2EUF

X-ray structure of human CDK6-Vcyclin in complex with the inhibitor PD0332991

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)
B	d2eufb_	Alpha and beta proteins (a+b)	Protein kinase-like (PK-like)	Protein kinase-like (PK-like)	Protein kinases, catalytic subunit	Cyclin-dependent PK, CDK6	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d2eufa1	All alpha proteins	Cyclin-like	Cyclin-like	Cyclin	Viral cyclin	(Herpesvirus saimiri (strain 11) ) [TaxId: 10383 ],	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)	8036604	3000066	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Cyclin-like	8037913	3000768	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Cyclin-like	8037912	3000768	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	e2eufB1	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	Cyclin_N	e2eufA1	A: alpha arrays	X: HTH	H: HTH	T: Cyclin-like	F: Cyclin_N	ECOD (1.6)
A	Herp-Cyclin	e2eufA2	A: alpha arrays	X: HTH	H: HTH	T: Cyclin-like	F: Herp-Cyclin	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	1.10.472.10	Mainly Alpha	Orthogonal Bundle	Cyclin A	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain	-	Domain
A	PF09241	Herpesviridae viral cyclin (Herp-Cyclin)	Herpesviridae viral cyclin	Members of this family of viral cyclins adopt a helical structure consisting of five alpha-helices, with one helix surrounded by the others. They specifically activate CDK6 of host cells to a very high degree [1].	Domain
A	PF00134	Cyclin, N-terminal domain (Cyclin_N)	Cyclin, N-terminal domain	Cyclins regulate cyclin dependent kinases (CDKs). Swiss:P22674 is a Uracil-DNA glycosylase that is related to other cyclins [4]. Cyclins contain two domains of similar all-alpha fold, of which this family corresponds with the N-terminal domain.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
B	Cell division protein kinase 6	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 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 protein serine/threonine kinase activity cyclin-dependent protein serine/threonine kinase activity catalytic activity, acting on a protein kinase activity protein kinase activity cyclin-dependent protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups protein binding cyclin binding protein serine kinase activity FBXO family protein binding	regulation of biological process regulation of cellular process regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion biological regulation positive regulation of biological process cell-substrate adhesion positive regulation of cell-matrix adhesion cell adhesion cell-matrix adhesion positive regulation of cell-substrate adhesion regulation of cell-matrix adhesion cellular process regulation of biological process regulation of cellular process regulation of cell-substrate adhesion positive regulation of cell adhesion regulation of cell adhesion biological regulation positive regulation of biological process cell-substrate adhesion positive regulation of cell-matrix adhesion cell adhesion cell-matrix adhesion positive regulation of cell-substrate adhesion regulation of cell-matrix adhesion cellular process positive regulation of cellular process cell division regulation of biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process regulation of gene expression positive regulation of metabolic process biosynthetic process positive regulation of gene expression positive regulation of biosynthetic process regulation of macromolecule biosynthetic process metabolic process positive regulation of macromolecule metabolic process macromolecule metabolic process regulation of metabolic process negative regulation of cellular process negative regulation of biological process negative regulation of cell cycle cell cycle regulation of cell cycle developmental process multicellular organismal process head development lateral ventricle development forebrain development animal organ development brain development nervous system development multicellular organism development central nervous system development ventricular system development anatomical structure development telencephalon development system development cellular developmental process regulation of developmental process homeostatic process cell development regulation of cell differentiation regulation of cell development cell differentiation regulation of immune system process regulation of multicellular organismal process myeloid cell homeostasis erythrocyte homeostasis regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation erythrocyte differentiation regulation of erythrocyte differentiation multicellular organismal-level homeostasis myeloid cell differentiation immune system process regulation of hemopoiesis homeostasis of number of cells astrocyte differentiation glial cell development neurogenesis astrocyte development gliogenesis glial cell differentiation cell activation mononuclear cell differentiation lymphocyte activation lymphocyte differentiation leukocyte activation T cell differentiation in thymus T cell activation T cell differentiation leukocyte differentiation protein phosphorylation phosphorylation primary metabolic process macromolecule modification phosphate-containing compound metabolic process protein metabolic process protein modification process phosphorus metabolic process mitotic cell cycle process cell cycle phase transition G1/S transition of mitotic cell cycle cell cycle G1/S phase transition mitotic cell cycle mitotic cell cycle phase transition cell cycle process generation of neurons cell cycle G2/M phase transition regulation of cell cycle phase transition regulation of G2/M transition of mitotic cell cycle regulation of cell cycle process G2/M transition of mitotic cell cycle regulation of cell cycle G2/M phase transition regulation of mitotic cell cycle phase transition regulation of mitotic cell cycle epithelial cell differentiation pancreas development columnar/cuboidal epithelial cell development endocrine pancreas development type B pancreatic cell differentiation epithelium development glandular epithelial cell development endocrine system development type B pancreatic cell development tissue development glandular epithelial cell differentiation epithelial cell development enteroendocrine cell differentiation columnar/cuboidal epithelial cell differentiation negative regulation of developmental process negative regulation of cell differentiation RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation regulation of epithelial cell proliferation epithelial cell proliferation negative regulation of epithelial cell proliferation myeloid leukocyte differentiation regulation of leukocyte differentiation monocyte differentiation negative regulation of hemopoiesis negative regulation of monocyte differentiation regulation of monocyte differentiation negative regulation of leukocyte differentiation regulation of myeloid leukocyte differentiation negative regulation of myeloid cell differentiation negative regulation of myeloid leukocyte differentiation negative regulation of cell development negative regulation of immune system process negative regulation of multicellular organismal process cellular response to stimulus cell surface receptor signaling pathway response to stimulus signaling cell communication Notch signaling pathway signal transduction regulation of hematopoietic stem cell differentiation stem cell differentiation regulation of stem cell differentiation hematopoietic stem cell differentiation regulation of hematopoietic progenitor cell differentiation hematopoietic progenitor cell differentiation regulation of osteoblast differentiation negative regulation of osteoblast differentiation osteoblast differentiation ossification fibroblast proliferation positive regulation of cell population proliferation regulation of fibroblast proliferation positive regulation of fibroblast proliferation regulation of cellular senescence cellular senescence negative regulation of cellular senescence cellular response to stress response to stress cell dedifferentiation dedifferentiation dentate gyrus development pallium development hippocampus development limbic system development biological process involved in interspecies interaction between organisms response to other organism response to external stimulus response to external biotic stimulus response to virus response to biotic stimulus regulation of cell motility regulation of locomotion cell motility locomotion	protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex cyclin D2-CDK6 complex catalytic complex serine/threonine protein kinase complex cyclin-dependent protein kinase holoenzyme complex transferase complex cyclin D3-CDK6 complex cellular anatomical structure intracellular anatomical structure cytoplasm cytosol ruffle protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex cyclin D2-CDK6 complex catalytic complex serine/threonine protein kinase complex cyclin-dependent protein kinase holoenzyme complex transferase complex cyclin D3-CDK6 complex cellular anatomical structure intracellular anatomical structure cytoplasm cytosol ruffle cell projection cell leading edge plasma membrane bounded cell projection cyclin D1-CDK6 complex intracellular organelle centrosome microtubule organizing center cytoskeleton organelle membraneless organelle intracellular membraneless organelle microtubule cytoskeleton membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
A	viral Cyclin	enzyme regulator activity cyclin-dependent protein serine/threonine kinase regulator activity molecular function regulator activity protein kinase regulator activity kinase regulator activity	cellular process cell division symbiont-mediated perturbation of host cellular process biological process involved in interspecies interaction between organisms symbiont-mediated perturbation of host process symbiont-mediated perturbation of host cell cycle progression modulation of process of another organism biological process involved in interaction with host biological process involved in symbiotic interaction	protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex catalytic complex serine/threonine protein kinase complex cyclin-dependent protein kinase holoenzyme complex transferase complex cellular anatomical structure intracellular anatomical structure cytoplasm

