent protein refolding chaperone-mediated protein folding 'de novo' protein folding 'de novo' post-translational protein folding mitotic cell cycle process cell cycle phase transition cell cycle G1/S transition of mitotic cell cycle cell cycle G1/S phase transition mitotic cell cycle mitotic cell cycle phase transition cell cycle process late endosomal microautophagy microautophagy cellular response to metal ion response to metal ion cellular response to cadmium ion response to cadmium ion adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity regulation of immune effector process T cell mediated immunity positive regulation of leukocyte mediated immunity positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of leukocyte mediated cytotoxicity leukocyte mediated immunity positive regulation of immune effector process positive regulation of adaptive immune response regulation of T cell mediated immunity T cell mediated cytotoxicity positive regulation of T cell mediated cytotoxicity regulation of adaptive immune response regulation of leukocyte mediated cytotoxicity leukocyte mediated cytotoxicity adaptive immune response immune effector process regulation of leukocyte mediated immunity regulation of T cell mediated cytotoxicity regulation of lymphocyte mediated immunity positive regulation of T cell mediated immunity regulation of cell killing positive regulation of cell killing cell killing kidney development renal system development response to nickel cation ribose phosphate metabolic process ATP metabolic process carbohydrate derivative metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process phosphate-containing compound metabolic process small molecule metabolic process phosphorus metabolic process ribonucleoside triphosphate metabolic process nucleoside phosphate metabolic process purine nucleoside triphosphate metabolic process nucleotide metabolic process purine-containing compound metabolic process organophosphate metabolic process nucleoside triphosphate metabolic process purine ribonucleotide metabolic process regulation of lysosomal membrane permeability vacuole organization lytic vacuole organization lysosomal membrane organization lysosome organization positive regulation of lysosomal membrane permeability regulation of membrane permeability positive regulation of membrane permeability muscle structure development skeletal muscle organ development skeletal muscle tissue development muscle tissue development muscle organ development tissue development striated muscle tissue development response to alcohol response to ethanol cellular response to oxidative stress cellular response to chemical stress cellular response to oxygen-containing compound cellular response to hydrogen peroxide response to reactive oxygen species response to hydrogen peroxide response to oxidative stress cellular response to reactive oxygen species protein transmembrane import into intracellular organelle transmembrane transport protein transmembrane transport regulation of cell cycle slow axonal transport axo-dendritic transport microtubule-based transport transport along microtubule cytoskeleton-dependent intracellular transport microtubule-based movement microtubule-based process	somatodendritic compartment cell body perikaryon neuronal cell body cellular anatomical entity intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle vacuole autophagosome intracellular membrane-bounded organelle somatodendritic compartment cell body perikaryon neuronal cell body cellular anatomical entity intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle organelle vacuole autophagosome intracellular membrane-bounded organelle protein-containing complex protein folding chaperone complex intracellular protein-containing complex neuron spine synapse neuron projection dendritic spine plasma membrane bounded cell projection cell projection postsynapse cell junction dendrite dendritic tree extracellular region extracellular space transport vesicle intracellular vesicle endomembrane system presynapse cytoplasmic vesicle synaptic vesicle secretory vesicle vesicle exocytic vesicle anchoring junction focal adhesion cell-substrate junction nucleus membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle cell surface cytosolic region presynaptic cytosol cell periphery plasma membrane membrane postsynaptic specialization membrane postsynaptic specialization synaptic membrane postsynaptic membrane plasma membrane region vesicle lumen cytoplasmic vesicle lumen secretory granule lumen secretory granule endosome late endosome ribonucleoprotein complex photoreceptor inner segment extracellular exosome extracellular vesicle extracellular organelle extracellular membrane-bounded organelle clathrin-sculpted gamma-aminobutyric acid transport vesicle clathrin-sculpted vesicle clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane coated vesicle membrane cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane clathrin-coated vesicle coated vesicle organelle membrane clathrin-coated vesicle membrane glutamatergic synapse vacuolar membrane lytic vacuole lytic vacuole membrane lysosomal membrane lysosome dendritic shaft perinuclear region of cytoplasm polymeric cytoskeletal fiber cytoskeleton supramolecular fiber microtubule supramolecular polymer supramolecular complex microtubule cytoskeleton pigment granule melanosome axon axon terminus distal axon terminal bouton neuron projection terminus vacuolar lumen lysosomal lumen intermediate filament cytoskeleton intermediate filament Prp19 complex glycinergic synapse ficolin-1-rich granule ficolin-1-rich granule lumen nucleoplasm blood microparticle photoreceptor ribbon synapse ribbon synapse lysosomal matrix nuclear protein-containing complex spliceosomal complex postsynaptic density neuron to neuron synapse asymmetric synapse side of membrane lumenal side of membrane lumenal side of lysosomal membrane postsynaptic cytosol
