7RT2

Crystal Structure of KRAS G12D with compound 25 (4-(4-[(1R,5S)-3,8-diazabicyclo[3.2.1]octan-3-yl]-8-fluoro-2-{[(2R,4R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy}pyrido[4,3-d]pyrimidin-7-yl)naphthalen-2-ol) bound

External Resource: Annotation

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: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	Ras-like P-loop GTPases	8060856	3002022	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)
A	Ras	e7rt2A1	A: a/b three-layered sandwiches	X: P-loop domains-like	H: P-loop domains-related	T: P-loop containing nucleoside triphosphate hydrolases	F: Ras	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00071	Ras family (Ras)	Ras family	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motil ...	Includes sub-families Ras, Rab, Rac, Ral, Ran, Rap Ypt1 and more. Shares P-loop motif with GTP_EFTU, arf and myosin_head. See Pfam:PF00009 Pfam:PF00025, Pfam:PF00063. As regards Rab GTPases, these are important regulators of vesicle formation, motility and fusion. They share a fold in common with all Ras GTPases: this is a six-stranded beta-sheet surrounded by five alpha-helices [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Isoform 2B of GTPase KRas	binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding organic cyclic compound binding purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding GDP binding protein-membrane adaptor activity protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding pyrophosphatase activity GTPase activity G protein activity ribonucleoside triphosphate phosphatase activity molecular function regulator activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity identical protein binding protein binding	cellular response to stimulus positive regulation of cell communication small GTPase-mediated signal transduction regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of small GTPase mediated signal transduction positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette cellular response to stimulus positive regulation of cell communication small GTPase-mediated signal transduction regulation of cellular process positive regulation of signal transduction response to stimulus signaling regulation of small GTPase mediated signal transduction positive regulation of biological process regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette signal transduction positive regulation of cellular process regulation of biological process regulation of signaling Rac protein signal transduction biological regulation positive regulation of intracellular signal transduction regulation of Rac protein signal transduction positive regulation of Rac protein signal transduction regulation of response to stimulus regulation of cell communication cellular process positive regulation of small GTPase mediated signal transduction positive regulation of signaling multicellular organismal process cellular developmental process astrocyte differentiation forebrain development cell development glial cell development multicellular organism development neurogenesis astrocyte development gliogenesis cell differentiation anatomical structure development system development developmental process head development forebrain astrocyte development animal organ development brain development nervous system development central nervous system development glial cell differentiation forebrain astrocyte differentiation multicellular organismal-level homeostasis homeostatic process homeostasis of number of cells within a tissue anatomical structure homeostasis tissue homeostasis homeostasis of number of cells epithelium development tube development respiratory tube development lung epithelium development type I pneumocyte differentiation tissue development epithelial cell differentiation lung epithelial cell differentiation lung cell differentiation lung development respiratory system development trans-synaptic signaling synaptic transmission, GABAergic modulation of chemical synaptic transmission cell-cell signaling chemical synaptic transmission synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of synaptic transmission, GABAergic 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 branching morphogenesis of an epithelial tube tube morphogenesis lung morphogenesis animal organ morphogenesis epithelial tube morphogenesis morphogenesis of an epithelium tissue morphogenesis anatomical structure morphogenesis morphogenesis of a branching structure epithelial tube branching involved in lung morphogenesis morphogenesis of a branching epithelium regulation of developmental process negative regulation of biological process regulation of cell differentiation regulation of epithelial cell differentiation negative regulation of cellular process regulation of multicellular organismal process negative regulation of cell differentiation regulation of multicellular organismal development negative regulation of epithelial cell differentiation negative regulation of developmental process cellular component organization organelle organization actin cytoskeleton organization actin filament-based process cellular component organization or biogenesis cytoskeleton organization skeletal muscle cell differentiation skeletal muscle tissue development striated muscle tissue development muscle structure development skeletal muscle organ development muscle tissue development muscle organ development response to light stimulus system process learning learning or memory nervous system process visual learning visual behavior cognition associative learning behavior response to radiation response to abiotic stimulus neuron apoptotic process negative regulation of neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death regulation of neuron apoptotic process MAPK cascade Ras protein signal transduction regulation of neuronal synaptic plasticity regulation of synaptic plasticity