2XP3

DISCOVERY OF CELL-ACTIVE PHENYL-IMIDAZOLE PIN1 INHIBITORS BY STRUCTURE-GUIDED FRAGMENT EVOLUTION

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	d2xp3a1	All beta proteins	WW domain-like	WW domain	WW domain	Mitotic rotamase PIN1	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2xp3a2	Alpha and beta proteins (a+b)	FKBP-like	FKBP-like	FKBP immunophilin/proline isomerase	Mitotic rotamase PIN1, domain 2	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	Rotamase-like	8036947	3000622	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	WW	e2xp3A3	A: beta meanders	X: WW domain-like	H: WW domain (From Topology)	T: WW domain	F: WW	ECOD (1.6)
A	Rotamase_3	e2xp3A2	A: a+b two layers	X: FKBP-like	H: FKBP-like	T: FKBP-like	F: Rotamase_3	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.20.70.10	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
A	3.10.50.40	Alpha Beta	Roll	Chitinase A	domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00639	PPIC-type PPIASE domain (Rotamase)	PPIC-type PPIASE domain	Rotamases increase the rate of protein folding by catalysing the interconversion of cis-proline and trans-proline.	Domain
A	PF00397	WW domain (WW)	WW domain	The WW domain is a protein module with two highly conserved tryptophans that binds proline-rich peptide motifs in vitro.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	PEPTIDYL-PROLYL CIS-TRANS ISOMERASE NIMA-INTERACTING 1	phosphoprotein binding protein binding binding kinase binding enzyme binding protein kinase binding mitogen-activated protein kinase kinase binding cytoskeletal motor activity isomerase activity catalytic activity cis-trans isomerase activity cytoskeletal protein binding tau protein binding catalytic activity, acting on a protein phosphoprotein binding protein binding binding kinase binding enzyme binding protein kinase binding mitogen-activated protein kinase kinase binding cytoskeletal motor activity isomerase activity catalytic activity cis-trans isomerase activity cytoskeletal protein binding tau protein binding catalytic activity, acting on a protein peptidyl-prolyl cis-trans isomerase activity enzyme regulator activity ubiquitin ligase activator activity enzyme activator activity ubiquitin-protein transferase regulator activity molecular function activator activity molecular function regulator activity ubiquitin-protein transferase activator activity phosphoserine residue binding protein phosphorylated amino acid binding GTPase activating protein binding phosphothreonine residue binding beta-catenin binding	regulation of protein stability biological regulation regulation of biological quality protein stabilization regulation of protein binding regulation of molecular function negative regulation of protein binding negative regulation of binding regulation of binding negative regulation of molecular function regulation of biosynthetic process regulation of biological process regulation of cellular process cellular biosynthetic process regulation of protein stability biological regulation regulation of biological quality protein stabilization regulation of protein binding regulation of molecular function negative regulation of protein binding negative regulation of binding regulation of binding negative regulation of molecular function regulation of biosynthetic process regulation of biological process regulation of cellular process cellular biosynthetic process cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process cellular response to stimulus response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction intracellular signaling cassette negative regulation of cellular process signal transduction regulation of signaling negative regulation of response to stimulus regulation of MAPK cascade negative regulation of signal transduction negative regulation of ERK1 and ERK2 cascade regulation of response to stimulus MAPK cascade regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade negative regulation of MAPK cascade protein localization regulation of localization cellular localization regulation of protein localization regulation of protein localization to nucleus protein localization to nucleus localization regulation of cellular localization cellular macromolecule localization macromolecule localization protein localization to organelle cell surface receptor protein serine/threonine kinase signaling pathway regulation of transmembrane receptor protein serine/threonine kinase signaling pathway enzyme-linked receptor protein signaling pathway cell surface receptor signaling pathway SMAD protein signal transduction regulation of SMAD protein signal transduction negative regulation of SMAD protein signal transduction negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway regulation of cytokinesis regulation of cell cycle process cytokinesis regulation of cell division cell division cell cycle regulation of cell cycle cell cycle process negative regulation of transforming growth factor beta receptor signaling pathway cellular response to growth factor stimulus cellular response to transforming growth factor beta stimulus regulation of transforming growth factor beta receptor signaling