2Z0P

Crystal structure of PH domain of Bruton's tyrosine kinase

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	d2z0pa_	All beta proteins	PH domain-like barrel	PH domain-like	Pleckstrin-homology domain (PH domain)	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d2z0pc_	All beta proteins	PH domain-like barrel	PH domain-like	Pleckstrin-homology domain (PH domain)	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2z0pb_	All beta proteins	PH domain-like barrel	PH domain-like	Pleckstrin-homology domain (PH domain)	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d2z0pd_	All beta proteins	PH domain-like barrel	PH domain-like	Pleckstrin-homology domain (PH domain)	automated matches	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	PH domain-like	8042560	3000134	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	PH domain-like	8042560	3000134	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	PH domain-like	8042560	3000134	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	PH domain-like	8042560	3000134	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	PH	e2z0pA1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PH	ECOD (1.6)
A	BTK	e2z0pA2	A: few secondary structure elements	X: Btk/CHORD zinc fingers (From Topology)	H: Btk/CHORD zinc fingers (From Topology)	T: Btk/CHORD zinc fingers	F: BTK	ECOD (1.6)
C	PH	e2z0pC1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PH	ECOD (1.6)
C	BTK	e2z0pC2	A: few secondary structure elements	X: Btk/CHORD zinc fingers (From Topology)	H: Btk/CHORD zinc fingers (From Topology)	T: Btk/CHORD zinc fingers	F: BTK	ECOD (1.6)
B	PH	e2z0pB1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PH	ECOD (1.6)
B	BTK	e2z0pB2	A: few secondary structure elements	X: Btk/CHORD zinc fingers (From Topology)	H: Btk/CHORD zinc fingers (From Topology)	T: Btk/CHORD zinc fingers	F: BTK	ECOD (1.6)
D	PH	e2z0pD1	A: beta barrels	X: PH domain-like	H: PH domain-like (From Topology)	T: PH domain-like	F: PH	ECOD (1.6)
D	BTK	e2z0pD2	A: few secondary structure elements	X: Btk/CHORD zinc fingers (From Topology)	H: Btk/CHORD zinc fingers (From Topology)	T: Btk/CHORD zinc fingers	F: BTK	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)
C	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)
D	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	PF00779	BTK motif (BTK)	BTK motif	-	Motif
A, B, C, D	PF00169	PH domain (PH)	PH domain	PH stands for pleckstrin homology.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D	Tyrosine-protein kinase BTK	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 binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate 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 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 non-membrane spanning protein tyrosine kinase activity cation binding metal ion binding identical protein binding protein binding phospholipase binding enzyme binding phosphatidylinositol-3,4,5-trisphosphate binding phospholipid binding lipid binding phosphatidylinositol phosphate binding phosphatidylinositol binding enzyme regulator activity enzyme activator activity molecular function activator activity phospholipase activator activity molecular function regulator activity lipase activator activity	negative regulation of lymphocyte proliferation multicellular organismal process regulation of cellular process regulation of leukocyte activation negative regulation of biological process regulation of cell activation lymphocyte activation negative regulation of lymphocyte activation leukocyte proliferation leukocyte activation negative regulation of mononuclear cell proliferation negative regulation of leukocyte proliferation regulation of B cell proliferation lymphocyte proliferation regulation of B cell activation negative regulation of lymphocyte proliferation multicellular organismal process regulation of cellular process regulation of leukocyte activation negative regulation of biological process regulation of cell activation lymphocyte activation negative regulation of lymphocyte activation leukocyte proliferation leukocyte activation negative regulation of mononuclear cell proliferation negative regulation of leukocyte proliferation regulation of B cell proliferation lymphocyte proliferation regulation of B cell activation negative regulation of cellular process regulation of multicellular organismal process regulation of immune system process negative regulation of B cell activation regulation of lymphocyte proliferation regulation of leukocyte proliferation regulation of biological process negative regulation of cell population proliferation cell population proliferation B cell activation biological regulation cell activation B cell proliferation negative regulation of B cell proliferation negative regulation of cell activation negative regulation of immune system process regulation of cell population proliferation mononuclear cell proliferation immune system process regulation of mononuclear cell proliferation cellular process negative regulation of multicellular organismal process negative regulation of leukocyte activation regulation of lymphocyte activation cellular response to stimulus regulation of defense response positive regulation of response to biotic stimulus regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms pattern recognition receptor signaling pathway response to stimulus regulation of response to external stimulus toll-like receptor signaling pathway signaling positive regulation of biological process response to biotic stimulus cell communication positive regulation of response to stimulus immune response-activating signaling pathway positive regulation of response to external stimulus immune response-regulating signaling pathway positive regulation of immune response regulation of response to stress response to stress innate immune response response to external biotic stimulus signal transduction positive regulation of immune system process innate immune response-activating signaling pathway MyD88-dependent toll-like receptor signaling pathway positive regulation of innate immune response defense response immune response response to other organism regulation of innate immune response defense response to symbiont response to external stimulus regulation of response to stimulus defense response to other organism positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response positive regulation of cell population proliferation positive regulation of epithelial cell