1D8D

CO-CRYSTAL STRUCTURE OF RAT PROTEIN FARNESYLTRANSFERASE COMPLEXED WITH A K-RAS4B PEPTIDE SUBSTRATE AND FPP ANALOG AT 2.0A RESOLUTION

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)
A	d1d8da_	All alpha proteins	alpha-alpha superhelix	Protein prenylyltransferase	Protein prenylyltransferase	Protein farnesyltransferase alpha-subunit	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)
B	d1d8db_	All alpha proteins	alpha/alpha toroid	Terpenoid cyclases/Protein prenyltransferases	Protein prenyltransferases	Protein farnesyltransferase, beta-subunit	Norway rat (Rattus norvegicus ) [TaxId: 10116 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Protein prenylyltransferase	8026255	4001331	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Protein prenylyltransferase	8038634	3001312	SCOP2 (2022-06-29)
B	SCOP2 Family	Protein prenyltransferases	8026028	4001193	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	Terpenoid cyclases/Protein prenyltransferases	8038407	3001024	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	PPTA	e1d8dA1	A: alpha superhelices	X: Repetitive alpha hairpins	H: ARM repeat (From Topology)	T: ARM repeat	F: PPTA	ECOD (1.6)
B	SQHop_cyclase_C	e1d8dB1	A: alpha superhelices	X: Repetitive alpha hairpins	H: alpha/alpha toroid (From Topology)	T: alpha/alpha toroid	F: SQHop_cyclase_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.25.40.120	Mainly Alpha	Alpha Horseshoe	Serine Threonine Protein Phosphatase 5, Tetratricopeptide repeat	Protein prenylyltransferase	CATH (4.3.0)
B	1.50.10.20	Mainly Alpha	Alpha/alpha barrel	Glycosyltransferase		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01239	Protein prenyltransferase alpha subunit repeat (PPTA)	Protein prenyltransferase alpha subunit repeat	-	Repeat
B	PF00432	Prenyltransferase alpha-alpha toroid domain (Prenyltrans)	Prenyltransferase and squalene oxidase repeat	-	Repeat

