5EAK

Optimization of Microtubule Affinity Regulating Kinase (MARK) Inhibitors with Improved Physical Properties

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
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)
B	d5eakb_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	automated matches	automated matches	Human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d5eaka_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	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)
B	SCOP2B Superfamily	Protein kinase-like (PK-like)	8069153	3000066	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	UBA-like	8090064	3001235	SCOP2B (2022-06-29)
A	SCOP2 Family	MARK4 variant UBA domain-like	8067073	4007155	SCOP2 (2022-06-29)
A	SCOP2 Family	Protein kinases catalytic domain-like	8069152	4003661	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	UBA-like	8090064	3001235	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Protein kinase-like (PK-like)	8069153	3000066	SCOP2 (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	UBA_MELK	e5eakB1	A: alpha arrays	X: RuvA-C	H: RuvA-C, UBA, CRAL/TRIO-N, HBS1 (From Topology)	T: RuvA-C, UBA, CRAL/TRIO-N, HBS1	F: UBA_MELK	ECOD (1.6)
B	Pkinase_Tyr	e5eakB2	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	UBA_MELK	e5eakA1	A: alpha arrays	X: RuvA-C	H: RuvA-C, UBA, CRAL/TRIO-N, HBS1 (From Topology)	T: RuvA-C, UBA, CRAL/TRIO-N, HBS1	F: UBA_MELK	ECOD (1.6)
A	Pkinase_Tyr	e5eakA2	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)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00627	UBA/TS-N domain (UBA)	UBA/TS-N domain	This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin a ...	This small domain is composed of three alpha helices. This family includes the previously defined UBA and TS-N domains. The UBA-domain (ubiquitin associated domain) is a novel sequence motif found in several proteins having connections to ubiquitin and the ubiquitination pathway. The structure of the UBA domain consists of a compact three helix bundle [1]. This domain is found at the N terminus of EF-TS hence the name TS-N. The structure of EF-TS is known and this domain is implicated in its interaction with EF-TU [2]. The domain has been found in non EF-TS proteins such as alpha-NAC Swiss:P70670 and MJ0280 Swiss:Q57728 [1].	Domain
A, B	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Serine/threonine-protein kinase MARK2	enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity RNA binding binding organic cyclic compound binding nucleic acid binding tau-protein kinase activity catalytic activity, acting on a protein enzyme regulator activity kinase activator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein kinase activator activity protein kinase regulator activity kinase regulator activity RNA binding binding organic cyclic compound binding nucleic acid binding tau-protein 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 protein serine kinase activity cation binding magnesium ion binding ion binding metal ion binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding cytoskeletal protein binding protein binding tau protein binding cell adhesion molecule binding cadherin binding lipid binding protein serine/threonine kinase activity	regulation of neuron projection development multicellular organismal process axonogenesis regulation of cellular component organization regulation of cellular process cellular developmental process regulation of developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis cellular component organization neurogenesis multicellular organism development regulation of neuron projection development multicellular organismal process axonogenesis regulation of cellular component organization regulation of cellular process cellular developmental process regulation of developmental process cell projection organization plasma membrane bounded cell projection morphogenesis cell development neuron projection development cell morphogenesis cellular component organization neurogenesis multicellular organism development cell projection morphogenesis neuron differentiation neuron projection morphogenesis regulation of axonogenesis cell differentiation anatomical structure development cellular component organization or biogenesis regulation of anatomical structure morphogenesis system development developmental process regulation of biological process plasma membrane bounded cell projection organization regulation of cell projection organization biological regulation nervous system development axon development cell morphogenesis involved in neuron differentiation generation of neurons anatomical structure morphogenesis neuron development cellular process regulation of plasma membrane bounded cell projection organization regulation of protein binding regulation of molecular function regulation of binding regulation of microtubule binding organonitrogen compound metabolic process protein phosphorylation phosphorylation cellular metabolic process primary metabolic process organic substance metabolic process macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process metabolic process peptidyl-threonine modification protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process peptidyl-threonine phosphorylation regulation of cytoskeleton organization regulation of organelle organization organelle organization cytoskeleton organization establishment of cell polarity establishment or maintenance of cell polarity positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of metabolic process regulation of phosphate metabolic process positive regulation of macromolecule metabolic process positive regulation of protein phosphorylation positive regulation of phosphorus metabolic process regulation of protein metabolic process regulation of cellular metabolic process positive regulation of kinase activity regulation of kinase activity activation of protein kinase activity regulation of phosphorus metabolic process regulation of metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of molecular function positive regulation of protein modification process positive regulation of protein kinase activity positive regulation of cellular process positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of macromolecule metabolic process regulation of phosphorylation protein autophosphorylation microtubule cytoskeleton organization regulation of microtubule-based process microtubule-based process regulation of microtubule cytoskeleton organization positive regulation of cellular component organization positive regulation of neuron projection development positive regulation of cell projection organization cellular component disassembly catabolic process autophagy cellular catabolic process organelle disassembly autophagy of mitochondrion process utilizing autophagic mechanism mitochondrion organization localization mitochondrion localization organelle localization peptidyl-serine modification peptidyl-serine phosphorylation cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling cell communication signal transduction Wnt signaling pathway neuron migration cell migration cell motility intracellular signal transduction establishment or maintenance of cell polarity regulating cell shape regulation of cell shape regulation of cell morphogenesis regulation of biological quality establishment or maintenance of bipolar cell polarity establishment or maintenance of epithelial cell apical/basal polarity establishment or maintenance of apical/basal cell polarity	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle membrane cell periphery plasma membrane somatodendritic compartment cell projection dendrite membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle membrane cell periphery plasma membrane somatodendritic compartment cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen polymeric cytoskeletal fiber actin filament actin cytoskeleton cytoskeleton intracellular non-membrane-bounded organelle supramolecular fiber supramolecular polymer supramolecular complex non-membrane-bounded organelle lateral plasma membrane microtubule bundle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
A, B	IPR001772	Kinase associated domain 1 (KA1)	Domain
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR015940	Ubiquitin-associated domain	Domain
A, B	IPR028375	KA1 domain/Ssp2, C-terminal	Homologous Superfamily
A, B	IPR049508	Serine/threonine-protein kinase MARK 1-4, catalytic domain	Domain
A, B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A, B	IPR008271	Serine/threonine-protein kinase, active site	Active Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q7KZI7	adenoid cystic carcinoma salivary gland adenoid cystic carcinoma malignant glioma osteosarcoma Salivary Gland Neoplasms bipolar disorder malignant mesothelioma schizophrenia endogenous depression salivary gland cancer

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.