4FL2 | pdb_00004fl2

Structural and Biophysical Characterization of the Syk Activation Switch

External Resource: Annotation

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

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)	8043784	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SH2 domain	8035677	3000197	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SH2 domain	8035682	3000197	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	SH2	e4fl2A2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: SH2	ECOD (1.6)
A	Pkinase_Tyr	e4fl2A1	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	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)
A	1.10.930.10	Mainly Alpha	Orthogonal Bundle	Syk Kinase	Chain A, domain 2	CATH (4.3.0)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00017	SH2 domain (SH2)	SH2 domain		Domain
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 triphospha ...	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	Tyrosine-protein kinase SYK	protein binding binding signaling receptor binding Toll-like receptor 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 adenyl ribonucleotide binding nucleotide binding protein binding binding signaling receptor binding Toll-like receptor 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 adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding non-membrane spanning protein tyrosine kinase activity scaffold protein binding kinase binding enzyme binding protein kinase binding protein serine/threonine kinase activity phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding phosphatase binding phospholipase binding cytokine receptor binding interleukin-15 receptor binding SH2 domain binding protein domain specific binding cell adhesion molecule binding protein-containing complex binding integrin binding	regulation of biological process regulation of cellular process reactive oxygen species metabolic process biological regulation positive regulation of biological process regulation of superoxide metabolic process positive regulation of reactive oxygen species metabolic process superoxide metabolic process positive regulation of metabolic process superoxide anion generation metabolic process cellular process positive regulation of superoxide anion generation regulation of superoxide anion generation regulation of biological process regulation of cellular process reactive oxygen species metabolic process biological regulation positive regulation of biological process regulation of superoxide metabolic process positive regulation of reactive oxygen species metabolic process superoxide metabolic process positive regulation of metabolic process superoxide anion generation metabolic process cellular process positive regulation of superoxide anion generation regulation of superoxide anion generation regulation of metabolic process regulation of reactive oxygen species metabolic process positive regulation of cellular process cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling signal transduction regulation of signaling positive regulation of intracellular signal transduction regulation of response to stimulus calcium-mediated signaling regulation of cell communication positive regulation of signaling multicellular organismal process cell activation establishment of organelle localization regulation of immune effector process regulation of localization regulated exocytosis regulation of myeloid leukocyte mediated immunity cell activation involved in immune response leukocyte degranulation myeloid leukocyte activation myeloid leukocyte mediated immunity vesicle-mediated transport localization positive regulation of leukocyte degranulation positive regulation of regulated secretory pathway establishment of localization in cell leukocyte mediated immunity regulation of immune system process positive regulation of mast cell degranulation positive regulation of immune system process immune response vacuolar localization mast cell degranulation establishment of localization immune effector process regulation of secretion regulation of leukocyte mediated immunity exocytosis lysosome localization cellular localization transport positive regulation of secretion by cell positive regulation of exocytosis regulation of mast cell degranulation leukocyte activation regulation of regulated secretory pathway secretion by cell regulation of secretion by cell positive regulation of secretion organelle localization leukocyte activation involved in immune response mast cell activation positive regulation of immune effector process regulation of leukocyte degranulation mast cell mediated immunity secretion regulation of transport export from cell regulation of vesicle-mediated transport myeloid cell activation involved in immune response mast cell activation involved in immune response positive regulation of transport immune system process regulation of exocytosis neutrophil activation neutrophil activation involved in immune response regulation of immune response neutrophil mediated immunity regulation of neutrophil degranulation neutrophil degranulation granulocyte activation cell chemotaxis chemotaxis neutrophil chemotaxis response to external stimulus neutrophil migration granulocyte migration leukocyte migration cellular response to chemical stimulus taxis granulocyte chemotaxis response to chemical myeloid leukocyte migration cell migration cell motility leukocyte chemotaxis