SHOC2_HUMAN
ID SHOC2_HUMAN Reviewed; 582 AA.
AC Q9UQ13; A8K9W8; B3KR23; O76063; Q5VZS8; Q5VZS9;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 20-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Leucine-rich repeat protein SHOC-2;
DE AltName: Full=Protein soc-2 homolog;
DE AltName: Full=Protein sur-8 homolog;
GN Name=SHOC2; Synonyms=KIAA0862;
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), AND INTERACTION WITH KRAS AND NRAS.
RX PubMed=9674433; DOI=10.1016/s0092-8674(00)81227-1;
RA Sieburth D.S., Sun Q., Han M.;
RT "SUR-8, a conserved Ras-binding protein with leucine-rich repeats,
RT positively regulates Ras-mediated signaling in C. elegans.";
RL Cell 94:119-130(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9618511; DOI=10.1073/pnas.95.12.6903;
RA Selfors L.M., Schutzman J.L., Borland C.Z., Stern M.J.;
RT "Soc-2 encodes a leucine-rich repeat protein implicated in fibroblast
RT growth factor receptor signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6903-6908(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 165-582 (ISOFORM 2).
RC TISSUE=Amygdala, and Trachea;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [8]
RP FUNCTION.
RX PubMed=10783161;
RA Li W., Han M., Guan K.-L.;
RT "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and
RT forms a complex with Ras and Raf.";
RL Genes Dev. 14:895-900(2000).
RN [9]
RP INTERACTION WITH ERBIN.
RX PubMed=16301319; DOI=10.1074/jbc.m507360200;
RA Dai P., Xiong W.C., Mei L.;
RT "Erbin inhibits RAF activation by disrupting the sur-8-Ras-Raf complex.";
RL J. Biol. Chem. 281:927-933(2006).
RN [10]
RP FUNCTION, INTERACTION WITH MRAS AND RAF1, AND IDENTIFICATION IN A COMPLEX
RP WITH PP1CA; PPP1CB; PPP1CC; RAF1 AND MRAS.
RX PubMed=16630891; DOI=10.1016/j.molcel.2006.03.027;
RA Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M.,
RA McCormick F.;
RT "A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit
RT of PP1 functions as an M-Ras effector to modulate Raf activity.";
RL Mol. Cell 22:217-230(2006).
RN [11]
RP INVOLVEMENT IN NSLH1, VARIANT NSLH1 GLY-2, CHARACTERIZATION OF VARIANT
RP NSLH1 GLY-2, AND SUBCELLULAR LOCATION.
RX PubMed=19684605; DOI=10.1038/ng.425;
RA Cordeddu V., Di Schiavi E., Pennacchio L.A., Ma'ayan A., Sarkozy A.,
RA Fodale V., Cecchetti S., Cardinale A., Martin J., Schackwitz W., Lipzen A.,
RA Zampino G., Mazzanti L., Digilio M.C., Martinelli S., Flex E., Lepri F.,
RA Bartholdi D., Kutsche K., Ferrero G.B., Anichini C., Selicorni A.,
RA Rossi C., Tenconi R., Zenker M., Merlo D., Dallapiccola B., Iyengar R.,
RA Bazzicalupo P., Gelb B.D., Tartaglia M.;
RT "Mutation of SHOC2 promotes aberrant protein N-myristoylation and causes
RT Noonan-like syndrome with loose anagen hair.";
RL Nat. Genet. 41:1022-1026(2009).
RN [12]
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., Buerckstuemmer T.,
RA 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 [13]
RP INTERACTION WITH LZTR1.
RX PubMed=30368668; DOI=10.1007/s00439-018-1951-7;
RA Umeki I., Niihori T., Abe T., Kanno S.I., Okamoto N., Mizuno S.,
RA Kurosawa K., Nagasaki K., Yoshida M., Ohashi H., Inoue S.I., Matsubara Y.,
RA Fujiwara I., Kure S., Aoki Y.;
RT "Delineation of LZTR1 mutation-positive patients with Noonan syndrome and
RT identification of LZTR1 binding to RAF1-PPP1CB complexes.";
RL Hum. Genet. 138:21-35(2019).
RN [14]
RP VARIANT NSLH1 GLY-2.