proliferation regulation of synoviocyte proliferation regulation of epithelial cell proliferation synoviocyte proliferation epithelial cell proliferation positive regulation of synoviocyte proliferation positive regulation of cellular process adaptive immune response developmental process anatomical structure development tissue development mesoderm development carbohydrate derivative catabolic process glycoprotein catabolic process catabolic process carbohydrate derivative metabolic process primary metabolic process protein catabolic process glycoprotein metabolic process macromolecule catabolic process metabolic process protein metabolic process macromolecule metabolic process proteoglycan catabolic process proteoglycan metabolic process regulation of leukocyte apoptotic process regulation of lymphocyte apoptotic process regulation of B cell apoptotic process leukocyte apoptotic process regulation of apoptotic process B cell apoptotic process regulation of programmed cell death cell death lymphocyte apoptotic process apoptotic process programmed cell death adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains lymphocyte mediated immunity regulation of immune effector process regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains cytokine production regulation of cytokine production leukocyte mediated immunity cytokine production involved in immune response production of molecular mediator of immune response regulation of biosynthetic process regulation of B cell cytokine production regulation of cytokine production involved in immune response regulation of adaptive immune response regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of B cell mediated immunity immune effector process regulation of gene expression B cell cytokine production regulation of leukocyte mediated immunity biosynthetic process regulation of lymphocyte mediated immunity B cell mediated immunity regulation of macromolecule biosynthetic process regulation of production of molecular mediator of immune response regulation of metabolic process establishment of organelle localization regulated exocytosis nitrogen compound transport cell activation involved in immune response leukocyte degranulation vesicle-mediated transport myeloid leukocyte activation myeloid leukocyte mediated immunity localization establishment of localization in cell regulation of biological quality regulation of hormone levels histamine secretion by mast cell vacuolar localization establishment of localization mast cell degranulation histamine secretion involved in inflammatory response exocytosis lysosome localization inflammatory response histamine production involved in inflammatory response cellular localization transport hormone secretion histamine secretion secretion by cell organelle localization signal release leukocyte activation involved in immune response histamine transport mast cell activation mast cell mediated immunity production of molecular mediator involved in inflammatory response secretion export from cell cell-cell signaling myeloid cell activation involved in immune response mast cell activation involved in immune response exocytic process hormone transport regulation of localization import into cell positive regulation of cellular component organization regulation of cellular component organization cellular component organization positive regulation of endocytosis phagocytosis cellular component organization or biogenesis regulation of endocytosis regulation of transport regulation of phagocytosis regulation of vesicle-mediated transport positive regulation of phagocytosis positive regulation of transport endocytosis cellular response to molecule of fungal origin cellular response to biotic stimulus response to molecule of fungal origin response to fungus positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process interleukin-17 production regulation of interleukin-17A production regulation of interleukin-17 production positive regulation of interleukin-17A production positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of interleukin-17 production interleukin-17A production positive regulation of cytokine production positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB 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 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 protein phosphorylation phosphorylation macromolecule modification phosphate-containing compound metabolic process protein modification process phosphorus metabolic process immunoglobulin production positive regulation of immune effector process positive regulation of immunoglobulin production regulation of immunoglobulin production positive regulation of production of molecular mediator of immune response immune response-regulating cell surface receptor signaling pathway cell surface receptor signaling pathway Fc receptor signaling pathway Fc-epsilon receptor signaling pathway positive regulation of B cell proliferation positive regulation of lymphocyte activation positive regulation of cell activation positive regulation of leukocyte activation positive regulation of mononuclear cell proliferation positive regulation of lymphocyte proliferation positive regulation of B cell activation positive regulation of leukocyte proliferation regulation of leukocyte differentiation mononuclear cell differentiation regulation of cell differentiation positive regulation of B cell differentiation lymphocyte differentiation regulation of cell development positive regulation of developmental process multicellular organism development cell differentiation positive regulation of cell development leukocyte differentiation cellular developmental process regulation of developmental process cell development regulation of B cell differentiation B cell differentiation positive regulation of hemopoiesis positive regulation of cell differentiation regulation of lymphocyte differentiation regulation of multicellular organismal development hemopoiesis regulation of hemopoiesis positive regulation of leukocyte differentiation positive regulation of lymphocyte differentiation monocyte proliferation positive regulation of acute inflammatory response to antigenic stimulus regulation of acute inflammatory response to antigenic stimulus positive regulation of leukocyte mediated immunity inflammatory response to antigenic stimulus positive regulation of hypersensitivity positive regulation of inflammatory response positive regulation of adaptive immune response