1IR3

PHOSPHORYLATED INSULIN RECEPTOR TYROSINE KINASE IN COMPLEX WITH PEPTIDE SUBSTRATE AND ATP ANALOG

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
Protein Modification Annotation
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1ir3a_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Insulin receptor	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	Protein kinase-like (PK-like)	8039520	3000066	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	Pkinase_Tyr	e1ir3A1	A: a+b complex topology	X: Protein kinase/SAICAR synthase/ATP-grasp (From Homology)	H: Protein kinase/SAICAR synthase/ATP-grasp	T: Protein kinase	F: Pkinase_Tyr	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF07714	Protein tyrosine and serine/threonine kinase (PK_Tyr_Ser-Thr)	Protein tyrosine and serine/threonine kinase	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosph ...	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [1]; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	INSULIN RECEPTOR	protein binding binding insulin receptor substrate binding amide binding amyloid-beta binding peptide binding peptide hormone binding hormone binding insulin binding molecular transducer activity catalytic activity, acting on a protein kinase activity protein kinase activity signaling receptor activity protein binding binding insulin receptor substrate binding amide binding amyloid-beta binding peptide binding peptide hormone binding hormone binding insulin binding molecular transducer activity catalytic activity, acting on a protein kinase activity protein kinase activity signaling receptor activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity protein-hormone receptor activity transmembrane receptor protein kinase activity transmembrane signaling receptor activity insulin receptor activity catalytic activity PTB domain binding protein domain specific binding phosphatidylinositol 3-kinase 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 protein-containing complex binding identical protein binding insulin-like growth factor receptor binding signaling receptor binding insulin-like growth factor binding insulin-like growth factor II binding growth factor binding cargo receptor activity guanyl nucleotide binding GTP binding guanyl ribonucleotide binding insulin-like growth factor I binding	developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development system development regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process cellular process metabolic process regulation of nitric oxide metabolic process positive regulation of nitric oxide biosynthetic process regulation of metabolic process positive regulation of cellular process cellular component disassembly positive regulation of cellular component organization regulation of cellular component organization protein-containing complex organization protein-containing complex disassembly regulation of protein-containing complex disassembly cellular component organization cellular component organization or biogenesis positive regulation of protein-containing complex disassembly behavior system process learning learning or memory nervous system process cognition localization import into cell receptor internalization transport receptor-mediated endocytosis endocytosis establishment of localization vesicle-mediated transport regulation of protein modification process positive regulation of phosphorylation regulation of catalytic activity regulation of protein phosphorylation positive regulation of protein metabolic process regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of molecular function positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process protein metabolic process activation of protein kinase B activity positive regulation of protein kinase activity phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of transferase activity positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process positive regulation of catalytic activity primary metabolic process regulation of protein kinase activity regulation of macromolecule metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity activation of protein kinase activity macromolecule modification regulation of phosphorylation regulation of phosphorus metabolic process macromolecule metabolic process biological process involved in interspecies interaction between organisms symbiont entry into host cell viral process symbiont entry into host viral life cycle biological process involved in interaction with host biological process involved in symbiotic interaction regulation of growth regulation of developmental growth regulation of developmental process developmental growth growth positive regulation of developmental process positive regulation of growth positive regulation of developmental growth memory positive regulation of organelle organization regulation of mitotic nuclear division positive regulation of mitotic nuclear division mitotic cell cycle regulation of mitotic cell cycle positive regulation of cell cycle process cell cycle regulation of cell cycle cell cycle process mitotic nuclear division regulation of cell cycle process organelle fission positive regulation of nuclear division regulation of organelle organization positive regulation of cell cycle organelle organization nuclear division mitotic cell cycle process regulation of nuclear division protein autophosphorylation heart development heart morphogenesis circulatory system development anatomical structure morphogenesis animal organ morphogenesis digestive system development gland development exocrine pancreas development pancreas development exocrine system development positive regulation of respiratory burst respiratory burst