8EXJ

Crystal structure of PTP1B D181A/Q262A phosphatase domain in complex with a JAK1 activation loop phosphopeptide

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	(Phosphotyrosine protein) phosphatases II	8040614	3000304	SCOP2B (2022-06-29)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00102	Protein-tyrosine phosphatase (Y_phosphatase)	Protein-tyrosine phosphatase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Tyrosine-protein phosphatase non-receptor type 1	protein binding binding signaling receptor binding insulin receptor binding cell adhesion molecule binding cadherin binding ephrin receptor binding protein tyrosine kinase binding kinase binding receptor tyrosine kinase binding enzyme binding protein kinase binding phosphoric ester hydrolase activity phosphoprotein phosphatase activity protein binding binding signaling receptor binding insulin receptor binding cell adhesion molecule binding cadherin binding ephrin receptor binding protein tyrosine kinase binding kinase binding receptor tyrosine kinase binding enzyme binding protein kinase binding phosphoric ester hydrolase activity phosphoprotein phosphatase activity non-membrane spanning protein tyrosine phosphatase activity catalytic activity, acting on a protein hydrolase activity, acting on ester bonds protein tyrosine phosphatase activity phosphatase activity hydrolase activity catalytic activity protein phosphatase binding phosphatase binding protein phosphatase 2A binding RNA binding organic cyclic compound binding nucleic acid binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus cellular response to stimulus regulation of signaling regulation of biological process regulation of cellular process response to stimulus negative regulation of signaling signaling negative regulation of response to stimulus biological regulation negative regulation of biological process regulation of signal transduction negative regulation of signal transduction negative regulation of cell communication cell communication regulation of response to stimulus negative regulation of cellular process regulation of cell communication cellular process signal transduction cellular response to nitrogen compound response to peptide hormone cellular response to growth hormone stimulus cell surface receptor protein tyrosine kinase signaling pathway cellular response to endogenous stimulus response to hormone growth hormone receptor signaling pathway via JAK-STAT enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus growth hormone receptor signaling pathway cell surface receptor signaling pathway response to endogenous stimulus cellular response to peptide hormone stimulus response to oxygen-containing compound response to nitrogen compound cellular response to oxygen-containing compound response to growth hormone cellular response to chemical stimulus response to chemical regulation of catalytic activity negative regulation of catalytic activity regulation of transferase activity regulation of MAP kinase activity intracellular signal transduction negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of kinase activity negative regulation of transferase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process intracellular signaling cassette negative regulation of protein modification process phosphorus metabolic process protein modification process negative regulation of protein metabolic process protein phosphorylation phosphorylation cellular metabolic process regulation of protein metabolic process negative regulation of metabolic process regulation of cellular metabolic process primary metabolic process regulation of MAPK cascade regulation of molecular function regulation of kinase activity negative regulation of protein phosphorylation regulation of protein serine/threonine kinase activity macromolecule modification regulation of phosphorus metabolic process metabolic process macromolecule metabolic process regulation of metabolic process regulation of protein modification process regulation of protein phosphorylation negative regulation of intracellular signal transduction negative regulation of phosphate metabolic process regulation of intracellular signal transduction negative regulation of protein serine/threonine kinase activity protein metabolic process negative regulation of macromolecule metabolic process negative regulation of molecular function negative regulation of MAP kinase activity regulation of protein kinase activity regulation of macromolecule metabolic process negative regulation of protein kinase activity negative regulation of phosphorus metabolic process MAPK cascade regulation of phosphorylation negative regulation of phosphorylation negative regulation of MAPK cascade regulation of localization import into cell regulation of cellular component organization regulation of transport transport regulation of vesicle-mediated transport establishment of localization vesicle-mediated transport cellular component organization localization cellular component organization or biogenesis endocytosis regulation of endocytosis protein dephosphorylation dephosphorylation platelet-derived growth factor receptor-beta signaling pathway platelet-derived growth factor receptor signaling pathway negative regulation of ERK1 and ERK2 cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade cellular response to growth factor stimulus negative regulation of cellular response to growth factor stimulus regulation of vascular endothelial growth factor receptor signaling pathway negative regulation of vascular endothelial growth factor receptor signaling pathway regulation of cellular response to growth factor stimulus vascular endothelial growth factor receptor signaling pathway response to growth factor peptidyl-tyrosine dephosphorylation peptidyl-tyrosine dephosphorylation involved in inactivation of protein kinase activity positive regulation of phosphorylation positive regulation of phosphate metabolic process positive regulation of metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation positive regulation of phosphorus metabolic process positive regulation of kinase activity regulation of protein tyrosine kinase activity positive regulation of protein metabolic process positive regulation of biological process positive regulation of cellular metabolic process peptidyl-tyrosine modification positive regulation of molecular function positive regulation of protein modification process positive regulation of peptidyl-tyrosine phosphorylation positive regulation of protein kinase activity positive regulation of cellular process positive regulation of transferase activity positive regulation of protein tyrosine kinase activity regulation of peptidyl-tyrosine phosphorylation positive regulation of catalytic activity peptidyl-tyrosine phosphorylation organelle organization actin cytoskeleton organization actin filament-based process cytoskeleton organization protein localization establishment of protein localization cellular localization nitrogen compound transport regulation of protein localization cellular macromolecule localization establishment of localization in cell regulation of intracellular transport regulation of establishment of protein localization intracellular transport regulation of protein transport protein transport regulation of cellular localization macromolecule localization regulation of intracellular protein transport intracellular protein transport receptor catabolic process catabolic process macromolecule catabolic process cellular catabolic process receptor metabolic process positive regulation of receptor catabolic process regulation of catabolic process positive regulation of catabolic process regulation of receptor catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process insulin receptor signaling pathway regulation of cellular response to insulin stimulus regulation of insulin receptor signaling pathway negative regulation of cellular response to insulin stimulus negative regulation of insulin receptor signaling pathway response to insulin cellular response to insulin stimulus positive regulation of IRE1-mediated unfolded protein response positive regulation of cell communication positive regulation of signal transduction regulation of cellular response to stress endoplasmic reticulum unfolded protein response regulation of response to endoplasmic reticulum stress positive regulation of response to stimulus regulation of endoplasmic reticulum unfolded protein response positive regulation of response to endoplasmic reticulum stress cellular response to stress response to stress regulation of response to stress positive regulation of endoplasmic reticulum unfolded protein response response to endoplasmic reticulum stress regulation of IRE1-mediated unfolded protein response cellular response to topologically incorrect protein positive regulation of intracellular signal transduction cellular response to unfolded protein response to unfolded protein response to topologically incorrect protein IRE1-mediated unfolded protein response positive regulation of signaling positive regulation of protein serine/threonine kinase activity positive regulation of MAP kinase activity positive regulation of MAPK cascade positive regulation of JUN kinase activity regulation of JUN kinase activity regulation of hepatocyte growth factor receptor signaling pathway hepatocyte growth factor receptor signaling pathway positive regulation of cellular response to insulin stimulus positive regulation of insulin receptor signaling pathway receptor recycling insulin receptor recycling negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway regulation of programmed cell death intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress regulation of intrinsic apoptotic signaling pathway regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway intrinsic apoptotic signaling pathway negative regulation of response to endoplasmic reticulum stress negative regulation of programmed cell death regulation of apoptotic process cell death apoptotic signaling pathway negative regulation of intrinsic apoptotic signaling pathway negative regulation of apoptotic process apoptotic process programmed cell death regulation of apoptotic signaling pathway regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus regulation of type I interferon-mediated signaling pathway response to cytokine response to biotic stimulus cytokine-mediated signaling pathway interferon-mediated signaling pathway cellular response to type I interferon innate immune response regulation of immune system process cellular response to cytokine stimulus response to external biotic stimulus immune response response to other organism defense response regulation of innate immune response regulation of cytokine-mediated signaling pathway defense response to symbiont response to external stimulus response to peptide regulation of response to cytokine stimulus immune system process defense response to other organism type I interferon-mediated signaling pathway regulation of immune response response to type I interferon PERK-mediated unfolded protein response integrated stress response signaling ER-nucleus signaling pathway negative regulation of endoplasmic reticulum unfolded protein response regulation of PERK-mediated unfolded protein response negative regulation of PERK-mediated unfolded protein response	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle organelle subcompartment cytoplasmic side of membrane membrane intracellular membrane-bounded organelle endomembrane system side of membrane endoplasmic reticulum subcompartment intracellular organelle organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle organelle subcompartment cytoplasmic side of membrane membrane intracellular membrane-bounded organelle endomembrane system side of membrane endoplasmic reticulum subcompartment intracellular organelle organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum cytoplasmic side of endoplasmic reticulum membrane organelle membrane endoplasmic reticulum membrane sorting endosome endosome intracellular vesicle cytoplasmic vesicle vesicle mitochondrial membrane organelle inner membrane mitochondrion mitochondrial inner membrane organelle envelope mitochondrial envelope mitochondrial crista protein-containing complex early endosome membrane-enclosed lumen intracellular organelle lumen organelle lumen endosome lumen mitochondrial matrix