positive regulation of immunoglobulin mediated immune response hypersensitivity regulation of inflammatory response regulation of acute inflammatory response positive regulation of type I hypersensitivity regulation of type I hypersensitivity positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains positive regulation of lymphocyte mediated immunity positive regulation of acute inflammatory response positive regulation of B cell mediated immunity type I hypersensitivity regulation of immunoglobulin mediated immune response acute inflammatory response regulation of hypersensitivity regulation of inflammatory response to antigenic stimulus acute inflammatory response to antigenic stimulus positive regulation of inflammatory response to antigenic stimulus immunoglobulin mediated immune response immune response-activating cell surface receptor signaling pathway B cell receptor signaling pathway antigen receptor-mediated signaling pathway T cell receptor signaling pathway regulation of myeloid leukocyte mediated immunity regulation of type III hypersensitivity positive regulation of myeloid leukocyte mediated immunity type III hypersensitivity positive regulation of type III hypersensitivity interleukin-6 production positive regulation of interleukin-6 production regulation of interleukin-6 production immunoglobulin production involved in immunoglobulin-mediated immune response B cell affinity maturation peripheral B cell selection B cell selection intracellular signal transduction calcium-mediated signaling intracellular signaling cassette negative regulation of interleukin-10 production interleukin-10 production regulation of interleukin-10 production negative regulation of macromolecule metabolic process negative regulation of metabolic process negative regulation of cytokine production negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process anatomical structure maturation cell maturation developmental maturation peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation positive regulation of cell communication positive regulation of signal transduction regulation of NLRP3 inflammasome complex assembly positive regulation of NLRP3 inflammasome complex assembly regulation of signal transduction 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 intracellular signal transduction positive regulation of inflammasome-mediated signaling pathway regulation of inflammasome-mediated signaling pathway regulation of pattern recognition receptor signaling pathway NLRP3 inflammasome complex assembly 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 regulation of intracellular signal transduction protein-containing complex assembly regulation of signaling protein-containing complex organization positive regulation of cellular component biogenesis regulation of cellular component biogenesis regulation of cell communication positive regulation of signaling cellular response to oxidative stress response to oxygen-containing compound cellular response to chemical stress cellular response to oxygen-containing compound response to reactive oxygen species cellular response to reactive oxygen species response to oxidative stress cellular response to chemical stimulus cellular response to stress response to chemical apoptotic signaling pathway multicellular organismal-level homeostasis leukocyte homeostasis homeostatic process homeostasis of number of cells myeloid cell homeostasis neutrophil homeostasis eosinophil homeostasis 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 lipid response to lipopolysaccharide response to bacterium response to molecule of bacterial origin response to peptide response to interleukin-7 response to cytokine cellular response to cytokine stimulus cellular response to interleukin-7	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm cell periphery plasma membrane membrane membrane microdomain membrane raft membrane-bounded organelle intracellular organelle cytoplasmic vesicle organelle cellular anatomical structure intracellular anatomical structure cytoplasm cytosol perinuclear region of cytoplasm cell periphery plasma membrane membrane membrane microdomain membrane raft membrane-bounded organelle intracellular organelle cytoplasmic vesicle organelle intracellular vesicle intracellular membrane-bounded organelle vesicle nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D	IPR008266	Tyrosine-protein kinase, active site	Active Site
A, B, C, D	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A, B, C, D	IPR035574	Tyrosine-protein kinase BTK, SH3 domain	Domain
A, B, C, D	IPR036028	SH3-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR000719	Protein kinase domain	Domain
A, B, C, D	IPR001562	Zinc finger, Btk motif	Conserved Site
A, B, C, D	IPR001452	SH3 domain	Domain
A, B, C, D	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B, C, D	IPR001849	Pleckstrin homology domain	Domain
A, B, C, D	IPR036860	SH2 domain superfamily	Homologous Superfamily
A, B, C, D	IPR000980	SH2 domain	Domain
A, B, C, D	IPR011993	PH-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A, B, C, D	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B, C, D	IPR050198	Non-receptor tyrosine kinases involved in cell signaling	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D	Pharos: Q06187	Bruton-type agammaglobulinemia agammaglobulinemia isolated growth hormone deficiency type III macroglobulinemia B-cell chronic lymphocytic leukemia lymphoma Malignant lymphoma - small lymphocytic osteosarcoma Sjogren syndrome ulcerative colitis breast adenocarcinoma cancer hematologic disease intellectual disability lung large cell carcinoma Bruton-type agammaglobulinemia agammaglobulinemia isolated growth hormone deficiency type III macroglobulinemia B-cell chronic lymphocytic leukemia lymphoma Malignant lymphoma - small lymphocytic osteosarcoma Sjogren syndrome ulcerative colitis breast adenocarcinoma cancer hematologic disease intellectual disability lung large cell carcinoma lymphoplasmacytic lymphoma non-small cell lung carcinoma primary central nervous system lymphoma B cell deficiency subependymal giant cell astrocytoma Waldenstrom macroglobulinemia breast carcinoma X-linked recessive disease interstitial cystitis lung cancer lymphatic system disease mantle cell lymphoma osteogenesis imperfecta psoriasis tuberculosis cutaneous lupus erythematosus IgA glomerulonephritis isolated congenital growth hormone deficiency lung carcinoma

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.