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   24-JAN-2024, entry version 187.
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; 42.
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; 9606-ENSP00000264554; -.
DR   PeptideAtlas; P98077; -.
DR   ProteomicsDB; 57785; -.
DR   Antibodypedia; 1493; 167 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   AGR; HGNC:29869; -.
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; GDEWSRK; -.
DR   OrthoDB; 2903566at2759; -.
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; 13 hits in 1149 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 164 other cell types or tissues.
DR   ExpressionAtlas; P98077; baseline and differential.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; 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: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; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 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; IPR035676; SHC_SH2.
DR   PANTHER; PTHR10337; SHC TRANSFORMING PROTEIN; 1.
DR   PANTHER; PTHR10337:SF5; SHC-TRANSFORMING PROTEIN 2; 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; SSF50729; PH domain-like; 1.
DR   SUPFAM; SSF55550; SH2 domain; 1.
DR   PROSITE; PS01179; PID; 1.
DR   PROSITE; PS50001; SH2; 1.
DR   Genevisible; P98077; HS.
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
//