ID SOS1_HUMAN Reviewed; 1333 AA. AC Q07889; A8K2G3; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 13-JUN-2012, entry version 139. DE RecName: Full=Son of sevenless homolog 1; DE Short=SOS-1; GN Name=SOS1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX MEDLINE=93262494; PubMed=8493579; DOI=10.1126/science.8493579; RA Chardin P., Camonis J.H., Gale N.W., van Aelst L., Wigler M.H., RA Bar-Sagi D.; RT "Human Sos1: a guanine nucleotide exchange factor for Ras that binds RT to GRB2."; RL Science 260:1338-1343(1993). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP IDENTIFICATION IN A COMPLEX WITH MUC1 AND GRB2, AND INTERACTION WITH RP MUC1. RX PubMed=7664271; RA Pandey P., Kharbanda S., Kufe D.; RT "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the RT Sos/Ras exchange protein."; RL Cancer Res. 55:4000-4003(1995). RN [5] RP INTERACTION WITH NCK1 AND NCK2. RX PubMed=10026169; DOI=10.1074/jbc.274.9.5542; RA Braverman L.E., Quilliam L.A.; RT "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain- RT containing adapter protein having similar binding and biological RT properties to Nck."; RL J. Biol. Chem. 274:5542-5549(1999). RN [6] RP INTERACTION WITH LAT2. RX MEDLINE=22373766; PubMed=12486104; DOI=10.1084/jem.20021405; RA Brdicka T., Imrich M., Angelisova P., Brdickova N., Horvath O., RA Spicka J., Hilgert I., Luskova P., Draber P., Novak P., Engels N., RA Wienands J., Simeoni L., Oesterreicher J., Aguado E., Malissen M., RA Schraven B., Horejsi V.; RT "Non-T cell activation linker (NTAL): a transmembrane adaptor protein RT involved in immunoreceptor signaling."; RL J. Exp. Med. 196:1617-1626(2002). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1082 AND SER-1210, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1134 AND SER-1137, AND RP MASS SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [10] RP STRUCTURE BY NMR OF 422-551. RX MEDLINE=98043737; PubMed=9374522; DOI=10.1074/jbc.272.48.30340; RA Zheng J., Chen R.H., Corblan-Garcia S., Cahill S.M., Bar-Sagi D., RA Cowburn D.; RT "The solution structure of the pleckstrin homology domain of human RT SOS1. A possible structural role for the sequential association of RT diffuse B cell lymphoma and pleckstrin homology domains."; RL J. Biol. Chem. 272:30340-30344(1997). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 198-551. RX MEDLINE=99005193; PubMed=9790532; DOI=10.1016/S0092-8674(00)81756-0; RA Soisson S.M., Nimnual A.S., Uy M., Bar-Sagi D., Kuriyan J.; RT "Crystal structure of the Dbl and pleckstrin homology domains from the RT human Son of sevenless protein."; RL Cell 95:259-268(1998). RN [12] RP INVOLVEMENT IN GGF1, AND TISSUE SPECIFICITY. RX MEDLINE=21881231; PubMed=11868160; DOI=10.1086/339689; RA Hart T.C., Zhang Y., Gorry M.C., Hart P.S., Cooper M., Marazita M.L., RA Marks J.M., Cortelli J.R., Pallos D.; RT "A mutation in the SOS1 gene causes hereditary gingival fibromatosis RT type 1."; RL Am. J. Hum. Genet. 