RIT1_HUMAN
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 03-AUG-2022, entry version 186.
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}.
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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; 20.
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; Q92963; -.
DR PeptideAtlas; Q92963; -.
DR PRIDE; Q92963; -.
DR ProteomicsDB; 4865; -.
DR ProteomicsDB; 75632; -. [Q92963-1]
DR Antibodypedia; 20423; 251 antibodies from 30 providers.
DR DNASU; 6016; -.
DR Ensembl; ENST00000368322.7; ENSP00000357305.3; ENSG00000143622.11. [Q92963-3]
DR Ensembl; ENST00000368323.8; ENSP00000357306.3; ENSG00000143622.11. [Q92963-1]
DR Ensembl; ENST00000539040.5; ENSP00000441950.1; ENSG00000143622.11. [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 CTD; 6016; -.
DR DisGeNET; 6016; -.
DR GeneCards; RIT1; -.
DR GeneReviews; RIT1; -.
DR HGNC; HGNC:10023; RIT1.
DR HPA; ENSG00000143622; Tissue enhanced (bone).
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; 1259506at2759; -.
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; 26 hits in 1083 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 181 other tissues.
DR ExpressionAtlas; Q92963; baseline and differential.
DR Genevisible; Q92963; HS.
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 Gene3D; 3.40.50.300; -; 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 PANTHER; PTHR24070; PTHR24070; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
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 (probable disease-associated variant found in
FT patients with features of Noonan syndrome;
FT 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 (probable disease-associated variant found in
FT patients with features of Noonan syndrome;
FT dbSNP:rs869025194)"
FT /evidence="ECO:0000269|PubMed:23791108"
FT /id="VAR_070153"
FT VARIANT 83
FT /note="T -> P (probable disease-associated variant found in
FT patients with features of Noonan syndrome;
FT dbSNP:rs869025195)"
FT /id="VAR_070154"
FT VARIANT 89
FT /note="Y -> H (probable disease-associated variant found in
FT patients with features of Noonan syndrome;
FT 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