locomotion biological process involved in interspecies interaction between organisms response to other organism defense response response to biotic stimulus defense response to bacterium defense response to other organism response to stress response to bacterium response to external biotic stimulus regulation of body fluid levels wound healing hemostasis blood coagulation coagulation regulation of biological quality response to wounding platelet activation positive regulation of interleukin-8 production positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process cytokine production regulation of cytokine production positive regulation of macromolecule metabolic process regulation of multicellular organismal process regulation of biosynthetic process interleukin-8 production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process macromolecule metabolic process positive regulation of cytokine production regulation of interleukin-8 production import into cell regulation of cellular component organization regulation of phagocytosis cellular component organization phagocytosis cellular component organization or biogenesis endocytosis regulation of endocytosis response to lectin cellular response to lectin protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process protein metabolic process protein modification process phosphorus metabolic process immune response-regulating cell surface receptor signaling pathway cell surface receptor signaling pathway Fc receptor signaling pathway immune response-regulating signaling pathway Fc-epsilon receptor signaling pathway interleukin-10 production regulation of interleukin-10 production positive regulation of interleukin-10 production regulation of defense response regulation of response to external stimulus negative regulation of inflammatory response negative regulation of biological process inflammatory response to antigenic stimulus regulation of response to stress negative regulation of inflammatory response to antigenic stimulus negative regulation of response to stimulus negative regulation of immune response regulation of inflammatory response to antigenic stimulus regulation of inflammatory response negative regulation of immune system process negative regulation of response to external stimulus negative regulation of defense response inflammatory response cell adhesion cell-cell adhesion leukocyte cell-cell adhesion regulation of leukocyte differentiation regulation of leukocyte activation regulation of cell activation mononuclear cell differentiation regulation of cell differentiation positive regulation of B cell differentiation lymphocyte differentiation regulation of cell development positive regulation of developmental process positive regulation of cell activation multicellular organism development cell differentiation positive regulation of leukocyte activation anatomical structure development developmental process positive regulation of cell development leukocyte differentiation cellular developmental process regulation of developmental process cell development lymphocyte activation positive regulation of lymphocyte activation regulation of B cell differentiation B cell differentiation positive regulation of hemopoiesis positive regulation of cell differentiation regulation of B cell activation regulation of lymphocyte differentiation regulation of multicellular organismal development hemopoiesis B cell activation positive regulation of B cell activation regulation of hemopoiesis positive regulation of leukocyte differentiation positive regulation of lymphocyte differentiation regulation of lymphocyte activation positive regulation of type I interferon production type I interferon production regulation of type I interferon production blood vessel morphogenesis tube development vasculature development circulatory system development anatomical structure morphogenesis tube morphogenesis blood vessel development system development regulation of alpha-beta T cell activation positive regulation of T cell differentiation T cell activation alpha-beta T cell activation T cell differentiation positive regulation of T cell activation positive regulation of alpha-beta T cell activation regulation of leukocyte cell-cell adhesion positive regulation of alpha-beta T cell differentiation positive regulation of leukocyte cell-cell adhesion regulation of alpha-beta T cell differentiation positive regulation of cell-cell adhesion regulation of T cell differentiation alpha-beta T cell differentiation regulation of cell-cell adhesion positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation icosanoid metabolic process leukotriene metabolic process oxoacid metabolic process small molecule biosynthetic process leukotriene biosynthetic process carboxylic acid metabolic process organic acid metabolic process organic acid biosynthetic process carboxylic acid biosynthetic process icosanoid biosynthetic process small molecule metabolic process 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 nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of molecular function regulation of DNA-binding transcription factor activity regulation of DNA-templated transcription positive regulation of response to biotic stimulus pattern recognition receptor signaling pathway immune response-activating signaling pathway positive regulation of immune response innate immune response-activating signaling pathway immune