70:943-954(2002). RN [13] RP VARIANTS NS4 LYS-266; ARG-269; TYR-309; CYS-337; ARG-434; ARG-548; RP GLY-552 AND LYS-846, AND VARIANT LEU-655. RX PubMed=17143285; DOI=10.1038/ng1926; RA Roberts A.E., Araki T., Swanson K.D., Montgomery K.T., Schiripo T.A., RA Joshi V.A., Li L., Yassin Y., Tamburino A.M., Neel B.G., RA Kucherlapati R.S.; RT "Germline gain-of-function mutations in SOS1 cause Noonan syndrome."; RL Nat. Genet. 39:70-74(2007). RN [14] RP VARIANTS NS4 LYS-108; ARG-269; ARG-432; LYS-433; TYR-441; ARG-548; RP PRO-550; GLY-552; LYS-552; SER-552; HIS-702; LEU-729; PHE-733 AND RP LYS-846, VARIANTS LEU-655; ARG-977 AND ARG-1320, AND CHARACTERIZATION RP OF VARIANTS NS4 GLY-552 AND LEU-729. RX PubMed=17143282; DOI=10.1038/ng1939; RA Tartaglia M., Pennacchio L.A., Zhao C., Yadav K.K., Fodale V., RA Sarkozy A., Pandit B., Oishi K., Martinelli S., Schackwitz W., RA Ustaszewska A., Martin J., Bristow J., Carta C., Lepri F., Neri C., RA Vasta I., Gibson K., Curry C.J., Lopez Siguero J.P., Digilio M.C., RA Zampino G., Dallapiccola B., Bar-Sagi D., Gelb B.D.; RT "Gain-of-function SOS1 mutations cause a distinctive form of Noonan RT syndrome."; RL Nat. Genet. 39:75-79(2007). RN [15] RP VARIANT NS4 GLU-170. RX PubMed=19020799; DOI=10.1007/s10038-008-0343-6; RA Ko J.M., Kim J.M., Kim G.H., Yoo H.W.; RT "PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype RT correlation in Korean patients with Noonan syndrome."; RL J. Hum. Genet. 53:999-1006(2008). RN [16] RP VARIANT NS4 ARG-432. RX PubMed=19438935; DOI=10.1111/j.1399-0004.2009.01149.x; RA Hanna N., Parfait B., Talaat I.M., Vidaud M., Elsedfy H.H.; RT "SOS1: a new player in the Noonan-like/multiple giant cell lesion RT syndrome."; RL Clin. Genet. 75:568-571(2009). RN [17] RP VARIANTS NS4 THR-269; ARG-477 AND HIS-702, VARIANT GLN-497, AND RP CHARACTERIZATION OF VARIANT GLN-497. RX PubMed=20683980; DOI=10.1002/ajmg.a.33564; RA Longoni M., Moncini S., Cisternino M., Morella I.M., Ferraiuolo S., RA Russo S., Mannarino S., Brazzelli V., Coi P., Zippel R., Venturin M., RA Riva P.; RT "Noonan syndrome associated with both a new Jnk-activating familial RT SOS1 and a de novo RAF1 mutations."; RL Am. J. Med. Genet. A 152:2176-2184(2010). RN [18] RP VARIANT NS4 ILE-623. RX PubMed=20673819; DOI=10.1016/j.ejmg.2010.07.011; RA Fabretto A., Kutsche K., Harmsen M.B., Demarini S., Gasparini P., RA Fertz M.C., Zenker M.; RT "Two cases of Noonan syndrome with severe respiratory and RT gastroenteral involvement and the SOS1 mutation F623I."; RL Eur. J. Med. Genet. 