ID RIT1_HUMAN Reviewed; 219 AA. AC Q92963; B4DQE8; O00646; O00720; Q5VY89; Q5VY90; DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 27-MAR-2024, entry version 194. DE RecName: Full=GTP-binding protein Rit1; DE EC=3.6.5.2 {ECO:0000269|PubMed:10545207}; DE AltName: Full=Ras-like protein expressed in many tissues; DE AltName: Full=Ras-like without CAAX protein 1; GN Name=RIT1; Synonyms=RIBB, RIT, ROC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8824319; DOI=10.1523/jneurosci.16-21-06784.1996; RA Lee C.H.J., Della N.G., Chew C.E., Zack D.J.; RT "Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit RT define a novel subfamily of ras proteins."; RL J. Neurosci. 16:6784-6794(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8918462; DOI=10.1002/j.1460-2075.1996.tb00971.x; RA Wes P.D., Yu M., Montell C.; RT "RIC, a calmodulin-binding Ras-like GTPase."; RL EMBO J. 15:5839-5848(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Kawasaki H., Housman D.E., Graybiel A.M.; RT "Characterization of new small G proteins in the Ras subfamily."; RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, INTERACTION RP WITH AFDN; RALGDS AND RLF, AND MUTAGENESIS OF SER-35; THR-53; GLU-55 AND RP GLN-79. RC TISSUE=Retina; RX PubMed=10545207; DOI=10.1006/abbi.1999.1448; RA Shao H., Kadono-Okuda K., Finlin B.S., Andres D.A.; RT "Biochemical characterization of the Ras-related GTPases Rit and Rin."; RL Arch. Biochem. Biophys. 371:207-219(1999). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Esophagus; 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP FUNCTION, AND INTERACTION WITH BRAF AND RAF1. RX PubMed=15632082; DOI=10.1128/mcb.25.2.830-846.2005; RA Shi G.-X., Andres D.A.; RT "Rit contributes to nerve growth factor-induced neuronal differentiation RT via activation of B-Raf-extracellular signal-regulated kinase and p38 RT mitogen-activated protein kinase cascades."; RL Mol. Cell. Biol. 25:830-846(2005). RN [12] RP FUNCTION, INVOLVEMENT IN NS8, VARIANTS NS8 GLY-57; GLY-81; LEU-82; ILE-90 RP AND ALA-95, CHARACTERIZATION OF VARIANTS NS8 GLY-57; GLY-81; LEU-82; ILE-90 RP AND ALA-95, AND VARIANTS THR-35; VAL-82; PRO-83 AND HIS-89. RX PubMed=23791108; DOI=10.1016/j.ajhg.2013.05.021; RA Aoki Y., Niihori T., Banjo T., Okamoto N., Mizuno S., Kurosawa K., RA Ogata T., Takada F., Yano M., Ando T., Hoshika T., Barnett C., Ohashi H., RA Kawame H., Hasegawa T., Okutani T., Nagashima T., Hasegawa S., Funayama R., RA Nagashima T., Nakayama K., Inoue S., Watanabe Y., Ogura T., Matsubara Y.; RT "Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK RT pathway syndrome."; RL Am. J. Hum. Genet. 93:173-180(2013). RN [13] RP VARIANTS NS8 GLY-57 AND ILE-90, AND CHARACTERIZATION OF VARIANTS NS8 GLY-57 RP AND ILE-90. RX PubMed=25959749; DOI=10.1111/cge.12608; RA Koenighofer M., Hung C.Y., McCauley J.L., Dallman J., Back E.J., RA Mihalek I., Gripp K.W., Sol-Church K., Rusconi P., Zhang Z., Shi G.X., RA Andres D.A., Bodamer O.A.; RT "Mutations in RIT1 cause Noonan syndrome - additional functional evidence RT and expanding the clinical phenotype."; RL Clin. Genet. 89:359-366(2016). CC -!- FUNCTION: Plays a crucial role in coupling NGF stimulation to the CC activation of both EPHB2 and MAPK14 signaling pathways and in NGF- CC dependent neuronal differentiation. Involved in ELK1 transactivation CC through the Ras-MAPK signaling cascade that mediates a wide variety of CC cellular functions, including cell proliferation, survival, and CC differentiation. {ECO:0000269|PubMed:15632082, CC ECO:0000269|PubMed:23791108}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2; CC Evidence={ECO:0000269|PubMed:10545207}; CC -!