4MHA

Crystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC1817

External Resource: Annotation

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: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Protein kinase-like (PK-like)	8069187	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Protein kinase-like (PK-like)	8069187	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)
B	Pkinase_Tyr	e4mhaB1	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)
A	Pkinase_Tyr	e4mhaA1	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)
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)
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)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
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 Mer	molecular transducer activity catalytic activity, acting on a protein kinase activity protein kinase activity signaling receptor activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity transmembrane receptor protein kinase activity transmembrane signaling receptor activity catalytic activity binding molecular transducer activity catalytic activity, acting on a protein kinase activity protein kinase activity signaling receptor activity transferase activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity transmembrane receptor protein kinase activity transmembrane signaling receptor activity catalytic activity 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	developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation genitalia development multicellular organismal process reproductive system development female genitalia development sex differentiation animal organ development developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation genitalia development multicellular organismal process reproductive system development female genitalia development sex differentiation animal organ development female sex differentiation vagina development multicellular organism development anatomical structure development reproductive structure development system development localization import into cell transport phagocytosis cellular process endocytosis establishment of localization vesicle-mediated transport sensory organ development eye development retina development in camera-type eye visual system development camera-type eye development sensory system development cell adhesion substrate adhesion-dependent cell spreading cell-substrate adhesion regulation of biological process signaling biological regulation cell-cell signaling cell communication regulation of localization positive regulation of cellular component organization regulation of cellular process regulation of cellular component organization positive regulation of biological process cellular component organization positive regulation of endocytosis cellular component organization or biogenesis positive regulation of cellular process regulation of endocytosis regulation of transport regulation of phagocytosis regulation of vesicle-mediated transport positive regulation of phagocytosis positive regulation of transport cellular response to stimulus positive regulation of cell communication regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signal transduction response to stimulus regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of response to stimulus regulation of cell communication phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of signaling cell migration cell motility cellular localization establishment of localization in cell negative regulation of biological process negative regulation of cellular process cytokine production regulation of cytokine production regulation of multicellular organismal process negative regulation of macromolecule metabolic process regulation of biosynthetic process negative regulation of metabolic process negative regulation of cytokine production regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process negative regulation of multicellular organismal process regulation of metabolic process 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 regulation of leukocyte apoptotic process negative regulation of programmed cell death leukocyte apoptotic process regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of leukocyte apoptotic process apoptotic process programmed cell death cell surface receptor signaling pathway protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process protein metabolic process protein modification process phosphorus metabolic process secretion by cell secretion export from cell nervous system development cellular developmental process hemopoiesis cell development mononuclear cell differentiation natural killer cell activation lymphocyte differentiation lymphocyte activation leukocyte activation cell differentiation immune system process natural killer cell differentiation leukocyte differentiation regulation of leukocyte activation regulation of cell activation negative regulation of lymphocyte activation negative regulation of cell activation negative regulation of immune system process regulation of immune system process negative regulation of leukocyte activation regulation of lymphocyte activation homeostatic process neutrophil clearance neutrophil homeostasis multicellular organismal-level homeostasis leukocyte homeostasis homeostasis of number of cells apoptotic cell clearance myeloid cell homeostasis	cell periphery cellular anatomical structure plasma membrane membrane intracellular anatomical structure cytoplasm membrane-bounded organelle non-motile cilium 9+0 non-motile cilium cilium neuron projection photoreceptor outer segment plasma membrane bounded cell projection cell projection cell periphery cellular anatomical structure plasma membrane membrane intracellular anatomical structure cytoplasm membrane-bounded organelle non-motile cilium 9+0 non-motile cilium cilium neuron projection photoreceptor outer segment plasma membrane bounded cell projection cell projection photoreceptor cell cilium organelle protein-containing complex receptor complex extracellular region extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B	IPR036179	Immunoglobulin-like domain superfamily	Homologous Superfamily
A, B	IPR008266	Tyrosine-protein kinase, active site	Active Site
A, B	IPR020635	Tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR003599	Immunoglobulin domain subtype	Domain
A, B	IPR001245	Serine-threonine/tyrosine-protein kinase, catalytic domain	Domain
A, B	IPR003961	Fibronectin type III	Domain
A, B	IPR013151	Immunoglobulin-like beta-sandwich domain	Domain
A, B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B	IPR013783	Immunoglobulin-like fold	Homologous Superfamily
A, B	IPR050122	Receptor Tyrosine Kinase	Family
A, B	IPR007110	Immunoglobulin-like domain	Domain
A, B	IPR036116	Fibronectin type III superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q12866	retinitis pigmentosa retinitis pigmentosa 38 IgA glomerulonephritis Thromboembolism carcinoma pulmonary embolism retinal degeneration sarcomatoid carcinoma large cell medulloblastoma malignant pancreatic neoplasm osteosarcoma acute myeloid leukemia pancreatic intraductal papillary-mucinous carcinoma benign neoplasm of adrenal gland pituitary cancer retinitis pigmentosa retinitis pigmentosa 38 IgA glomerulonephritis Thromboembolism carcinoma pulmonary embolism retinal degeneration sarcomatoid carcinoma large cell medulloblastoma malignant pancreatic neoplasm osteosarcoma acute myeloid leukemia pancreatic intraductal papillary-mucinous carcinoma benign neoplasm of adrenal gland pituitary cancer cancer cone-rod dystrophy gastrointestinal stromal tumor heart disease malignant ependymoma medulloblastoma ovarian cancer adrenal cortex adenoma pancreatic intraductal papillary-mucinous neoplasm astrocytic tumor peripheral nervous system disease psoriasis renal cell carcinoma glioblastoma idiopathic pulmonary fibrosis undifferentiated carcinoma interstitial lung disease non-small cell lung carcinoma pancreatic ductal adenocarcinoma adrenal medulla cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia atopic eczema peripheral neuropathy breast cancer exocrine pancreatic carcinoma head and neck squamous cell carcinoma thrombotic disease

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.