3O8I

Structure of 14-3-3 isoform sigma in complex with a C-Raf1 peptide and a stabilizing small molecule fragment

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	d3o8ia1	All alpha proteins	alpha-alpha superhelix	14-3-3 protein	14-3-3 protein	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3o8ia2	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	14-3-3 protein	8082819	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	e3o8iA1	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)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	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
A	14-3-3 protein sigma	phosphoprotein binding protein binding binding phosphoserine residue binding protein phosphorylated amino acid binding enzyme regulator activity protein kinase inhibitor activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity protein kinase C inhibitor activity protein kinase regulator activity protein serine/threonine kinase inhibitor activity kinase inhibitor activity phosphoprotein binding protein binding binding phosphoserine residue binding protein phosphorylated amino acid binding enzyme regulator activity protein kinase inhibitor activity molecular function inhibitor activity molecular function regulator activity enzyme inhibitor activity protein kinase C inhibitor activity protein kinase regulator activity protein serine/threonine kinase inhibitor activity kinase inhibitor activity kinase regulator activity molecular sequestering activity protein sequestering activity kinase binding enzyme binding protein kinase binding cell adhesion molecule binding cadherin binding identical protein binding	regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis positive regulation of cellular process protein localization localization cellular localization cellular macromolecule localization macromolecule localization regulation of localization regulation of protein localization negative regulation of biological process negative regulation of protein localization to plasma membrane negative regulation of cellular process regulation of protein localization to membrane negative regulation of protein localization protein localization to cell periphery protein localization to plasma membrane localization within membrane regulation of protein localization to cell periphery protein localization to membrane negative regulation of protein localization to membrane regulation of cellular localization negative regulation of protein localization to cell periphery regulation of protein localization to plasma membrane establishment of protein localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein export from nucleus establishment of localization protein transport establishment of localization in cell nuclear export intracellular protein transport epidermal cell division cell division regulation of epidermal cell division regulation of cell division developmental process establishment of skin barrier epithelium development skin development skin epidermis development epidermis development anatomical structure development animal organ development tissue development 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 response to stimulus regulation of response to external stimulus response to biotic stimulus response to stress 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 cell population proliferation epithelial cell proliferation keratinocyte proliferation cellular response to stimulus signaling intracellular signal transduction cell communication protein kinase A signaling signal transduction cell adhesion cell-cell adhesion regulation of cell adhesion regulation of cell-cell adhesion negative regulation of cell population proliferation regulation of stem cell proliferation negative regulation of stem cell proliferation stem cell proliferation regulation of cell population proliferation positive regulation of cell adhesion regulation of protein modification process regulation of catalytic activity regulation of protein phosphorylation negative regulation of phosphate metabolic process negative regulation of catalytic activity regulation of transferase activity regulation of primary metabolic process negative regulation of kinase activity negative regulation of transferase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process protein metabolic process phosphorus metabolic process protein modification process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process negative regulation of metabolic process negative regulation of molecular function primary metabolic process negative regulation of protein kinase activity regulation of protein kinase activity regulation of macromolecule metabolic process regulation of molecular function regulation of kinase activity negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process metabolic process macromolecule metabolic process negative regulation of phosphorylation regulation of metabolic process positive regulation of nucleocytoplasmic transport positive regulation of establishment of protein localization positive regulation of protein transport positive regulation of intracellular transport regulation of protein export from nucleus regulation of intracellular transport regulation of transport regulation of establishment of protein localization regulation of nucleocytoplasmic transport regulation of protein transport positive regulation of protein export from nucleus positive regulation of transport positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport cell death apoptotic signaling pathway cellular response to stress DNA damage response intrinsic apoptotic signaling pathway in response to DNA damage apoptotic process intrinsic apoptotic signaling pathway programmed cell death multicellular organismal process keratinization epidermal cell differentiation cellular developmental process epithelial cell differentiation cell differentiation keratinocyte differentiation keratinocyte development cell development epithelial cell development regulation of keratinocyte proliferation negative regulation of keratinocyte proliferation regulation of epithelial cell proliferation negative regulation of epithelial cell proliferation cell cycle regulation of cell cycle RNA 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 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 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 negative regulation of RNA metabolic process apoptotic mitochondrial changes release of cytochrome c from mitochondria organelle organization mitochondrion organization regulation of developmental process regulation of epidermal cell differentiation regulation of cell differentiation regulation of epithelial cell differentiation positive regulation of developmental process multicellular organism development positive regulation of cell differentiation regulation of multicellular organismal process regulation of multicellular organismal development positive regulation of epidermis development positive regulation of epithelial cell differentiation regulation of epidermis development positive regulation of epidermal cell differentiation	extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol intracellular organelle extracellular exosome membrane-bounded organelle extracellular vesicle cellular anatomical structure extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol intracellular organelle nucleus intracellular membrane-bounded organelle
B	14-3-3 binding site 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 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

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR023409	14-3-3 protein, conserved site	Conserved Site
A	IPR023410	14-3-3 domain	Domain
A	IPR037435	14-3-3 protein sigma	Family
A	IPR036815	14-3-3 domain superfamily	Homologous Superfamily
A	IPR000308	14-3-3 protein	Family
B	IPR003116	Raf-like Ras-binding	Domain
B	IPR020454	Diacylglycerol/phorbol-ester binding	Domain
B	IPR000719	Protein kinase domain	Domain
B	IPR017441	Protein kinase, ATP binding site	Binding Site
B	IPR002219	Protein kinase C-like, phorbol ester/diacylglycerol-binding domain	Domain
B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
B	IPR050167	Serine/threonine-protein kinase	Family
B	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily
B	IPR046349	C1-like domain superfamily	Homologous Superfamily
B	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P31947	esophageal squamous cell carcinoma squamous cell carcinoma esophageal cancer Lymphatic Metastasis keloid lung adenocarcinoma malignant pancreatic neoplasm non-small cell lung carcinoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm sarcoidosis cystic fibrosis interstitial cystitis malignant mesothelioma oral cavity neoplasm esophageal squamous cell carcinoma squamous cell carcinoma esophageal cancer Lymphatic Metastasis keloid lung adenocarcinoma malignant pancreatic neoplasm non-small cell lung carcinoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm sarcoidosis cystic fibrosis interstitial cystitis malignant mesothelioma oral cavity neoplasm pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia atypical teratoid rhabdoid tumor spina bifida diabetes mellitus malignant ependymoma neoplasm of esophagus osteosarcoma pancreatic intraductal papillary-mucinous carcinoma psoriasis breast cancer ductal breast carcinoma in situ hepatocellular carcinoma large cell medulloblastoma lung cancer malignant glioma
B	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

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
B	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.