6NJA

Structure of WT RET protein tyrosine kinase domain at 1.92A resolution.

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d6njaa1	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d6njaa2	Artifacts	Tags	Tags	Tags	N-terminal Tags	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)	8069207	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	e6njaA1	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 (utative)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (utative)

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	Proto-oncogene tyrosine-protein kinase receptor Ret	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 transmembrane receptor protein kinase activity transmembrane signaling receptor activity catalytic activity 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 transmembrane receptor protein kinase activity transmembrane signaling receptor activity catalytic activity 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 cation binding calcium ion binding metal ion binding	response to stimulus response to chemical response to xenobiotic stimulus regulation of biological process cell adhesion regulation of cellular process regulation of cell adhesion biological regulation cellular process developmental process multicellular organismal process morphogenesis of embryonic epithelium embryonic epithelial tube formation epithelium development response to stimulus response to chemical response to xenobiotic stimulus regulation of biological process cell adhesion regulation of cellular process regulation of cell adhesion biological regulation cellular process developmental process multicellular organismal process morphogenesis of embryonic epithelium embryonic epithelial tube formation epithelium development tube development embryonic morphogenesis morphogenesis of an epithelium tube formation tissue development embryo development epithelial tube formation tissue morphogenesis anatomical structure morphogenesis multicellular organism development tube morphogenesis anatomical structure development anatomical structure formation involved in morphogenesis epithelial tube morphogenesis cellular response to stimulus cell surface receptor signaling pathway signaling GDF15-GFRAL signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication cellular response to stress response to stress glial cell-derived neurotrophic factor receptor signaling pathway signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cell communication positive regulation of signal transduction signal transduction in absence of ligand positive regulation of biological process regulation of signal transduction regulation of programmed cell death positive regulation of extrinsic apoptotic signaling pathway in absence of ligand extrinsic apoptotic signaling pathway positive regulation of apoptotic signaling pathway positive regulation of response to stimulus extrinsic apoptotic signaling pathway in absence of ligand positive regulation of cellular process regulation of signaling positive regulation of programmed cell death regulation of apoptotic process positive regulation of extrinsic apoptotic signaling pathway cell death positive regulation of apoptotic process regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway regulation of response to stimulus regulation of extrinsic apoptotic signaling pathway in absence of ligand regulation of cell communication apoptotic process programmed cell death regulation of apoptotic signaling pathway positive regulation of signaling regulation of biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process regulation of gene expression positive regulation of metabolic process biosynthetic process positive regulation of gene expression positive regulation of biosynthetic process regulation of macromolecule biosynthetic process metabolic process positive regulation of macromolecule metabolic process macromolecule metabolic process regulation of metabolic process sensory organ development eye development animal organ development retina development in camera-type eye visual system development camera-type eye development sensory system development system development positive regulation of metanephric glomerulus development regulation of developmental process metanephric glomerulus development regulation of kidney development renal system development positive regulation of developmental process metanephros development regulation of glomerulus development regulation of multicellular organismal process nephron development metanephric nephron development regulation of metanephric glomerulus development positive regulation of glomerulus development positive regulation of kidney development glomerulus development positive regulation of multicellular organismal process regulation of metanephros development kidney development positive regulation of metanephros development proteolysis membrane protein proteolysis primary metabolic process protein metabolic process response to lipid response to oxygen-containing compound cellular response to oxygen-containing compound response to retinoic acid cellular response to chemical stimulus cellular response to retinoic acid cellular response to lipid ureter development developmental maturation ureter maturation anatomical structure maturation animal organ maturation intracellular signal transduction intracellular signaling cassette MAPK cascade regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization cellular developmental process cell projection organization cell development neuron projection development cellular component organization neurogenesis neuron differentiation positive regulation of neuron projection development cell differentiation positive regulation of cell projection organization cellular component organization or biogenesis plasma membrane bounded cell projection organization regulation of cell projection organization nervous system development generation of neurons neuron development regulation of plasma membrane bounded cell projection organization cell-cell adhesion neuron cell-cell adhesion protein phosphorylation phosphorylation macromolecule modification phosphate-containing compound metabolic process protein modification process phosphorus metabolic process leukocyte migration lymphocyte migration into lymphoid organs immune system process mononuclear cell migration lymphocyte migration cell migration cell motility cell-cell adhesion via plasma-membrane adhesion molecules homophilic cell adhesion via plasma membrane adhesion molecules regulation of cell differentiation positive regulation of cell maturation regulation of neuron maturation regulation of cell development positive regulation of cell differentiation cell maturation regulation of cell maturation positive regulation of neuron maturation positive regulation of cell development neuron maturation regulation of neuron differentiation multicellular organismal response to stress response to pain immune system development hematopoietic or lymphoid organ development Peyer's patch morphogenesis Peyer's patch development mucosa-associated lymphoid tissue development axonogenesis plasma membrane bounded cell projection morphogenesis cell morphogenesis cell projection morphogenesis neuron projection morphogenesis regulation of axonogenesis regulation of anatomical structure morphogenesis axon development cell morphogenesis involved in neuron differentiation digestive system development posterior midgut development midgut development digestive tract development regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of intracellular signal transduction positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction stem cell development neural crest cell differentiation neural crest cell development mesenchyme development mesenchymal cell migration stem cell differentiation ameboidal-type cell migration mesenchymal cell differentiation neural crest cell migration positive regulation of cell adhesion mediated by integrin positive regulation of cell adhesion regulation of cell adhesion mediated by integrin cell adhesion mediated by integrin ureteric bud development mesonephric epithelium development kidney epithelium development mesonephros development mesonephric tubule development positive regulation of MAPK cascade regulation of MAPK cascade axon guidance neuron projection guidance 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 locomotion positive regulation of DNA-templated transcription RNA metabolic process regulation of primary 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 positive regulation of nucleobase-containing compound metabolic process 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 enteric nervous system development autonomic nervous system development positive regulation of cell size regulation of cellular component size regulation of biological quality regulation of cell size regulation of anatomical structure size nerve development innervation positive regulation of phosphorylation regulation of peptidyl-serine phosphorylation positive regulation of phosphate metabolic process regulation of phosphate metabolic process peptidyl-amino acid modification regulation of receptor signaling pathway via JAK-STAT positive regulation of protein phosphorylation positive regulation of peptidyl-serine phosphorylation of STAT protein positive regulation of phosphorus metabolic process regulation of protein metabolic process serine phosphorylation of STAT protein regulation of phosphorus metabolic process regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via STAT regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-serine phosphorylation of STAT protein peptidyl-serine modification positive regulation of protein modification process peptidyl-serine phosphorylation positive regulation of peptidyl-serine phosphorylation regulation of phosphorylation cell surface receptor signaling pathway via JAK-STAT	somatodendritic compartment cell projection cellular anatomical structure dendrite dendritic tree neuron projection plasma membrane bounded cell projection protein-containing complex receptor complex cell periphery plasma membrane protein complex membrane plasma membrane membrane protein complex somatodendritic compartment cell projection cellular anatomical structure dendrite dendritic tree neuron projection plasma membrane bounded cell projection protein-containing complex receptor complex cell periphery plasma membrane protein complex membrane plasma membrane membrane protein complex endosome membrane membrane-bounded organelle 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 organelle cytoplasm vesicle organelle membrane cell body neuronal cell body axon early endosome

