3ENE

Complex of PI3K gamma with an inhibitor

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

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3enea3	All alpha proteins	alpha-alpha superhelix	ARM repeat	Phoshoinositide 3-kinase (PI3K) helical domain	Phoshoinositide 3-kinase (PI3K) helical domain	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3enea2	All beta proteins	C2 domain-like	C2 domain (Calcium/lipid-binding domain, CaLB)	PLC-like (P variant)	Phoshoinositide 3-kinase (PI3K)	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3enea1	Alpha and beta proteins (a+b)	beta-Grasp (ubiquitin-like)	Ubiquitin-like	Ras-binding domain, RBD	Phoshoinositide 3-kinase (PI3K)	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3enea4	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Phoshoinositide 3-kinase (PI3K), catalytic domain	Phoshoinositide 3-kinase (PI3K), catalytic domain	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8036675	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	C2 domain (calcium/lipid-binding domain, calb)	8040718	3000965	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Ubiquitin-like	8034490	3000157	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	ARM repeat-like	8038599	3000116	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	PI3K_C2	e3eneA1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: C2 domain (From Topology)	T: C2 domain	F: PI3K_C2	ECOD (1.6)
A	PI3Ka	e3eneA5	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: PI3Ka	ECOD (1.6)
A	PI3K_rbd	e3eneA2	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PI3K_rbd	ECOD (1.6)
A	PI3_PI4_kinase	e3eneA4	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: PI3_PI4_kinase	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.10.20.90	Alpha Beta	Roll	Ubiquitin-like (UB roll)	Phosphatidylinositol 3-kinase Catalytic Subunit	CATH (4.3.0)
A	2.60.40.150	Mainly Beta	Sandwich	Immunoglobulin-like	C2 domain	CATH (4.3.0)
A	1.25.40.70	Mainly Alpha	Alpha Horseshoe	Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat	Phosphatidylinositol 3-kinase, accessory domain (PIK)	CATH (4.3.0)
A	3.30.1010.10	Alpha Beta	2-Layer Sandwich	Phosphatidylinositol 3-kinase Catalytic Subunit	Chain A, domain 4	CATH (4.3.0)
A	1.10.1070.11	Mainly Alpha	Orthogonal Bundle	Phosphatidylinositol 3-kinase Catalytic Subunit	Chain A, Domain 5	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00792	Phosphoinositide 3-kinase C2 (PI3K_C2)	Phosphoinositide 3-kinase C2	Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of Pfam:PF00168 family.	Domain
A	PF00794	PI3-kinase family, ras-binding domain (PI3K_rbd)	PI3-kinase family, ras-binding domain	Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding Pfam:PF00788 domains (unpublished observation).	Domain
A	PF00454	Phosphatidylinositol 3- and 4-kinase (PI3_PI4_kinase)	Phosphatidylinositol 3- and 4-kinase	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform	kinase activity transferase activity catalytic activity transferase activity, transferring phosphorus-containing groups phosphatidylinositol kinase activity lipid kinase activity 1-phosphatidylinositol-3-kinase activity phosphotransferase activity, alcohol group as acceptor 1-phosphatidylinositol-4-phosphate 3-kinase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding kinase activity transferase activity catalytic activity transferase activity, transferring phosphorus-containing groups phosphatidylinositol kinase activity lipid kinase activity 1-phosphatidylinositol-3-kinase activity phosphotransferase activity, alcohol group as acceptor 1-phosphatidylinositol-4-phosphate 3-kinase activity binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding catalytic activity, acting on a protein protein kinase activity protein binding signaling receptor binding ephrin receptor binding identical protein binding 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity protein serine kinase activity protein serine/threonine kinase activity histone H2AS1 kinase activity histone modifying activity histone H2A kinase activity histone kinase activity	vesicle localization localization organelle localization secretory granule localization developmental process multicellular organismal process regulation of multicellular organismal development regulation of biological process regulation of developmental process blood vessel morphogenesis tube development biological regulation angiogenesis vasculature development vesicle localization localization organelle localization secretory granule localization developmental process multicellular organismal process regulation of multicellular organismal development regulation of biological process regulation of developmental process blood vessel morphogenesis tube development biological regulation angiogenesis vasculature development regulation of vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis regulation of angiogenesis anatomical structure development anatomical structure formation involved in morphogenesis regulation of multicellular organismal process regulation of anatomical structure morphogenesis blood vessel development system development phosphatidylinositol metabolic process glycerophospholipid biosynthetic process phosphatidylinositol-3-phosphate biosynthetic process glycerophospholipid metabolic process lipid biosynthetic process primary metabolic process phosphatidylinositol phosphate biosynthetic process phospholipid biosynthetic process phosphatidylinositol biosynthetic process phospholipid metabolic process biosynthetic process glycerolipid biosynthetic process organophosphate metabolic process organophosphate biosynthetic process phosphate-containing compound metabolic process metabolic process cellular process glycerolipid metabolic process phosphorus metabolic process lipid metabolic process response to stimulus immune response immune system process adaptive immune response regulation of defense response regulation of response to external stimulus defense response positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of acute inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus response to stress regulation of response to stress positive regulation of defense response regulation of acute inflammatory response inflammatory response acute inflammatory response cell chemotaxis cellular response to stimulus chemotaxis neutrophil chemotaxis 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 to symbiont response to biotic stimulus defense response to other organism innate immune response response to external biotic stimulus regulation of body fluid levels wound healing homotypic cell-cell adhesion cell activation hemostasis platelet aggregation blood coagulation cell adhesion cell-cell adhesion coagulation regulation of biological quality response to wounding platelet activation neutral lipid metabolic process negative regulation of triglyceride metabolic process catabolic process regulation of cellular process regulation of triglyceride metabolic process regulation of lipid metabolic process glycerolipid catabolic process negative regulation of biological process regulation of primary metabolic process triglyceride catabolic process triglyceride metabolic process negative regulation of cellular process negative regulation of lipid catabolic process negative regulation of catabolic process lipid catabolic process neutral lipid