Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q6S5L8

- SHC4_HUMAN

UniProt

Q6S5L8 - SHC4_HUMAN

Protein

SHC-transforming protein 4

Gene

SHC4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 1 (05 Jul 2004)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Activates both Ras-dependent and Ras-independent migratory pathways in melanomas. Contributes to the early phases of agrin-induced tyrosine phosphorylation of CHRNB1.1 Publication

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. intracellular signal transduction Source: InterPro

    Enzyme and pathway databases

    SignaLinkiQ6S5L8.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    SHC-transforming protein 4
    Alternative name(s):
    Rai-like protein
    Short name:
    RaLP
    SHC-transforming protein D
    Short name:
    hShcD
    Src homology 2 domain-containing-transforming protein C4
    Short name:
    SH2 domain protein C4
    Gene namesi
    Name:SHC4
    Synonyms:SHCD
    ORF Names:UNQ6438/PRO21364
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:16743. SHC4.

    Subcellular locationi

    Cell junctionsynapsepostsynaptic cell membrane
    Note: Colocalized with MUSK at the neuromuscular junction.By similarity

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-KW
    2. postsynaptic membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi315 – 3151R → Q: Phosphorylation is markedly decreased. Completely reduces the phosphorylation and interaction with MUSK; when associated with K-549. 1 Publication
    Mutagenesisi374 – 3752YY → F: Remains phosphorylated. Contains a residual phosphorylation; when associated with F-465. Retains the ability to bind MUSK. Reduced the phosphorylation in presence of MUSK; when associated with F-424 and F-465. Completely abolishes the phosphorylation in presence of MUSK; when associated with F-403; F-413; F-424 and F-465. Retains the ability to bind MUSK; when associated with F-465. Retains the ability to bind MUSK; when associated with F-424 and F-465. Retains the ability to bind MUSK; when associated with F-403; F-413; F-424 and F-465.
    Mutagenesisi403 – 4031Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-413; F-424 and F-465. 1 Publication
    Mutagenesisi413 – 4131Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-424 and F-465. 1 Publication
    Mutagenesisi424 – 4241Y → F: Significantly decreased GRB2 interaction. Reduced the phosphorylation in presence of MUSK; when associated with 374-F-F-375 and F-465. Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-413 and F-465. 1 Publication
    Mutagenesisi465 – 4651Y → F: Remains phosphorylated. Contains a residual phosphorylation; when associated with 374-F-F-375. Reduced the phosphorylation in presence of MUSK; when associated with 374-F-F-375 and 424. Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-413 and F-424. Retains the ability to bind MUSK. Retains the ability to bind MUSK; when associated with 374-F-F-375. Retains the ability to bind MUSK; when associated with 374-F-F-375 and F-424. Retains the ability to bind MUSK; when associated with 374-F-F-375; F-403; F-413 and F-424. 1 Publication
    Mutagenesisi549 – 5491R → K: Completely reduces the phosphorylation and interaction with MUSK; when associated with Q-315. 1 Publication

    Organism-specific databases

    PharmGKBiPA142670917.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 630630SHC-transforming protein 4PRO_0000337200Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei424 – 4241Phosphotyrosine1 Publication

    Post-translational modificationi

    Phosphorylated; the phosphorylation is enhanced by EGF. Phosphorylation at Tyr-424 is required for the interaction with GRB2.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ6S5L8.
    PaxDbiQ6S5L8.
    PRIDEiQ6S5L8.

    PTM databases

    PhosphoSiteiQ6S5L8.

    Expressioni

    Tissue specificityi

    Only expressed in melanomas. Weakly expressed in normal melanocytes and benign nevi. Highly expressed at the transition from radial growth phase to vertical growth phase and metastatic melanomas, when tumor cells acquire migratory competence and invasive potential.1 Publication

    Gene expression databases

    ArrayExpressiQ6S5L8.
    BgeeiQ6S5L8.
    CleanExiHS_SHC4.
    GenevestigatoriQ6S5L8.

    Interactioni

    Subunit structurei

    Interacts (via PID domain) with phosphorylated MUSK (via NPXY motif); undergoes tyrosine phosphorylation downstream of activated MUSK. Interacts with GRB2; the interaction is dependent of Tyr-424 phosphorylation and increased by EGF.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARP102753EBI-9453524,EBI-608057
    METP085813EBI-9453524,EBI-1039152

    Protein-protein interaction databases

    BioGridi134386. 1 interaction.
    IntActiQ6S5L8. 3 interactions.
    STRINGi9606.ENSP00000329668.