53:322-324(2010). RN [19] RP VARIANTS NS4 ARG-102; GLU-170; LYS-266; THR-269; LYS-433 AND GLY-552, RP AND VARIANTS ALA-378; VAL-569 AND LEU-655. RX PubMed=19953625; DOI=10.1002/gcc.20735; RA Denayer E., Devriendt K., de Ravel T., Van Buggenhout G., Smeets E., RA Francois I., Sznajer Y., Craen M., Leventopoulos G., Mutesa L., RA Vandecasseye W., Massa G., Kayserili H., Sciot R., Fryns J.P., RA Legius E.; RT "Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 RT mutations."; RL Genes Chromosomes Cancer 49:242-252(2010). RN [20] RP VARIANTS NS4 LYS-108; ARG-112; GLU-170; THR-252; LYS-266; THR-269; RP ARG-269; VAL-422; LYS-424; 427-LYS--ASP-430 DELINS ASN; ARG-432; RP 432-TRP-GLU-433 DEL; LYS-433; ARG-434; LYS-434; THR-437; TYR-441; RP ARG-477; ARG-478; ARG-482; ARG-490; GLN-497; ARG-548; LYS-549; RP GLY-552; LYS-552; MET-552; THR-552; SER-552; 554-LEU--MET-558 DELINS RP LYS; PHE-733; LYS-846 AND ARG-894, AND VARIANTS ALA-37; LEU-478; RP VAL-569; LEU-655; THR-708; THR-784; SER-1011; LYS-1131; ILE-1140; RP ALA-1257 AND ARG-1320. RX PubMed=21387466; DOI=10.1002/humu.21492; RA Lepri F., De Luca A., Stella L., Rossi C., Baldassarre G., RA Pantaleoni F., Cordeddu V., Williams B.J., Dentici M.L., Caputo V., RA Venanzi S., Bonaguro M., Kavamura I., Faienza M.F., Pilotta A., RA Stanzial F., Faravelli F., Gabrielli O., Marino B., Neri G., RA Silengo M.C., Ferrero G.B., Torrrente I., Selicorni A., Mazzanti L., RA Digilio M.C., Zampino G., Dallapiccola B., Gelb B.D., Tartaglia M.; RT "SOS1 mutations in Noonan syndrome: molecular spectrum, structural RT insights on pathogenic effects, and genotype-phenotype correlations."; RL Hum. Mutat. 32:760-772(2011). CC -!- FUNCTION: Promotes the exchange of Ras-bound GDP by GTP. CC -!- SUBUNIT: Interacts with GRB2. Forms a complex with phosphorylated CC MUC1 and GRB2 (via its SH3 domains). Interacts with phosphorylated CC LAT2. Interacts with NCK1 and NCK2. CC -!- INTERACTION: CC P46108:CRK; NbExp=2; IntAct=EBI-297487, EBI-886; CC P62993:GRB2; NbExp=8; IntAct=EBI-297487, EBI-401755; CC P01112:HRAS; NbExp=6; IntAct=EBI-297487, EBI-350145; CC P16333:NCK1; NbExp=5; IntAct=EBI-297487, EBI-389883; CC Q9UKS6:PACSIN3; NbExp=2; IntAct=EBI-297487, EBI-77926; CC P27986:PIK3R1; NbExp=2; IntAct=EBI-297487, EBI-79464; CC P19174:PLCG1; NbExp=2; IntAct=EBI-297487, EBI-79387; CC Q9Y5X1:SNX9; NbExp=2; IntAct=EBI-297487, EBI-77848; CC -!- TISSUE SPECIFICITY: Expressed in gingival tissues. CC -!- DISEASE: Defects in SOS1 are the cause of gingival fibromatosis 1 CC (GGF1) [MIM:135300]; also known as GINGF1. Gingival fibromatosis CC is a rare overgrowth condition characterized by a benign, slowly CC progressive, nonhemorrhagic, fibrous enlargement of maxillary and CC mandibular keratinized gingiva. GGF1 is usually transmitted as an CC autosomal dominant trait, although sporadic cases are common. CC -!