SHC2_HUMAN
ID SHC2_HUMAN Reviewed; 582 AA.
AC P98077; O60230; Q9NPL5; Q9UCX4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 4.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=SHC-transforming protein 2;
DE AltName: Full=Protein Sck;
DE AltName: Full=SHC-transforming protein B;
DE AltName: Full=Src homology 2 domain-containing-transforming protein C2;
DE Short=SH2 domain protein C2;
GN Name=SHC2; Synonyms=SCK, SHCB;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 45-582, INTERACTION WITH THE TRK RECEPTORS,
RP AND TISSUE SPECIFICITY.
RX PubMed=9507002; DOI=10.1074/jbc.273.12.6960;
RA Nakamura T., Muraoka S., Sanokawa R., Mori N.;
RT "N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their
RT differential regional expression in the brain and roles in neurotrophin and
RT Src signaling.";
RL J. Biol. Chem. 273:6960-6967(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 96-582.
RC TISSUE=Fetal brain;
RX PubMed=8760305;
RA Pelicci G., Dente L., De Giuseppe A., Verducci-Galletti B., Giuli S.,
RA Mele S., Vetriani C., Giorgio M., Pandolfi P.P., Cesareni G.,
RA Pelicci P.-G.;
RT "A family of Shc related proteins with conserved PTB, CH1 and SH2
RT regions.";
RL Oncogene 13:633-641(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 114-541.
RX PubMed=7527937; DOI=10.1126/science.7527937;
RA Kavanaugh W.M., Williams L.T.;
RT "An alternative to SH2 domains for binding tyrosine-phosphorylated
RT proteins.";
RL Science 266:1862-1865(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 191-582.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP PHOSPHORYLATION AT TYR-338; TYR-339 AND TYR-414, AND INTERACTION WITH THE
RP TRK RECEPTORS.
RX PubMed=12006576; DOI=10.1074/jbc.m111659200;
RA Liu H.Y., Meakin S.O.;
RT "ShcB and ShcC activation by the Trk family of receptor tyrosine kinases.";
RL J. Biol. Chem. 277:26046-26056(2002).
RN [7]
RP INTERACTION WITH MEGF12.
RC TISSUE=Platelet;
RX PubMed=15851471; DOI=10.1074/jbc.m413411200;
RA Nanda N., Bao M., Lin H., Clauser K., Komuves L., Quertermous T.,
RA Conley P.B., Phillips D.R., Hart M.J.;
RT "Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal
RT growth factor repeat-containing transmembrane receptor, participates in
RT platelet contact-induced activation.";
RL J. Biol. Chem. 280:24680-24689(2005).
CC -!- FUNCTION: Signaling adapter that couples activated growth factor
CC receptors to signaling pathway in neurons. Involved in the signal
CC transduction pathways of neurotrophin-activated Trk receptors in
CC cortical neurons (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with the Trk receptors in a phosphotyrosine-
CC dependent manner and MEGF12. Once activated, binds to GRB2.
CC {ECO:0000269|PubMed:12006576, ECO:0000269|PubMed:15851471,
CC ECO:0000269|PubMed:9507002}.
CC -!- INTERACTION:
CC P98077; P00533: EGFR; NbExp=3; IntAct=EBI-7256023, EBI-297353;
CC P98077; P04626: ERBB2; NbExp=3; IntAct=EBI-7256023, EBI-641062;
CC P98077; P10721: KIT; NbExp=5; IntAct=EBI-7256023, EBI-1379503;
CC P98077; P08581: MET; NbExp=2; IntAct=EBI-7256023, EBI-1039152;
CC -!- TISSUE SPECIFICITY: Expressed in brain. Expressed at high level in the
CC hypothalamus and at low level in the caudate nucleus.
CC {ECO:0000269|PubMed:9507002}.
CC -!- DOMAIN: The PID domain mediates binding to the TrkA receptor.
CC -!- PTM: Phosphorylated on tyrosines by the Trk receptors.
CC {ECO:0000269|PubMed:12006576}.
CC -!- MISCELLANEOUS: PubMed:15057824 has shown that SHC2 is poorly
CC phosphorylated by the Trk receptors, in opposite to PubMed:12006576.
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DR EMBL; AC008988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138433; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006124; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB001451; BAA25798.1; -; mRNA.
DR EMBL; AL360254; CAB96175.1; -; mRNA.
DR CCDS; CCDS45891.1; -.
DR RefSeq; NP_036567.2; NM_012435.2.
DR AlphaFoldDB; P98077; -.
DR SMR; P98077; -.
DR BioGRID; 117302; 41.
DR IntAct; P98077; 64.
DR MINT; P98077; -.
DR STRING; 9606.ENSP00000264554; -.
DR BindingDB; P98077; -.
DR ChEMBL; CHEMBL3299; -.
DR iPTMnet; P98077; -.
DR PhosphoSitePlus; P98077; -.
DR BioMuta; SHC2; -.
DR DMDM; 193806386; -.
DR jPOST; P98077; -.
DR MassIVE; P98077; -.
DR MaxQB; P98077; -.
DR PaxDb; P98077; -.