    Structurei

    3D structure databases

    ProteinModelPortaliQ6S5L8.
    SMRiQ6S5L8. Positions 185-377, 520-619.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini186 – 369184PIDPROSITE-ProRule annotationAdd
    BLAST
    Domaini526 – 61792SH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 185185CH2Add
    BLAST
    Regioni370 – 525156CH1Add
    BLAST

    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.
    InParanoidiQ6S5L8.
    KOiK17449.
    OMAiPRMASMK.
    OrthoDBiEOG7MD4QK.
    PhylomeDBiQ6S5L8.
    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.
    IPR029596. SHC4.
    [Graphical view]
    PANTHERiPTHR10337:SF12. PTHR10337:SF12. 1 hit.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q6S5L8-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRERGQDSLA GLVLYVGLFG HPGMLHRAKY SRFRNESITS LDEGSSGGSV    50
    GNKGSPQPPH PALAPHLPTE DATLPSQESP TPLCTLIPRM ASMKLANPAT 100
    LLSLKNFCLG TKEVPRLKLQ ESRDPGSSGP SSPETSLSRS GTAPPPQQDL 150
    VGHRATALTP DSCPLPGPGE PTLRSRQDRH FLQHLLGMGM NYCVRYMGCV 200
    EVLQSMRSLD FGMRTQVTRE AISRLCEAVP GANGAIKKRK PPVKFLSTVL 250
    GKSNLQFSGM NIKLTISTCS LTLMNLDNQQ IIANHHMQSI SFASGGDPDT 300
    TDYVAYVAKD PVNQRACHIL ECHNGMAQDV ISTIGQAFEL RFKQYLKNPS 350
    LNTSCESEEV HIDSHAEERE DHEYYNEIPG KQPPVGGVSD MRIKVQATEQ 400
    MAYCPIQCEK LCYLPGNSKC SSVYENCLEQ SRAIGNVHPR GVQSQRDTSL 450
    LKHTCRVDLF DDPCYINTQA LQSTPGSAGN QRSAQPLGSP WHCGKAPETV 500
    QPGATAQPAS SHSLPHIKQQ LWSEECYHGK LSRKAAESLL VKDGDFLVRE 550
    SATSPGQYVL SGLQGGQAKH LLLVDPEGKV RTKDHVFDNV GHLIRYHMDN 600
    SLPIISSGSE VSLKQPVRKD NNPALLHSNK 630
    Length:630
    Mass (Da):68,785
    Last modified:July 5, 2004 - v1
    Checksum:i504F3FCB894E2C59
    GO
    Isoform 2 (identifier: Q6S5L8-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-243: Missing.
         244-280: KFLSTVLGKSNLQFSGMNIKLTISTCSLTLMNLDNQQ → MLPALEHWIPKFFSFRTRTGSPLSLACRQPIVGPCDH

    Note: No experimental confirmation available.

    Show »
    Length:387
    Mass (Da):42,782
    Checksum:i558D4E2167B69AF7
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti52 – 521N → D.1 Publication
    Corresponds to variant rs17856991 [ dbSNP | Ensembl ].
    VAR_043672
    Natural varianti244 – 2441K → E.1 Publication
    Corresponds to variant rs17856990 [ dbSNP | Ensembl ].
    VAR_043673
    Natural varianti400 – 4001Q → H.
    Corresponds to variant rs16961728 [ dbSNP | Ensembl ].
    VAR_043674
    Natural varianti447 – 4471D → G.1 Publication
    Corresponds to variant rs17856992 [ dbSNP | Ensembl ].
    VAR_043675

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 243243Missing in isoform 2. 1 PublicationVSP_033965Add
    BLAST
    Alternative sequencei244 – 28037KFLST…LDNQQ → MLPALEHWIPKFFSFRTRTG SPLSLACRQPIVGPCDH in isoform 2. 1 PublicationVSP_033966Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY464565 mRNA. Translation: AAR19363.1.
    AY358250 mRNA. Translation: AAQ88617.1.
    BC033907 mRNA. Translation: AAH33907.1.
    CCDSiCCDS10130.1. [Q6S5L8-1]
    RefSeqiNP_976224.3. NM_203349.3. [Q6S5L8-1]
    XP_005254433.1. XM_005254376.2. [Q6S5L8-2]
    UniGeneiHs.642615.

