9AYA

Crystal structure of CRAF/MEK complex with NST-628 and active RAF dimer

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	Protein kinase-like (PK-like)	8069273	3000066	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Protein kinase-like (PK-like)	8069273	3000066	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Protein kinase-like (PK-like)	8042320	3000066	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Protein kinase-like (PK-like)	8042320	3000066	SCOP2B (2022-06-29)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain
B, D	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	RAF proto-oncogene serine/threonine-protein kinase	protein serine/threonine kinase activity MAP kinase kinase 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 binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding protein serine/threonine kinase activity MAP kinase kinase 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 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 metal ion binding identical protein binding protein binding protein serine kinase activity enzyme binding	negative regulation of hydrolase activity regulation of cellular process negative regulation of proteolysis regulation of catalytic activity negative regulation of biological process negative regulation of catalytic activity regulation of programmed cell death negative regulation of endopeptidase activity regulation of primary metabolic process negative regulation of peptidase activity regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of proteolysis proteolysis regulation of endopeptidase activity negative regulation of cellular process negative regulation of hydrolase activity regulation of cellular process negative regulation of proteolysis regulation of catalytic activity negative regulation of biological process negative regulation of catalytic activity regulation of programmed cell death negative regulation of endopeptidase activity regulation of primary metabolic process negative regulation of peptidase activity regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of proteolysis proteolysis regulation of endopeptidase activity negative regulation of cellular process negative regulation of cysteine-type endopeptidase activity involved in apoptotic process protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process regulation of cysteine-type endopeptidase activity regulation of biological process organonitrogen compound metabolic process negative regulation of programmed cell death regulation of protein metabolic process regulation of apoptotic process negative regulation of metabolic process regulation of peptidase activity biological regulation negative regulation of molecular function primary metabolic process regulation of macromolecule metabolic process cell death regulation of molecular function negative regulation of apoptotic process regulation of hydrolase activity negative regulation of cysteine-type endopeptidase activity metabolic process cellular process macromolecule metabolic process apoptotic process regulation of metabolic process programmed cell death cellular response to stimulus extrinsic apoptotic signaling pathway via death domain receptors response to stimulus signaling negative regulation of signaling regulation of signal transduction extrinsic apoptotic signaling pathway negative regulation of cell communication cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway signal transduction regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of extrinsic apoptotic signaling pathway via death domain receptors negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway regulation of response to stimulus regulation of extrinsic apoptotic signaling pathway via death domain receptors regulation of cell communication regulation of apoptotic signaling pathway positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of biological process regulation of peptidyl-serine phosphorylation positive regulation of cellular metabolic process positive regulation of phosphate metabolic process peptidyl-serine modification positive regulation of metabolic process positive regulation of protein modification process peptidyl-serine phosphorylation regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process positive regulation of cellular process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation cellular metabolic process regulation of cellular metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation regulation of cellular component organization negative regulation of cellular component organization protein-containing complex organization regulation of cellular component biogenesis negative regulation of protein-containing complex assembly cellular component organization cellular component biogenesis regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly cellular component organization or biogenesis insulin-like growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway small GTPase-mediated signal transduction regulation of small GTPase mediated signal transduction regulation of Rho protein signal transduction intracellular signal transduction Rho protein signal transduction regulation of intracellular signal transduction intracellular signaling cassette MAPK cascade ERBB2 signaling pathway ERBB2-ERBB3 signaling pathway ERBB signaling pathway ERBB3 signaling pathway biological process involved in interspecies interaction between organisms response to type II interferon response to cytokine cytokine-mediated signaling pathway cellular response to type II interferon response to biotic stimulus