9BFX

Tri-complex of Elironrasib (RMC-6291), KRAS G12C, and CypA

External Resource: Annotation

Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C [auth B]	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, motili ...	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
B [auth D], D [auth C]	PF00160	Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD (Pro_isomerase)	Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD	The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organisms studied so far and catalyse peptidyl-prolyl isomerisation during which the peptide bond pr ...	The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organisms studied so far and catalyse peptidyl-prolyl isomerisation during which the peptide bond preceding proline (the peptidyl-prolyl bond) is stabilised in the cis conformation. Mammalian cyclophilin A (CypA) is a major cellular target for the immunosuppressive drug cyclosporin A (CsA). Other roles for cyclophilins may include chaperone and cell signalling function [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C [auth B]	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 purine nucleotide binding anion binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding binding guanyl nucleotide binding GTP binding nucleotide binding guanyl ribonucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion 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
B [auth D], D [auth C]	Peptidyl-prolyl cis-trans isomerase A	isomerase activity RNA polymerase II CTD heptapeptide repeat modifying activity catalytic activity, acting on a protein RNA polymerase II CTD heptapeptide repeat peptidyl-prolyl isomerase activity RNA polymerase II CTD heptapeptide repeat P6 isomerase activity peptidyl-prolyl cis-trans isomerase activity catalytic activity cis-trans isomerase activity RNA polymerase II CTD heptapeptide repeat P3 isomerase activity amide binding binding cyclosporin A binding glycosaminoglycan binding organic acid binding isomerase activity RNA polymerase II CTD heptapeptide repeat modifying activity catalytic activity, acting on a protein RNA polymerase II CTD heptapeptide repeat peptidyl-prolyl isomerase activity RNA polymerase II CTD heptapeptide repeat P6 isomerase activity peptidyl-prolyl cis-trans isomerase activity catalytic activity cis-trans isomerase activity RNA polymerase II CTD heptapeptide repeat P3 isomerase activity amide binding binding cyclosporin A binding glycosaminoglycan binding organic acid binding ion binding heparan sulfate binding anion binding carboxylic acid binding carbohydrate derivative binding small molecule binding sulfur compound binding RNA binding nucleic acid binding cell adhesion molecule binding protein-containing complex binding protein binding integrin binding signaling receptor binding unfolded protein binding virion binding	cellular response to stimulus regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of stress-activated MAPK cascade negative regulation of biological process regulation of cellular response to stress regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication stress-activated MAPK cascade cellular response to stress cellular response to stimulus regulation of cellular process response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of stress-activated MAPK cascade negative regulation of biological process regulation of cellular response to stress regulation of signal transduction intracellular signal transduction negative regulation of cell communication cell communication stress-activated MAPK cascade cellular response to stress regulation of intracellular signal transduction response to stress regulation of response to stress intracellular signaling cassette negative regulation of cellular process signal transduction regulation of biological process regulation of signaling negative regulation of response to stimulus biological regulation regulation of stress-activated protein kinase signaling cascade regulation of MAPK cascade negative regulation of signal transduction regulation of stress-activated MAPK cascade stress-activated protein kinase signaling cascade regulation of response to stimulus negative regulation of stress-activated protein kinase signaling cascade MAPK cascade regulation of cell communication cellular process negative regulation of MAPK cascade regulation of apoptotic process regulation of programmed cell death cell death apoptotic signaling pathway apoptotic process programmed cell death regulation of apoptotic signaling pathway protein folding biosynthetic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process gene expression macromolecule biosynthetic process protein maturation regulation of protein modification process positive regulation of phosphorylation regulation of catalytic activity regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of biological process regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of molecular function positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process activation of protein kinase B activity positive regulation of protein kinase activity phosphorus metabolic process protein modification process positive regulation of protein phosphorylation positive regulation of cellular process protein phosphorylation positive regulation of transferase activity positive regulation of phosphorus metabolic process phosphorylation regulation of protein metabolic process positive regulation of catalytic activity regulation of protein kinase activity regulation of macromolecule metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity activation of protein kinase activity macromolecule modification regulation of phosphorylation regulation of phosphorus metabolic process regulation of metabolic process cell chemotaxis chemotaxis neutrophil chemotaxis response to external stimulus neutrophil migration granulocyte migration leukocyte migration cellular response to chemical stimulus taxis immune system process granulocyte chemotaxis response to chemical myeloid leukocyte migration cell migration cell motility leukocyte chemotaxis locomotion negative regulation of phosphate metabolic process negative regulation of protein modification process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process negative regulation of metabolic process negative regulation of protein phosphorylation negative regulation of phosphorus metabolic process negative regulation of phosphorylation multicellular organismal process regulation of body fluid levels wound healing homotypic cell-cell adhesion cell activation hemostasis platelet aggregation blood coagulation cell adhesion cell-cell adhesion coagulation regulation of biological quality response to wounding platelet activation response to oxidative stress cellular response to oxidative stress cellular response to chemical stress negative regulation of catalytic activity negative regulation of kinase activity negative regulation of transferase activity negative regulation of molecular function negative regulation of protein kinase activity negative regulation of viral process regulation of viral process regulation of viral life cycle negative regulation of viral life cycle viral process viral life cycle positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity RNA metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of gene expression regulation of DNA-binding transcription factor activity regulation of macromolecule biosynthetic process regulation of DNA-templated transcription cellular component organization organelle organization lipid droplet organization cellular component organization or biogenesis positive regulation of viral genome replication positive regulation of viral process viral genome replication regulation of viral genome replication peptidyl-amino acid modification peptidyl-proline modification protein peptidyl-prolyl isomerization developmental process cellular developmental process nervous system development generation of neurons neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development system development negative regulation of post-translational protein modification regulation of protein K48-linked ubiquitination regulation of protein ubiquitination protein ubiquitination regulation of protein modification by small protein conjugation or removal negative regulation of protein ubiquitination regulation of protein polyubiquitination negative regulation of protein modification by small protein conjugation or removal regulation of post-translational protein modification protein polyubiquitination negative regulation of protein K48-linked ubiquitination negative regulation of protein polyubiquitination post-translational protein modification protein modification by small protein conjugation protein K48-linked ubiquitination protein modification by small protein conjugation or removal positive regulation of cell communication positive regulation of signal transduction positive regulation of response to stimulus positive regulation of MAPK cascade positive regulation of intracellular signal transduction positive regulation of signaling protein localization regulation of localization establishment of protein localization cellular localization nitrogen compound transport regulation of protein localization transport positive regulation of establishment of protein localization positive regulation of secretion by cell protein localization to extracellular region positive regulation of protein transport localization regulation of secretion by cell secretion by cell positive regulation of secretion cellular macromolecule localization regulation of transport secretion regulation of establishment of protein localization establishment of protein localization to extracellular region export from cell regulation of protein transport protein secretion establishment of localization positive regulation of protein secretion regulation of protein secretion regulation of secretion positive regulation of transport protein transport regulation of cellular localization macromolecule localization positive regulation of protein localization intrinsic apoptotic signaling pathway in response to oxidative stress regulation of oxidative stress-induced intrinsic apoptotic signaling pathway regulation of intrinsic apoptotic signaling pathway negative regulation of apoptotic signaling pathway intrinsic apoptotic signaling pathway negative regulation of programmed cell death negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway negative regulation of intrinsic apoptotic signaling pathway negative regulation of apoptotic process exit from host cell biological process involved in interspecies interaction between organisms viral release from host cell biological process involved in interaction with host biological process involved in symbiotic interaction cell adhesion molecule production endothelial cell activation	cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol cellular anatomical structure membrane extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol anchoring junction cell junction focal adhesion cell-substrate junction membrane-enclosed lumen intracellular vesicle ficolin-1-rich granule intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen intracellular organelle organelle lumen cytoplasmic vesicle ficolin-1-rich granule lumen secretory granule secretory vesicle protein-containing complex vesicle lumen cytoplasmic vesicle lumen secretory granule lumen nucleus