catabolic process negative regulation of metabolic process negative regulation of triglyceride catabolic process acylglycerol catabolic process regulation of catabolic process regulation of lipid catabolic process acylglycerol metabolic process regulation of metabolic process regulation of triglyceride catabolic process negative regulation of lipid metabolic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process fibroblast apoptotic process negative regulation of fibroblast apoptotic process apoptotic process programmed cell death regulation of fibroblast apoptotic process signaling intracellular signal transduction cell communication phosphatidylinositol-mediated signaling signal transduction cell population proliferation lymphocyte activation leukocyte proliferation leukocyte activation mononuclear cell proliferation T cell activation lymphocyte proliferation T cell proliferation dendritic cell chemotaxis dendritic cell migration mononuclear cell migration phospholipase C-activating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway phosphorylation sphingolipid mediated signaling pathway sphingosine-1-phosphate receptor signaling pathway positive regulation of cell communication small GTPase-mediated signal transduction positive regulation of signal transduction regulation of small GTPase mediated signal transduction regulation of signal transduction regulation of intracellular signal transduction intracellular signaling cassette positive regulation of cellular process regulation of signaling Rac protein signal transduction positive regulation of intracellular signal transduction regulation of Rac protein signal transduction positive regulation of Rac protein signal transduction regulation of cell communication positive regulation of small GTPase mediated signal transduction positive regulation of signaling positive regulation of cytosolic calcium ion concentration positive regulation of locomotion regulation of cell motility endothelial cell migration positive regulation of cell migration regulation of locomotion positive regulation of endothelial cell migration positive regulation of cell motility regulation of cell migration regulation of endothelial cell migration cell adhesion mediated by integrin regulation of cell adhesion mediated by integrin regulation of cell adhesion phosphatidylinositol 3-kinase/protein kinase B signal transduction import into cell transport endocytosis establishment of localization vesicle-mediated transport regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction lymphocyte chemotaxis lymphocyte migration natural killer cell chemotaxis cellular response to nitrogen compound response to organophosphorus cellular response to organic cyclic compound response to oxygen-containing compound response to nitrogen compound response to purine-containing compound response to cAMP cellular response to oxygen-containing compound cellular response to cAMP response to organic cyclic compound positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of MAP kinase activity positive regulation of protein serine/threonine kinase activity positive regulation of metabolic process regulation of phosphate metabolic process positive regulation of macromolecule metabolic process protein modification process positive regulation of protein phosphorylation positive regulation of MAP kinase activity protein phosphorylation positive regulation of phosphorus metabolic process positive regulation of MAPK cascade regulation of protein metabolic process regulation of MAPK cascade regulation of molecular function positive regulation of kinase activity regulation of kinase activity regulation of protein serine/threonine kinase activity macromolecule modification regulation of phosphorus metabolic process macromolecule 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 positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of macromolecule metabolic process MAPK cascade regulation of phosphorylation establishment of organelle localization regulated exocytosis cellular localization cell activation involved in immune response leukocyte degranulation myeloid leukocyte activation myeloid leukocyte mediated immunity secretion by cell leukocyte activation involved in immune response establishment of localization in cell mast cell activation leukocyte mediated immunity mast cell mediated immunity secretion vacuolar localization export from cell mast cell degranulation myeloid cell activation involved in immune response immune effector process mast cell activation involved in immune response exocytosis lysosome localization hepatocyte apoptotic process epithelial cell apoptotic process neutrophil extravasation cellular extravasation positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process cytokine production regulation of cytokine production regulation of biosynthetic process gene expression macromolecule biosynthetic process regulation of gene expression positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process positive regulation of cytokine production regulation of calcium ion transport regulation of localization monoatomic ion transmembrane transport regulation of monoatomic ion transmembrane transport calcium ion transport metal ion transport regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport monoatomic ion transport monoatomic cation transport regulation of metal ion transport regulation of transport regulation of monoatomic ion transport inorganic ion transmembrane transport inorganic cation transmembrane transport transmembrane transport regulation of transmembrane transport regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport respiratory burst respiratory burst involved in defense response T cell chemotaxis T cell migration heart process system process regulation of heart contraction regulation of system process cardiac muscle contraction striated muscle contraction negative regulation of muscle contraction circulatory system process negative regulation of cardiac muscle contraction blood circulation negative regulation of blood circulation regulation of cardiac muscle contraction muscle contraction muscle system process regulation of muscle system process negative regulation of heart contraction regulation of blood circulation regulation of striated muscle contraction regulation of muscle contraction heart contraction negative regulation of multicellular organismal process negative regulation of striated muscle contraction	cellular anatomical structure membrane intracellular anatomical structure cytoplasm cytosol protein-containing complex catalytic complex phosphatidylinositol 3-kinase complex, class I membrane protein complex transferase complex phosphatidylinositol 3-kinase complex, class IA phosphatidylinositol 3-kinase complex transferase complex, transferring phosphorus-containing groups extrinsic component of membrane cellular anatomical structure membrane intracellular anatomical structure cytoplasm cytosol protein-containing complex catalytic complex phosphatidylinositol 3-kinase complex, class I membrane protein complex transferase complex phosphatidylinositol 3-kinase complex, class IA phosphatidylinositol 3-kinase complex transferase complex, transferring phosphorus-containing groups extrinsic component of membrane cell periphery plasma membrane phosphatidylinositol 3-kinase complex, class IB