RX PubMed=23918763; DOI=10.1002/ajmg.a.36098;
RA Gripp K.W., Zand D.J., Demmer L., Anderson C.E., Dobyns W.B., Zackai E.H.,
RA Denenberg E., Jenny K., Stabley D.L., Sol-Church K.;
RT "Expanding the SHOC2 mutation associated phenotype of Noonan syndrome with
RT loose anagen hair: structural brain anomalies and myelofibrosis.";
RL Am. J. Med. Genet. A 161A:2420-2430(2013).
RN [15]
RP VARIANT NSLH1 ILE-173, CHARACTERIZATION OF VARIANT NSLH1 ILE-173, FUNCTION,
RP INTERACTION WITH MRAS AND RAF1 AND PHOSPHATASE 1C, AND SUBCELLULAR
RP LOCATION.
RX PubMed=25137548; DOI=10.1002/humu.22634;
RA Hannig V., Jeoung M., Jang E.R., Phillips J.A. III, Galperin E.;
RT "A Novel SHOC2 Variant in Rasopathy.";
RL Hum. Mutat. 35:1290-1294(2014).
CC -!- FUNCTION: Regulatory subunit of protein phosphatase 1 (PP1c) that acts
CC as a M-Ras/MRAS effector and participates in MAPK pathway activation.
CC Upon M-Ras/MRAS activation, targets PP1c to specifically
CC dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and
CC stimulate RAF1 activity at specialized signaling complexes.
CC {ECO:0000269|PubMed:10783161, ECO:0000269|PubMed:16630891,
CC ECO:0000269|PubMed:25137548}.
CC -!- SUBUNIT: Interacts with M-Ras/MRAS, and RAF1 (PubMed:16630891,
CC PubMed:25137548). Forms a multiprotein complex with Ras (M-Ras/MRAS),
CC Raf (RAF1) and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC)
CC (PubMed:16630891, PubMed:25137548). Interacts with ERBIN; disrupts the
CC interaction with RAF1 and Ras, leading to prevent activation of the Ras
CC signaling pathway (PubMed:16301319). Specifically binds K-Ras/KRAS, M-
CC Ras/MRAS and N-Ras/NRAS but not H-Ras/HRAS (PubMed:9674433). Interacts
CC with LZTR1 (PubMed:30368668). {ECO:0000269|PubMed:16301319,
CC ECO:0000269|PubMed:16630891, ECO:0000269|PubMed:25137548,
CC ECO:0000269|PubMed:30368668, ECO:0000269|PubMed:9674433}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19684605,
CC ECO:0000269|PubMed:25137548}. Nucleus {ECO:0000269|PubMed:19684605,
CC ECO:0000269|PubMed:25137548}. Note=Translocates from cytoplasm to
CC nucleus upon growth factor stimulation. {ECO:0000269|PubMed:19684605}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UQ13-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UQ13-2; Sequence=VSP_038188;
CC -!- DISEASE: Noonan syndrome-like disorder with loose anagen hair 1 (NSLH1)
CC [MIM:607721]: A syndrome characterized by Noonan dysmorphic features
CC such as macrocephaly, high forehead, hypertelorism, palpebral ptosis,
CC low-set and posteriorly rotated ears, short and webbed neck, pectus
CC anomalies, in association with pluckable, sparse, thin and slow-growing
CC hair. {ECO:0000269|PubMed:19684605, ECO:0000269|PubMed:23918763,
CC ECO:0000269|PubMed:25137548}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SHOC2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74885.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG52235.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The matchmaker - Issue 121
CC of September 2010;
CC URL="https://web.expasy.org/spotlight/back_issues/121";
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DR EMBL; AF068920; AAC39856.1; -; mRNA.
DR EMBL; AF054828; AAC25698.1; -; mRNA.
DR EMBL; AB020669; BAA74885.2; ALT_INIT; mRNA.
DR EMBL; AK090820; BAG52235.1; ALT_INIT; mRNA.
DR EMBL; AK292833; BAF85522.1; -; mRNA.
DR EMBL; AL158163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49548.1; -; Genomic_DNA.
DR EMBL; BC050445; AAH50445.1; -; mRNA.
DR CCDS; CCDS58095.1; -. [Q9UQ13-2]
DR CCDS; CCDS7568.1; -. [Q9UQ13-1]
DR RefSeq; NP_001255968.1; NM_001269039.2. [Q9UQ13-2]
DR RefSeq; NP_001311265.1; NM_001324336.1. [Q9UQ13-1]
DR RefSeq; NP_001311266.1; NM_001324337.1. [Q9UQ13-1]
DR RefSeq; NP_031399.2; NM_007373.3. [Q9UQ13-1]
DR RefSeq; XP_016872191.1; XM_017016702.1.
