Annotations: 4TUU

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PI3K_C2	e4tuuA4	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: C2 domain (From Topology)	T: C2 domain	F: PI3K_C2	ECOD (1.6)
A	PI3Ka	e4tuuA1	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: PI3Ka	ECOD (1.6)
A	PI3K_rbd	e4tuuA3	A: a+b two layers	X: beta-Grasp	H: Ubiquitin-related	T: Ubiquitin-like	F: PI3K_rbd	ECOD (1.6)
A	PI3_PI4_kinase	e4tuuA2	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	PF00613	Phosphoinositide 3-kinase family, accessory domain (PIK domain) (PI3Ka)	Phosphoinositide 3-kinase family, accessory domain (PIK domain)	-	Repeat
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 These regions show some similarity (although not highly significant similarity) to Ras-binding Pfam:PF00788 domains (unpublished observation).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 alpha isoform	kinase activity transferase activity catalytic activity transferase activity, transferring phosphorus-containing groups protein binding binding insulin receptor substrate binding phosphatidylinositol kinase activity lipid kinase activity 1-phosphatidylinositol-3-kinase activity phosphotransferase activity, alcohol group as acceptor 1-phosphatidylinositol-4-phosphate 3-kinase activity adenyl ribonucleotide binding nucleotide binding kinase activity transferase activity catalytic activity transferase activity, transferring phosphorus-containing groups protein binding binding insulin receptor substrate binding phosphatidylinositol kinase activity lipid kinase activity 1-phosphatidylinositol-3-kinase activity phosphotransferase activity, alcohol group as acceptor 1-phosphatidylinositol-4-phosphate 3-kinase activity 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 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity catalytic activity, acting on a protein protein kinase activity protein serine kinase activity protein serine/threonine kinase activity	cellular biosynthetic process glycerophospholipid metabolic process lipid biosynthetic process phospholipid metabolic process phosphate-containing compound metabolic process phosphorus metabolic process phosphatidylinositol metabolic process glycerophospholipid biosynthetic process phosphatidylinositol-3-phosphate biosynthetic process cellular metabolic process primary metabolic process phosphatidylinositol phosphate biosynthetic process phospholipid biosynthetic process phosphatidylinositol biosynthetic process cellular biosynthetic process glycerophospholipid metabolic process lipid biosynthetic process phospholipid metabolic process phosphate-containing compound metabolic process phosphorus metabolic process phosphatidylinositol metabolic process glycerophospholipid biosynthetic process phosphatidylinositol-3-phosphate biosynthetic process cellular metabolic process primary metabolic process phosphatidylinositol phosphate biosynthetic process phospholipid biosynthetic process phosphatidylinositol biosynthetic process biosynthetic process glycerolipid biosynthetic process organophosphate metabolic process organophosphate biosynthetic process cellular lipid metabolic process metabolic process cellular process glycerolipid metabolic process lipid metabolic process localization import into cell transport phagocytosis endocytosis establishment of localization vesicle-mediated transport cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of TOR signaling signal transduction positive regulation of cellular process TOR signaling regulation of biological process regulation of signaling regulation of TOR signaling biological regulation positive regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication positive regulation of signaling endothelial cell migration cell migration cell motility cellular response to growth factor stimulus cell surface receptor signaling pathway response to endogenous stimulus cell surface receptor protein tyrosine kinase signaling pathway vascular endothelial growth factor signaling pathway cellular response to endogenous stimulus cellular response to vascular endothelial growth factor stimulus response to growth factor enzyme-linked receptor protein signaling pathway negative regulation of programmed cell death regulation of apoptotic process regulation of anoikis negative regulation of biological process regulation of programmed cell death cell death negative regulation of anoikis negative regulation of apoptotic process anoikis negative regulation of cellular process apoptotic process programmed cell death regulation of cytoskeleton organization regulation of actin filament organization regulation of cellular component organization regulation of actin filament-based process actin cytoskeleton organization actin filament organization regulation of organelle organization cellular component organization organelle organization regulation of actin cytoskeleton organization actin filament-based process regulation of supramolecular fiber organization cellular component organization or biogenesis supramolecular fiber organization cytoskeleton organization insulin-like growth factor receptor signaling pathway response to muscle inactivity response to inactivity fibroblast apoptotic process negative regulation of fibroblast apoptotic process regulation of fibroblast apoptotic process protein localization regulation of localization cellular localization regulation of protein localization positive regulation of protein localization to membrane localization within membrane protein localization to membrane regulation of cellular localization cellular macromolecule localization macromolecule localization positive regulation of protein localization regulation of protein localization to membrane regulation of multicellular organism growth developmental process multicellular organismal process regulation of growth regulation of developmental growth regulation of developmental process developmental growth growth multicellular organism growth regulation of multicellular