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR015433	Phosphatidylinositol kinase	Family
A	IPR016024	Armadillo-type fold	Homologous Superfamily
A	IPR002420	C2 phosphatidylinositol 3-kinase-type domain	Domain
A	IPR018936	Phosphatidylinositol 3/4-kinase, conserved site	Conserved Site
A	IPR000403	Phosphatidylinositol 3-/4-kinase, catalytic domain	Domain
A	IPR001263	Phosphoinositide 3-kinase, accessory (PIK) domain	Domain
A	IPR042236	Phosphoinositide 3-kinase, accessory (PIK) domain superfamily	Homologous Superfamily
A	IPR036940	Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily	Homologous Superfamily
A	IPR003113	Phosphatidylinositol 3-kinase, adaptor-binding domain	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR000341	Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain	Domain
A	IPR035892	C2 domain superfamily	Homologous Superfamily
A	IPR045580	PIK3 catalytic subunit gamma, adaptor-binding domain	Domain
A	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P48736	medulloblastoma diffuse large B-cell lymphoma medullomyoblastoma with myogenic differentiation adult medulloblastoma congestive heart failure Fibrosis melanotic medulloblastoma childhood medulloblastoma malignant glioma non-small cell lung carcinoma periodontitis pilocytic astrocytoma B-cell chronic lymphocytic leukemia ulcerative colitis carotid artery disease medulloblastoma diffuse large B-cell lymphoma medullomyoblastoma with myogenic differentiation adult medulloblastoma congestive heart failure Fibrosis melanotic medulloblastoma childhood medulloblastoma malignant glioma non-small cell lung carcinoma periodontitis pilocytic astrocytoma B-cell chronic lymphocytic leukemia ulcerative colitis carotid artery disease heart failure interstitial cystitis lung cancer osteosarcoma autism peripheral nervous system disease Sjogren syndrome desmoplastic/nodular medulloblastoma invasive ductal breast carcinoma lung carcinoma ovarian cancer peripheral neuropathy subependymal giant cell astrocytoma hypertensive disorder

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.