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C [auth B]	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, C [auth B]	IPR005225	Small GTP-binding domain	Domain
A, C [auth B]	IPR020849	Small GTPase, Ras-type	Family
A, C [auth B]	IPR001806	Small GTPase	Family
B [auth D], D [auth C]	IPR029000	Cyclophilin-like domain superfamily	Homologous Superfamily
B [auth D], D [auth C]	IPR002130	Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain	Domain
B [auth D], D [auth C]	IPR024936	Cyclophilin-type peptidyl-prolyl cis-trans isomerase	Family
B [auth D], D [auth C]	IPR020892	Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C [auth B]	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 gastric carcinoma papillary adenoma liver cancer colorectal cancer uterine cancer myelodysplastic syndrome 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 familial pancreatic carcinoma juvenile idiopathic arthritis malignant pancreatic neoplasm follicular thyroid adenoma anemia tubular adenocarcinoma microcystic adenoma atypical teratoid rhabdoid tumor B-cell chronic lymphocytic leukemia liver neoplasm congenital anemia uterine disease benign neoplasm of pancreas lung benign neoplasm craniosynostosis hepatocellular carcinoma lung disease breast disease Lynch syndrome digestive system disease hydrops fetalis encephalocraniocutaneous lipomatosis oral cavity neoplasm cardiofaciocutaneous syndrome 1 epidermal nevus syndrome osteosarcoma ovarian disease cerebral astrocytoma pancreatic intraductal papillary-mucinous carcinoma medullary thyroid gland carcinoma pancreatic neoplasm linear nevus sebaceus syndrome colonic neoplasm myopathy gastric neoplasm Parkinson disease colorectal carcinoma glioblastoma benign colon neoplasm Pick disease hematologic disease bile duct cancer cribriform carcinoma dermatomyositis rheumatoid arthritis inflammatory linear verrucous epidermal nevus juvenile dermatomyositis thyroid gland follicular carcinoma ovarian neoplasm cervical carcinoma pancreatic intraductal papillary-mucinous neoplasm large cell medulloblastoma ulcerative colitis medulloblastoma astrocytoma (excluding glioblastoma) pancreatitis colorectal adenocarcinoma urinary bladder neoplasm gastrointestinal stromal tumor penile cancer uterine cervix carcinoma in situ benign neoplasm verrucous nevus bladder transitional cell carcinoma lung carcinoma cribriform carcinoma of breast psoriasis diffuse astrocytoma malignant ependymoma Emery-Dreifuss muscular dystrophy 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
B [auth D], D [auth C]	Pharos: P62937	squamous cell carcinoma non-small cell lung carcinoma Neoplasm Metastasis rheumatoid arthritis breast cancer gastric neoplasm mucocutaneous lymph node syndrome ovarian cancer peripheral nervous system disease schizophrenia dry eye syndrome hereditary diffuse gastric adenocarcinoma myopathy oral cavity neoplasm pancreatic intraductal papillary-mucinous carcinoma squamous cell carcinoma non-small cell lung carcinoma Neoplasm Metastasis rheumatoid arthritis breast cancer gastric neoplasm mucocutaneous lymph node syndrome ovarian cancer peripheral nervous system disease schizophrenia dry eye syndrome hereditary diffuse gastric adenocarcinoma myopathy oral cavity neoplasm pancreatic intraductal papillary-mucinous carcinoma peripheral neuropathy gastric cancer juvenile dermatomyositis osteosarcoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia

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.