organismal process monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process small molecule metabolic process glucose metabolic process phosphatidylinositol-mediated signaling regulation of body fluid levels wound healing cell activation hemostasis blood coagulation response to stress coagulation regulation of biological quality response to wounding platelet activation ERBB signaling pathway epidermal growth factor receptor signaling pathway response to ketone response to lipid response to glucocorticoid response to oxygen-containing compound response to corticosteroid response to hormone response to steroid hormone response to chemical response to dexamethasone response to organic cyclic compound cell population proliferation regulation of smooth muscle cell proliferation positive regulation of cell population proliferation smooth muscle cell proliferation positive regulation of smooth muscle cell proliferation regulation of cell population proliferation muscle cell proliferation phosphorylation regulation of leukocyte activation regulation of cell activation positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte cell-cell adhesion leukocyte activation positive regulation of cell-cell adhesion positive regulation of lymphocyte activation positive regulation of cell activation cell adhesion cell-cell adhesion T cell activation positive regulation of leukocyte activation regulation of immune system process regulation of cell-cell adhesion positive regulation of immune system process positive regulation of T cell activation positive regulation of cell adhesion regulation of cell adhesion regulation of T cell activation immune system process lymphocyte costimulation regulation of leukocyte cell-cell adhesion positive regulation of multicellular organismal process T cell costimulation regulation of lymphocyte activation multicellular organism development anatomical structure development vasculature development system development circulatory system development hepaticobiliary system development gland development animal organ development liver development system process relaxation of cardiac muscle muscle system process relaxation of muscle connective tissue development adipose tissue development tissue development immune response-regulating cell surface receptor signaling pathway immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of immune response antigen receptor-mediated signaling pathway activation of immune response blood vessel morphogenesis tube development angiogenesis anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development intracellular signaling cassette phosphatidylinositol 3-kinase/protein kinase B signal transduction homeostatic process cellular response to glucose stimulus intracellular glucose homeostasis cellular response to oxygen-containing compound response to hexose cellular response to carbohydrate stimulus cellular response to chemical stimulus cellular homeostasis response to monosaccharide response to carbohydrate chemical homeostasis response to glucose glucose homeostasis carbohydrate homeostasis cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus response to activity response to butyrate response to fatty acid multicellular organismal-level homeostasis energy homeostasis negative regulation of cellular catabolic process catabolic process macroautophagy autophagy regulation of autophagy negative regulation of cellular metabolic process cellular catabolic process process utilizing autophagic mechanism negative regulation of catabolic process negative regulation of metabolic process regulation of cellular metabolic process regulation of catabolic process negative regulation of macroautophagy regulation of macroautophagy negative regulation of autophagy regulation of cellular catabolic process regulation of metabolic process regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction neuron apoptotic process negative regulation of neuron apoptotic process regulation of neuron apoptotic process cellular response to acid chemical response to water cellular response to chemical stress cellular response to environmental stimulus response to acid chemical cellular response to hydrostatic pressure cellular response to stress cellular response to water stimulus response to hydrostatic pressure response to abiotic stimulus cellular response to abiotic stimulus sexual reproduction cellular developmental process reproductive process cell development cellular process involved in reproduction in multicellular organism developmental process involved in reproduction gamete generation cell differentiation chromatin organization chromatin remodeling regulation of biosynthetic process epigenetic programming of gene expression epigenetic regulation of gene expression multicellular organismal reproductive process regulation of macromolecule metabolic process gene expression genomic imprinting macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression autosome genomic imprinting germ cell development regulation of macromolecule biosynthetic process macromolecule metabolic process cellular response to nitrogen compound response to peptide hormone insulin receptor signaling pathway cellular response to hormone stimulus cellular response to peptide hormone stimulus response to nitrogen compound response to insulin cellular response to insulin stimulus heart process circulatory system process cardiac muscle contraction heart contraction muscle contraction blood circulation striated muscle contraction regulation of protein modification process regulation of protein phosphorylation regulation of primary metabolic process regulation of phosphate metabolic process protein metabolic process protein modification process protein phosphorylation regulation of protein metabolic process macromolecule modification regulation of phosphorylation regulation of phosphorus metabolic process cardiac muscle cell contraction actin filament-based movement actin-mediated cell contraction regulation of cellular