DR RefSeq; XP_016872192.1; XM_017016703.1.
DR RefSeq; XP_016872193.1; XM_017016704.1.
DR AlphaFoldDB; Q9UQ13; -.
DR SASBDB; Q9UQ13; -.
DR SMR; Q9UQ13; -.
DR BioGRID; 113729; 64.
DR IntAct; Q9UQ13; 42.
DR MINT; Q9UQ13; -.
DR STRING; 9606.ENSP00000358464; -.
DR GlyGen; Q9UQ13; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UQ13; -.
DR PhosphoSitePlus; Q9UQ13; -.
DR BioMuta; SHOC2; -.
DR DMDM; 14423936; -.
DR CPTAC; CPTAC-1562; -.
DR EPD; Q9UQ13; -.
DR jPOST; Q9UQ13; -.
DR MassIVE; Q9UQ13; -.
DR MaxQB; Q9UQ13; -.
DR PaxDb; Q9UQ13; -.
DR PeptideAtlas; Q9UQ13; -.
DR PRIDE; Q9UQ13; -.
DR ProteomicsDB; 85490; -. [Q9UQ13-1]
DR ProteomicsDB; 85491; -. [Q9UQ13-2]
DR Antibodypedia; 1953; 237 antibodies from 32 providers.
DR DNASU; 8036; -.
DR Ensembl; ENST00000265277.10; ENSP00000265277.5; ENSG00000108061.13. [Q9UQ13-2]
DR Ensembl; ENST00000369452.9; ENSP00000358464.5; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000685059.1; ENSP00000510210.1; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000688928.1; ENSP00000509273.1; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000689118.1; ENSP00000510554.1; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000689300.1; ENSP00000510639.1; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000691369.1; ENSP00000509754.1; ENSG00000108061.13. [Q9UQ13-1]
DR Ensembl; ENST00000691441.1; ENSP00000509686.1; ENSG00000108061.13. [Q9UQ13-1]
DR GeneID; 8036; -.
DR KEGG; hsa:8036; -.
DR MANE-Select; ENST00000369452.9; ENSP00000358464.5; NM_007373.4; NP_031399.2.
DR UCSC; uc001kzl.5; human. [Q9UQ13-1]
DR CTD; 8036; -.
DR DisGeNET; 8036; -.
DR GeneCards; SHOC2; -.
DR HGNC; HGNC:15454; SHOC2.
DR HPA; ENSG00000108061; Low tissue specificity.
DR MalaCards; SHOC2; -.
DR MIM; 602775; gene.
DR MIM; 607721; phenotype.
DR neXtProt; NX_Q9UQ13; -.
DR OpenTargets; ENSG00000108061; -.
DR Orphanet; 2701; Noonan syndrome-like disorder with loose anagen hair.
DR PharmGKB; PA37960; -.
DR VEuPathDB; HostDB:ENSG00000108061; -.
DR eggNOG; KOG0619; Eukaryota.
DR GeneTree; ENSGT00940000156270; -.
DR HOGENOM; CLU_000288_18_23_1; -.
DR InParanoid; Q9UQ13; -.
DR OMA; NQFTSYP; -.
DR OrthoDB; 287114at2759; -.
DR PhylomeDB; Q9UQ13; -.
DR TreeFam; TF315742; -.
DR PathwayCommons; Q9UQ13; -.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-9726840; SHOC2 M1731 mutant abolishes MRAS complex function.
DR Reactome; R-HSA-9726842; Gain-of-function MRAS complexes activate RAF signaling.
DR SignaLink; Q9UQ13; -.
DR SIGNOR; Q9UQ13; -.
DR BioGRID-ORCS; 8036; 165 hits in 1091 CRISPR screens.
DR ChiTaRS; SHOC2; human.
DR GeneWiki; SHOC2; -.
DR GenomeRNAi; 8036; -.
DR Pharos; Q9UQ13; Tbio.
DR PRO; PR:Q9UQ13; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9UQ13; protein.
DR Bgee; ENSG00000108061; Expressed in calcaneal tendon and 209 other tissues.
DR ExpressionAtlas; Q9UQ13; baseline and differential.
DR Genevisible; Q9UQ13; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000164; C:protein phosphatase type 1 complex; IDA:UniProtKB.
DR GO; GO:0008157; F:protein phosphatase 1 binding; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IDA:UniProtKB.