- DISEASE: Defects in SOS1 are the cause of Noonan syndrome type 4 CC (NS4) [MIM:610733]. NS4 is an autosomal dominant disorder CC characterized by dysmorphic facial features, short stature, CC hypertelorism, cardiac anomalies, deafness, motor delay, and a CC bleeding diathesis. It is a genetically heterogeneous and CC relatively common syndrome, with an estimated incidence of 1 in CC 1000-2500 live births. Rarely, NS4 is associated with juvenile CC myelomonocytic leukemia (JMML). SOS1 mutations engender a high CC prevalence of pulmonary valve disease; atrial septal defects are CC less common. CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain. CC -!- SIMILARITY: Contains 1 N-terminal Ras-GEF domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-GEF domain. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/SOS1"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Son of sevenless entry; CC URL="http://en.wikipedia.org/wiki/Son_of_Sevenless"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L13857; AAA35913.1; -; mRNA. DR EMBL; AK290228; BAF82917.1; -; mRNA. DR EMBL; CH471053; EAX00351.1; -; Genomic_DNA. DR IPI; IPI00020131; -. DR PIR; A37488; A37488. DR RefSeq; NP_005624.2; NM_005633.3. DR UniGene; Hs.709893; -. DR UniGene; Hs.732497; -. DR PDB; 1AWE; NMR; -; A=422-551. DR PDB; 1BKD; X-ray; 2.80 A; S=568-1044. DR PDB; 1DBH; X-ray; 2.30 A; A=198-551. DR PDB; 1NVU; X-ray; 2.20 A; S=566-1046. DR PDB; 1NVV; X-ray; 2.18 A; S=566-1046. DR PDB; 1NVW; X-ray; 2.70 A; S=566-1046. DR PDB; 1NVX; X-ray; 3.20 A; S=566-1046. DR PDB; 1Q9C; X-ray; 3.21 A; A/B/C/D/E/F/G/H/I=1-191. DR PDB; 1XD2; X-ray; 2.70 A; C=566-1049. DR PDB; 1XD4; X-ray; 3.64 A; A/B=198-1049. DR PDB; 1XDV; X-ray; 4.10 A; A/B=198-1044. DR PDB; 2II0; X-ray; 2.02 A; A=564-1049. DR PDB; 3KSY; X-ray; 3.18 A; A=1-1049. DR PDBsum; 1AWE; -. DR PDBsum; 1BKD; -. DR PDBsum; 1DBH; -. DR PDBsum; 1NVU; -. DR PDBsum; 1NVV; -. DR PDBsum; 1NVW; -. DR PDBsum; 1NVX; -. DR PDBsum; 1Q9C; -. DR PDBsum; 1XD2; -. DR PDBsum; 1XD4; -. DR PDBsum; 1XDV; -. DR PDBsum; 2II0; -. DR PDBsum; 3KSY; -. DR ProteinModelPortal; Q07889; -. DR SMR; Q07889; 6-183, 198-1046. DR DIP; DIP-31802N; -. DR IntAct; Q07889; 22. DR MINT; MINT-106583; -. DR STRING; Q07889; -. DR PhosphoSite; Q07889; -. DR DMDM; 6094322; -. DR PRIDE; Q07889; -. DR DNASU; 6654; -. DR Ensembl; ENST00000402219; ENSP00000384675; ENSG00000115904. DR Ensembl; ENST00000426016; ENSP00000387784; ENSG00000115904. DR GeneID; 6654; -. DR KEGG; hsa:6654; -. DR UCSC; uc002rrk.4; human. DR CTD; 6654; -. DR GeneCards; GC02M039208; -. DR HGNC; HGNC:11187; SOS1. DR HPA; CAB005396; -. DR HPA; HPA012613; -. DR MIM; 135300; phenotype. DR MIM; 182530; gene. DR MIM; 610733; phenotype. DR neXtProt; NX_Q07889; -. DR Orphanet; 2024; Autosomal dominant gingival fibromatosis. DR Orphanet; 648; Noonan syndrome. DR PharmGKB; PA36024; -. DR eggNOG; NOG265981; -. DR GeneTree; ENSGT00650000092922; -. DR HOGENOM; HOG000013040; -. DR HOVERGEN; HBG017831; -. DR InParanoid; Q07889; -. DR KO; K03099; -. DR OMA; REHTHPS; -. DR OrthoDB; EOG4J9MZ2; -. DR