1S9I

X-ray structure of the human mitogen-activated protein kinase kinase 2 (MEK2)in a complex with ligand and MgATP

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
Structure Motif: Primary M-CSA Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1s9ib_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Dual specificity mitogen-activated protein kinase kinase 2, Mek2	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1s9ia_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Dual specificity mitogen-activated protein kinase kinase 2, Mek2	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)	8042318	3000066	SCOP2B (2022-06-29)
A	SCOP2 Family	Protein kinases catalytic domain-like	8029939	4003661	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Protein kinase-like (PK-like)	8042318	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	Pkinase_Tyr	e1s9iB1	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	e1s9iA1	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	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	Dual specificity mitogen-activated protein kinase kinase 2	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 MAP kinase kinase activity protein serine/threonine/tyrosine kinase activity MAP-kinase scaffold activity protein-macromolecule adaptor activity molecular adaptor activity signaling adaptor activity enzyme regulator activity protein serine/threonine kinase activator 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 cation binding metal ion binding protein binding PDZ domain binding protein domain specific binding scaffold protein binding protein serine kinase activity protein serine/threonine kinase activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process organic substance metabolic process positive regulation of biosynthetic process organic substance biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process positive regulation of nervous system development axonogenesis cell projection organization regulation of cell differentiation regulation of neurogenesis neuron projection development regulation of cell development positive regulation of developmental process cell projection morphogenesis neuron differentiation neuron projection morphogenesis cell differentiation positive regulation of cell projection organization regulation of cell projection organization positive regulation of cell development nervous system development generation of neurons positive regulation of multicellular organismal process regulation of neuron projection development regulation of cellular component organization positive regulation of cellular component organization cellular developmental process regulation of developmental process plasma membrane bounded cell projection morphogenesis cell development cell morphogenesis cellular component organization regulation of nervous system development neurogenesis positive regulation of cell differentiation regulation of axonogenesis positive regulation of neurogenesis regulation of multicellular organismal process cellular component organization or biogenesis positive regulation of axonogenesis regulation of anatomical structure morphogenesis regulation of multicellular organismal development plasma membrane bounded cell projection organization axon development cell morphogenesis involved in neuron differentiation anatomical structure morphogenesis neuron development regulation of plasma membrane bounded cell projection organization cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling insulin-like growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication signal transduction enzyme-linked receptor protein signaling pathway Golgi inheritance organelle inheritance regulation of organelle organization regulation of Golgi organization organelle organization regulation of Golgi inheritance Golgi organization endomembrane system organization intracellular signal transduction intracellular signaling cassette MAPK cascade ERBB2 signaling pathway ERBB2-ERBB3 signaling pathway ERBB signaling pathway ERBB3 signaling pathway 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 protein serine/threonine kinase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity macromolecule modification regulation of protein serine/threonine kinase activity regulation of phosphorus metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of molecular function positive regulation of protein modification process protein metabolic process positive regulation of protein kinase activity organonitrogen compound metabolic process positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of phosphorylation positive regulation of locomotion regulation of cell motility regulation of locomotion positive regulation of cell motility cell motility locomotion head development face development immune system development gland development hematopoietic or lymphoid organ development thymus development immune system process thyroid gland development endocrine system development ERK1 and ERK2 cascade peripheral nervous system development glial cell development Schwann cell development gliogenesis glial cell differentiation Schwann cell differentiation regulation of cellular response to stress regulation of signal transduction stress-activated MAPK cascade cellular response to stress regulation of intracellular signal transduction response to stress regulation of response to stress regulation of signaling regulation of stress-activated protein kinase signaling cascade regulation of MAPK cascade regulation of stress-activated MAPK cascade stress-activated protein kinase signaling cascade regulation of response to stimulus regulation of cell communication trachea morphogenesis trachea formation trachea development anatomical structure formation involved in morphogenesis respiratory system development animal organ morphogenesis animal organ formation regulation of localization cellular localization transport regulation of transport intracellular transport regulation of vesicle-mediated transport establishment of localization vesicle-mediated transport endosomal transport vesicle-mediated transport between endosomal compartments regulation of early endosome to late endosome transport localization early endosome to late endosome transport regulation of cellular localization establishment of localization in cell regulation of intracellular transport nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of RNA metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process protein autophosphorylation peptidyl-serine modification peptidyl-serine phosphorylation peptidyl-amino acid modification peptidyl-serine autophosphorylation myelination axon ensheathment ensheathment of neurons regulation of response to external stimulus regeneration response to axon injury neuron projection regeneration regulation of response to wounding axon regeneration response to wounding regulation of axon regeneration response to external stimulus regulation of neuron projection regeneration epithelium development cell population proliferation tube development respiratory tube development lung epithelium development tissue development epithelial cell proliferation involved in lung morphogenesis lung development lung morphogenesis epithelial cell proliferation	cell-cell junction anchoring junction cell junction cellular anatomical entity intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system perinuclear region of cytoplasm cell-cell junction anchoring junction cell junction cellular anatomical entity intracellular anatomical structure cytoplasm cytosol membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system perinuclear region of cytoplasm membrane peroxisome microbody membrane bounding membrane of organelle peroxisomal membrane microbody organelle membrane polymeric cytoskeletal fiber cytoskeleton intracellular non-membrane-bounded organelle supramolecular fiber microtubule supramolecular polymer supramolecular complex microtubule cytoskeleton non-membrane-bounded organelle mitochondrion focal adhesion cell-substrate junction early endosome endosome intracellular vesicle cytoplasmic vesicle vesicle extracellular region late endosome cell periphery cytoplasmic side of plasma membrane cytoplasmic side of membrane plasma membrane side of membrane nucleus endoplasmic reticulum

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR000719	Protein kinase domain	Domain
A, B	IPR017441	Protein kinase, ATP binding site	Binding Site
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: P36507	cardiofaciocutaneous syndrome Costello syndrome Noonan syndrome melanoma cardiofaciocutaneous syndrome 4 neurofibromatosis-Noonan syndrome salivary gland adenoid cystic carcinoma adenoid cystic carcinoma cardiomyopathy intellectual disability cutaneous melanoma Noonan syndrome with multiple lentigines plasma cell myeloma Cafe-au-lait macules with pulmonary stenosis chronic obstructive pulmonary disease cardiofaciocutaneous syndrome Costello syndrome Noonan syndrome melanoma cardiofaciocutaneous syndrome 4 neurofibromatosis-Noonan syndrome salivary gland adenoid cystic carcinoma adenoid cystic carcinoma cardiomyopathy intellectual disability cutaneous melanoma Noonan syndrome with multiple lentigines plasma cell myeloma Cafe-au-lait macules with pulmonary stenosis chronic obstructive pulmonary disease hypertrophic cardiomyopathy non-small cell lung carcinoma osteosarcoma psoriasis B-cell chronic lymphocytic leukemia neurofibromatosis type 1 ovarian cancer cardiofaciocutaneous syndrome 1 Charcot-Marie-Tooth disease hydrops fetalis juvenile dermatomyositis

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	mitogen-activated protein kinase kinase M-CSA #282	mitogen-activated protein (MAP) kinase kinase is a member of the protein kinase superfamily and is a Ser/Thr type kinase. It catalyses the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. It also acts on serine residues.	Defined by 2 residues: ASP:A-140 [auth A-194]ASP:A-167 [auth A-221] \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 2.7.1.37 (PDB Primary Data) Search M-CSA Motif + EC 2.7.1.37

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.