- ACTIVITY REGULATION: Alternates between an inactive form bound to GDP CC and an active form bound to GTP. CC -!- SUBUNIT: Interacts with AFDN, the C-terminal domain of RALGDS and RLF, CC but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP- CC bound form. Strongly interacts with BRAF, but only weakly with RAF1. CC BARF and RAF1 association is dependent upon the GTP-bound state. CC Interacts with RGL3 (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q92963; P60953: CDC42; NbExp=6; IntAct=EBI-365845, EBI-81752; CC Q92963; Q13153: PAK1; NbExp=4; IntAct=EBI-365845, EBI-1307; CC Q92963; P63000: RAC1; NbExp=5; IntAct=EBI-365845, EBI-413628; CC Q92963; Q3MIN7: RGL3; NbExp=3; IntAct=EBI-365845, EBI-2856274; CC Q92963; Q13129: RLF; NbExp=3; IntAct=EBI-365845, EBI-958266; CC -!- SUBCELLULAR LOCATION: Cell membrane. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92963-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92963-2; Sequence=VSP_045306; CC Name=3; CC IsoId=Q92963-3; Sequence=VSP_047114; CC -!- TISSUE SPECIFICITY: Expressed in many tissues. CC -!- DISEASE: Noonan syndrome 8 (NS8) [MIM:615355]: A form of Noonan CC syndrome, a disease characterized by short stature, facial dysmorphic CC features such as hypertelorism, a downward eyeslant and low-set CC posteriorly rotated ears, and a high incidence of congenital heart CC defects and hypertrophic cardiomyopathy. Other features can include a CC short neck with webbing or redundancy of skin, deafness, motor delay, CC variable intellectual deficits, multiple skeletal defects, CC cryptorchidism, and bleeding diathesis. Individuals with Noonan CC syndrome are at risk of juvenile myelomonocytic leukemia, a CC myeloproliferative disorder characterized by excessive production of CC myelomonocytic cells. {ECO:0000269|PubMed:23791108, CC ECO:0000269|PubMed:25959749}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Stimulation of the NGF and EGF receptor signaling CC pathways results in rapid and prolonged activation. CC -!- MISCELLANEOUS: Shows rapid uncatalyzed guanine nucleotide dissociation CC rates, which are much faster than those of most Ras subfamily members. CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Ras family. CC {ECO:0000305}. 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; U71203; AAB42213.1; -; mRNA. DR EMBL; Y07566; CAA68851.1; -; mRNA. DR EMBL; U78165; AAB64246.1; -; mRNA. DR EMBL; AF084462; AAD13021.1; -; mRNA. DR EMBL; AF493923; AAM12637.1; -; mRNA. DR EMBL; AK298768; BAG60910.1; -; mRNA. DR EMBL; AK314239; BAG36908.1; -; mRNA. DR EMBL; CR407639; CAG28567.1; -; mRNA. DR EMBL; AL139128; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL355388; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW53024.1; -; Genomic_DNA. DR EMBL; BC104186; AAI04187.1; -; mRNA. DR EMBL; BC104187; AAI04188.1; -; mRNA. DR CCDS; CCDS1123.1; -. [Q92963-1] DR CCDS; CCDS58036.1; -. [Q92963-2] DR CCDS; CCDS58037.1; -. [Q92963-3] DR RefSeq; NP_001243749.1; NM_001256820.1. [Q92963-2] DR RefSeq; NP_001243750.1; NM_001256821.1. [Q92963-3] DR RefSeq; NP_008843.1; NM_006912.5. [Q92963-1] DR PDB; 4KLZ; X-ray; 2.30 A; A=19-189. DR PDBsum; 4KLZ; -. DR AlphaFoldDB; Q92963; -. DR SMR; Q92963; -. DR BioGRID; 111948; 1223. DR IntAct; Q92963; 20. DR STRING; 9606.ENSP00000357305; -. DR iPTMnet; Q92963; -. DR PhosphoSitePlus; Q92963; -. DR