PhylomeDB; Q07889; -. DR Pathway_Interaction_DB; bcr_5pathway; BCR signaling pathway. DR Pathway_Interaction_DB; pi3kcipathway; Class I PI3K signaling events. DR Pathway_Interaction_DB; endothelinpathway; Endothelins. DR Pathway_Interaction_DB; epopathway; EPO signaling pathway. DR Pathway_Interaction_DB; fcer1pathway; Fc-epsilon receptor I signaling in mast cells. DR Pathway_Interaction_DB; fgf_pathway; FGF signaling pathway. DR Pathway_Interaction_DB; igf1_pathway; IGF1 pathway. DR Pathway_Interaction_DB; il2_pi3kpathway; IL2 signaling events mediated by PI3K. DR Pathway_Interaction_DB; il2_stat5pathway; IL2 signaling events mediated by STAT5. DR Pathway_Interaction_DB; il2_1pathway; IL2-mediated signaling events. DR Pathway_Interaction_DB; il6_7pathway; IL6-mediated signaling events. DR Pathway_Interaction_DB; insulin_pathway; Insulin Pathway. DR Pathway_Interaction_DB; trkrpathway; Neurotrophic factor-mediated Trk receptor signaling. DR Pathway_Interaction_DB; pdgfrapathway; PDGFR-alpha signaling pathway. DR Pathway_Interaction_DB; pdgfrbpathway; PDGFR-beta signaling pathway. DR Pathway_Interaction_DB; er_nongenomic_pathway; Plasma membrane estrogen receptor signaling. DR Pathway_Interaction_DB; met_pathway; Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met). DR Pathway_Interaction_DB; kitpathway; Signaling events mediated by Stem cell factor receptor (c-Kit). DR Pathway_Interaction_DB; vegfr1_2_pathway; Signaling events mediated by VEGFR1 and VEGFR2. DR Pathway_Interaction_DB; ret_pathway; Signaling events regulated by Ret tyrosine kinase. DR Pathway_Interaction_DB; tcrpathway; TCR signaling in naive CD4+ T cells. DR Pathway_Interaction_DB; cd8tcrpathway; TCR signaling in naive CD8+ T cells. DR Pathway_Interaction_DB; tgfbrpathway; TGF-beta receptor signaling. DR Pathway_Interaction_DB; pi3kplctrkpathway; Trk receptor signaling mediated by PI3K and PLC-gamma. DR Pathway_Interaction_DB; lymphangiogenesis_pathway; VEGFR3 signaling in lymphatic endothelium. DR Reactome; REACT_111045; Developmental Biology. DR Reactome; REACT_111102; Signal Transduction. DR Reactome; REACT_116125; Disease. DR Reactome; REACT_604; Hemostasis. DR Reactome; REACT_6900; Immune System. DR EvolutionaryTrace; Q07889; -. DR NextBio; 25939; -. DR ArrayExpress; Q07889; -. DR Bgee; Q07889; -. DR CleanEx; HS_SOS1; -. DR Genevestigator; Q07889; -. DR GermOnline; ENSG00000115904; Homo sapiens. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0005100; F:Rho GTPase activator activity; TAS:ProtInc. DR GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; TAS:ProtInc. DR GO; GO:0006915; P:apoptotic process; TAS:Reactome. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0008624; P:induction of apoptosis by extracellular signals; TAS:Reactome. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome. DR GO; GO:0050900; P:leukocyte migration; TAS:Reactome. DR GO; GO:0048011; P:nerve growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome. DR Gene3D; G3DSA:1.10.20.10; Histone-fold; 1. DR Gene3D; G3DSA:2.30.29.30; PH_type; 1. DR Gene3D; G3DSA:1.10.840.10; RasGRF_CDC25; 1. DR Gene3D; G3DSA:1.20.900.10; RhoGEF; 1. DR InterPro; IPR000219; DH-domain. DR InterPro; IPR009072; Histone-fold. DR InterPro; IPR007125; Histone_core_D. DR InterPro; IPR011993; PH_like_dom. DR InterPro; IPR001849; Pleckstrin_homology. DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N. DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS. DR InterPro; IPR008937; Ras_GEF. DR InterPro; IPR023578; Ras_GEF_dom. DR InterPro; IPR001895; RasGRF_CDC25. DR InterPro; IPR015759; Sos. DR PANTHER; PTHR23113; Ras_GEF; 1. DR PANTHER; PTHR23113:SF47; Sos; 1. DR Pfam; PF00125; Histone; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00617; RasGEF; 1. DR Pfam; PF00618; RasGEF_N; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00147; RasGEF; 1. DR SMART; SM00229; RasGEFN; 1. DR SMART; SM00325; RhoGEF; 1. DR SUPFAM; SSF48065; DH-domain; 1. DR SUPFAM; SSF47113; Histone-fold; 1. DR SUPFAM; SSF48366; Ras_GEF; 1. DR PROSITE; PS00741; DH_1; FALSE_NEG. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00720; RASGEF; 1. DR PROSITE; PS50009; RASGEF_CAT; 1. DR PROSITE; PS50212; RASGEF_NTER; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Disease mutation; KW Guanine-nucleotide releasing factor; Phosphoprotein; Polymorphism; KW Reference proteome. FT CHAIN 1 1333 Son of sevenless homolog 1. FT /FTId=PRO_0000068894. FT DOMAIN 200 390 DH. FT DOMAIN 444 548 PH. FT DOMAIN 597 741 N-terminal Ras-GEF. FT DOMAIN 780 1019 Ras-GEF. FT COMPBIAS 1258 1261 Poly-Pro. FT MOD_RES 1043 1043 Phosphoserine. FT MOD_RES 1078 1078 Phosphoserine (By similarity). FT MOD_RES 1082 1082 Phosphoserine. FT MOD_RES 1134 1134 Phosphoserine. FT MOD_RES 1137 1137 Phosphoserine. FT MOD_RES 1210 1210 Phosphoserine. FT VARIANT 37 37 T -> A (in a patient with Noonan FT syndrome; dbSNP:rs150565592). FT /FTId=VAR_066031. FT VARIANT 102 102 P -> R (in NS4). FT /FTId=VAR_066032. FT VARIANT 108 108 E -> K (in NS4). FT /FTId=VAR_030423. FT VARIANT 112 112 P -> R (in NS4). FT /FTId=VAR_066033. FT VARIANT 170 170 K -> E (in NS4). FT /FTId=VAR_066034. FT VARIANT 252 252 I -> T (in NS4; dbSNP:rs142094234). FT /FTId=VAR_066035. FT VARIANT 266 266 T -> K (in NS4; dbSNP:rs137852812). FT /FTId=VAR_030424. FT VARIANT 269 269 M -> R (in NS4; dbSNP:rs137852813). FT /FTId=VAR_030425. FT VARIANT 269 269 M -> T (in NS4). FT /FTId=VAR_064504. FT VARIANT 309 309 D -> Y (in NS4). FT /FTId=VAR_030426. FT VARIANT 337 337 Y -> C (in NS4). FT /FTId=VAR_030427. FT VARIANT 378 378 T -> A (in a patient with Noonan FT syndrome). FT /FTId=VAR_066036. FT VARIANT 422 422 M -> V (in NS4). FT /FTId=VAR_066037. FT VARIANT 424 