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P98077

- SHC2_HUMAN

UniProt

P98077 - SHC2_HUMAN

Protein

SHC-transforming protein 2

Gene

SHC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 4 (01 Jul 2008)
      Previous versions | rss
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    Functioni

    Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons By similarity.By similarity

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. insulin receptor signaling pathway Source: Reactome
    2. neurotrophin TRK receptor signaling pathway Source: Reactome
    3. Ras protein signal transduction Source: Reactome

    Enzyme and pathway databases

    ReactomeiREACT_12033. Signalling to RAS.
    REACT_508. Signal attenuation.
    REACT_661. SHC-mediated signalling.
    SignaLinkiP98077.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    SHC-transforming protein 2
    Alternative name(s):
    Protein Sck
    SHC-transforming protein B
    Src homology 2 domain-containing-transforming protein C2
    Short name:
    SH2 domain protein C2
    Gene namesi
    Name:SHC2
    Synonyms:SCK, SHCB
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:29869. SHC2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134971076.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 582582SHC-transforming protein 2PRO_0000097732Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei338 – 3381Phosphotyrosine1 Publication
    Modified residuei339 – 3391Phosphotyrosine1 Publication
    Modified residuei414 – 4141Phosphotyrosine1 Publication

    Post-translational modificationi

    Phosphorylated on tyrosines by the Trk receptors.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP98077.
    PRIDEiP98077.

    PTM databases

    PhosphoSiteiP98077.

    Expressioni

    Tissue specificityi

    Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus.1 Publication

    Gene expression databases

    ArrayExpressiP98077.
    BgeeiP98077.
    CleanExiHS_SHC2.
    GenevestigatoriP98077.

    Organism-specific databases

    HPAiHPA006136.

    Interactioni

    Subunit structurei

    Interacts with the Trk receptors in a phosphotyrosine-dependent manner and MEGF12. Once activated, binds to GRB2.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EGFRP005333EBI-7256023,EBI-297353
    ERBB2P046263EBI-7256023,EBI-641062
    KITP107215EBI-7256023,EBI-1379503
    METP085812EBI-7256023,EBI-1039152

    Protein-protein interaction databases

    BioGridi117302. 5 interactions.
    IntActiP98077. 5 interactions.
    MINTiMINT-127694.
    STRINGi9606.ENSP00000264554.

    Structurei

    3D structure databases

    ProteinModelPortaliP98077.
    SMRiP98077. Positions 124-306, 480-581.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini147 – 329183PIDPROSITE-ProRule annotationAdd
    BLAST
    Domaini487 – 57892SH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni330 – 486157CH1Add
    BLAST

    Domaini

    The PID domain mediates binding to the TrkA receptor.

    Sequence similaritiesi

    Contains 1 PID domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG315087.
    HOGENOMiHOG000231974.
    HOVERGENiHBG050121.
    InParanoidiP98077.
    KOiK17447.
    OMAiGACEPRC.
    OrthoDBiEOG7MD4QK.
    PhylomeDBiP98077.
    TreeFamiTF315807.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR011993. PH_like_dom.
    IPR006019. PID_Shc-like.
    IPR006020. PTB/PI_dom.
    IPR000980. SH2.
    [Graphical view]
    PfamiPF00640. PID. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00629. SHCPIDOMAIN.
    SMARTiSM00462. PTB. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    PROSITEiPS01179. PID. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P98077-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTQGPGGRAP PAPPAPPEPE APTTFCALLP RMPQWKFAAP GGFLGRGPAA    50
    ARAAGASGGA DPQPEPAGPG GVPALAAAVL GACEPRCAAP CPLPALSRCR 100
    GAGSRGSRGG RGAAGSGDAA AAAEWIRKGS FIHKPAHGWL HPDARVLGPG 150
    VSYVVRYMGC IEVLRSMRSL DFNTRTQVTR EAINRLHEAV PGVRGSWKKK 200
    APNKALASVL GKSNLRFAGM SISIHISTDG LSLSVPATRQ VIANHHMPSI 250
    SFASGGDTDM TDYVAYVAKD PINQRACHIL ECCEGLAQSI ISTVGQAFEL 300
    RFKQYLHSPP KVALPPERLA GPEESAWGDE EDSLEHNYYN SIPGKEPPLG 350
    GLVDSRLALT QPCALTALDQ GPSPSLRDAC SLPWDVGSTG TAPPGDGYVQ 400
    ADARGPPDHE EHLYVNTQGL DAPEPEDSPK KDLFDMRPFE DALKLHECSV 450
    AAGVTAAPLP LEDQWPSPPT RRAPVAPTEE QLRQEPWYHG RMSRRAAERM 500
    LRADGDFLVR DSVTNPGQYV LTGMHAGQPK HLLLVDPEGV VRTKDVLFES 550
    ISHLIDHHLQ NGQPIVAAES ELHLRGVVSR EP 582
    Length:582
    Mass (Da):61,916
    Last modified:July 1, 2008 - v4
    Checksum:iF640AC298DA37B68
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti45 – 5612GRGPA…RAAGA → IRGSNAQKVVGASG in BAA25798. (PubMed:9507002)CuratedAdd
    BLAST
    Sequence conflicti61 – 611D → G in BAA25798. (PubMed:9507002)Curated
    Sequence conflicti65 – 651E → D in BAA25798. (PubMed:9507002)Curated
    Sequence conflicti96 – 12530LSRCR…AAAEW → MAFAGLASHVWWWRPSSQNR IWFRRGSPEF(PubMed:8760305)CuratedAdd
    BLAST
    Sequence conflicti114 – 1141A → P(PubMed:7527937)Curated
    Sequence conflicti188 – 1881E → I(PubMed:8760305)Curated
    Sequence conflicti226 – 2261I → T(PubMed:8760305)Curated
    Sequence conflicti272 – 2721I → E(PubMed:8760305)Curated
    Sequence conflicti440 – 4401Missing(PubMed:8760305)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC008988 Genomic DNA. No translation available.
    AC138433 Genomic DNA. No translation available.
    AC006124 Genomic DNA. No translation available.
    AB001451 mRNA. Translation: BAA25798.1.
    AL360254 mRNA. Translation: CAB96175.1.
    CCDSiCCDS45891.1.
    RefSeqiNP_036567.2. NM_012435.2.
    UniGeneiHs.30965.

