2W2W

PLCg2 Split Pleckstrin Homology (PH) Domain

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF00169	e2w2wA1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
B	PF00169	e2w2wB1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
C	PF00169	e2w2wC1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
D	PF00169	e2w2wD1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
E	PF00169	e2w2wE1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
G	PF00169	e2w2wG1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
H	PF00169	e2w2wH1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
I	PF00169	e2w2wI1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
J	PF00169	e2w2wJ1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
K	PF00169	e2w2wK1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
L	PF00169	e2w2wL1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)
F	PF00169	e2w2wF1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PF00169	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
B	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
C	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
D	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
E	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
G	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
H	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
I	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
J	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
K	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
L	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)
F	2.30.29.30	Mainly Beta	Roll	PH-domain like	Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB)	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	PF00018	SH3 domain (SH3_1)	SH3 domain	SH3 (Src homology 3) domains are often indicative of a protein involved in signal transduction related to cytoskeletal organisation. First described in the Src cytoplasmic tyrosine kinase Swiss:P12931. The structure is a partly opened beta barrel.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	1-PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHODIESTERASE GAMMA-2	phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity phospholipase C activity hydrolase activity catalytic activity phospholipase activity lipase activity protein tyrosine kinase binding phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphoric diester hydrolase activity phospholipase C activity hydrolase activity catalytic activity phospholipase activity lipase activity protein tyrosine kinase binding kinase binding enzyme binding protein kinase binding phosphatidylinositol phospholipase C activity scaffold protein binding phosphorylation-dependent protein binding modification-dependent protein binding	response to stimulus response to stress response to wounding response to axon injury cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction signaling positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus response to stimulus response to stress response to wounding response to axon injury cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction 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 intracellular signaling cassette regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling signal transduction positive regulation of cellular process regulation of biological process regulation of signaling biological regulation positive regulation of intracellular signal transduction regulation of response to stimulus calcium-mediated signaling regulation of cell communication cellular process positive regulation of signaling multicellular organismal process cell activation cellular developmental process cell development mononuclear cell differentiation mature B cell differentiation B cell activation involved in immune response lymphocyte activation cell activation involved in immune response lymphocyte differentiation leukocyte activation B cell differentiation cell differentiation leukocyte activation involved in immune response anatomical structure development lymphocyte activation involved in immune response developmental process mature B cell differentiation involved in immune response immune response hemopoiesis follicular B cell differentiation B cell activation immune effector process immune system process leukocyte differentiation cellular biosynthetic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process organic substance metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of biosynthetic process cellular metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process biological process involved in interspecies interaction between organisms response to other organism response to yeast response to external stimulus response to fungus response to external biotic stimulus response to biotic stimulus positive regulation of DNA-binding transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process primary metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of molecular function organic cyclic compound metabolic process regulation of DNA-binding transcription factor activity organic cyclic compound biosynthetic process regulation of DNA-templated transcription cell death programmed cell death lipid catabolic process catabolic process phospholipid catabolic process organophosphate catabolic process cellular lipid catabolic process cellular catabolic process phospholipid metabolic process organophosphate metabolic process cellular lipid metabolic process phosphate-containing compound metabolic process phosphorus metabolic process organic substance catabolic process lipid metabolic process regulation of immune effector process positive regulation of leukocyte mediated immunity dendritic cell cytokine production cytokine production leukocyte mediated immunity regulation of immune system process positive regulation of immune system process regulation of cytokine production involved in immune response regulation of leukocyte mediated immunity positive regulation of production of molecular mediator of immune response positive regulation of multicellular organismal process regulation of production of molecular mediator of immune response positive regulation of cytokine production positive regulation of dendritic cell cytokine production regulation of dendritic cell cytokine production regulation of cytokine production regulation of multicellular organismal