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	farnesyltransferase (alpha subunit)	catalytic activity, acting on a protein protein geranylgeranyltransferase activity protein prenyltransferase activity prenyltransferase activity transferase activity catalytic activity transferase activity, transferring alkyl or aryl (other than methyl) groups cytoskeletal protein binding protein binding binding tubulin binding alpha-tubulin binding microtubule binding Rab geranylgeranyltransferase activity catalytic activity, acting on a protein protein geranylgeranyltransferase activity protein prenyltransferase activity prenyltransferase activity transferase activity catalytic activity transferase activity, transferring alkyl or aryl (other than methyl) groups cytoskeletal protein binding protein binding binding tubulin binding alpha-tubulin binding microtubule binding Rab geranylgeranyltransferase activity molecular adaptor activity protein farnesyltransferase activity protein tyrosine kinase binding kinase binding signaling receptor binding receptor tyrosine kinase binding enzyme binding protein kinase binding CAAX-protein geranylgeranyltransferase activity	regulation of biological process regulation of cellular process biological regulation positive regulation of biological process cellular process cell cycle regulation of cell cycle positive regulation of cell cycle positive regulation of cellular process cellular response to stimulus positive regulation of cell communication small GTPase-mediated signal transduction positive regulation of signal transduction response to stimulus regulation of biological process regulation of cellular process biological regulation positive regulation of biological process cellular process cell cycle regulation of cell cycle positive regulation of cell cycle positive regulation of cellular process cellular response to stimulus positive regulation of cell communication small GTPase-mediated signal transduction positive regulation of signal transduction response to stimulus signaling regulation of small GTPase mediated signal transduction 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 regulation of signaling Rac protein signal transduction 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 positive regulation of small GTPase mediated signal transduction positive regulation of signaling protein localization regulation of localization cellular localization regulation of protein localization cellular component organization localization neuromuscular junction development receptor clustering cellular macromolecule localization synapse organization cellular component organization or biogenesis regulation of skeletal muscle acetylcholine-gated channel clustering regulation of receptor clustering postsynaptic membrane organization regulation of protein localization to membrane membrane organization postsynapse organization positive regulation of receptor clustering skeletal muscle acetylcholine-gated channel clustering positive regulation of protein localization to membrane localization within membrane protein localization to membrane positive regulation of skeletal muscle acetylcholine-gated channel clustering cell junction organization regulation of cellular localization macromolecule localization positive regulation of protein localization negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death protein farnesylation macromolecule modification protein prenylation metabolic process primary metabolic process protein metabolic process macromolecule metabolic process prenylation protein modification process response to peptide response to chemical response to cytokine protein geranylgeranylation regulation of biosynthetic process regulation of macromolecule metabolic process macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of nitric-oxide synthase biosynthetic process biosynthetic process positive regulation of biosynthetic process regulation of macromolecule biosynthetic process positive regulation of macromolecule metabolic process positive regulation of nitric-oxide synthase biosynthetic process regulation of metabolic process nitric-oxide synthase biosynthetic process cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation negative regulation of metabolic process negative regulation of nitric-oxide synthase biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of macromolecule metabolic process regulation of protein modification process positive regulation of protein deacetylation positive regulation of protein metabolic process macromolecule deacylation positive regulation of tubulin deacetylation protein deacetylation regulation of primary metabolic process positive regulation of protein modification process regulation of protein deacetylation tubulin deacetylation regulation of protein metabolic process protein deacylation regulation of tubulin deacetylation cell surface receptor signaling pathway enzyme-linked receptor protein signaling pathway response to organic cyclic compound	protein-containing complex protein farnesyltransferase complex cellular anatomical structure intracellular anatomical structure catalytic complex polyprenyl diphosphate synthase complex cytoplasm transferase complex intracellular organelle cytoskeleton organelle membraneless organelle microtubule associated complex intracellular membraneless organelle protein-containing complex protein farnesyltransferase complex cellular anatomical structure intracellular anatomical structure catalytic complex polyprenyl diphosphate synthase complex cytoplasm transferase complex intracellular organelle cytoskeleton organelle membraneless organelle microtubule associated complex intracellular membraneless organelle microtubule cytoskeleton CAAX-protein geranylgeranyltransferase complex intracellular protein-containing complex
B	farnesyltransferase (beta subunit)	farnesyltranstransferase activity prenyltransferase activity transferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups catalytic activity protein farnesyltransferase activity catalytic activity, acting on a protein protein prenyltransferase activity cation binding transition metal ion binding zinc ion binding ion binding binding metal ion binding farnesyltranstransferase activity prenyltransferase activity transferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups catalytic activity protein farnesyltransferase activity catalytic activity, acting on a protein protein prenyltransferase activity cation binding transition metal ion binding zinc ion binding ion binding binding metal ion binding small molecule binding	regulation of biological process regulation of cellular process biological regulation positive regulation of biological process cellular process cell cycle regulation of cell cycle positive regulation of cell cycle positive regulation of cellular process regulation of biosynthetic process regulation of macromolecule metabolic process macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of biological process regulation of cellular process biological regulation positive regulation of biological process cellular process cell cycle regulation of cell cycle positive regulation of cell cycle positive regulation of cellular process regulation of biosynthetic process regulation of macromolecule metabolic process macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of nitric-oxide synthase biosynthetic process biosynthetic process positive regulation of biosynthetic process regulation of macromolecule biosynthetic process metabolic process positive regulation of macromolecule metabolic process macromolecule metabolic process positive regulation of nitric-oxide synthase biosynthetic process regulation of metabolic process nitric-oxide synthase biosynthetic process cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation fibroblast proliferation negative regulation of cell population proliferation negative regulation of cellular process negative regulation of biological process wound healing response to stimulus response to stress response to wounding regulation of fibroblast proliferation positive regulation of fibroblast proliferation primary metabolic process lipid metabolic process response to chemical response to organic cyclic compound protein farnesylation macromolecule modification protein prenylation protein metabolic process prenylation protein modification process response to peptide response to cytokine	protein-containing complex protein farnesyltransferase complex cellular anatomical structure intracellular anatomical structure catalytic complex polyprenyl diphosphate synthase complex cytoplasm transferase complex intracellular organelle cytoskeleton organelle membraneless organelle microtubule associated complex intracellular membraneless organelle protein-containing complex protein farnesyltransferase complex cellular anatomical structure intracellular anatomical structure catalytic complex polyprenyl diphosphate synthase complex cytoplasm transferase complex intracellular organelle cytoskeleton organelle membraneless organelle microtubule associated complex intracellular membraneless organelle microtubule cytoskeleton
C [auth P]	K-RAS4B PEPTIDE SUBSTRATE	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	IPR002088	Protein prenyltransferase, alpha subunit	Repeat
B	IPR026872	Protein farnesyltransferase subunit beta	Family
B	IPR045089	Prenyltransferase subunit beta	Family
B	IPR008930	Terpenoid cyclases/protein prenyltransferase alpha-alpha toroid	Homologous Superfamily
B	IPR001330	Prenyltransferase alpha-alpha toroid domain	Domain
C [auth P]	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
C [auth P]	IPR005225	Small GTP-binding domain	Domain
C [auth P]	IPR020849	Small GTPase, Ras-type	Family
C [auth P]	IPR001806	Small GTPase	Family

Pharos: Disease Associations Pharos Homepage Annotation

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

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

Chains	Enzyme Name	Description	Catalytic Residues
A, B	protein farnesyltransferase M-CSA #484	Farnesyltransferase (FTase) is an important zinc metalloenzyme that is responsible for the specific transfer of a 15 carbon isoprenoid farnesyl from farnesyldiphosphate (FPP) to peptide substrates containing a characteristic carboxy-terminal CAAX motif. Within the motif, C is the cysteine that is farnesylated, 'A' represents an aliphatic residue and X is the terminal residue, normally methionine, serine, alanine or glutamine. Much research has been carried out on FTase since the group of substrate peptides it farnesylates includes the Ras family of proteins, the oncogenic forms of which are implicated in cell transformation.	Defined by 10 residues: LYS:A-164HIS:B-248ARG:B-291LYS:B-294ASP:B-297CYS:B-299TYR:B-300ASP:B-352ASP:B-359HIS:B-362 \| Explore in 3D: M-CSA Motif Definition Search M-CSA Motif EC: 2.5.1.21 (PDB Primary Data) Search M-CSA Motif + EC 2.5.1.21 EC: 2.5.1.58 (UniProt) Search M-CSA Motif + EC 2.5.1.58 EC: 2.5.1.59 (UniProt) Search M-CSA Motif + EC 2.5.1.59

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.