424 E -> K (in NS4). FT /FTId=VAR_066038. FT VARIANT 427 430 KNID -> N (in NS4). FT /FTId=VAR_066039. FT VARIANT 432 433 Missing (in NS4). FT /FTId=VAR_066040. FT VARIANT 432 432 W -> R (in NS4). FT /FTId=VAR_030428. FT VARIANT 433 433 E -> K (in NS4). FT /FTId=VAR_030429. FT VARIANT 434 434 G -> K (in NS4; requires 2 nucleotide FT substitutions). FT /FTId=VAR_066041. FT VARIANT 434 434 G -> R (in NS4). FT /FTId=VAR_030430. FT VARIANT 437 437 I -> T (in NS4). FT /FTId=VAR_066042. FT VARIANT 441 441 C -> Y (in NS4). FT /FTId=VAR_030431. FT VARIANT 477 477 Q -> R (in NS4). FT /FTId=VAR_064505. FT VARIANT 478 478 P -> L (found in patients with Noonan FT syndrome). FT /FTId=VAR_066043. FT VARIANT 478 478 P -> R (in NS4). FT /FTId=VAR_066044. FT VARIANT 482 482 G -> R (in NS4). FT /FTId=VAR_066045. FT VARIANT 490 490 L -> R (in NS4). FT /FTId=VAR_066046. FT VARIANT 497 497 R -> Q (in NS4; one patient with Noonan FT syndrome also carries a likely pathogenic FT mutation Ser-261 in RAF1; the mutant FT protein cannot induce ERK1 FT phosphorylation). FT /FTId=VAR_064506. FT VARIANT 548 548 S -> R (in NS4). FT /FTId=VAR_030432. FT VARIANT 549 549 T -> K (in NS4). FT /FTId=VAR_066047. FT VARIANT 550 550 L -> P (in NS4). FT /FTId=VAR_030433. FT VARIANT 552 552 R -> G (in NS4; increases the basal level FT of active RAS; prolonges RAS activation FT after EGF stimulation and enhances ERK FT activation; dbSNP:rs137852814). FT /FTId=VAR_030434. FT VARIANT 552 552 R -> K (in NS4). FT /FTId=VAR_030435. FT VARIANT 552 552 R -> M (in NS4). FT /FTId=VAR_066048. FT VARIANT 552 552 R -> S (in NS4). FT /FTId=VAR_030436. FT VARIANT 552 552 R -> T (in NS4). FT /FTId=VAR_066049. FT VARIANT 554 558 LDVTM -> K (in NS4). FT /FTId=VAR_066050. FT VARIANT 569 569 L -> V. FT /FTId=VAR_066051. FT VARIANT 623 623 F -> I (in NS4). FT /FTId=VAR_066052. FT VARIANT 655 655 P -> L (in dbSNP:rs56219475). FT /FTId=VAR_030437. FT VARIANT 702 702 Y -> H (in NS4). FT /FTId=VAR_030438. FT VARIANT 708 708 A -> T (in dbSNP:rs140811086). FT /FTId=VAR_066053. FT VARIANT 729 729 W -> L (in NS4; promotes constitutive RAS FT activation and enhances ERK activation). FT /FTId=VAR_030439. FT VARIANT 733 733 I -> F (in NS4). FT /FTId=VAR_030440. FT VARIANT 784 784 I -> T (in a patient with Noonan FT syndrome). FT /FTId=VAR_066054. FT VARIANT 846 846 E -> K (in NS4). FT /FTId=VAR_030441. FT VARIANT 894 894 P -> R (in NS4). FT /FTId=VAR_066055. FT VARIANT 977 977 Q -> R. FT /FTId=VAR_030442. FT VARIANT 1011 1011 N -> S (in dbSNP:rs8192671). FT /FTId=VAR_066056. FT VARIANT 1131 1131 R -> K (in a patient with Noonan FT syndrome; dbSNP:rs141676532). FT /FTId=VAR_066057. FT VARIANT 1140 1140 L -> I (in a patient with Noonan FT syndrome). FT /FTId=VAR_066058. FT VARIANT 1257 1257 T -> A (in a patient with Noonan FT syndrome). FT /FTId=VAR_066059. FT VARIANT 1320 1320 