interferon-mediated signaling pathway response to stress innate immune response cellular response to cytokine stimulus 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 response to peptide response to chemical immune system process defense response to other organism cell population proliferation type B pancreatic cell proliferation epithelial cell proliferation intermediate filament-based process organelle organization cytoskeleton organization intermediate filament cytoskeleton organization developmental process multicellular organismal process somatic stem cell population maintenance maintenance of cell number stem cell population maintenance positive regulation of adenylate cyclase activity positive regulation of cyclase activity positive regulation of catalytic activity positive regulation of molecular function regulation of lyase activity activation of adenylate cyclase activity regulation of adenylate cyclase activity regulation of cyclase activity positive regulation of lyase activity death-inducing signaling complex assembly positive regulation of DNA-templated transcription cellular biosynthetic process RNA metabolic process positive regulation of macromolecule biosynthetic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of biosynthetic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of 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 gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA metabolic process regulation of gene expression biosynthetic process positive regulation of RNA biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription positive regulation of cellular biosynthetic process head development anatomical structure development face development immune system development animal organ development gland development hematopoietic or lymphoid organ development multicellular organism development thymus development system development thyroid gland development endocrine system development cellular developmental process peripheral nervous system development cell development nervous system development glial cell development neurogenesis Schwann cell development gliogenesis glial cell differentiation cell differentiation Schwann cell differentiation protein localization establishment of protein localization nitrogen compound transport localization carbohydrate homeostasis cellular macromolecule localization establishment of localization in cell regulation of biological quality regulation of hormone levels establishment of protein localization to extracellular region intracellular glucose homeostasis protein secretion establishment of localization cellular response to oxygen-containing compound cellular response to carbohydrate stimulus chemical homeostasis response to glucose glucose homeostasis insulin secretion involved in cellular response to glucose stimulus cellular localization transport homeostatic process hormone secretion protein localization to extracellular region peptide secretion secretion by cell response to monosaccharide response to carbohydrate amide transport signal release cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus secretion cell-cell signaling export from cell response to oxygen-containing compound cellular response to glucose stimulus peptide transport response to hexose cellular response to chemical stimulus cellular homeostasis protein transport peptide hormone secretion macromolecule localization hormone transport insulin secretion positive regulation of cell communication positive regulation of signal transduction positive regulation of response to stimulus positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade positive regulation of signaling cellular response to nitrogen compound response to peptide hormone insulin receptor signaling pathway cellular response to endogenous stimulus response to hormone cellular response to hormone stimulus response to endogenous stimulus response to organonitrogen compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to organonitrogen compound response to insulin cellular response to insulin stimulus negative regulation of cell population proliferation regulation of cell population proliferation wound healing response to wounding cellular response to growth factor stimulus neurotrophin TRK receptor signaling pathway neurotrophin signaling pathway response to growth factor myelination axon ensheathment ensheathment of neurons regulation of cell motility regulation of locomotion cell motility locomotion response to mechanical stimulus response to abiotic stimulus response to muscle stretch regulation of developmental process regulation of cell differentiation	cell projection pseudopodium cellular anatomical entity plasma membrane bounded cell projection intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system mitochondrial membrane cell projection pseudopodium cellular anatomical entity plasma membrane bounded cell projection intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system mitochondrial membrane mitochondrion membrane organelle outer membrane organelle envelope bounding membrane of organelle mitochondrial envelope mitochondrial outer membrane outer membrane organelle membrane cell periphery plasma membrane nucleus
