Entry Database : PDB / ID : 6d5v Structure visualization Downloads & linksTitle Ras:SOS:Ras in complex with a small molecule activator Components(GTPase HRas HRAS ) x 2 Son of sevenless homolog 1 DetailsKeywords SIGNALING PROTEIN / Ras / SOS / inhibitor / ONCOPROTEIN / Protein-protein complex / MAPKFunction / homology Function and homology informationFunction Domain/homology Component
midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling ... midbrain morphogenesis / regulation of pro-B cell differentiation / vitellogenesis / pericardium morphogenesis / cardiac atrium morphogenesis / heart trabecula morphogenesis / regulation of T cell differentiation in thymus / GTPase complex / positive regulation of small GTPase mediated signal transduction / Interleukin-15 signaling / Activation of RAC1 / oncogene-induced cell senescence / positive regulation of ruffle assembly / blood vessel morphogenesis / negative regulation of GTPase activity / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of epidermal growth factor receptor signaling pathway / T-helper 1 type immune response / epidermal growth factor receptor binding / Regulation of KIT signaling / positive regulation of wound healing / positive regulation of miRNA metabolic process / leukocyte migration / NRAGE signals death through JNK / regulation of T cell proliferation / roof of mouth development / eyelid development in camera-type eye / defense response to protozoan / Fc-epsilon receptor signaling pathway / Signaling by RAS GAP mutants / Signaling by RAS GTPase mutants / Activation of RAS in B cells / neurotrophin TRK receptor signaling pathway / GRB2:SOS provides linkage to MAPK signaling for Integrins / B cell homeostasis / RAS signaling downstream of NF1 loss-of-function variants / SOS-mediated signalling / RET signaling / Activated NTRK3 signals through RAS / Activated NTRK2 signals through RAS / hair follicle development / SHC1 events in ERBB4 signaling / Signalling to RAS / positive regulation of protein targeting to membrane / fibroblast growth factor receptor signaling pathway / SHC-related events triggered by IGF1R / Activated NTRK2 signals through FRS2 and FRS3 / Role of LAT2/NTAL/LAB on calcium mobilization / Signal attenuation / Estrogen-stimulated signaling through PRKCZ / adipose tissue development / Interleukin receptor SHC signaling / SHC-mediated cascade:FGFR3 / MET activates RAS signaling / : / Schwann cell development / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants / Signaling by PDGFRA extracellular domain mutants / SHC-mediated cascade:FGFR2 / SHC-mediated cascade:FGFR4 / Signaling by FGFR4 in disease / SHC-mediated cascade:FGFR1 / Erythropoietin activates RAS / protein-membrane adaptor activity / FRS-mediated FGFR3 signaling / Signaling by FLT3 ITD and TKD mutants / FRS-mediated FGFR2 signaling / FRS-mediated FGFR4 signaling / Signaling by FGFR3 in disease / FRS-mediated FGFR1 signaling / p38MAPK events / Tie2 Signaling / Signaling by FGFR2 in disease / RAC1 GTPase cycle / GRB2 events in EGFR signaling / EPHB-mediated forward signaling / SHC1 events in EGFR signaling / EGFR Transactivation by Gastrin / Signaling by FLT3 fusion proteins / FLT3 Signaling / myelination / Signaling by FGFR1 in disease / Ras activation upon Ca2+ influx through NMDA receptor / GRB2 events in ERBB2 signaling / NCAM signaling for neurite out-growth / CD209 (DC-SIGN) signaling / SHC1 events in ERBB2 signaling / Downstream signal transduction / FCERI mediated Ca+2 mobilization / Constitutive Signaling by Overexpressed ERBB2 / Insulin receptor signalling cascade / intrinsic apoptotic signaling pathway / GTPase activator activity / guanyl-nucleotide exchange factor activity / small monomeric GTPase / insulin-like growth factor receptor signaling pathway / G protein activity / Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers Similarity search - Function Son of sevenless (SoS) protein; Chain S, domain 1 / Son of sevenless (SoS) protein Chain: S domain 1 / Son of Sevenless (SoS) protein; Chain S, domain 2 / Ras guanine-nucleotide exchange factors catalytic domain / Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras guanine-nucleotide exchange factors N-terminal domain profile. ... Son of sevenless (SoS) protein; Chain S, domain 1 / Son of sevenless (SoS) protein Chain: S domain 1 / Son of Sevenless (SoS) protein; Chain S, domain 2 / Ras guanine-nucleotide exchange factors catalytic domain / Ras guanine-nucleotide exchange factor, conserved site / Ras Guanine-nucleotide exchange factors domain signature. / RasGEF N-terminal motif / Guanine nucleotide exchange factor for Ras-like GTPases; N-terminal motif / Ras-like guanine nucleotide exchange factor, N-terminal / Ras guanine-nucleotide exchange factors N-terminal domain profile. / Ras-like guanine nucleotide exchange factor / Ras guanine-nucleotide exchange factor, catalytic domain superfamily / Ras guanine nucleotide exchange factor domain superfamily / RasGEF domain / Ras guanine-nucleotide exchange factors catalytic domain profile. / Guanine nucleotide exchange factor for Ras-like small GTPases / Ras guanine-nucleotide exchange factors catalytic domain / Dbl homology (DH) domain superfamily / RhoGEF domain / Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases / Dbl homology (DH) domain / Dbl homology (DH) domain profile. / Small GTPase, Ras-type / small GTPase Ras family profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Histone-fold / Small GTP-binding protein domain / PH-like domain superfamily / P-loop containing nucleotide triphosphate hydrolases / Up-down Bundle / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta Similarity search - Domain/homologyBiological species Homo sapiens (human)Method X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution : 2.04 Å DetailsAuthors Phan, J. / Hodges, T. / Fesik, S.W. Funding support United States, 1items Details Hide detailsOrganization Grant number Country Lustgarten United States
CitationJournal : J. Med. Chem. / Year : 2018Title : Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS.
Authors: Hodges, T.R. / Abbott, J.R. / Little, A.J. / Sarkar, D. / Salovich, J.M. / Howes, J.E. / Akan, D.T. / Sai, J. / Arnold, A.L. / Browning, C. / Burns, M.C. / Sobolik, T. / Sun, Q. / Beesetty, ... Authors : Hodges, T.R. / Abbott, J.R. / Little, A.J. / Sarkar, D. / Salovich, J.M. / Howes, J.E. / Akan, D.T. / Sai, J. / Arnold, A.L. / Browning, C. / Burns, M.C. / Sobolik, T. / Sun, Q. / Beesetty, Y. / Coker, J.A. / Scharn, D. / Stadtmueller, H. / Rossanese, O.W. / Phan, J. / Waterson, A.G. / McConnell, D.B. / Fesik, S.W. Show more 1 items Show less#1: Journal : Proc. Natl. Acad. Sci. U.S.A. / Year : 2014Title : Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange.
Authors :
Burns, M.C. / Sun, Q. / Daniels, R.N. / Camper, D. / Kennedy, J.P. / Phan, J. / Olejniczak, E.T. / Lee, T. / Waterson, A.G. / Rossanese, O.W. / Fesik, S.W. History Deposition Apr 19, 2018 Deposition site : RCSB / Processing site : RCSBRevision 1.0 Sep 19, 2018 Provider : repository / Type : Initial releaseRevision 1.1 Nov 7, 2018 Group : Data collection / Database references / Category : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.name Revision 1.2 Oct 4, 2023 Group : Data collection / Database references / Refinement descriptionCategory : chem_comp_atom / chem_comp_bond ... chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model Item : _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Show all Show less