pathway cellular response to endogenous stimulus regulation of cellular response to transforming growth factor beta stimulus response to endogenous stimulus regulation of cellular response to growth factor stimulus response to transforming growth factor beta transforming growth factor beta receptor signaling pathway response to growth factor transforming growth factor beta receptor superfamily signaling pathway amyloid precursor protein catabolic process regulation of amide metabolic process regulation of amyloid-beta formation regulation of amyloid precursor protein catabolic process regulation of primary metabolic process negative regulation of amyloid precursor protein catabolic process amyloid-beta metabolic process protein metabolic process amide metabolic process amyloid precursor protein metabolic process negative regulation of protein metabolic process amyloid-beta formation negative regulation of macromolecule metabolic process negative regulation of amyloid-beta formation negative regulation of amide metabolic process regulation of protein metabolic process negative regulation of metabolic process primary metabolic process mitotic nuclear division regulation of cellular component organization organelle fission regulation of mitotic nuclear division regulation of organelle organization mitotic cell cycle cellular component organization regulation of mitotic cell cycle organelle organization nuclear division mitotic cell cycle process regulation of nuclear division cellular component organization or biogenesis response to decreased oxygen levels response to hypoxia response to stress response to oxygen levels response to abiotic stimulus negative regulation of catabolic process catabolic process protein catabolic process regulation of catabolic process macromolecule catabolic process negative regulation of protein catabolic process regulation of protein catabolic process positive regulation of DNA-templated transcription positive regulation of biological process RNA metabolic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process positive regulation of cellular process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription positive regulation of cellular biosynthetic process positive regulation of molecular function positive regulation of protein binding positive regulation of binding positive regulation of hydrolase activity regulation of catalytic activity regulation of hydrolase activity positive regulation of catalytic activity regulation of GTPase activity positive regulation of GTPase activity macromolecule modification peptidyl-amino acid modification peptidyl-proline modification protein modification process protein peptidyl-prolyl isomerization developmental process multicellular organismal process cellular developmental process nervous system development generation of neurons neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development system development cell junction organization synapse organization negative regulation of locomotion regulation of cell motility regulation of locomotion negative regulation of cell motility cell motility locomotion regulation of protein modification process regulation of protein phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process protein phosphorylation phosphorylation regulation of phosphorylation regulation of phosphorus metabolic process positive regulation of phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process positive regulation of protein modification process positive regulation of protein phosphorylation positive regulation of phosphorus metabolic process positive regulation of cell communication positive regulation of signal transduction regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway positive regulation of response to stimulus positive regulation of Wnt signaling pathway Wnt signaling pathway positive regulation of canonical Wnt signaling pathway regulation of Wnt signaling pathway positive regulation of signaling	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen cytoplasm cytosol synapse cell junction glutamatergic synapse cilium plasma membrane bounded cell projection ciliary basal body cell projection microtubule organizing center cytoskeleton intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle midbody cytosolic region postsynapse postsynaptic cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR036020	WW domain superfamily	Homologous Superfamily
A	IPR023058	Peptidyl-prolyl cis-trans isomerase, PpiC-type, conserved site	Conserved Site
A	IPR046357	Peptidyl-prolyl cis-trans isomerase domain superfamily	Homologous Superfamily
A	IPR000297	Peptidyl-prolyl cis-trans isomerase, PpiC-type	Domain
A	IPR051370	Peptidyl-prolyl cis-trans isomerase Pin1	Family
A	IPR001202	WW domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q13526	breast carcinoma ovarian cancer Severe Recalcitrant Nodular Acne atypical teratoid rhabdoid tumor glioblastoma large cell medulloblastoma medulloblastoma pilocytic astrocytoma acute promyelocytic leukemia breast cancer malignant ependymoma primitive neuroectodermal tumor astrocytic tumor malignant glioma

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.