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 01-MAY-2013, entry version 148.
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 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 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-1134, AND MASS
RP 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 [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1134, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [12]
RP STRUCTURE BY NMR OF 422-551.
RX 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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 198-551.
RX 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 [14]
RP INVOLVEMENT IN GGF1, AND TISSUE SPECIFICITY.
RX 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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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 [21]
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 [22]
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. Catalytic
CC component of a trimeric complex that participates in transduction
CC of signals from Ras to Rac by promoting the Rac-specific guanine
CC nucleotide exchange factor (GEF) activity (By similarity).
CC -!- SUBUNIT: Part of a complex consisting of ABI1, EPS8 and SOS1 (By
CC similarity). Interacts with GRB2. Forms a complex with
CC phosphorylated MUC1 and GRB2 (via its SH3 domains). Interacts with
CC phosphorylated LAT2. Interacts with NCK1 and NCK2.
CC -!- INTERACTION:
CC P46108:CRK; NbExp=2; IntAct=EBI-297487, EBI-886;
CC P62993:GRB2; NbExp=9; 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: Gingival fibromatosis 1 (GGF1) [MIM:135300]: Gingival
CC fibromatosis is a rare overgrowth condition characterized by a
CC benign, slowly progressive, nonhemorrhagic, fibrous enlargement of
CC maxillary and mandibular keratinized gingiva. GGF1 is usually
CC transmitted as an autosomal dominant trait, although sporadic
CC cases are common. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- DISEASE: Noonan syndrome 4 (NS4) [MIM:610733]: A syndrome
CC characterized by facial dysmorphic features such as hypertelorism,
CC a downward eyeslant and low-set posteriorly rotated ears. Other
CC features can include short stature, a short neck with webbing or
CC redundancy of skin, cardiac anomalies, deafness, motor delay and
CC variable intellectual deficits. Some patients with Noonan syndrome
CC type 1 develop multiple giant cell lesions of the jaw or other
CC bony or soft tissues, which are classified as pigmented
CC villomoduolar synovitis (PVNS) when occurring in the jaw or
CC joints. Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
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";
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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 DIP; DIP-31802N; -.
DR IntAct; Q07889; 22.
DR MINT; MINT-106583; -.
DR STRING; 9606.ENSP00000384675; -.
DR PhosphoSite; Q07889; -.
DR DMDM; 6094322; -.
DR PaxDb; Q07889; -.
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 HOGENOM; HOG000013040; -.
DR HOVERGEN; HBG017831; -.
DR InParanoid; Q07889; -.
DR KO; K03099; -.
DR OMA; NEYKHAF; -.
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 ChiTaRS; SOS1; human.
DR EvolutionaryTrace; Q07889; -.
DR GenomeRNAi; 6654; -.
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: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: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; 1.10.20.10; -; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 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; PTHR23113; 1.
DR PANTHER; PTHR23113:SF47; PTHR23113:SF47; 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 (By similarity).
FT MOD_RES 1134 1134 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 STRAND 19 23
FT HELIX 24 34
FT STRAND 36 39
FT HELIX 42 61
FT HELIX 67 77
FT HELIX 82 94
FT STRAND 100 102
FT HELIX 107 118
FT HELIX 124 151
FT HELIX 159 168
FT HELIX 172 175
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 TURN 453 456
FT STRAND 459 473
FT HELIX 480 482
FT STRAND 487 496
FT STRAND 500 503
FT STRAND 507 509
FT STRAND 512 516
FT TURN 519 521
FT STRAND 524 527
FT HELIX 531 545
FT TURN 546 549
FT TURN 572 574
FT HELIX 576 578
FT TURN 583 585
FT STRAND 586 588
FT STRAND 590 592
FT STRAND 601 604
FT HELIX 606 613
FT STRAND 616 618
FT HELIX 621 630
FT HELIX 631 633
FT HELIX 637 648
FT HELIX 657 664
FT STRAND 665 667
FT HELIX 672 680
FT HELIX 682 699
FT HELIX 702 706
FT HELIX 708 718
FT TURN 724 726
FT HELIX 727 742
FT STRAND 764 766
FT HELIX 771 773
FT TURN 776 778
FT HELIX 781 798
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 887 892
FT HELIX 895 920
FT HELIX 931 942
FT STRAND 946 950
FT STRAND 953 957
FT HELIX 958 971
FT HELIX 972 974
FT HELIX 985 992
FT TURN 996 999
FT HELIX 1002 1016
FT STRAND 1020 1022
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
//