DR GO; GO:0019888; F:protein phosphatase regulator activity; TAS:UniProtKB.
DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; NAS:UniProtKB.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; NAS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 3.80.10.10; -; 4.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR027036; SHOC2.
DR PANTHER; PTHR48051:SF9; PTHR48051:SF9; 1.
DR Pfam; PF13855; LRR_8; 5.
DR SMART; SM00369; LRR_TYP; 16.
DR PROSITE; PS51450; LRR; 17.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Disease variant; Leucine-rich repeat;
KW Nucleus; Reference proteome; Repeat.
FT CHAIN 1..582
FT /note="Leucine-rich repeat protein SHOC-2"
FT /id="PRO_0000097737"
FT REPEAT 101..122
FT /note="LRR 1"
FT REPEAT 124..145
FT /note="LRR 2"
FT REPEAT 147..169
FT /note="LRR 3"
FT REPEAT 170..191
FT /note="LRR 4"
FT REPEAT 193..214
FT /note="LRR 5"
FT REPEAT 216..237
FT /note="LRR 6"
FT REPEAT 239..260
FT /note="LRR 7"
FT REPEAT 262..283
FT /note="LRR 8"
FT REPEAT 285..307
FT /note="LRR 9"
FT REPEAT 308..329
FT /note="LRR 10"
FT REPEAT 332..353
FT /note="LRR 11"
FT REPEAT 356..377
FT /note="LRR 12"
FT REPEAT 380..400
FT /note="LRR 13"
FT REPEAT 403..424
FT /note="LRR 14"
FT REPEAT 426..448
FT /note="LRR 15"
FT REPEAT 449..470
FT /note="LRR 16"
FT REPEAT 472..494
FT /note="LRR 17"
FT REPEAT 495..516
FT /note="LRR 18"
FT REPEAT 518..540
FT /note="LRR 19"
FT REPEAT 542..563
FT /note="LRR 20"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..56
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 234..279
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038188"
FT VARIANT 2
FT /note="S -> G (in NSLH1; creates a N-myristoylation site,
FT resulting in myristoylation of the protein and aberrant
FT targeting to the plasma membrane; dbSNP:rs267607048)"
FT /evidence="ECO:0000269|PubMed:19684605,
FT ECO:0000269|PubMed:23918763"
FT /id="VAR_060199"
FT VARIANT 173
FT /note="M -> I (in NSLH1; significantly decreases ERK1/2
FT activity; does not affect cytoplasm and nucleus
FT localization; does not affect SHOC2-MRAS-RAF1 complex
FT assembly; impairs interaction with phosphatase 1c;
FT dbSNP:rs730881020)"
FT /evidence="ECO:0000269|PubMed:25137548"
FT /id="VAR_074030"
FT CONFLICT 475
FT /note="K -> E (in Ref. 4; BAF85522)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="F -> L (in Ref. 3; BAA74885)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 582 AA; 64888 MW; F3F828646642A855 CRC64;
MSSSLGKEKD SKEKDPKVPS AKEREKEAKA SGGFGKESKE KEPKTKGKDA KDGKKDSSAA
QPGVAFSVDN TIKRPNPAPG TRKKSSNAEV IKELNKCREE NSMRLDLSKR SIHILPSSIK
ELTQLTELYL YSNKLQSLPA EVGCLVNLMT LALSENSLTS LPDSLDNLKK LRMLDLRHNK
LREIPSVVYR LDSLTTLYLR FNRITTVEKD IKNLSKLSML SIRENKIKQL PAEIGELCNL
ITLDVAHNQL EHLPKEIGNC TQITNLDLQH NELLDLPDTI GNLSSLSRLG LRYNRLSAIP
RSLAKCSALE ELNLENNNIS TLPESLLSSL VKLNSLTLAR NCFQLYPVGG PSQFSTIYSL
NMEHNRINKI PFGIFSRAKV LSKLNMKDNQ LTSLPLDFGT WTSMVELNLA TNQLTKIPED
VSGLVSLEVL ILSNNLLKKL PHGLGNLRKL RELDLEENKL ESLPNEIAYL KDLQKLVLTN
NQLTTLPRGI GHLTNLTHLG LGENLLTHLP EEIGTLENLE ELYLNDNPNL HSLPFELALC
SKLSIMSIEN CPLSHLPPQI VAGGPSFIIQ FLKMQGPYRA MV