BioMuta; RIT1; -. DR DMDM; 38258628; -. DR EPD; Q92963; -. DR jPOST; Q92963; -. DR MassIVE; Q92963; -. DR MaxQB; Q92963; -. DR PaxDb; 9606-ENSP00000357305; -. DR PeptideAtlas; Q92963; -. DR ProteomicsDB; 4865; -. DR ProteomicsDB; 75632; -. [Q92963-1] DR Pumba; Q92963; -. DR Antibodypedia; 20423; 269 antibodies from 30 providers. DR DNASU; 6016; -. DR Ensembl; ENST00000368322.7; ENSP00000357305.3; ENSG00000143622.12. [Q92963-3] DR Ensembl; ENST00000368323.8; ENSP00000357306.3; ENSG00000143622.12. [Q92963-1] DR Ensembl; ENST00000539040.6; ENSP00000441950.1; ENSG00000143622.12. [Q92963-2] DR GeneID; 6016; -. DR KEGG; hsa:6016; -. DR MANE-Select; ENST00000368323.8; ENSP00000357306.3; NM_006912.6; NP_008843.1. DR UCSC; uc001fmh.3; human. [Q92963-1] DR AGR; HGNC:10023; -. DR CTD; 6016; -. DR DisGeNET; 6016; -. DR GeneCards; RIT1; -. DR GeneReviews; RIT1; -. DR HGNC; HGNC:10023; RIT1. DR HPA; ENSG00000143622; Low tissue specificity. DR MalaCards; RIT1; -. DR MIM; 609591; gene. DR MIM; 615355; phenotype. DR neXtProt; NX_Q92963; -. DR OpenTargets; ENSG00000143622; -. DR Orphanet; 648; Noonan syndrome. DR PharmGKB; PA35528; -. DR VEuPathDB; HostDB:ENSG00000143622; -. DR eggNOG; KOG0395; Eukaryota. DR GeneTree; ENSGT00940000160132; -. DR HOGENOM; CLU_041217_9_5_1; -. DR InParanoid; Q92963; -. DR OrthoDB; 2601998at2759; -. DR PhylomeDB; Q92963; -. DR TreeFam; TF315072; -. DR PathwayCommons; Q92963; -. DR Reactome; R-HSA-187706; Signalling to p38 via RIT and RIN. DR SignaLink; Q92963; -. DR SIGNOR; Q92963; -. DR BioGRID-ORCS; 6016; 28 hits in 1169 CRISPR screens. DR ChiTaRS; RIT1; human. DR GeneWiki; RIT1; -. DR GenomeRNAi; 6016; -. DR Pharos; Q92963; Tbio. DR PRO; PR:Q92963; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q92963; Protein. DR Bgee; ENSG00000143622; Expressed in monocyte and 182 other cell types or tissues. DR ExpressionAtlas; Q92963; baseline and differential. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central. DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC. DR GO; GO:0019003; F:GDP binding; IBA:GO_Central. DR GO; GO:0005525; F:GTP binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0003924; F:GTPase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0007265; P:Ras protein signal transduction; IDA:UniProtKB. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd04141; Rit_Rin_Ric; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR005225; Small_GTP-bd_dom. DR InterPro; IPR001806; Small_GTPase. DR InterPro; IPR020849; Small_GTPase_Ras-type. DR NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR24070:SF208; GTP-BINDING PROTEIN RIT1; 1. DR PANTHER; PTHR24070; RAS, DI-RAS, AND RHEB FAMILY MEMBERS OF SMALL GTPASE SUPERFAMILY; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51421; RAS; 1. DR Genevisible; Q92963; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW GTP-binding; Hydrolase; Membrane; Nucleotide-binding; Reference proteome. FT CHAIN 1..219 FT /note="GTP-binding protein Rit1" FT /id="PRO_0000082725" FT REGION 193..219 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 28..35 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 75..79 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT BINDING 134..137 FT /ligand="GTP" FT /ligand_id="ChEBI:CHEBI:37565" FT /evidence="ECO:0000250" FT VAR_SEQ 1..36 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045306" FT VAR_SEQ 1 FT /note="M -> MERWLFLGATEEGPKRTM (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_047114" FT VARIANT 35 FT /note="S -> T (found in patients with features of Noonan FT syndrome; likely pathogenic; dbSNP:rs869025189)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070149" FT VARIANT 57 FT /note="A -> G (in NS8; results in increased ELK1 FT transcriptional activation; results in increased MAPK-ERK FT signaling; dbSNP:rs672601334)" FT /evidence="ECO:0000269|PubMed:23791108, FT ECO:0000269|PubMed:25959749" FT /id="VAR_070150" FT VARIANT 81 FT /note="E -> G (in NS8; results in increased ELK1 FT transcriptional activation; dbSNP:rs869025193)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070151" FT VARIANT 82 FT /note="F -> L (in NS8; results in increased ELK1 FT transcriptional activation; dbSNP:rs730881014)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070152" FT VARIANT 82 FT /note="F -> V (found in patients with features of Noonan FT syndrome; likely pathogenic; dbSNP:rs869025194)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070153" FT VARIANT 83 FT /note="T -> P (found in patients with features of Noonan FT syndrome; likely pathogenic; dbSNP:rs869025195)" FT /id="VAR_070154" FT VARIANT 89 FT /note="Y -> H (found in patients with features of Noonan FT syndrome; likely pathogenic; dbSNP:rs869025197)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070155" FT VARIANT 90 FT /note="M -> I (in NS8; results in increased MAPK-ERK FT signaling; dbSNP:rs483352822)" FT /evidence="ECO:0000269|PubMed:23791108, FT ECO:0000269|PubMed:25959749" FT /id="VAR_070156" FT VARIANT 95 FT /note="G -> A (in NS8; results in increased ELK1 FT transcriptional activation; dbSNP:rs672601335)" FT /evidence="ECO:0000269|PubMed:23791108" FT /id="VAR_070157" FT MUTAGEN 35 FT /note="S->N: Dominant negative. Loss of interaction with FT AFDN, RLF and RALGDS." FT /evidence="ECO:0000269|PubMed:10545207" FT MUTAGEN 53 FT /note="T->S: Loss of interaction with AFDN, RLF and RALGDS; FT when associated with L-79." FT /evidence="ECO:0000269|PubMed:10545207" FT MUTAGEN 55 FT /note="E->G: Loss of interaction with AFDN, but not with FT RLF and RALGDS; when associated with L-79." FT /evidence="ECO:0000269|PubMed:10545207" FT MUTAGEN 79 FT /note="Q->L: Constitutively active. Dramatic reduction of FT the rate of GTP hydrolysis. Loss of interaction with AFDN, FT RLF and RALGDS; when associated with S-53. Loss of FT interaction with AFDN; when associated with G-55." FT /evidence="ECO:0000269|PubMed:10545207" FT STRAND 22..27 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 34..43 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 56..62 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 64..67 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 69..75 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 95..101 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 105..109 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 111..121 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 129..134 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 139..141 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 146..155 FT /evidence="ECO:0007829|PDB:4KLZ" FT STRAND 160..162 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:4KLZ" FT HELIX 171..182 FT /evidence="ECO:0007829|PDB:4KLZ" SQ SEQUENCE 219 AA; 25145 MW; 7F957871F836AE92 CRC64; MDSGTRPVGS CCSSPAGLSR EYKLVMLGAG GVGKSAMTMQ FISHRFPEDH DPTIEDAYKI RIRIDDEPAN LDILDTAGQA EFTAMRDQYM RAGEGFIICY SITDRRSFHE VREFKQLIYR VRRTDDTPVV LVGNKSDLKQ LRQVTKEEGL ALAREFSCPF FETSAAYRYY IDDVFHALVR EIRRKEKEAV LAMEKKSKPK NSVWKRLKSP FRKKKDSVT //