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	IPR015919	Cadherin-like superfamily	Homologous Superfamily
A	IPR041317	RET, cadherin-like domain 4	Domain
A	IPR016249	Tyrosine-protein kinase, Ret receptor	Family
A	IPR000719	Protein kinase domain	Domain
A	IPR041163	Ret, cadherin like domain 1	Domain
A	IPR002126	Cadherin-like	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A	IPR040667	Tyrosine-protein kinase receptor Ret, cadherin like domain 3	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR050122	Receptor Tyrosine Kinase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P07949	Hirschsprung disease multiple endocrine neoplasia type 2A multiple endocrine neoplasia type 2B medullary thyroid gland carcinoma phaeochromocytoma congenital central hypoventilation syndrome multiple endocrine neoplasia familial medullary thyroid carcinoma Hirschsprung disease, susceptibility to, 1 status epilepticus Burkitt lymphoma colorectal cancer cancer thyroid gland papillary carcinoma thyroid adenoma Hirschsprung disease multiple endocrine neoplasia type 2A multiple endocrine neoplasia type 2B medullary thyroid gland carcinoma phaeochromocytoma congenital central hypoventilation syndrome multiple endocrine neoplasia familial medullary thyroid carcinoma Hirschsprung disease, susceptibility to, 1 status epilepticus Burkitt lymphoma colorectal cancer cancer thyroid gland papillary carcinoma thyroid adenoma thyroid gland carcinoma non-small cell lung carcinoma Pheochromocytoma thyroid cancer paraganglioma medulloblastoma colorectal carcinoma endometrial carcinoma ovarian cancer adenoma hereditary amyloidosis pituitary cancer atypical teratoid rhabdoid tumor renal cell carcinoma bladder transitional cell carcinoma large cell medulloblastoma breast carcinoma malignant ependymoma melanoma colorectal adenocarcinoma extra-adrenal sympathetic paraganglioma adrenal gland pheochromocytoma familial nonmedullary thyroid carcinoma Haddad syndrome psoriasis benign neoplasm of adrenal gland intellectual disability renal hypodysplasia/aplasia 1 bowel dysfunction lung cancer malignant glioma thyroid gland follicular carcinoma neuroendocrine carcinoma cutaneous melanoma osteosarcoma adrenal medulla cancer gastrointestinal stromal tumor hepatocellular carcinoma astrocytic tumor renal agenesis, unilateral intestinal disease breast cancer lung disease thymic carcinoma

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

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.