response-activating cell surface receptor signaling pathway regulation of innate immune response positive regulation of defense response activation of innate immune response activation of immune response regulation of response to biotic stimulus innate immune response activating cell surface receptor signaling pathway positive regulation of response to external stimulus innate immune response cell surface pattern recognition receptor signaling pathway positive regulation of innate immune response defense response to symbiont collagen-activated tyrosine kinase receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway collagen-activated signaling pathway enzyme-linked receptor protein signaling pathway gamma-delta T cell activation gamma-delta T cell differentiation monoamine transport nitrogen compound transport serotonin secretion involved in inflammatory response organic hydroxy compound transport serotonin secretion by platelet signal release serotonin secretion serotonin production involved in inflammatory response production of molecular mediator involved in inflammatory response platelet degranulation cell-cell signaling serotonin transport exocytic process regulation of interleukin-12 production interleukin-12 production positive regulation of interleukin-12 production cell death apoptotic signaling pathway apoptotic process programmed cell death regulation of tumor necrosis factor production positive regulation of tumor necrosis factor superfamily cytokine production tumor necrosis factor superfamily cytokine production positive regulation of tumor necrosis factor production tumor necrosis factor production regulation of tumor necrosis factor superfamily cytokine production response to cytokine cytokine-mediated signaling pathway response to peptide cellular response to cytokine stimulus interleukin-3-mediated signaling pathway cellular response to nitrogen compound response to oxygen-containing compound response to nitrogen compound cellular response to amyloid-beta cellular response to oxygen-containing compound response to amyloid-beta lymph vessel development immune response-regulating cell surface receptor signaling pathway involved in phagocytosis Fc-gamma receptor signaling pathway involved in phagocytosis Fc-gamma receptor signaling pathway Fc receptor mediated stimulatory signaling pathway adaptive immune response beta selection T cell selection receptor internalization receptor-mediated endocytosis positive regulation of cellular component organization protein-containing complex organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis cellular component biogenesis positive regulation of protein-containing complex assembly regulation of protein-containing complex assembly cellular component assembly protein-containing complex assembly cellular response to molecule of fungal origin cellular response to biotic stimulus response to molecule of fungal origin response to fungus protein localization establishment of protein localization nucleocytoplasmic transport nuclear transport intracellular transport protein localization to nucleus import into nucleus establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle protein import into nucleus intracellular protein transport macrophage activation involved in immune response macrophage activation positive regulation of myeloid leukocyte cytokine production involved in immune response mast cell cytokine production myeloid leukocyte cytokine production cytokine production involved in immune response production of molecular mediator of immune response regulation of cytokine production involved in immune response regulation of mast cell cytokine production positive regulation of cytokine production involved in immune response positive regulation of production of molecular mediator of immune response regulation of production of molecular mediator of immune response positive regulation of mast cell cytokine production cellular response to low-density lipoprotein particle stimulus response to endogenous stimulus response to lipoprotein particle cellular response to lipoprotein particle stimulus regulation of MAPK cascade MAPK cascade ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade regulation of platelet activation homeostatic process regulation of bone remodeling tissue homeostasis regulation of tissue remodeling regulation of bone resorption bone resorption multicellular organismal-level homeostasis tissue remodeling bone remodeling anatomical structure homeostasis positive regulation of bone resorption cellular response to tumor necrosis factor tumor necrosis factor-mediated signaling pathway regulation of tumor necrosis factor-mediated signaling pathway regulation of cytokine-mediated signaling pathway regulation of response to cytokine stimulus response to tumor necrosis factor B cell receptor signaling pathway antigen receptor-mediated signaling pathway regulation of gamma-delta T cell differentiation regulation of gamma-delta T cell activation positive regulation of gamma-delta T cell differentiation positive regulation of gamma-delta T cell activation animal organ development animal organ morphogenesis angiogenesis anatomical structure formation involved in morphogenesis interleukin-6 production positive regulation of interleukin-6 production regulation of interleukin-6 production positive regulation of cell population proliferation positive regulation of alpha-beta T cell proliferation