3VS0

Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor N-[4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]benzamide

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
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3vs0a1	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	Hemapoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3vs0a2	Alpha and beta proteins (a+b)	SH2-like	SH2 domain	SH2 domain	Hemopoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3vs0a3	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Haemopoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d3vs0a4	Artifacts	Tags	Tags	Tags	N-terminal Tags	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3vs0b1	All beta proteins	SH3-like barrel	SH3-domain	SH3-domain	Hemapoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3vs0b2	Alpha and beta proteins (a+b)	SH2-like	SH2 domain	SH2 domain	Hemopoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3vs0b3	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Haemopoetic cell kinase Hck	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3vs0b4	Artifacts	Tags	Tags	Tags	N-terminal Tags	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	8035661	3000197	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SH3-domain	8041589	3000153	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8036656	3000066	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SH2 domain	8035661	3000197	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SH3-domain	8041589	3000153	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Protein kinase-like (PK-like)	8036656	3000066	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	e3vs0A1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
A	SH2	e3vs0A2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: SH2	ECOD (1.6)
A	Pkinase_Tyr	e3vs0A3	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: Pkinase_Tyr	ECOD (1.6)
B	SH3_1	e3vs0B1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: SH3_1	ECOD (1.6)
B	SH2	e3vs0B2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: SH2	ECOD (1.6)
B	Pkinase_Tyr	e3vs0B3	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: Pkinase_Tyr	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)
A	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
A	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)
B	2.30.30.40	Mainly Beta	Roll	SH3 type barrels.	SH3 Domains	CATH (4.3.0)
B	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)
B	3.30.200.20	Alpha Beta	2-Layer Sandwich	Phosphorylase Kinase	domain 1	CATH (4.3.0)
B	1.10.510.10	Mainly Alpha	Orthogonal Bundle	Transferase(Phosphotransferase)	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00017	SH2 domain (SH2)	SH2 domain	-	Domain
A, B	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
A, B	PF07714	Protein tyrosine and serine/threonine kinase (PK_Tyr_Ser-Thr)	Protein tyrosine and serine/threonine kinase	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosph ...	Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity [1]; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Tyrosine-protein kinase HCK	phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid 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 adenyl ribonucleotide binding phosphoprotein binding phosphotyrosine residue binding protein binding binding protein phosphorylated amino acid 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 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 signaling receptor binding lipid binding	cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication response to peptide response to chemical cellular response to cytokine stimulus cellular process cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication response to peptide response to chemical cellular response to cytokine stimulus cellular process signal transduction developmental process anatomical structure development tissue development mesoderm development regulated exocytosis cellular localization transport secretion export from cell leukocyte degranulation establishment of localization vesicle-mediated transport immune effector process localization secretion by cell exocytosis immune system process establishment of localization in cell 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 defense response to other organism response to stress innate immune response response to external biotic stimulus regulation of defense response positive regulation of response to biotic stimulus regulation of response to biotic stimulus regulation of response to external stimulus positive regulation of biological process 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 regulation of immune system process positive regulation of immune system process innate immune response-activating signaling pathway positive regulation of innate immune response regulation of innate immune response regulation of response to stimulus positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response protein phosphorylation protein autophosphorylation phosphorylation cellular metabolic process primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process response to type II interferon cellular response to type II interferon interferon-mediated signaling pathway type II interferon-mediated signaling pathway import into cell regulation of localization regulation of cellular component organization regulation of transport regulation of phagocytosis regulation of vesicle-mediated transport cellular component organization phagocytosis cellular component organization or biogenesis endocytosis regulation of endocytosis respiratory burst respiratory burst involved in defense response respiratory burst after phagocytosis cell adhesion negative regulation of inflammatory response negative regulation of biological process inflammatory response to antigenic stimulus negative regulation of inflammatory response to antigenic stimulus negative regulation of response to stimulus negative regulation of immune response regulation of inflammatory response to antigenic stimulus regulation of inflammatory response negative regulation of immune system process negative regulation of response to external stimulus negative regulation of defense