3NKX

Impaired binding of 14-3-3 to Raf1 is linked to Noonan and LEOPARD syndrome

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	d3nkxa_	All alpha proteins	alpha-alpha superhelix	14-3-3 protein	14-3-3 protein	zeta isoform	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3nkxb_	All alpha proteins	alpha-alpha superhelix	14-3-3 protein	14-3-3 protein	zeta isoform	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	14-3-3 protein	8034961	3001329	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	14-3-3 protein	8034961	3001329	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	14-3-3	e3nkxA1	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: 14-3-3	ECOD (1.6)
B	14-3-3	e3nkxB1	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: 14-3-3	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.190.20	Mainly Alpha	Up-down Bundle	Delta-Endotoxin	domain 1	CATH (4.3.0)
B	1.20.190.20	Mainly Alpha	Up-down Bundle	Delta-Endotoxin	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00244	14-3-3 protein (14-3-3)	14-3-3 protein	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
C [auth P], D [auth Q]	Peptide of 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 histone H2AS1 kinase activity histone modifying activity histone H2A kinase activity histone kinase activity enzyme binding	cellular response to stimulus extrinsic apoptotic signaling pathway via death domain receptors regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of biological process regulation of signal transduction regulation of programmed cell death extrinsic apoptotic signaling pathway negative regulation of cell communication cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway negative regulation of cellular process cellular response to stimulus extrinsic apoptotic signaling pathway via death domain receptors regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of biological process regulation of signal transduction regulation of programmed cell death extrinsic apoptotic signaling pathway negative regulation of cell communication cell communication negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway negative regulation of cellular process signal transduction regulation of biological process regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of programmed cell death regulation of apoptotic process biological regulation negative regulation of extrinsic apoptotic signaling pathway via death domain receptors cell death negative regulation of signal transduction regulation of extrinsic apoptotic signaling pathway apoptotic signaling pathway negative regulation of apoptotic process regulation of response to stimulus regulation of extrinsic apoptotic signaling pathway via death domain receptors regulation of cell communication cellular process apoptotic process programmed cell death 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 phosphate metabolic process peptidyl-serine modification regulation of primary metabolic process 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 protein 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 regulation of protein metabolic process primary metabolic process regulation of macromolecule metabolic process positive regulation of peptidyl-serine phosphorylation macromolecule modification regulation of phosphorus metabolic process metabolic process regulation of phosphorylation macromolecule metabolic process regulation of metabolic process 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 regulation of catalytic activity positive regulation of catalytic activity positive regulation of molecular function 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 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 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 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 cellular response to peptide hormone stimulus response to nitrogen 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 cellular anatomical structure pseudopodium 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 cellular anatomical structure pseudopodium 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
A, B	14-3-3 protein zeta/delta	protein binding binding protein domain specific binding phosphoprotein binding phosphoserine residue binding protein phosphorylated amino acid binding molecular sequestering activity protein sequestering activity RNA binding organic cyclic compound binding nucleic acid binding transmembrane transporter binding kinase binding enzyme binding protein binding binding protein domain specific binding phosphoprotein binding phosphoserine residue binding protein phosphorylated amino acid binding molecular sequestering activity protein sequestering activity RNA binding organic cyclic compound binding nucleic acid binding transmembrane transporter binding kinase binding enzyme binding protein kinase binding cell adhesion molecule binding cadherin binding transcription factor binding DNA-binding transcription factor binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding identical protein binding	Golgi localization establishment of organelle localization localization cellular localization establishment of Golgi localization organelle localization establishment of localization in cell cellular process establishment of localization protein localization cellular macromolecule localization macromolecule localization developmental process multicellular organismal process Golgi localization establishment of organelle localization localization cellular localization establishment of Golgi localization organelle localization establishment of localization in cell cellular process establishment of localization protein localization cellular macromolecule localization macromolecule localization developmental process multicellular organismal process blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis anatomical structure development anatomical structure formation involved in morphogenesis blood vessel development system development regulation of biological process regulation of cellular process negative regulation of programmed cell death regulation of apoptotic process biological regulation negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death cellular response to stimulus