alpha-beta T cell proliferation lymphocyte proliferation regulation of leukocyte proliferation cell population proliferation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation regulation of cell population proliferation mononuclear cell proliferation positive regulation of leukocyte proliferation leukocyte proliferation regulation of alpha-beta T cell proliferation positive regulation of mononuclear cell proliferation T cell proliferation regulation of lymphocyte proliferation regulation of T cell proliferation regulation of mononuclear cell proliferation regulation of receptor internalization positive regulation of endocytosis positive regulation of receptor-mediated endocytosis regulation of receptor-mediated endocytosis positive regulation of receptor internalization amyloid-beta clearance integrin-mediated signaling pathway stimulatory C-type lectin receptor signaling pathway regulation of monocyte chemotactic protein-1 production positive regulation of monocyte chemotactic protein-1 production monocyte chemotactic protein-1 production regulation of chemokine production chemokine production positive regulation of chemokine production regulation of lipid transport regulation of arachidonate secretion arachidonate secretion monocarboxylic acid transport fatty acid transport icosanoid transport regulation of icosanoid secretion icosanoid secretion long-chain fatty acid transport organic anion transport carboxylic acid transport arachidonate transport lipid localization lipid transport regulation of fatty acid transport organic acid transport regulation of lipid localization regulation of organic acid transport positive regulation of TORC1 signaling positive regulation of TOR signaling regulation of TORC1 signaling TOR signaling regulation of TOR signaling TORC1 signaling positive regulation of cell adhesion mediated by integrin regulation of cell adhesion mediated by integrin cell adhesion mediated by integrin peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation adaptive thermogenesis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of MAPK cascade granulocyte macrophage colony-stimulating factor production positive regulation of protein metabolic process positive regulation of granulocyte macrophage colony-stimulating factor production regulation of granulocyte macrophage colony-stimulating factor production regulation of protein metabolic process positive regulation of interleukin-3 production interleukin-3 production regulation of interleukin-3 production homotypic cell-cell adhesion regulation of homotypic cell-cell adhesion platelet aggregation regulation of platelet aggregation regulation of interleukin-4 production positive regulation of interleukin-4 production interleukin-4 production response to lipid cellular response to lipid	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane membrane-bounded organelle early phagosome intracellular vesicle phagocytic vesicle intracellular membrane-bounded organelle intracellular organelle cytoplasmic vesicle cellular anatomical structure intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane membrane-bounded organelle early phagosome intracellular vesicle phagocytic vesicle intracellular membrane-bounded organelle intracellular organelle cytoplasmic vesicle organelle vesicle endocytic vesicle protein-containing complex plasma membrane protein complex membrane protein complex immunoglobulin complex receptor complex B cell receptor complex plasma membrane signaling receptor complex T cell receptor complex nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A	IPR000719	Protein kinase domain	Domain
A	IPR012234	Tyrosine-protein kinase, non-receptor SYK/ZAP-70	Family
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR036860	SH2 domain superfamily	Homologous Superfamily
A	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A	IPR008266	Tyrosine-protein kinase, active site	Active Site
A	IPR023420	Tyrosine-protein kinase SYK/ZAP-70, inter-SH2 domain superfamily	Homologous Superfamily
A	IPR035838	SYK/ZAP-70, N-terminal SH2 domain	Domain
A	IPR000980	SH2 domain	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR050198	Non-receptor tyrosine kinases involved in cell signaling	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P43405	melanoma pancreatic intraductal papillary-mucinous neoplasm plasma cell myeloma subependymal giant cell astrocytoma tuberculosis B-cell chronic lymphocytic leukemia cutaneous melanoma hematologic disease lung cancer lymphoplasmacytic lymphoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis thrombocytopenia due to immune destruction vascular dementia melanoma pancreatic intraductal papillary-mucinous neoplasm plasma cell myeloma subependymal giant cell astrocytoma tuberculosis B-cell chronic lymphocytic leukemia cutaneous melanoma hematologic disease lung cancer lymphoplasmacytic lymphoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia psoriasis thrombocytopenia due to immune destruction vascular dementia benign mesothelioma diabetes mellitus invasive ductal breast carcinoma lung carcinoma malignant glioma mesothelioma pancreatic intraductal papillary-mucinous carcinoma pilocytic astrocytoma Sjogren syndrome transitional cell carcinoma cancer glioblastoma large cell medulloblastoma lymphatic system disease Malignant lymphoma, lymphocytic, intermediate differentiation, diffuse osteosarcoma

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.