1BI7

MECHANISM OF G1 CYCLIN DEPENDENT KINASE INHIBITION FROM THE STRUCTURE OF THE CDK6-P16INK4A TUMOR SUPPRESSOR COMPLEX

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)
A	d1bi7a_	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)
B	d1bi7b_	Alpha and beta proteins (a+b)	beta-hairpin-alpha-hairpin repeat	Ankyrin repeat	Ankyrin repeat	Cell cycle inhibitor p16ink4A	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	Protein kinase-like (PK-like)	8036604	3000066	SCOP2B (2022-06-29)
B	SCOP2 Family	Ankyrin repeat	8004107	4000366	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	Ankyrin repeat	8044602	3000154	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)
A	PF00069	e1bi7A1	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: PF00069	ECOD (1.6)
B	PF00023	e1bi7B2	A: alpha superhelices	X: Repetitive alpha hairpins	H: Ankyrin repeat (From Topology)	T: Ankyrin repeat	F: PF00023	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
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	1.25.40.20	Mainly Alpha	Alpha Horseshoe	Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat	Ankyrin repeat-containing domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	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	CYCLIN-DEPENDENT 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	response to organic substance response to stimulus response to chemical 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 response to organic substance response to stimulus response to chemical 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 cellular biosynthetic 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 regulation of biosynthetic process cellular metabolic process 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 macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic 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 organonitrogen compound metabolic process 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 negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription 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 transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process negative regulation of biosynthetic 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 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 intracellular anatomical structure cytoplasm cellular anatomical entity cytosol ruffle cell projection 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 intracellular anatomical structure cytoplasm cellular anatomical entity cytosol ruffle cell projection cell leading edge plasma membrane bounded cell projection intracellular organelle centrosome microtubule organizing center cytoskeleton organelle intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
B	MULTIPLE TUMOR SUPPRESSOR	transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding protein binding binding DNA-binding transcription factor binding NF-kappaB binding kinase binding enzyme binding protein kinase binding enzyme regulator activity enzyme inhibitor activity protein kinase regulator activity protein kinase inhibitor activity molecular function inhibitor activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding protein binding binding DNA-binding transcription factor binding NF-kappaB binding kinase binding enzyme binding protein kinase binding enzyme regulator activity enzyme inhibitor activity protein kinase regulator activity protein kinase inhibitor activity molecular function inhibitor activity cyclin-dependent protein serine/threonine kinase inhibitor activity molecular function regulator activity cyclin-dependent protein serine/threonine kinase regulator activity protein serine/threonine kinase inhibitor activity kinase inhibitor activity kinase regulator activity RNA binding organic cyclic compound binding nucleic acid binding	regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription regulation of biological process cellular metabolic process regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription regulation of biological process cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process negative regulation of cellular process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process cellular process cell cycle phosphorylation negative regulation of phosphate metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of phosphorus metabolic process regulation of phosphorus metabolic process regulation of phosphorylation negative regulation of phosphorylation phosphorus metabolic process positive regulation of programmed cell death positive regulation of smooth muscle cell apoptotic process muscle cell apoptotic process smooth muscle cell apoptotic process regulation of apoptotic process positive regulation of biological process regulation of muscle cell apoptotic process regulation of programmed cell death cell death regulation of smooth muscle cell apoptotic process positive regulation of apoptotic process positive regulation of muscle cell apoptotic process apoptotic process programmed cell death positive regulation of cellular process negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation regulation of cell-substrate adhesion regulation of cell adhesion cell-substrate adhesion negative regulation of cell-matrix adhesion negative regulation of cell adhesion cell adhesion cell-matrix adhesion regulation of cell-matrix adhesion negative regulation of cell-substrate adhesion replicative senescence regulation of growth regulation of cellular component organization growth negative regulation of cell growth regulation of cell growth cell growth cellular component organization negative regulation of growth cellular component organization or biogenesis regulation of cell cycle leukocyte apoptotic process macrophage apoptotic process positive regulation of myeloid cell apoptotic process positive regulation of macrophage apoptotic process positive regulation of leukocyte apoptotic process myeloid cell apoptotic process regulation of leukocyte apoptotic process regulation of macrophage apoptotic process inflammatory cell apoptotic process regulation of myeloid cell apoptotic process regulation of cell cycle phase transition regulation of cell cycle process cell cycle phase transition regulation of cell cycle G1/S phase transition cell cycle G1/S phase transition mitotic cell cycle regulation of mitotic cell cycle phase transition regulation