B [auth D]	Tyrosine-protein kinase JAK1 activation loop peptide	CCR5 chemokine receptor binding CCR chemokine receptor binding protein binding binding signaling receptor binding cytokine receptor binding G protein-coupled receptor binding chemokine receptor binding protein phosphatase binding phosphatase binding enzyme binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity CCR5 chemokine receptor binding CCR chemokine receptor binding protein binding binding signaling receptor binding cytokine receptor binding G protein-coupled receptor binding chemokine receptor binding protein phosphatase binding phosphatase binding enzyme binding protein tyrosine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups 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 non-membrane spanning protein tyrosine kinase activity ubiquitin protein ligase binding ubiquitin-like protein ligase binding cation binding metal ion binding growth hormone receptor binding hormone receptor binding	cellular response to stimulus cellular response to nitrogen compound regulation of cellular process response to stimulus signaling response to peptide hormone cellular response to growth hormone stimulus cell surface receptor protein tyrosine kinase signaling pathway cell communication cellular response to endogenous stimulus response to hormone growth hormone receptor signaling pathway via JAK-STAT signal transduction enzyme-linked receptor protein signaling pathway cellular response to stimulus cellular response to nitrogen compound regulation of cellular process response to stimulus signaling response to peptide hormone cellular response to growth hormone stimulus cell surface receptor protein tyrosine kinase signaling pathway cell communication cellular response to endogenous stimulus response to hormone growth hormone receptor signaling pathway via JAK-STAT signal transduction enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus regulation of biological process growth hormone receptor signaling pathway cell surface receptor signaling pathway response to endogenous stimulus biological regulation cellular response to peptide hormone stimulus response to oxygen-containing compound response to nitrogen compound cellular response to oxygen-containing compound response to growth hormone cellular response to chemical stimulus response to chemical cellular process response to cytokine cytokine-mediated signaling pathway response to peptide cellular response to cytokine stimulus interleukin-7-mediated signaling pathway response to interleukin-7 cellular response to interleukin-7 response to antibiotic interleukin-15-mediated signaling pathway cellular response to interleukin-15 response to interleukin-15 biological process involved in interspecies interaction between organisms response to type II interferon cellular response to type II interferon response to biotic stimulus interferon-mediated signaling pathway response to stress innate immune response response to external biotic stimulus immune response response to other organism defense response type II interferon-mediated signaling pathway defense response to symbiont response to external stimulus immune system process defense response to other organism cell surface receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT protein phosphorylation phosphorylation cellular metabolic process primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process regulation of homotypic cell-cell adhesion positive regulation of cell adhesion regulation of cell adhesion homotypic cell-cell adhesion positive regulation of biological process positive regulation of cell-cell adhesion cell adhesion cell-cell adhesion positive regulation of homotypic cell-cell adhesion regulation of cell-cell adhesion positive regulation of cellular process protein localization localization cellular localization cellular macromolecule localization macromolecule localization protein localization to cell junction protein localization to cell-cell junction response to interleukin-9 interleukin-9-mediated signaling pathway cellular response to interleukin-9 cellular response to type I interferon type I interferon-mediated signaling pathway response to type I interferon regulation of localization regulation of protein localization positive regulation of protein localization to nucleus regulation of protein localization to nucleus protein localization to nucleus regulation of cellular localization protein localization to organelle positive regulation of protein localization developmental process cellular developmental process cell differentiation interleukin-2-mediated signaling pathway cellular response to interleukin-2 response to interleukin-2 response to type III interferon type III interferon-mediated signaling pathway cellular response to type III interferon interleukin-4-mediated signaling pathway response to interleukin-4 cellular response to interleukin-4 interleukin-6-mediated signaling pathway response to interleukin-6 cellular response to interleukin-6 interleukin-10-mediated signaling pathway multicellular organismal process regulation of sprouting angiogenesis regulation of developmental process angiogenesis regulation of vasculature development positive regulation of developmental process multicellular organism development tube morphogenesis anatomical structure development positive regulation of sprouting angiogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development system development regulation of multicellular organismal development blood vessel morphogenesis tube development positive regulation of angiogenesis sprouting