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B	IPR000719	Protein kinase domain	Domain
B	IPR050108	Cyclin-dependent kinase	Family
B	IPR017441	Protein kinase, ATP binding site	Binding Site
B	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
B	IPR028788	Cyclin-dependent kinase 6	Family
B	IPR008271	Serine/threonine-protein kinase, active site	Active Site
A	IPR015322	Cyclin domain, herpesvirus	Domain
A	IPR048258	Cyclins, cyclin-box	Conserved Site
A	IPR017285	Cyclin, herpesvirus	Family
A	IPR036915	Cyclin-like superfamily	Homologous Superfamily
A	IPR039361	Cyclin	Family
A	IPR013763	Cyclin-like domain	Domain
A	IPR006671	Cyclin, N-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: Q00534	rheumatoid arthritis medulloblastoma microcephaly 12, primary, autosomal recessive glioblastoma acute myeloid leukemia microcephaly giant cell glioblastoma anemia childhood medulloblastoma Chromosome Aberrations atrial fibrillation cancer medullomyoblastoma with myogenic differentiation adult medulloblastoma malignant mesothelioma rheumatoid arthritis medulloblastoma microcephaly 12, primary, autosomal recessive glioblastoma acute myeloid leukemia microcephaly giant cell glioblastoma anemia childhood medulloblastoma Chromosome Aberrations atrial fibrillation cancer medullomyoblastoma with myogenic differentiation adult medulloblastoma malignant mesothelioma melanotic medulloblastoma childhood acute lymphoblastic leukemia ovarian cancer cholangiocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia desmoplastic/nodular medulloblastoma primitive neuroectodermal tumor sarcoidosis lung cancer autosomal recessive primary microcephaly malignant ependymoma malignant pancreatic neoplasm breast disease cerebrovascular disorder pancreatic ductal adenocarcinoma pilocytic astrocytoma psoriasis invasive ductal breast carcinoma transitional cell carcinoma adrenal cortex adenoma liposarcoma lung carcinoma malignant glioma brainstem cancer metastatic melanoma osteosarcoma pancreatic intraductal papillary-mucinous carcinoma cystic fibrosis eye disease large cell medulloblastoma tuberculosis lung adenocarcinoma atypical teratoid rhabdoid tumor lymphoma breast cancer

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.