cellular response to nutrient levels response to nutrient levels response to stimulus cellular response to stress response to stress response to starvation cellular response to glucose starvation cellular response to starvation signaling intracellular signal transduction cell communication intracellular signaling cassette MAPK cascade ERK1 and ERK2 cascade signal transduction regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms negative regulation of response to biotic stimulus regulation of response to external stimulus response to biotic stimulus regulation of response to stress innate immune response regulation of immune system process response to external biotic stimulus negative regulation of response to stimulus immune response response to other organism defense response regulation of innate immune response negative regulation of immune response defense response to symbiont response to external stimulus regulation of response to stimulus negative regulation of immune system process immune system process defense response to other organism negative regulation of response to external stimulus negative regulation of defense response regulation of immune response negative regulation of innate immune response animal organ development respiratory tube development lung development respiratory system development Golgi inheritance organelle inheritance Golgi reassembly cellular component organization cellular component biogenesis organelle organization cellular component assembly cellular component organization or biogenesis Golgi organization endomembrane system organization regulation of cellular component organization regulation of developmental process nervous system development developmental maturation synapse maturation regulation of synapse organization regulation of synapse maturation cell junction organization regulation of synapse structure or activity synapse organization regulation of biological quality regulation of protein stability system process respiratory system process respiratory gaseous exchange by respiratory system protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process establishment of protein localization protein targeting regulation of signaling regulation of signal transduction regulation of MAPK cascade regulation of intracellular signal transduction regulation of cell communication regulation of ERK1 and ERK2 cascade negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of cell communication negative regulation of TORC1 signaling negative regulation of TOR signaling regulation of TORC1 signaling TOR signaling regulation of TOR signaling negative regulation of signal transduction TORC1 signaling neuron recognition cellular developmental process cell development synaptic target recognition generation of neurons neurogenesis neuron differentiation cell differentiation neuron development cell recognition regulation of localization regulation of protein localization regulation of protein localization to nucleus protein localization to nucleus negative regulation of protein localization to nucleus regulation of cellular localization protein localization to organelle negative regulation of protein localization RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process tube formation	cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cytoplasmic vesicle organelle cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction membrane-bounded organelle intracellular anatomical structure pigment granule intracellular vesicle intracellular membrane-bounded organelle intracellular organelle melanosome cytoplasmic vesicle organelle cytoplasm vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space extracellular membrane-bounded organelle cytosol nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen synapse glutamatergic synapse blood microparticle neuron to neuron synapse hippocampal mossy fiber to CA3 synapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C [auth P], D [auth Q]	IPR003116	Raf-like Ras-binding	Domain
C [auth P], D [auth Q]	IPR020454	Diacylglycerol/phorbol-ester binding	Domain
C [auth P], D [auth Q]	IPR000719	Protein kinase domain	Domain
C [auth P], D [auth Q]	IPR017441	Protein kinase, ATP binding site	Binding Site
C [auth P], D [auth Q]	IPR002219	Protein kinase C-like, phorbol ester/diacylglycerol-binding domain	Domain
C [auth P], D [auth Q]	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
C [auth P], D [auth Q]	IPR050167	Serine/threonine-protein kinase	Family
C [auth P], D [auth Q]	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
C [auth P], D [auth Q]	IPR046349	C1-like domain superfamily	Homologous Superfamily
C [auth P], D [auth Q]	IPR008271	Serine/threonine-protein kinase, active site	Active Site
A, B	IPR023409	14-3-3 protein, conserved site	Conserved Site
A, B	IPR023410	14-3-3 domain	Domain
A, B	IPR036815	14-3-3 domain superfamily	Homologous Superfamily
A, B	IPR000308	14-3-3 protein	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C [auth P], D [auth Q]	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
A, B	Pharos: P63104	Mammary Neoplasms, Experimental Parkinson disease carcinoma sarcomatoid carcinoma mammary neoplasms, animal myopathy ovarian cancer paranoid schizophrenia plasma cell myeloma atypical teratoid rhabdoid tumor undifferentiated carcinoma breast carcinoma Creutzfeldt Jacob disease invasive ductal breast carcinoma lung adenocarcinoma Mammary Neoplasms, Experimental Parkinson disease carcinoma sarcomatoid carcinoma mammary neoplasms, animal myopathy ovarian cancer paranoid schizophrenia plasma cell myeloma atypical teratoid rhabdoid tumor undifferentiated carcinoma breast carcinoma Creutzfeldt Jacob disease invasive ductal breast carcinoma lung adenocarcinoma malignant glioma pancreatic ductal adenocarcinoma primitive neuroectodermal tumor bipolar disorder glioblastoma large cell medulloblastoma lung cancer medulloblastoma oligodendroglioma pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma astrocytic tumor breast cancer IgA glomerulonephritis malignant ependymoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C [auth P], D [auth Q]	SEP	Parent Component: SER RESID: AA0037 PSI-MOD : O-phospho-L-serine MOD:00046

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.