4D8K

Crystal structure of a SH3-SH2 domains of a lymphocyte-specific protein tyrosine kinase (LCK) from Homo sapiens at 2.36 A resolution

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	d4d8ka1	All beta proteins	SH3-like barrel	SH3-domain	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4d8ka2	Alpha and beta proteins (a+b)	SH2-like	SH2 domain	automated matches	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	SH2 domain	8035564	3000197	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SH3-domain	8042747	3000153	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	SH3_1	e4d8kA4	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
A	SH2	e4d8kA3	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: SH2	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)
A	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00017	SH2 domain (SH2)	SH2 domain	-	Domain
A	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	Tyrosine-protein kinase Lck	phosphoric ester hydrolase activity phosphoprotein phosphatase activity protein serine/threonine phosphatase activity catalytic activity, acting on a protein hydrolase activity, acting on ester bonds phosphatase activity hydrolase activity catalytic activity phosphatidylinositol 3-kinase binding protein binding binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding phosphoric ester hydrolase activity phosphoprotein phosphatase activity protein serine/threonine phosphatase activity catalytic activity, acting on a protein hydrolase activity, acting on ester bonds phosphatase activity hydrolase activity catalytic activity phosphatidylinositol 3-kinase binding protein binding binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding protein phosphatase binding phosphatase binding enzyme binding protein tyrosine kinase activity kinase activity protein kinase activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding 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 protein-containing complex binding signaling receptor binding T cell receptor binding ATPase binding identical protein binding phospholipase binding CD8 receptor binding SH2 domain binding protein domain specific binding CD4 receptor binding kinase binding protein kinase binding enzyme regulator activity enzyme activator activity molecular function activator activity phospholipase activator activity molecular function regulator activity lipase activator activity	response to stimulus response to chemical response to xenobiotic stimulus organonitrogen compound metabolic process protein phosphorylation protein autophosphorylation phosphorylation cellular metabolic process primary metabolic process peptidyl-tyrosine modification peptidyl-tyrosine autophosphorylation organic substance metabolic process macromolecule modification peptidyl-amino acid modification response to stimulus response to chemical response to xenobiotic stimulus organonitrogen compound metabolic process protein phosphorylation protein autophosphorylation phosphorylation cellular metabolic process primary metabolic process peptidyl-tyrosine modification peptidyl-tyrosine autophosphorylation organic substance metabolic process macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process metabolic process cellular process protein metabolic process macromolecule metabolic process peptidyl-tyrosine phosphorylation protein modification process phosphorus metabolic process biological process involved in interspecies interaction between organisms immune response response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus immune system process defense response to other organism response to stress innate immune response response to external biotic stimulus developmental process cellular developmental process hemopoiesis cell differentiation anatomical structure development cell development multicellular organismal process cell activation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell activation T cell differentiation leukocyte differentiation regulation of body fluid levels wound healing hemostasis biological regulation blood coagulation coagulation regulation of biological quality response to wounding platelet activation cellular response to stimulus positive regulation of cell communication immune response-regulating cell surface receptor signaling pathway regulation of cellular process positive regulation of signal transduction positive regulation of T cell receptor signaling pathway signaling positive regulation of biological process regulation of antigen receptor-mediated signaling pathway regulation of signal transduction cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway regulation of T cell receptor signaling pathway T cell receptor signaling pathway regulation of response to stimulus regulation of immune response regulation of cell communication antigen receptor-mediated signaling pathway activation of immune response positive regulation of antigen receptor-mediated signaling pathway positive regulation of signaling regulation of programmed cell death regulation of intrinsic apoptotic signaling pathway intracellular signal transduction positive regulation of apoptotic signaling pathway regulation of intracellular signal transduction intrinsic apoptotic signaling pathway positive regulation of programmed cell death regulation of apoptotic process positive regulation of intracellular signal transduction cell death positive regulation of apoptotic process apoptotic signaling pathway positive regulation of intrinsic apoptotic signaling pathway apoptotic process programmed cell death regulation of apoptotic signaling pathway positive regulation of cell adhesion regulation of cell adhesion positive regulation of cell-cell adhesion heterotypic cell-cell adhesion cell adhesion cell-cell adhesion positive regulation of heterotypic cell-cell adhesion regulation of cell-cell adhesion regulation of heterotypic cell-cell adhesion regulation of leukocyte activation regulation of cell activation positive regulation of leukocyte cell-cell adhesion leukocyte cell-cell adhesion positive regulation of lymphocyte activation positive regulation of cell activation positive regulation of leukocyte activation regulation of multicellular organismal process positive regulation of T cell activation regulation of T cell activation lymphocyte costimulation regulation of leukocyte cell-cell adhesion positive regulation of multicellular organismal process T cell costimulation regulation of lymphocyte activation B cell receptor signaling pathway regulation of catalytic activity positive regulation of protein metabolic process positive regulation of peptidase activity positive regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of primary metabolic process positive regulation of molecular function positive regulation of metabolic process regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of proteolysis proteolysis regulation of endopeptidase activity positive regulation of macromolecule metabolic process activation of cysteine-type endopeptidase activity involved in apoptotic process regulation of cysteine-type endopeptidase activity regulation of protein metabolic process regulation of peptidase activity positive regulation of catalytic activity regulation of macromolecule metabolic process regulation of molecular function positive regulation of hydrolase activity positive regulation of cysteine-type endopeptidase activity regulation of hydrolase activity positive regulation of endopeptidase activity positive regulation of proteolysis regulation of metabolic process Fc receptor signaling pathway Fc-gamma receptor signaling pathway inorganic ion homeostasis cellular homeostasis chemical homeostasis homeostatic process intracellular monoatomic cation homeostasis intracellular zinc ion homeostasis monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis intracellular monoatomic ion homeostasis leukocyte migration cell migration cell motility regulation of localization cellular localization intracellular calcium ion homeostasis transport monoatomic ion transmembrane transport negative regulation of biological process 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 localization negative regulation of cellular process monoatomic ion transport monoatomic cation transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol sequestering of calcium ion inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol calcium ion transmembrane transport cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway	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 pericentriolar material 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 pericentriolar material intracellular organelle centrosome microtubule organizing center cytoskeleton intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle cell periphery extrinsic component of plasma membrane cytoplasmic side of plasma membrane cytoplasmic side of membrane membrane plasma membrane extrinsic component of membrane extrinsic component of cytoplasmic side of plasma membrane side of membrane membrane microdomain membrane raft immunological synapse

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR008266	Tyrosine-protein kinase, active site	Active Site
A	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A	IPR036028	SH3-like domain superfamily	Homologous Superfamily
A	IPR000719	Protein kinase domain	Domain
A	IPR035850	Tyrosine-protein kinase Lck, SH2 domain	Domain
A	IPR001452	SH3 domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR036860	SH2 domain superfamily	Homologous Superfamily
A	IPR000980	SH2 domain	Domain
A	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A	IPR035749	Lck, SH3 domain	Domain
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P06239	severe combined immunodeficiency due to LCK deficiency cancer atopic eczema cutaneous lupus erythematosus Philadelphia Chromosome Positive Chronic Myelocytic Leukemia renal cell carcinoma B-cell chronic lymphocytic leukemia interstitial cystitis sarcoidosis Sjogren syndrome osteosarcoma psoriasis ulcerative colitis

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), 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.