B, D	Dual specificity mitogen-activated protein kinase kinase 1	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 binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate 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 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 MAP kinase kinase activity protein serine/threonine/tyrosine kinase activity MAP-kinase scaffold activity protein-macromolecule adaptor activity molecular adaptor activity signaling adaptor activity enzyme regulator activity protein serine/threonine kinase activator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity scaffold protein binding protein binding protein serine kinase activity protein serine/threonine kinase activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development placenta development chordate embryonic development labyrinthine layer development embryo development in utero embryonic development embryonic placenta development developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development placenta development chordate embryonic development labyrinthine layer development embryo development in utero embryonic development embryonic placenta development embryo development ending in birth or egg hatching embryonic organ development regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation 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 positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process positive regulation of nervous system development axonogenesis cell projection organization regulation of cell differentiation regulation of neurogenesis neuron projection development regulation of cell development positive regulation of developmental process cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation positive regulation of cell projection organization regulation of cell projection organization positive regulation of cell development nervous system development generation of neurons positive regulation of multicellular organismal process regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization cellular developmental process regulation of developmental process plasma membrane bounded cell projection morphogenesis cell development cell morphogenesis cellular component organization regulation of nervous system development neurogenesis positive regulation of cell differentiation regulation of axonogenesis positive regulation of neurogenesis regulation of multicellular organismal process cellular component organization or biogenesis positive regulation of axonogenesis regulation of anatomical structure morphogenesis regulation of multicellular organismal development plasma membrane bounded cell projection organization axon development cell morphogenesis involved in neuron differentiation anatomical structure morphogenesis neuron development regulation of plasma membrane bounded cell projection organization cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling insulin-like growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication signal transduction enzyme-linked receptor protein signaling pathway placenta blood vessel development vasculature development blood vessel development Golgi inheritance organelle inheritance regulation of organelle organization regulation of Golgi organization organelle organization regulation of Golgi inheritance Golgi organization endomembrane system organization cellular response to stress response to stress cellular senescence intracellular signal transduction intracellular signaling cassette MAPK cascade chemotaxis taxis response to chemical response to external stimulus locomotion ERBB2 signaling pathway ERBB2-ERBB3 signaling pathway ERBB signaling pathway ERBB3 signaling pathway cell population proliferation type B pancreatic cell proliferation epithelial cell proliferation positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of protein serine/threonine kinase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity macromolecule modification regulation of protein serine/threonine kinase activity regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of molecular function positive regulation of protein modification process protein metabolic process positive regulation of protein kinase activity organonitrogen compound metabolic process positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of phosphorylation cerebellum morphogenesis cerebellar cortex morphogenesis head development hindbrain morphogenesis brain development cerebellar cortex development cerebellum development central nervous system development metencephalon development anatomical structure formation involved in morphogenesis cerebellar cortex formation hindbrain development cell motility face development epithelium development epidermal cell differentiation epidermis development tissue development epithelial cell differentiation skin development keratinocyte differentiation immune system development gland development hematopoietic or lymphoid organ development thymus development immune system process positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction positive regulation of response to stimulus positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction regulation of signaling positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling thyroid gland development endocrine system development formation of primary germ layer embryonic morphogenesis gastrulation endoderm development endoderm formation endodermal cell differentiation peripheral nervous system development glial cell development Schwann cell development gliogenesis glial cell differentiation Schwann cell differentiation regulation of cellular response to stress stress-activated MAPK cascade regulation of response to stress regulation of stress-activated protein kinase signaling cascade regulation of stress-activated MAPK cascade stress-activated protein kinase signaling cascade trachea morphogenesis trachea formation trachea development respiratory system development animal organ morphogenesis animal