    Genome annotation databases

    EnsembliENST00000264554; ENSP00000264554; ENSG00000129946.
    GeneIDi25759.
    KEGGihsa:25759.
    UCSCiuc002loq.4. human.

    Polymorphism databases

    DMDMi193806386.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AC008988 Genomic DNA. No translation available.
    AC138433 Genomic DNA. No translation available.
    AC006124 Genomic DNA. No translation available.
    AB001451 mRNA. Translation: BAA25798.1 .
    AL360254 mRNA. Translation: CAB96175.1 .
    CCDSi CCDS45891.1.
    RefSeqi NP_036567.2. NM_012435.2.
    UniGenei Hs.30965.

    3D structure databases

    ProteinModelPortali P98077.
    SMRi P98077. Positions 124-306, 480-581.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117302. 5 interactions.
    IntActi P98077. 5 interactions.
    MINTi MINT-127694.
    STRINGi 9606.ENSP00000264554.

    Chemistry

    BindingDBi P98077.
    ChEMBLi CHEMBL3299.

    PTM databases

    PhosphoSitei P98077.

    Polymorphism databases

    DMDMi 193806386.

    Proteomic databases

    PaxDbi P98077.
    PRIDEi P98077.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264554 ; ENSP00000264554 ; ENSG00000129946 .
    GeneIDi 25759.
    KEGGi hsa:25759.
    UCSCi uc002loq.4. human.

    Organism-specific databases

    CTDi 25759.
    GeneCardsi GC19M000369.
    H-InvDB HIX0027436.
    HGNCi HGNC:29869. SHC2.
    HPAi HPA006136.
    MIMi 605217. gene.
    neXtProti NX_P98077.
    PharmGKBi PA134971076.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG315087.
    HOGENOMi HOG000231974.
    HOVERGENi HBG050121.
    InParanoidi P98077.
    KOi K17447.
    OMAi GACEPRC.
    OrthoDBi EOG7MD4QK.
    PhylomeDBi P98077.
    TreeFami TF315807.

    Enzyme and pathway databases

    Reactomei REACT_12033. Signalling to RAS.
    REACT_508. Signal attenuation.
    REACT_661. SHC-mediated signalling.
    SignaLinki P98077.

    Miscellaneous databases

    GeneWikii SHC2.
    GenomeRNAii 25759.
    NextBioi 46868.
    PROi P98077.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P98077.
    Bgeei P98077.
    CleanExi HS_SHC2.
    Genevestigatori P98077.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR011993. PH_like_dom.
    IPR006019. PID_Shc-like.
    IPR006020. PTB/PI_dom.
    IPR000980. SH2.
    [Graphical view ]
    Pfami PF00640. PID. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00629. SHCPIDOMAIN.
    SMARTi SM00462. PTB. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    PROSITEi PS01179. PID. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The DNA sequence and biology of human chromosome 19."
      Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
      , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
      Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    2. "N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling."
      Nakamura T., Muraoka S., Sanokawa R., Mori N.
      J. Biol. Chem. 273:6960-6967(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-582, INTERACTION WITH THE TRK RECEPTORS, TISSUE SPECIFICITY.
    3. "A family of Shc related proteins with conserved PTB, CH1 and SH2 regions."
      Pelicci G., Dente L., De Giuseppe A., Verducci-Galletti B., Giuli S., Mele S., Vetriani C., Giorgio M., Pandolfi P.P., Cesareni G., Pelicci P.-G.
      Oncogene 13:633-641(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-582.
      Tissue: Fetal brain.
    4. "An alternative to SH2 domains for binding tyrosine-phosphorylated proteins."
      Kavanaugh W.M., Williams L.T.
      Science 266:1862-1865(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-541.
    5. The European IMAGE consortium
      Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 191-582.
    6. "ShcB and ShcC activation by the Trk family of receptor tyrosine kinases."
      Liu H.Y., Meakin S.O.
      J. Biol. Chem. 277:26046-26056(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, INTERACTION WITH THE TRK RECEPTORS.
    7. "Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal growth factor repeat-containing transmembrane receptor, participates in platelet contact-induced activation."
      Nanda N., Bao M., Lin H., Clauser K., Komuves L., Quertermous T., Conley P.B., Phillips D.R., Hart M.J.
      J. Biol. Chem. 280:24680-24689(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MEGF12.
      Tissue: Platelet.

    Entry informationi

    Entry nameiSHC2_HUMAN
    AccessioniPrimary (citable) accession number: P98077
    Secondary accession number(s): O60230, Q9NPL5, Q9UCX4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: July 1, 2008
    Last modified: October 1, 2014
    This is version 119 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    PubMed:15057824 has shown that SHC2 is poorly phosphorylated by the Trk receptors, in opposite to PubMed:12006576.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3