angiogenesis vasculature development circulatory system development anatomical structure morphogenesis positive regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis positive regulation of multicellular organismal process intracellular signal transduction interleukin-11-mediated signaling pathway cellular response to virus response to virus CD4-positive or CD8-positive, alpha-beta T cell lineage commitment adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains cell development mononuclear cell differentiation lymphocyte activation lymphocyte differentiation cell activation involved in immune response CD4-positive, alpha-beta T cell differentiation CD4-positive, alpha-beta T cell differentiation involved in immune response alpha-beta T cell differentiation involved in immune response leukocyte activation alpha-beta T cell differentiation T cell activation involved in immune response alpha-beta T cell activation involved in immune response T cell activation CD4-positive, alpha-beta T cell activation leukocyte activation involved in immune response alpha-beta T cell activation T cell differentiation CD4-positive, alpha-beta T cell lineage commitment lymphocyte activation involved in immune response T-helper cell differentiation alpha-beta T cell lineage commitment hemopoiesis cell activation T-helper cell lineage commitment T cell differentiation involved in immune response T cell lineage commitment adaptive immune response immune effector process T-helper 17 cell lineage commitment positive T cell selection T cell selection T-helper 17 cell differentiation cell fate commitment leukocyte differentiation T-helper 17 type immune response	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol intracellular organelle cytoskeleton organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle cell periphery extrinsic component of plasma membrane cytoplasmic side of plasma membrane cytoplasmic side of membrane membrane intracellular anatomical structure cytoplasm cellular anatomical entity cytosol intracellular organelle cytoskeleton organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle cell periphery extrinsic component of plasma membrane cytoplasmic side of plasma membrane cytoplasmic side of membrane membrane plasma membrane extrinsic component of membrane extrinsic component of cytoplasmic side of plasma membrane side of membrane anchoring junction cell junction focal adhesion cell-substrate junction membrane-bounded organelle endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system cytoplasmic vesicle vesicle nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR016130	Protein-tyrosine phosphatase, active site	Active Site
A	IPR051985	Non-receptor type tyrosine-specific phosphatase	Family
A	IPR012265	Protein-tyrosine phosphatase, non-receptor type-1/2	Family
A	IPR003595	Protein-tyrosine phosphatase, catalytic	Domain
A	IPR029021	Protein-tyrosine phosphatase-like	Homologous Superfamily
A	IPR000242	Tyrosine-specific protein phosphatase, PTPase domain	Domain
A	IPR000387	Tyrosine-specific protein phosphatases domain	Domain
B [auth D]	IPR000299	FERM domain	Domain
B [auth D]	IPR016251	Tyrosine-protein kinase, non-receptor Jak/Tyk2	Family
B [auth D]	IPR008266	Tyrosine-protein kinase, active site	Active Site
B [auth D]	IPR019748	FERM central domain	Domain
B [auth D]	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
B [auth D]	IPR000719	Protein kinase domain	Domain
B [auth D]	IPR035963	FERM superfamily, second domain	Homologous Superfamily
B [auth D]	IPR041381	JAK1-3/TYK2, pleckstrin homology-like domain	Domain
B [auth D]	IPR017441	Protein kinase, ATP binding site	Binding Site
B [auth D]	IPR036860	SH2 domain superfamily	Homologous Superfamily
B [auth D]	IPR000980	SH2 domain	Domain
B [auth D]	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
B [auth D]	IPR051286	Janus Kinase (JAK)	Family
B [auth D]	IPR041046	JAK, FERM F2 lobe domain	Domain
B [auth D]	IPR019749	Band 4.1 domain	Domain
B [auth D]	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
B [auth D]	IPR020776	Tyrosine-protein kinase, non-receptor Jak1	Family
B [auth D]	IPR041155	FERM F1 lobe ubiquitin-like domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P18031	type 2 diabetes mellitus Insulin Resistance Rett syndrome obesity disorder hypertensive disorder hyperinsulinism B-cell neoplasm Hodgkins lymphoma lung cancer maturity-onset diabetes of the young colorectal adenoma ovarian cancer schizophrenia Hodgkin's lymphoma, mixed cellularity Huntington disease type 2 diabetes mellitus Insulin Resistance Rett syndrome obesity disorder hypertensive disorder hyperinsulinism B-cell neoplasm Hodgkins lymphoma lung cancer maturity-onset diabetes of the young colorectal adenoma ovarian cancer schizophrenia Hodgkin's lymphoma, mixed cellularity Huntington disease inborn carbohydrate metabolic disorder mediastinal cancer nodular lymphocyte predominant Hodgkin lymphoma colorectal cancer Hodgkin's lymphoma, lymphocytic depletion sarcoidosis vitiligo Hodgkin's lymphoma, lymphocytic-histiocytic predominance
B [auth D]	Pharos: P23458	acquired polycythemia vera prostate cancer rheumatoid arthritis medulloblastoma pituitary cancer Precursor Cell Lymphoblastic Leukemia Lymphoma ulcerative colitis astrocytic tumor autoimmune disease brain glioma exocrine pancreatic carcinoma large cell medulloblastoma malignant mesothelioma osteosarcoma plasma cell myeloma acquired polycythemia vera prostate cancer rheumatoid arthritis medulloblastoma pituitary cancer Precursor Cell Lymphoblastic Leukemia Lymphoma ulcerative colitis astrocytic tumor autoimmune disease brain glioma exocrine pancreatic carcinoma large cell medulloblastoma malignant mesothelioma osteosarcoma plasma cell myeloma primary myelofibrosis psoriatic arthritis acute myeloid leukemia atopic eczema bone marrow disease cancer glioblastoma lung cancer malignant pancreatic neoplasm ovarian cancer arthritic joint disease atypical teratoid rhabdoid tumor bone marrow neoplasm dermatomyositis Hashimoto thyroiditis malignant ependymoma