regulation of respiratory burst RNA metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of meiotic cell cycle sexual reproduction regulation of reproductive process meiotic cell cycle positive regulation of meiotic cell cycle positive regulation of reproductive process circulatory system process vascular process in circulatory system vascular transport transport across blood-brain barrier chemical homeostasis homeostatic process glucose homeostasis carbohydrate homeostasis ribonucleotide catabolic process pyridine nucleotide catabolic process oxoacid metabolic process carbohydrate catabolic process carbohydrate derivative metabolic process organophosphate catabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process regulation of ATP metabolic process regulation of purine nucleotide catabolic process positive regulation of nucleotide catabolic process regulation of small molecule metabolic process glycolytic process regulation of nucleotide metabolic process pyridine-containing compound metabolic process small molecule metabolic process purine ribonucleotide catabolic process pyridine nucleotide metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process regulation of carbohydrate catabolic process positive regulation of nucleobase-containing compound metabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process nucleotide metabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process positive regulation of ATP metabolic process nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process nucleoside triphosphate metabolic process positive regulation of carbohydrate metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process catabolic process positive regulation of nucleotide metabolic process positive regulation of purine nucleotide catabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process regulation of carbohydrate metabolic process ribonucleoside triphosphate metabolic process nucleotide catabolic process purine nucleoside triphosphate metabolic process carbohydrate metabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process positive regulation of glycolytic process ADP catabolic process carboxylic acid metabolic process generation of precursor metabolites and energy regulation of catabolic process regulation of glycolytic process purine-containing compound metabolic process positive regulation of purine nucleotide metabolic process positive regulation of catabolic process ADP metabolic process organophosphate metabolic process purine ribonucleoside diphosphate metabolic process positive regulation of small molecule metabolic process purine ribonucleoside diphosphate catabolic process sex determination male sex determination positive regulation of macromolecule biosynthetic process positive regulation of glycogen metabolic process carbohydrate biosynthetic process hexose metabolic process positive regulation of glucose metabolic process positive regulation of glycogen biosynthetic process energy reserve metabolic process regulation of glycogen metabolic process monosaccharide metabolic process regulation of glycogen biosynthetic process glucan biosynthetic process energy derivation by oxidation of organic compounds regulation of glucan biosynthetic process regulation of polysaccharide metabolic process polysaccharide metabolic process glucan metabolic process regulation of glucose metabolic process polysaccharide biosynthetic process glycogen metabolic process glycogen biosynthetic process regulation of polysaccharide biosynthetic process regulation of carbohydrate biosynthetic process glucose metabolic process regulation of localization regulation of receptor internalization positive regulation of endocytosis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport positive regulation of receptor internalization positive regulation of transport amyloid-beta clearance epidermis development tissue development cellular response to stimulus positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction response to stimulus signaling regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of response to stimulus regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling regulation of gonad development development of primary female sexual characteristics regulation of female gonad development regulation of multicellular organismal process regulation of multicellular organismal development female gonad development female sex differentiation cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation regulation of MAP kinase activity positive regulation of protein serine/threonine kinase activity positive regulation of MAP kinase activity positive regulation of MAPK cascade regulation of MAPK cascade regulation of protein serine/threonine kinase activity MAPK cascade dendritic spine maintenance dendritic spine organization postsynapse organization plasma membrane bounded cell projection organization cell projection organization cellular component maintenance cell junction organization neuron projection organization synapse organization adrenal gland development endocrine system development cellular response to nitrogen compound response to peptide hormone insulin receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cellular response to endogenous stimulus response to hormone enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus cell surface receptor signaling pathway response to endogenous stimulus response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to chemical stimulus response to chemical response to insulin cellular response to insulin stimulus cellular response to growth factor stimulus response to growth factor positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration cell migration cell motility locomotion positive regulation of DNA-templated transcription positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of embryonic development embryo development G protein-coupled receptor signaling pathway neuron projection maintenance hexose transmembrane transport D-glucose import carbohydrate transport positive regulation of D-glucose transmembrane transport positive regulation of transmembrane transport regulation of D-glucose import positive regulation of D-glucose import transmembrane transport regulation of transmembrane transport D-glucose transmembrane transport regulation of D-glucose transmembrane transport monosaccharide transmembrane transport carbohydrate transmembrane transport	cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cell periphery cellular anatomical structure cell surface membrane plasma membrane external side of plasma membrane side of membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex receptor complex endosome membrane intracellular anatomical structure endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle vesicle membrane cytoplasmic vesicle cytoplasm organelle membrane somatodendritic compartment neuronal cell body membrane cell body cell body membrane neuronal cell body axon cell projection neuron projection plasma membrane bounded cell projection membrane microdomain membrane raft plasma membrane raft plasma membrane region caveola lytic vacuole vacuole lysosome cell leading edge leading edge membrane neuron projection membrane dendrite membrane dendrite dendritic tree cell projection membrane catalytic complex plasma membrane protein complex membrane protein complex transferase complex protein kinase complex transferase complex, transferring phosphorus-containing groups insulin receptor complex plasma membrane signaling receptor complex late endosome
B	PEPTIDE SUBSTRATE	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR008266	Tyrosine-protein kinase, active site	Active Site
A	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A	IPR000719	Protein kinase domain	Domain
A	IPR036941	Receptor L-domain superfamily	Homologous Superfamily
A	IPR006212	Furin-like repeat	Repeat
A	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A	IPR000494	Receptor L-domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A	IPR002011	Tyrosine-protein kinase, receptor class II, conserved site	Conserved Site
A	IPR003961	Fibronectin type III	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR006211	Furin-like cysteine-rich domain	Domain
A	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
A	IPR050122	Receptor Tyrosine Kinase	Family
A	IPR016246	Tyrosine-protein kinase, insulin-like receptor	Family
A	IPR040969	Insulin receptor, trans-membrane domain	Domain
A	IPR036116	Fibronectin type III superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P06213	Donohue syndrome type 2 diabetes mellitus hyperinsulinism due to INSR deficiency Rabson-Mendenhall syndrome Insulin Resistance Alzheimer disease glucose intolerance hyperinsulinism insulin-resistance syndrome type A polycystic ovary syndrome Parkinson disease diabetic autonomic neuropathy diabetic neuropathy congenital diaphragmatic hernia hyperglycemia Donohue syndrome type 2 diabetes mellitus hyperinsulinism due to INSR deficiency Rabson-Mendenhall syndrome Insulin Resistance Alzheimer disease glucose intolerance hyperinsulinism insulin-resistance syndrome type A polycystic ovary syndrome Parkinson disease diabetic autonomic neuropathy diabetic neuropathy congenital diaphragmatic hernia hyperglycemia diabetic polyneuropathy Lewy body dementia diabetes mellitus psoriasis spina bifida intellectual disability substance-related disorder lung disease acquired metabolic disease drug dependence malignant glioma maturity-onset diabetes of the young glioblastoma osteogenesis imperfecta pancreatic ductal adenocarcinoma hyperinsulinemic hypoglycemia hypertensive disorder substance dependence large cell medulloblastoma type 1 diabetes mellitus esophageal adenocarcinoma malignant mesothelioma osteosarcoma atypical teratoid rhabdoid tumor pancreatic intraductal papillary-mucinous neoplasm plasma cell myeloma dermatomyositis hypothyroidism Sjogren syndrome substance abuse malignant ependymoma exocrine pancreatic carcinoma malignant pancreatic neoplasm gastric adenocarcinoma astrocytic tumor ovarian cancer breast cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	receptor protein-tyrosine kinase M-CSA #246	Phosphorylated insulin receptor tyrosine kinase from Homo sapiens catalyses the phosphorylation of Tyr on intracellular proteins that are related to the STATK pathway. The phosphoryl group is transferred from ATP to form ADP. On carrying out this function, the enzyme activates the signalling cascade inside the cell. Insulin receptor tyrosine kinase is thought to have a restricted range of protein substrates, with a consensus YMXM phosphorylation motif having been defined [PMID:17085043]. There are two alternative mechanisms suggested for this enzyme, and there is still some debate as to whether this enzyme works via the associative (S_N2-type) mechanism or the dissociative (S_N1-type) mechanism. However, experimental and QM/MM studies, as well as crystallographic evidence, seems to support the dissociative mechanism [PMID:17085043, PMID:16023488, PMID:19334696 and Pichierri et al.].	Defined by 4 residues: ASP:A-155 [auth A-1132]ARG:A-159 [auth A-1136]ASN:A-160 [auth A-1137]ASP:A-173 [auth A-1150] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 2.7.1.112 (PDB Primary Data) Search M-CSA Motif + EC 2.7.1.112 EC: 2.7.10.1 (UniProt) Search M-CSA Motif + EC 2.7.10.1

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.