DR PeptideAtlas; P98077; -.
DR PRIDE; P98077; -.
DR ProteomicsDB; 57785; -.
DR Antibodypedia; 1493; 148 antibodies from 29 providers.
DR DNASU; 25759; -.
DR Ensembl; ENST00000264554.11; ENSP00000264554.4; ENSG00000129946.11.
DR GeneID; 25759; -.
DR KEGG; hsa:25759; -.
DR MANE-Select; ENST00000264554.11; ENSP00000264554.4; NM_012435.3; NP_036567.2.
DR UCSC; uc002loq.4; human.
DR CTD; 25759; -.
DR DisGeNET; 25759; -.
DR GeneCards; SHC2; -.
DR HGNC; HGNC:29869; SHC2.
DR HPA; ENSG00000129946; Tissue enhanced (pancreas).
DR MIM; 605217; gene.
DR neXtProt; NX_P98077; -.
DR OpenTargets; ENSG00000129946; -.
DR PharmGKB; PA134971076; -.
DR VEuPathDB; HostDB:ENSG00000129946; -.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000183520; -.
DR HOGENOM; CLU_029532_2_0_1; -.
DR InParanoid; P98077; -.
DR OMA; HGGQPKH; -.
DR OrthoDB; 1351843at2759; -.
DR PhylomeDB; P98077; -.
DR TreeFam; TF315807; -.
DR PathwayCommons; P98077; -.
DR Reactome; R-HSA-167044; Signalling to RAS.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR SignaLink; P98077; -.
DR SIGNOR; P98077; -.
DR BioGRID-ORCS; 25759; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; SHC2; human.
DR GeneWiki; SHC2; -.
DR GenomeRNAi; 25759; -.
DR Pharos; P98077; Tbio.
DR PRO; PR:P98077; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P98077; protein.
DR Bgee; ENSG00000129946; Expressed in body of pancreas and 162 other tissues.
DR ExpressionAtlas; P98077; baseline and differential.
DR Genevisible; P98077; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:InterPro.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd01209; PTB_Shc; 1.
DR CDD; cd09925; SH2_SHC; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006019; PID_Shc-like.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029591; SHC2.
DR InterPro; IPR035676; SHC_SH2.
DR PANTHER; PTHR10337:SF5; PTHR10337:SF5; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00629; SHCPIDOMAIN.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..582
FT /note="SHC-transforming protein 2"
FT /id="PRO_0000097732"
FT DOMAIN 147..329
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 487..578
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..70
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..486
FT /note="CH1"
FT REGION 460..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..23
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 338
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:12006576"
FT MOD_RES 339
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:12006576"
FT MOD_RES 414
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000305|PubMed:12006576"
FT CONFLICT 45..56
FT /note="GRGPAAARAAGA -> IRGSNAQKVVGASG (in Ref. 2;
FT BAA25798)"
FT /evidence="ECO:0000305"
FT CONFLICT 61
FT /note="D -> G (in Ref. 2; BAA25798)"
FT /evidence="ECO:0000305"
FT CONFLICT 65
FT /note="E -> D (in Ref. 2; BAA25798)"
FT /evidence="ECO:0000305"
FT CONFLICT 96..125
FT /note="LSRCRGAGSRGSRGGRGAAGSGDAAAAAEW -> MAFAGLASHVWWWRPSSQ
FT NRIWFRRGSPEF (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="A -> P (in Ref. 4)"
FT /evidence="ECO:0000305"
FT CONFLICT 188
FT /note="E -> I (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="I -> T (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="I -> E (in Ref. 3)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="Missing (in Ref. 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 582 AA; 61916 MW; F640AC298DA37B68 CRC64;
MTQGPGGRAP PAPPAPPEPE APTTFCALLP RMPQWKFAAP GGFLGRGPAA ARAAGASGGA
DPQPEPAGPG GVPALAAAVL GACEPRCAAP CPLPALSRCR GAGSRGSRGG RGAAGSGDAA
AAAEWIRKGS FIHKPAHGWL HPDARVLGPG VSYVVRYMGC IEVLRSMRSL DFNTRTQVTR
EAINRLHEAV PGVRGSWKKK APNKALASVL GKSNLRFAGM SISIHISTDG LSLSVPATRQ
VIANHHMPSI SFASGGDTDM TDYVAYVAKD PINQRACHIL ECCEGLAQSI ISTVGQAFEL
RFKQYLHSPP KVALPPERLA GPEESAWGDE EDSLEHNYYN SIPGKEPPLG GLVDSRLALT
QPCALTALDQ GPSPSLRDAC SLPWDVGSTG TAPPGDGYVQ ADARGPPDHE EHLYVNTQGL
DAPEPEDSPK KDLFDMRPFE DALKLHECSV AAGVTAAPLP LEDQWPSPPT RRAPVAPTEE
QLRQEPWYHG RMSRRAAERM LRADGDFLVR DSVTNPGQYV LTGMHAGQPK HLLLVDPEGV
VRTKDVLFES ISHLIDHHLQ NGQPIVAAES ELHLRGVVSR EP