component size protein-containing complex disassembly regulation of protein-containing complex disassembly actin filament depolymerization regulation of actin filament depolymerization negative regulation of protein-containing complex disassembly negative regulation of supramolecular fiber organization cellular component disassembly actin polymerization or depolymerization negative regulation of cellular component organization protein-containing complex organization regulation of protein depolymerization negative regulation of cytoskeleton organization regulation of actin polymerization or depolymerization negative regulation of protein depolymerization negative regulation of organelle organization regulation of actin filament length negative regulation of actin filament depolymerization protein depolymerization regulation of anatomical structure size negative regulation of macromolecule metabolic process negative regulation of cellular biosynthetic process negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process cellular respiration energy derivation by oxidation of organic compounds regulation of generation of precursor metabolites and energy generation of precursor metabolites and energy regulation of cellular respiration positive regulation of cellular component organization cell projection organization plasma membrane bounded cell projection assembly cellular component biogenesis cellular component assembly regulation of lamellipodium assembly regulation of lamellipodium organization positive regulation of cell projection organization lamellipodium assembly plasma membrane bounded cell projection organization positive regulation of cellular component biogenesis regulation of cell projection organization regulation of cell projection assembly positive regulation of lamellipodium assembly regulation of cellular component biogenesis positive regulation of lamellipodium organization regulation of plasma membrane bounded cell projection assembly lamellipodium organization cell projection assembly regulation of plasma membrane bounded cell projection organization positive regulation of plasma membrane bounded cell projection assembly response to mechanical stimulus response to external stimulus response to muscle stretch response to amino acid response to L-leucine	cell projection cell leading edge cellular anatomical entity plasma membrane bounded cell projection lamellipodium intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm protein-containing complex catalytic complex membrane phosphatidylinositol 3-kinase complex, class I membrane protein complex cell projection cell leading edge cellular anatomical entity plasma membrane bounded cell projection lamellipodium intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm protein-containing complex catalytic complex membrane 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-cell junction intercalated disc anchoring junction cell junction cell-cell contact zone 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	IPR037704	PI3Kalpha, catalytic domain	Domain
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	IPR029071	Ubiquitin-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P42336	seborrheic keratosis squamous cell carcinoma ovarian cancer CLOVES syndrome Cowden disease colorectal cancer Cowden syndrome 5 renal cell carcinoma megalencephaly-capillary malformation-polymicrogyria syndrome nevus, epidermal cancer head and neck squamous cell carcinoma diffuse large B-cell lymphoma nasopharyngeal carcinoma esophageal adenocarcinoma seborrheic keratosis squamous cell carcinoma ovarian cancer CLOVES syndrome Cowden disease colorectal cancer Cowden syndrome 5 renal cell carcinoma megalencephaly-capillary malformation-polymicrogyria syndrome nevus, epidermal cancer head and neck squamous cell carcinoma diffuse large B-cell lymphoma nasopharyngeal carcinoma esophageal adenocarcinoma hepatocellular carcinoma skin basal cell carcinoma lung cancer papillary renal cell carcinoma salivary gland adenoid cystic carcinoma adenocarcinoma Mouth Neoplasms hyperplasia gastric cancer prostate cancer sarcoma hereditary diffuse gastric adenocarcinoma adenoid cystic carcinoma breast adenocarcinoma tubular adenocarcinoma breast carcinoma chromophobe renal cell carcinoma collecting duct carcinoma penile neoplasm granular cell carcinoma sarcomatoid renal cell carcinoma spindle cell sarcoma breast cancer clear cell renal carcinoma ovarian disease gastric neoplasm colon carcinoma glioblastoma colorectal carcinoma polydactyly psoriasis head and neck neoplasm hepatoblastoma cutaneous melanoma schizophrenia hereditary breast carcinoma skin pigmented basal cell carcinoma angioosteohypertrophic syndrome endometriosis benign neoplasm of stomach epithelioid sarcoma thyroid gland carcinoma invasive ductal breast carcinoma non-small cell lung carcinoma fetal alcohol spectrum disorder uterine disease large cell medulloblastoma lung adenocarcinoma cholangiocarcinoma ovarian epithelial tumor genetic endocrine growth disease lung carcinoma colorectal adenocarcinoma penile cancer glioma Lynch syndrome head and neck cancer renal carcinoma cribriform carcinoma megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 atypical teratoid rhabdoid tumor IgA glomerulonephritis inverted follicular keratosis oral cavity neoplasm fetal alcohol syndrome liver cancer cerebral cortical dysplasia ovarian carcinoma gastric carcinoma lung benign neoplasm ovarian neoplasm lung disease head and neck carcinoma hemimegalencephaly cribriform carcinoma of breast melanoma digestive system disease hereditary hemorrhagic telangiectasia adult hepatocellular carcinoma ductal breast carcinoma in situ hydrocephalus B-cell chronic lymphocytic leukemia stomach carcinoma in situ intellectual disability familial prostate carcinoma urinary bladder cancer juvenile dermatomyositis breast disease oral cavity squamous cell carcinoma follicular lymphoma cerebrovascular 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.