process positive regulation of immune effector process cytokine production involved in immune response production of molecular mediator of immune response positive regulation of cytokine production involved in immune response negative regulation of programmed cell death negative regulation of cellular process negative regulation of biological process regulation of programmed cell death cellular response to inorganic substance cellular response to metal ion response to inorganic substance cellular response to chemical stimulus response to metal ion response to chemical cellular response to calcium ion response to calcium ion phosphatidylinositol-mediated signaling regulation of body fluid levels wound healing hemostasis blood coagulation coagulation regulation of biological quality platelet activation antifungal innate immune response defense response defense response to symbiont defense response to fungus defense response to other organism innate immune response macrophage activation involved in immune response myeloid cell activation involved in immune response myeloid leukocyte activation macrophage activation response to lectin cellular response to lectin positive regulation of NF-kappaB transcription factor activity 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 regulation of immune response interleukin-10 production regulation of interleukin-10 production positive regulation of interleukin-10 production regulation of macrophage cytokine production positive regulation of macrophage cytokine production positive regulation of myeloid leukocyte cytokine production involved in immune response myeloid leukocyte cytokine production macrophage cytokine production positive regulation of phosphorylation positive regulation of phosphate metabolic process regulation of phosphate metabolic process protein modification process positive regulation of protein phosphorylation I-kappaB phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process macromolecule modification regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of protein modification process positive regulation of I-kappaB phosphorylation protein metabolic process organonitrogen compound metabolic process canonical NF-kappaB signal transduction regulation of phosphorylation regulation of I-kappaB phosphorylation polyol metabolic process small molecule biosynthetic process inositol trisphosphate biosynthetic process organic hydroxy compound metabolic process alcohol metabolic process inositol phosphate metabolic process organophosphate biosynthetic process inositol phosphate biosynthetic process organic hydroxy compound biosynthetic process polyol biosynthetic process alcohol biosynthetic process inositol trisphosphate metabolic process small molecule metabolic process positive regulation of type I interferon production type I interferon production regulation of type I interferon production immune response-activating signaling pathway positive regulation of immune response immune response-activating cell surface receptor signaling pathway B cell receptor signaling pathway antigen receptor-mediated signaling pathway activation of immune response regulation of lipid metabolic process T cell receptor signaling pathway import into cell regulation of localization regulation of cellular component organization positive regulation of cellular component organization transport positive regulation of membrane invagination vesicle-mediated transport cellular component organization localization positive regulation of endocytosis regulation of phagocytosis, engulfment membrane invagination phagocytosis cellular component organization or biogenesis plasma membrane invagination regulation of endocytosis membrane organization regulation of transport regulation of phagocytosis regulation of vesicle-mediated transport establishment of localization phagocytosis, engulfment positive regulation of phagocytosis positive regulation of transport positive regulation of phagocytosis, engulfment regulation of membrane invagination endocytosis interleukin-6 production positive regulation of interleukin-6 production regulation of interleukin-6 production receptor internalization regulation of receptor internalization positive regulation of receptor-mediated endocytosis regulation of receptor-mediated endocytosis positive regulation of receptor internalization receptor-mediated endocytosis response to organic substance response to lipid cellular response to lipopolysaccharide lipopolysaccharide-mediated signaling pathway cellular response to biotic stimulus response to bacterium cellular response to organic substance response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to lipid response to molecule of bacterial origin positive regulation of response to biotic stimulus innate immune response-activating signaling pathway regulation of innate immune response positive regulation of defense response activation of innate immune response regulation of defense response regulation of response to biotic stimulus regulation of response to external stimulus innate immune response activating cell surface receptor signaling pathway positive regulation of response to external stimulus regulation of response to stress positive regulation of innate immune response stimulatory C-type lectin receptor signaling pathway regulation of interleukin-12 production interleukin-12 production positive regulation of interleukin-12 production glycerophospholipid metabolic process lipid biosynthetic process phosphatidylinositol metabolic process glycerophospholipid biosynthetic process phospholipid biosynthetic process phosphatidylinositol biosynthetic process glycerolipid biosynthetic process glycerolipid metabolic process positive regulation of MAPK cascade regulation of MAPK cascade MAPK cascade pattern recognition receptor signaling pathway regulation of NLRP3 inflammasome complex assembly positive regulation of NLRP3 inflammasome complex assembly cellular component biogenesis cellular component assembly inflammasome-mediated signaling pathway canonical inflammasome complex assembly positive regulation of pattern recognition receptor signaling pathway positive regulation of inflammasome-mediated signaling pathway regulation of inflammasome-mediated signaling pathway regulation of pattern recognition receptor signaling pathway NLRP3 inflammasome complex assembly inflammatory response