B	BAG FAMILY MOLECULAR CHAPERONE REGULATOR 1	molecular function regulator activity adenyl-nucleotide exchange factor activity ATPase regulator activity ubiquitin protein ligase binding protein binding binding ubiquitin-like protein ligase binding enzyme binding protein-folding chaperone binding	regulation of biological process regulation of cellular process positive regulation of programmed cell death positive regulation of smooth muscle cell apoptotic process muscle cell apoptotic process smooth muscle cell apoptotic process regulation of apoptotic process biological regulation positive regulation of biological process regulation of muscle cell apoptotic process regulation of programmed cell death cell death regulation of smooth muscle cell apoptotic process positive regulation of apoptotic process positive regulation of muscle cell apoptotic process regulation of biological process regulation of cellular process positive regulation of programmed cell death positive regulation of smooth muscle cell apoptotic process muscle cell apoptotic process smooth muscle cell apoptotic process regulation of apoptotic process biological regulation positive regulation of biological process regulation of muscle cell apoptotic process regulation of programmed cell death cell death regulation of smooth muscle cell apoptotic process positive regulation of apoptotic process positive regulation of muscle cell apoptotic process cellular process apoptotic process programmed cell death positive regulation of cellular process regulation of protein stability regulation of biological quality protein stabilization cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling signal transduction cell communication cellular biosynthetic process chaperone cofactor-dependent protein refolding cellular metabolic process primary metabolic process gene expression chaperone-mediated protein folding macromolecule biosynthetic process protein maturation protein folding biosynthetic process metabolic process protein metabolic process macromolecule metabolic process 'de novo' protein folding 'de novo' post-translational protein folding negative regulation of programmed cell death negative regulation of biological process negative regulation of apoptotic process negative regulation of cellular process	membrane cellular anatomical entity 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 membrane cellular anatomical entity 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

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR013126	Heat shock protein 70 family	Family
A	IPR018181	Heat shock protein 70, conserved site	Conserved Site
A	IPR043129	ATPase, nucleotide binding domain	Homologous Superfamily
A	IPR029048	Heat shock protein 70kD, C-terminal domain superfamily	Homologous Superfamily
A	IPR029047	Heat shock protein 70kD, peptide-binding domain superfamily	Homologous Superfamily
B	IPR003103	BAG domain	Domain
B	IPR000626	Ubiquitin-like domain	Domain
B	IPR036533	BAG domain superfamily	Homologous Superfamily
B	IPR039773	Molecular chaperone regulator BAG	Family
B	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P11142	spinocerebellar ataxia type 17 squamous cell carcinoma acute coronary syndrome tubular adenocarcinoma adenocarcinoma granular cell carcinoma Adenocarcinoma, Oxyphilic gastric cancer hereditary diffuse gastric adenocarcinoma cribriform carcinoma gastric neoplasm ischemia reperfusion injury cribriform carcinoma of breast oral cavity neoplasm
B	Pharos: Q99933	breast carcinoma invasive ductal breast carcinoma pancreatic intraductal papillary-mucinous neoplasm Sjogren syndrome astrocytic tumor breast cancer ductal breast carcinoma in situ malignant mesothelioma Mammary Ductal Carcinoma pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia spina bifida atypical teratoid rhabdoid tumor interstitial cystitis osteosarcoma breast carcinoma invasive ductal breast carcinoma pancreatic intraductal papillary-mucinous neoplasm Sjogren syndrome astrocytic tumor breast cancer ductal breast carcinoma in situ malignant mesothelioma Mammary Ductal Carcinoma pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia spina bifida atypical teratoid rhabdoid tumor interstitial cystitis osteosarcoma pancreatic intraductal papillary-mucinous carcinoma schizophrenia swine influenza bipolar disorder depressive disorder malignant pancreatic neoplasm ovarian 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.