organ formation regulation of localization cellular localization transport regulation of transport intracellular transport regulation of vesicle-mediated transport establishment of localization vesicle-mediated transport endosomal transport vesicle-mediated transport between endosomal compartments regulation of early endosome to late endosome transport localization early endosome to late endosome transport regulation of cellular localization establishment of localization in cell regulation of intracellular transport astrocyte differentiation Bergmann glial cell differentiation negative regulation of cell population proliferation regulation of cell population proliferation negative regulation of cellular process negative regulation of biological process regulation of endodermal cell differentiation positive regulation of endodermal cell differentiation positive regulation of DNA-templated transcription 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 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 myelination axon ensheathment ensheathment of neurons regulation of response to external stimulus regeneration response to axon injury neuron projection regeneration regulation of response to wounding axon regeneration response to wounding regulation of axon regeneration regulation of neuron projection regeneration tube development respiratory tube development lung epithelium development epithelial cell proliferation involved in lung morphogenesis lung development lung morphogenesis	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system mitochondrion anchoring junction cell junction focal adhesion intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system mitochondrion anchoring junction cell junction focal adhesion cell-substrate junction centrosome microtubule organizing center cytoskeleton intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle cell periphery plasma membrane membrane early endosome endosome intracellular vesicle cytoplasmic vesicle vesicle spindle pole body late endosome nucleus endoplasmic reticulum

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C	IPR003116	Raf-like Ras-binding	Domain
A, C	IPR020454	Diacylglycerol/phorbol-ester binding	Domain
A, C	IPR000719	Protein kinase domain	Domain
A, C	IPR017441	Protein kinase, ATP binding site	Binding Site
A, C	IPR002219	Protein kinase C-like, phorbol ester/diacylglycerol-binding domain	Domain
A, C	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, C	IPR050167	Serine/threonine-protein kinase	Family
A, C	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
A, C	IPR046349	C1-like domain superfamily	Homologous Superfamily
A, C	IPR008271	Serine/threonine-protein kinase, active site	Active Site
B, D	IPR000719	Protein kinase domain	Domain
B, D	IPR050915	MAP kinase kinase	Family
B, D	IPR017441	Protein kinase, ATP binding site	Binding Site
B, D	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
B, D	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C	Pharos: P04049	Noonan syndrome with multiple lentigines Noonan syndrome Noonan syndrome 5 LEOPARD syndrome 2 dilated cardiomyopathy 1NN hypertrophic cardiomyopathy malignant glioma dilated cardiomyopathy pilocytic astrocytoma mixed glioma non-small cell lung carcinoma Hyperalgesia liver cancer breast carcinoma cancer Noonan syndrome with multiple lentigines Noonan syndrome Noonan syndrome 5 LEOPARD syndrome 2 dilated cardiomyopathy 1NN hypertrophic cardiomyopathy malignant glioma dilated cardiomyopathy pilocytic astrocytoma mixed glioma non-small cell lung carcinoma Hyperalgesia liver cancer breast carcinoma cancer malignant mesothelioma cardiomyopathy hydrops fetalis osteogenesis imperfecta intellectual disability urinary bladder cancer lung adenocarcinoma breast cancer malignant ependymoma Charcot-Marie-Tooth disease dilated cardiomyopathy 1A medulloblastoma familial isolated dilated cardiomyopathy glioma ovarian cancer plasma cell myeloma kidney cancer astrocytic tumor lung benign neoplasm cutaneous melanoma melanoma neurofibromatosis type 1 hepatocellular carcinoma oligodendroglioma ovarian serous adenocarcinoma renal cell carcinoma kidney neoplasm liver neoplasm familial dilated cardiomyopathy glioblastoma non-alcoholic fatty liver disease
B, D	Pharos: Q02750	cardiofaciocutaneous syndrome Noonan syndrome Costello syndrome hairy cell leukemia melanoma cardiofaciocutaneous syndrome 3 intellectual disability cardiomyopathy brain ischemia neurofibromatosis type 1 cancer cutaneous melanoma prostate carcinoma testicular germ cell tumor Unresectable malignant melanoma with BRAF gene mutation cardiofaciocutaneous syndrome Noonan syndrome Costello syndrome hairy cell leukemia melanoma cardiofaciocutaneous syndrome 3 intellectual disability cardiomyopathy brain ischemia neurofibromatosis type 1 cancer cutaneous melanoma prostate carcinoma testicular germ cell tumor Unresectable malignant melanoma with BRAF gene mutation lung adenocarcinoma malignant ependymoma melorheostosis colorectal adenocarcinoma oligodendroglioma ovarian neoplasm primitive neuroectodermal tumor hydrops fetalis Langerhans cell histiocytosis lung cancer astrocytic tumor medulloblastoma cardiofaciocutaneous syndrome 1 Noonan syndrome 1 ovarian cancer dermatomyositis Pick disease glioblastoma hypertrophic cardiomyopathy subependymal giant cell astrocytoma large cell medulloblastoma major depressive disorder atypical teratoid rhabdoid tumor non-small cell lung carcinoma Charcot-Marie-Tooth disease Noonan syndrome with multiple lentigines ovarian carcinoma plasma cell myeloma

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 R01GM133198.