cytoplasmic pattern recognition receptor signaling pathway intracellular receptor signaling pathway regulation of cytoplasmic pattern recognition receptor signaling pathway regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly protein-containing complex assembly protein-containing complex organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis regulation of interleukin-2 production interleukin-2 production positive regulation of interleukin-2 production cellular localization inorganic ion homeostasis intracellular calcium ion homeostasis homeostatic process monoatomic ion transmembrane transport calcium ion homeostasis negative regulation of sequestering of calcium ion calcium ion transport metal ion transport maintenance of location in cell monoatomic cation transmembrane transport intracellular monoatomic cation homeostasis monoatomic ion homeostasis monoatomic ion transport intracellular chemical homeostasis monoatomic cation homeostasis monoatomic cation transport regulation of sequestering of calcium ion intracellular monoatomic ion homeostasis calcium ion transmembrane import into cytosol sequestering of calcium ion inorganic ion transmembrane transport inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol cellular homeostasis chemical homeostasis calcium ion transmembrane transport positive regulation of interleukin-23 production interleukin-23 production regulation of interleukin-23 production reactive oxygen species biosynthetic process positive regulation of reactive oxygen species biosynthetic process reactive oxygen species metabolic process regulation of reactive oxygen species biosynthetic process positive regulation of reactive oxygen species metabolic process regulation of reactive oxygen species metabolic process regulation of cell cycle phase transition regulation of cell cycle process cell cycle phase transition regulation of cell cycle G1/S phase transition cell cycle G1/S phase transition positive regulation of cell cycle positive regulation of cell cycle G1/S phase transition positive regulation of cell cycle phase transition positive regulation of cell cycle process cell cycle regulation of cell cycle cell cycle process calcineurin-NFAT signaling cascade regulation of calcineurin-mediated signaling regulation of calcineurin-NFAT signaling cascade calcineurin-mediated signaling Wnt signaling pathway 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 positive regulation of neuroinflammatory response regulation of inflammatory response positive regulation of inflammatory response regulation of neuroinflammatory response neuroinflammatory response toll-like receptor signaling pathway peptidyl-tyrosine modification positive regulation of peptidyl-tyrosine phosphorylation peptidyl-amino acid modification regulation of peptidyl-tyrosine phosphorylation peptidyl-tyrosine phosphorylation regulation of canonical NF-kappaB signal transduction positive regulation of locomotion regulation of cell motility positive regulation of cell migration positive regulation of epithelial cell migration tissue migration ameboidal-type cell migration positive regulation of cell motility regulation of cell migration cell migration epithelial cell migration cell motility regulation of epithelial cell migration locomotion epithelium migration regulation of locomotion	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm intracellular organelle intracellular vesicle intracellular membrane-bounded organelle ruffle cell leading edge plasma membrane membrane leading edge membrane plasma membrane bounded cell projection cell periphery cell projection ruffle membrane plasma membrane region cell projection membrane membrane microdomain membrane raft

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR036028	SH3-like domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR001192	Phosphoinositide phospholipase C family	Family
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR035723	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, SH3 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR001452	SH3 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR001849	Pleckstrin homology domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR036860	SH2 domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR035023	PLC-gamma, C-terminal SH2 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR001711	Phospholipase C, phosphatidylinositol-specific, Y domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR000980	SH2 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR016279	Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma	Family
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR000008	C2 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR011993	PH-like domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR000909	Phosphatidylinositol-specific phospholipase C, X domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR011992	EF-hand domain pair	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR035024	PLC-gamma, N-terminal SH2 domain	Domain
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR017946	PLC-like phosphodiesterase, TIM beta/alpha-barrel domain superfamily	Homologous Superfamily
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	IPR035892	C2 domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D, E A, B, C, D, E, F, G, H, I, J, K, L	Pharos: P16885	autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation familial cold autoinflammatory syndrome 3 Alzheimer disease inflammatory bowel disease B-cell chronic lymphocytic leukemia cryopyrin-associated periodic syndrome nasopharyngeal carcinoma Sjogren syndrome ulcerative colitis Acute Confusional Senile Dementia heart disease lung cancer malignant mesothelioma osteosarcoma spina bifida autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation familial cold autoinflammatory syndrome 3 Alzheimer disease inflammatory bowel disease B-cell chronic lymphocytic leukemia cryopyrin-associated periodic syndrome nasopharyngeal carcinoma Sjogren syndrome ulcerative colitis Acute Confusional Senile Dementia heart disease lung cancer malignant mesothelioma osteosarcoma spina bifida vascular disease familial cold autoinflammatory syndrome lung carcinoma Muckle-Wells syndrome subependymal giant cell astrocytoma interstitial cystitis malignant colon neoplasm

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 R01GM133198.