regulation of long-term neuronal synaptic plasticity regulation of biological quality positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process protein metabolic process positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process primary metabolic process macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation striated muscle cell differentiation muscle cell differentiation positive regulation of nervous system development positive regulation of cell population proliferation regulation of neurogenesis regulation of gliogenesis positive regulation of glial cell proliferation positive regulation of gliogenesis regulation of cell development regulation of nervous system development positive regulation of developmental process regulation of glial cell proliferation positive regulation of cell differentiation positive regulation of neurogenesis cell population proliferation positive regulation of cell development regulation of cell population proliferation positive regulation of multicellular organismal process glial cell proliferation	cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane-bounded organelle organelle subcompartment intracellular membrane-bounded organelle cellular anatomical structure anchoring junction cell junction focal adhesion cell-substrate junction membrane intracellular anatomical structure cytoplasm cytosol cell periphery plasma membrane membrane-bounded organelle organelle subcompartment intracellular membrane-bounded organelle endomembrane system endoplasmic reticulum subcompartment intracellular organelle organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum organelle membrane endoplasmic reticulum membrane Golgi membrane Golgi apparatus bounding membrane of organelle mitochondrial membrane mitochondrion organelle outer membrane organelle envelope mitochondrial envelope mitochondrial outer membrane outer membrane cytoplasmic side of plasma membrane cytoplasmic side of membrane side of membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A	IPR005225	Small GTP-binding domain	Domain
A	IPR020849	Small GTPase, Ras-type	Family
A	IPR001806	Small GTPase	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P01116	Noonan syndrome juvenile myelomonocytic leukemia cardiofaciocutaneous syndrome acute myeloid leukemia gastric cancer cancer Noonan syndrome 3 cholangiocarcinoma Costello syndrome nasopharyngeal carcinoma subependymal giant cell astrocytoma angiosarcoma astrocytic tumor urinary bladder cancer neuroblastoma Noonan syndrome juvenile myelomonocytic leukemia cardiofaciocutaneous syndrome acute myeloid leukemia gastric cancer cancer Noonan syndrome 3 cholangiocarcinoma Costello syndrome nasopharyngeal carcinoma subependymal giant cell astrocytoma angiosarcoma astrocytic tumor urinary bladder cancer neuroblastoma squamous cell carcinoma adenoma cardiofaciocutaneous syndrome 2 ovarian cancer pilocytic astrocytoma non-small cell lung carcinoma endometriosis exocrine pancreatic carcinoma pancreatic ductal adenocarcinoma uterine cancer myelodysplastic syndrome gastric carcinoma papillary adenoma liver cancer colorectal cancer gemistocytic astrocytoma penile neoplasm granular cell carcinoma plasma cell myeloma breast adenocarcinoma nevus, epidermal hereditary diffuse gastric adenocarcinoma adenocarcinoma carcinoma Splenomegaly cecal neoplasm thyroid gland carcinoma anaplastic astrocytoma childhood cerebral astrocytoma autoimmune lymphoproliferative syndrome lung cancer breast cancer protoplasmic astrocytoma malignant colon neoplasm thyroid adenoma cecum cancer fibrillary astrocytoma juvenile pilocytic astrocytoma Toriello-Lacassie-Droste syndrome gallbladder cancer arteriovenous malformations of the brain autoimmune lymphoproliferative syndrome type 4 lung adenocarcinoma prostate cancer breast carcinoma lymphoma sarcomatoid carcinoma intellectual disability intrahepatic cholangiocarcinoma cardiomyopathy malignant pancreatic neoplasm familial pancreatic carcinoma juvenile idiopathic arthritis follicular thyroid adenoma anemia tubular adenocarcinoma microcystic adenoma atypical teratoid rhabdoid tumor uterine disease B-cell chronic lymphocytic leukemia liver neoplasm congenital anemia craniosynostosis benign neoplasm of pancreas lung benign neoplasm hepatocellular carcinoma lung disease digestive system disease breast disease Lynch syndrome encephalocraniocutaneous lipomatosis hydrops fetalis epidermal nevus syndrome oral cavity neoplasm cardiofaciocutaneous syndrome 1 osteosarcoma ovarian disease cerebral astrocytoma medullary thyroid gland carcinoma pancreatic intraductal papillary-mucinous carcinoma pancreatic neoplasm linear nevus sebaceus syndrome colonic neoplasm myopathy gastric neoplasm Parkinson disease colorectal carcinoma glioblastoma benign colon neoplasm Pick disease cribriform carcinoma hematologic disease bile duct cancer dermatomyositis rheumatoid arthritis inflammatory linear verrucous epidermal nevus juvenile dermatomyositis thyroid gland follicular carcinoma ovarian neoplasm cervical carcinoma medulloblastoma pancreatic intraductal papillary-mucinous neoplasm large cell medulloblastoma ulcerative colitis urinary bladder neoplasm astrocytoma (excluding glioblastoma) pancreatitis colorectal adenocarcinoma uterine cervix carcinoma in situ gastrointestinal stromal tumor penile cancer verrucous nevus benign neoplasm cribriform carcinoma of breast bladder transitional cell carcinoma lung carcinoma diffuse astrocytoma psoriasis Emery-Dreifuss muscular dystrophy malignant ependymoma oligodendroglioma squamous cell lung carcinoma osteogenesis imperfecta thyroid cancer amyotrophic lateral sclerosis ovarian carcinoma thyroid gland papillary carcinoma Charcot-Marie-Tooth disease gallbladder neoplasm pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia chronic myelomonocytic leukemia undifferentiated carcinoma

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.