response inflammatory response cellular biosynthetic process RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of cellular metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process regulation of gene expression regulation of molecular function biosynthetic process regulation of DNA-binding transcription factor activity regulation of macromolecule biosynthetic process regulation of DNA-templated transcription regulation of metabolic process cellular developmental process cell differentiation negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of cytoskeleton organization regulation of actin filament-based process actin cytoskeleton organization regulation of organelle organization organelle organization regulation of actin cytoskeleton organization actin filament-based process cytoskeleton organization integrin-mediated signaling pathway response to lipid cellular response to lipopolysaccharide lipopolysaccharide-mediated signaling pathway cellular response to biotic stimulus response to bacterium response to oxygen-containing compound cellular response to molecule of bacterial origin response to lipopolysaccharide cellular response to oxygen-containing compound cellular response to chemical stimulus cellular response to lipid response to molecule of bacterial origin regulation of developmental process regulation of cell shape cell morphogenesis regulation of cell morphogenesis anatomical structure morphogenesis regulation of biological quality regulation of anatomical structure morphogenesis cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of cellular process peptidyl-tyrosine modification peptidyl-amino acid modification peptidyl-tyrosine phosphorylation positive regulation of organelle organization positive regulation of cellular component organization regulation of cellular component size cellular component biogenesis regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly cellular component assembly positive regulation of protein polymerization protein-containing complex assembly regulation of actin filament polymerization protein polymerization actin polymerization or depolymerization regulation of actin filament organization actin filament polymerization protein-containing complex organization positive regulation of cellular component biogenesis positive regulation of cytoskeleton organization actin filament organization regulation of actin polymerization or depolymerization positive regulation of supramolecular fiber organization regulation of cellular component biogenesis regulation of protein polymerization regulation of actin filament length regulation of supramolecular fiber organization supramolecular fiber organization positive regulation of actin filament polymerization regulation of anatomical structure size cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway leukocyte migration cell migration cell motility leukocyte migration involved in immune response organelle assembly podosome assembly non-membrane-bounded organelle assembly regulation of podosome assembly regulation of organelle assembly intracellular signal transduction immune response-regulating cell surface receptor signaling pathway involved in phagocytosis immune response-regulating cell surface receptor signaling pathway Fc-gamma receptor signaling pathway involved in phagocytosis Fc receptor signaling pathway Fc-gamma receptor signaling pathway immune response-activating cell surface receptor signaling pathway Fc receptor mediated stimulatory signaling pathway	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system cytoskeleton intracellular non-membrane-bounded organelle non-membrane-bounded organelle anchoring junction intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system cytoskeleton intracellular non-membrane-bounded organelle non-membrane-bounded organelle anchoring junction cell junction focal adhesion cell-substrate junction membrane microdomain cell periphery membrane raft plasma membrane raft membrane plasma membrane plasma membrane region caveola transport vesicle intracellular vesicle cytoplasmic vesicle vesicle lytic vacuole vacuole lysosome cytoplasmic side of plasma membrane cytoplasmic side of membrane side of membrane cell projection nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR008266	Tyrosine-protein kinase, active site	Active Site
A, B	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR036028	SH3-like domain superfamily	Homologous Superfamily
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR001452	SH3 domain	Domain
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B	IPR036860	SH2 domain superfamily	Homologous Superfamily
A, B	IPR000980	SH2 domain	Domain
A, B	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR035851	Tyrosine-protein kinase HCK, SH2 domain	Domain
A, B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B	IPR050198	Non-receptor tyrosine kinases involved in cell signaling	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P08631	Liver Cirrhosis, Experimental osteosarcoma pancreatic intraductal papillary-mucinous carcinoma tuberculosis adrenal cortex carcinoma cancer chronic obstructive pulmonary disease glioblastoma interstitial cystitis nephrosclerosis ovarian cancer pancreatic intraductal papillary-mucinous neoplasm ulcerative colitis B-cell chronic lymphocytic leukemia childhood acute lymphoblastic leukemia Liver Cirrhosis, Experimental osteosarcoma pancreatic intraductal papillary-mucinous carcinoma tuberculosis adrenal cortex carcinoma cancer chronic obstructive pulmonary disease glioblastoma interstitial cystitis nephrosclerosis ovarian cancer pancreatic intraductal papillary-mucinous neoplasm ulcerative colitis B-cell chronic lymphocytic leukemia childhood acute lymphoblastic leukemia cutaneous lupus erythematosus head and neck cancer invasive ductal breast carcinoma lung carcinoma non-small cell lung carcinoma ovarian mucinous adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia subependymal giant cell astrocytoma gastric carcinoma inflammatory bowel disease MALT lymphoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A, B	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

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.