    Genome annotation databases

    EnsembliENST00000332408; ENSP00000329668; ENSG00000185634. [Q6S5L8-1]
    ENST00000396535; ENSP00000379786; ENSG00000185634. [Q6S5L8-2]
    GeneIDi399694.
    KEGGihsa:399694.
    UCSCiuc001zxb.1. human. [Q6S5L8-1]
    uc010uey.1. human. [Q6S5L8-2]

    Polymorphism databases

    DMDMi74722804.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY464565 mRNA. Translation: AAR19363.1 .
    AY358250 mRNA. Translation: AAQ88617.1 .
    BC033907 mRNA. Translation: AAH33907.1 .
    CCDSi CCDS10130.1. [Q6S5L8-1 ]
    RefSeqi NP_976224.3. NM_203349.3. [Q6S5L8-1 ]
    XP_005254433.1. XM_005254376.2. [Q6S5L8-2 ]
    UniGenei Hs.642615.

    3D structure databases

    ProteinModelPortali Q6S5L8.
    SMRi Q6S5L8. Positions 185-377, 520-619.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 134386. 1 interaction.
    IntActi Q6S5L8. 3 interactions.
    STRINGi 9606.ENSP00000329668.

    PTM databases

    PhosphoSitei Q6S5L8.

    Polymorphism databases

    DMDMi 74722804.

    Proteomic databases

    MaxQBi Q6S5L8.
    PaxDbi Q6S5L8.
    PRIDEi Q6S5L8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000332408 ; ENSP00000329668 ; ENSG00000185634 . [Q6S5L8-1 ]
    ENST00000396535 ; ENSP00000379786 ; ENSG00000185634 . [Q6S5L8-2 ]
    GeneIDi 399694.
    KEGGi hsa:399694.
    UCSCi uc001zxb.1. human. [Q6S5L8-1 ]
    uc010uey.1. human. [Q6S5L8-2 ]

    Organism-specific databases

    CTDi 399694.
    GeneCardsi GC15M049115.
    H-InvDB HIX0202177.
    HGNCi HGNC:16743. SHC4.
    neXtProti NX_Q6S5L8.
    PharmGKBi PA142670917.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG315087.
    HOGENOMi HOG000231974.
    HOVERGENi HBG050121.
    InParanoidi Q6S5L8.
    KOi K17449.
    OMAi PRMASMK.
    OrthoDBi EOG7MD4QK.
    PhylomeDBi Q6S5L8.
    TreeFami TF315807.

    Enzyme and pathway databases

    SignaLinki Q6S5L8.

    Miscellaneous databases

    ChiTaRSi SHC4. human.
    GenomeRNAii 399694.
    NextBioi 105503.
    PROi Q6S5L8.

    Gene expression databases

    ArrayExpressi Q6S5L8.
    Bgeei Q6S5L8.
    CleanExi HS_SHC4.
    Genevestigatori Q6S5L8.

    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.
    IPR029596. SHC4.
    [Graphical view ]
    PANTHERi PTHR10337:SF12. PTHR10337:SF12. 1 hit.
    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. "RaLP, a new member of the Src homology and collagen family, regulates cell migration and tumor growth of metastatic melanomas."
      Fagiani E., Giardina G., Luzi L., Cesaroni M., Quarto M., Capra M., Germano G., Bono M., Capillo M., Pelicci P., Lanfrancone L.
      Cancer Res. 67:3064-3073(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ASP-52; GLU-244 AND GLY-447.
      Tissue: Testis.
    4. "Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase."
      Jones N., Hardy W.R., Friese M.B., Jorgensen C., Smith M.J., Woody N.M., Burden S.J., Pawson T.
      Mol. Cell. Biol. 27:4759-4773(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MUSK AND GRB2, PHOSPHORYLATION AT TYR-424, MUTAGENESIS OF ARG-315; 374-TYR-TYR-375; TYR-403; TYR-413; TYR-424; TYR-465 AND ARG-549.

    Entry informationi

    Entry nameiSHC4_HUMAN
    AccessioniPrimary (citable) accession number: Q6S5L8
    Secondary accession number(s): Q6UXQ3, Q8IYW3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 20, 2008
    Last sequence update: July 5, 2004
    Last modified: October 1, 2014
    This is version 96 of the entry and version 1 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3