H -> R. FT /FTId=VAR_030443. FT TURN 13 15 FT HELIX 16 19 FT HELIX 24 34 FT STRAND 36 39 FT HELIX 42 60 FT HELIX 69 76 FT HELIX 82 94 FT HELIX 107 118 FT HELIX 124 152 FT HELIX 159 167 FT HELIX 170 175 FT HELIX 201 224 FT TURN 225 227 FT HELIX 228 232 FT TURN 234 236 FT HELIX 239 246 FT HELIX 249 268 FT STRAND 274 276 FT HELIX 280 288 FT TURN 289 292 FT HELIX 293 302 FT HELIX 307 316 FT HELIX 320 327 FT HELIX 331 337 FT HELIX 339 342 FT HELIX 345 363 FT HELIX 367 379 FT HELIX 381 392 FT HELIX 394 402 FT HELIX 420 426 FT STRAND 429 431 FT HELIX 437 439 FT STRAND 444 452 FT STRAND 459 473 FT STRAND 487 496 FT STRAND 500 503 FT STRAND 507 509 FT STRAND 512 516 FT STRAND 524 527 FT HELIX 531 545 FT TURN 546 549 FT HELIX 551 561 FT TURN 572 574 FT HELIX 576 578 FT TURN 583 585 FT STRAND 586 588 FT STRAND 601 604 FT HELIX 606 613 FT HELIX 621 630 FT HELIX 631 633 FT HELIX 637 648 FT HELIX 657 664 FT HELIX 672 680 FT HELIX 682 699 FT HELIX 702 706 FT HELIX 708 720 FT TURN 724 726 FT HELIX 727 742 FT TURN 771 773 FT TURN 776 778 FT HELIX 781 797 FT HELIX 801 803 FT HELIX 805 810 FT HELIX 814 817 FT HELIX 819 840 FT HELIX 845 864 FT HELIX 868 878 FT HELIX 881 884 FT HELIX 887 891 FT HELIX 895 921 FT HELIX 931 942 FT STRAND 946 950 FT STRAND 953 957 FT HELIX 958 975 FT HELIX 985 992 FT TURN 996 999 FT HELIX 1002 1016 SQ SEQUENCE 1333 AA; 152464 MW; C6B99CCA11A8DE45 CRC64; MQAQQLPYEF FSEENAPKWR GLLVPALKKV QGQVHPTLES NDDALQYVEE LILQLLNMLC QAQPRSASDV EERVQKSFPH PIDKWAIADA QSAIEKRKRR NPLSLPVEKI HPLLKEVLGY KIDHQVSVYI VAVLEYISAD ILKLVGNYVR NIRHYEITKQ DIKVAMCADK VLMDMFHQDV EDINILSLTD EEPSTSGEQT YYDLVKAFMA EIRQYIRELN LIIKVFREPF VSNSKLFSAN DVENIFSRIV DIHELSVKLL GHIEDTVEMT DEGSPHPLVG SCFEDLAEEL AFDPYESYAR DILRPGFHDR FLSQLSKPGA ALYLQSIGEG FKEAVQYVLP RLLLAPVYHC LHYFELLKQL EEKSEDQEDK ECLKQAITAL LNVQSGMEKI CSKSLAKRRL SESACRFYSQ QMKGKQLAIK KMNEIQKNID GWEGKDIGQC CNEFIMEGTL TRVGAKHERH IFLFDGLMIC CKSNHGQPRL PGASNAEYRL KEKFFMRKVQ INDKDDTNEY KHAFEIILKD ENSVIFSAKS AEEKNNWMAA LISLQYRSTL ERMLDVTMLQ EEKEEQMRLP SADVYRFAEP DSEENIIFEE NMQPKAGIPI IKAGTVIKLI ERLTYHMYAD PNFVRTFLTT YRSFCKPQEL LSLIIERFEI PEPEPTEADR IAIENGDQPL SAELKRFRKE YIQPVQLRVL NVCRHWVEHH FYDFERDAYL LQRMEEFIGT VRGKAMKKWV ESITKIIQRK KIARDNGPGH NITFQSSPPT VEWHISRPGH IETFDLLTLH PIEIARQLTL LESDLYRAVQ PSELVGSVWT KEDKEINSPN LLKMIRHTTN LTLWFEKCIV ETENLEERVA VVSRIIEILQ VFQELNNFNG VLEVVSAMNS SPVYRLDHTF EQIPSRQKKI LEEAHELSED HYKKYLAKLR SINPPCVPFF GIYLTNILKT EEGNPEVLKR HGKELINFSK RRKVAEITGE IQQYQNQPYC LRVESDIKRF FENLNPMGNS MEKEFTDYLF NKSLEIEPRN PKPLPRFPKK YSYPLKSPGV RPSNPRPGTM RHPTPLQQEP RKISYSRIPE SETESTASAP NSPRTPLTPP PASGASSTTD VCSVFDSDHS SPFHSSNDTV FIQVTLPHGP RSASVSSISL TKGTDEVPVP PPVPPRRRPE SAPAESSPSK IMSKHLDSPP AIPPRQPTSK AYSPRYSISD RTSISDPPES PPLLPPREPV RTPDVFSSSP LHLQPPPLGK KSDHGNAFFP NSPSPFTPPP PQTPSPHGTR RHLPSPPLTQ EVDLHSIAGP PVPPRQSTSQ HIPKLPPKTY KREHTHPSMH RDGPPLLENA HSS //