of mitotic cell cycle regulation of G1/S transition of mitotic cell cycle mitotic cell cycle process G1/S transition of mitotic cell cycle cell cycle process mitotic cell cycle phase transition regulation of catalytic activity negative regulation of cell cycle negative regulation of catalytic activity regulation of cyclin-dependent protein kinase activity regulation of transferase activity negative regulation of kinase activity negative regulation of transferase activity regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of protein modification process protein modification process negative regulation of protein metabolic process protein phosphorylation regulation of protein metabolic process regulation of molecular function regulation of kinase activity negative regulation of protein phosphorylation macromolecule modification regulation of protein serine/threonine kinase activity regulation of protein modification process regulation of protein phosphorylation negative regulation of cyclin-dependent protein serine/threonine kinase activity negative regulation of protein serine/threonine kinase activity protein metabolic process organonitrogen compound metabolic process negative regulation of cyclin-dependent protein kinase activity negative regulation of molecular function negative regulation of protein kinase activity regulation of protein kinase activity cellular response to stimulus cellular response to stress response to stimulus response to stress cellular senescence negative regulation of DNA-binding transcription factor activity negative regulation of NF-kappaB transcription factor activity regulation of DNA-binding transcription factor activity small GTPase-mediated signal transduction signaling Ras protein signal transduction intracellular signal transduction cell communication intracellular signaling cassette signal transduction	protein-containing complex intracellular anatomical structure protein-DNA complex chromatin chromosome cellular anatomical entity senescence-associated heterochromatin focus heterochromatin intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle cytoplasm cytosol protein-containing complex intracellular anatomical structure protein-DNA complex chromatin chromosome cellular anatomical entity senescence-associated heterochromatin focus heterochromatin intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle cytoplasm cytosol membrane-bounded organelle nucleus intracellular membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR000719	Protein kinase domain	Domain
A	IPR017441	Protein kinase, ATP binding site	Binding Site
A	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A	IPR028788	Cyclin-dependent kinase 6	Family
A	IPR008271	Serine/threonine-protein kinase, active site	Active Site
B	IPR036770	Ankyrin repeat-containing domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	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 medullomyoblastoma with myogenic differentiation cancer 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 medullomyoblastoma with myogenic differentiation cancer 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
B	Pharos: P42771	melanoma plasma cell myeloma cutaneous melanoma malignant glioma cancer melanoma and neural system tumor syndrome dysplastic nevus syndrome adrenal cortex carcinoma melanoma-pancreatic cancer syndrome diffuse large B-cell lymphoma esophageal adenocarcinoma familial melanoma lymphoma non-small cell lung carcinoma Sezary syndrome melanoma plasma cell myeloma cutaneous melanoma malignant glioma cancer melanoma and neural system tumor syndrome dysplastic nevus syndrome adrenal cortex carcinoma melanoma-pancreatic cancer syndrome diffuse large B-cell lymphoma esophageal adenocarcinoma familial melanoma lymphoma non-small cell lung carcinoma Sezary syndrome Li-Fraumeni syndrome breast carcinoma malignant mesothelioma head and neck squamous cell carcinoma pancreatic ductal adenocarcinoma thymoma urinary bladder cancer esophageal squamous cell carcinoma nasopharyngeal carcinoma neuroblastoma glaucoma lung adenocarcinoma exocrine pancreatic carcinoma poisoning vulvar lichen sclerosus breast cancer gastric cancer glioblastoma adenocarcinoma primary cutaneous T-cell non-Hodgkin lymphoma squamous cell carcinoma thymic carcinoma trisomy peripheral neuropathy mixed glioma esophageal cancer Neoplasm Invasiveness acute lymphoblastic leukemia perineurioma peripheral nervous system disease liver cancer bone disease tubular adenocarcinoma lung cancer granular cell carcinoma peripheral nervous system neoplasm brain aneurysm ulcerative colitis pituitary cancer brain glioma urinary bladder neoplasm myeloid neoplasm lung disease nasopharyngeal disease neoplasm of neck abdominal aortic aneurysm Burkitt lymphoma nerve sheath neoplasm carotid artery disease granulomatous slack skin disease prostate carcinoma oral cavity neoplasm hematologic disease adrenal gland cancer ovarian carcinoma atypical teratoid rhabdoid tumor cribriform carcinoma of breast pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia large cell medulloblastoma benign neoplasm melanoma, cutaneous malignant, susceptibility to, 1 biliary tract neoplasm digestive system disease liver neoplasm brain cancer lung benign neoplasm urogenital neoplasm myocardial infarction eye disease familial pancreatic carcinoma gastric neoplasm glioma cataract open-angle glaucoma adrenal carcinoma psoriasis osteosarcoma hepatocellular carcinoma skin basal cell carcinoma congenital anemia B-cell acute lymphoblastic leukemia cutaneous lupus erythematosus pancreatic neoplasm leukemia depressive disorder mesothelioma pilocytic astrocytoma low tension glaucoma brain disease plasma cell neoplasm uterine disease precancerous condition lymphatic system disease brainstem cancer neoplasm of esophagus major depressive disorder breast disease acute T cell leukemia primary cutaneous T-cell lymphoma primitive neuroectodermal tumor childhood acute lymphoblastic leukemia oral cavity cancer heart disease malignant pancreatic neoplasm colorectal cancer ovarian cancer hereditary diffuse gastric adenocarcinoma astrocytic tumor skin disease cribriform carcinoma pancreatic intraductal papillary-mucinous neoplasm inflammatory bowel disease benign mesothelioma thoracic aortic aneurysm peripheral arterial disease benign neoplasm of pancreas

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.