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B5KFD7

- GRB10_PIG

UniProt

B5KFD7 - GRB10_PIG

Protein

Growth factor receptor-bound protein 10

Gene

Grb10

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 3 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 41 (01 Oct 2014)
      Sequence version 1 (14 Oct 2008)
      Previous versions | rss
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    Functioni

    Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. A similar role in the mediation of ubiquitination has also been suggested with INSR. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2 By similarity.By similarity

    Enzyme regulationi

    Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling.By similarity

    GO - Biological processi

    1. insulin-like growth factor receptor signaling pathway Source: Ensembl
    2. negative regulation of glucose import Source: Ensembl
    3. negative regulation of insulin receptor signaling pathway Source: Ensembl
    4. negative regulation of phosphorylation Source: Ensembl
    5. negative regulation of Wnt signaling pathway Source: UniProtKB
    6. positive regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB

    Enzyme and pathway databases

    ReactomeiREACT_192916. Signaling by SCF-KIT.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Growth factor receptor-bound protein 10
    Alternative name(s):
    GRB10 adapter protein
    Gene namesi
    Name:Grb10
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Chromosome 9

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 589589Growth factor receptor-bound protein 10PRO_0000392073Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei99 – 991PhosphoserineBy similarity
    Modified residuei145 – 1451Phosphoserine; by MTOR, MAPK1 and MAPK3By similarity
    Modified residuei413 – 4131Phosphoserine; by MAPK1 and MAPK3; in vitroBy similarity
    Modified residuei423 – 4231Phosphoserine; by MTOR and PKB/AKT1By similarity
    Modified residuei426 – 4261PhosphoserineBy similarity
    Modified residuei471 – 4711Phosphoserine; by MTOR, MAPK1 and MAPK3By similarity

    Post-translational modificationi

    Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation.By similarity

    Keywords - PTMi

    Phosphoprotein

    Interactioni

    Subunit structurei

    Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain. Poorly binds to the EGFR. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15. When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6. Binds relatively non-specifically to several phosphoinositides, including PI5P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities through the PH domain. Binds to activated NRAS By similarity.By similarity

    Protein-protein interaction databases

    STRINGi9823.ENSSSCP00000016570.

    Structurei

    3D structure databases

    ProteinModelPortaliB5KFD7.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini161 – 24585Ras-associatingPROSITE-ProRule annotationAdd
    BLAST
    Domaini285 – 394110PHPROSITE-ProRule annotationAdd
    BLAST
    Domaini488 – 58497SH2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the GRB7/10/14 family.Curated
    Contains 1 PH domain.PROSITE-ProRule annotation
    Contains 1 Ras-associating domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG307156.
    GeneTreeiENSGT00550000074537.
    HOGENOMiHOG000231904.
    HOVERGENiHBG000468.
    OMAiESTMGSE.
    OrthoDBiEOG7SFHW7.
    TreeFamiTF317511.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR015042. BPS-dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000159. Ras-assoc.
    IPR000980. SH2.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PfamiPF08947. BPS. 1 hit.
    PF00169. PH. 1 hit.
    PF00788. RA. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00233. PH. 1 hit.
    SM00314. RA. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF54236. SSF54236. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS50200. RA. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    This entry describes 4 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: B5KFD7-1) [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

    MALAGGPDSF LHHPYYQDQV EQTSPHHPRD LAGPGFPAQP DRLAPHQEDD    50
    VDLEALVNDM DASLESLCSA SETAPLLHNG QHARGPPPPG ARPLRPQASP 100
    RHRVPRSQPL HILAARRLQE EDQQFRTSSL PAIPNPFPEL CGPGSPPVLS 150
    PGSLPPGQAA AKQDVKVFSE DGTCKVVEIL ADMTARDLCQ LLVYRSHCVD 200
    DNSWTLVEHH PHLGLERGLE DHERVTQVQH TLASESKFLF RKNYAKYEFF 250
    KNPTNFFPEQ MVTWCQQSNG SQTQLLQNFL NSSSCPEIQG FLHVKELGRK 300
    SWKKLYVCLR RSGLYCSTKG ASKEPRHLQL LADLEDSSIF SLIAGRKQYG 350
    APTDYGFCIK PNRVRTEAKE LRLLCAEDEQ SRTCWMTAFR LLKYGMLLYQ 400
    NYRVPQQRKA VLSPFSAPVR SVSENSLVAM DFSGQTGRVI ENPAEAQSAA 450
    LEEGHAWRKR STRMNILGSQ SPLHPSTLST VIHRTQHWFH GRISREESHR 500
    IIKQQGLVDG LFLLRDSQSN PKAFVLTLCH HQKIKNFQIL PCEDDGQTFF 550
    SLDDGNTKFS DLIQLVDFYQ LNKGVLPCKL KHHCIRVAL 589
    Length:589
    Mass (Da):66,386
    Last modified:October 14, 2008 - v1
    Checksum:i7F7F32CC84042B4D
    GO
    Isoform 2 (identifier: B5KFD7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-59: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:530
    Mass (Da):59,890
    Checksum:i638E6F5F222D713D
    GO
    Isoform 3 (identifier: B5KFD7-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-59: Missing.
         511-548: LFLLRDSQSN...ILPCEDDGQT → RCTRLQWPSS...DPVGGIAYSI
         549-589: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:489
    Mass (Da):54,924
    Checksum:i624A5272DA396169
    GO
    Isoform 4 (identifier: B5KFD7-4) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         511-548: LFLLRDSQSN...ILPCEDDGQT → RCTRLQWPSS...DPVGGIAYSI
         549-589: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:548
    Mass (Da):61,420
    Checksum:i0BE86E93396C4F3B
    GO

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 5959Missing in isoform 2 and isoform 3. 1 PublicationVSP_038785Add
    BLAST
    Alternative sequencei511 – 54838LFLLR…DDGQT → RCTRLQWPSSKSLQTISAGE GVEKKEPYDPVGGIAYSI in isoform 3 and isoform 4. 1 PublicationVSP_038786Add
    BLAST
    Alternative sequencei549 – 58941Missing in isoform 3 and isoform 4. 1 PublicationVSP_038787Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF174191 mRNA. Translation: ABO93312.1.
    EF174192 mRNA. Translation: ABO93313.1.
    EF174193 mRNA. Translation: ABO93314.1.
    EF174194 mRNA. Translation: ABO93315.1.
    EF174195 mRNA. Translation: ABO93316.1.
    EF174196 mRNA. Translation: ABO93317.1.
    EF174197 mRNA. Translation: ABO93318.1.
    EF174198 mRNA. Translation: ABO93319.1.
    EF174199 mRNA. Translation: ABO93320.1.
    RefSeqiNP_001128437.1. NM_001134965.1. [B5KFD7-1]
    UniGeneiSsc.21857.
    Ssc.95889.

    Genome annotation databases

    EnsembliENSSSCT00000017025; ENSSSCP00000016570; ENSSSCG00000015631. [B5KFD7-4]
    ENSSSCT00000031836; ENSSSCP00000020573; ENSSSCG00000015631. [B5KFD7-1]
    GeneIDi100188977.
    KEGGissc:100188977.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    EF174191 mRNA. Translation: ABO93312.1 .
    EF174192 mRNA. Translation: ABO93313.1 .
    EF174193 mRNA. Translation: ABO93314.1 .
    EF174194 mRNA. Translation: ABO93315.1 .
    EF174195 mRNA. Translation: ABO93316.1 .
    EF174196 mRNA. Translation: ABO93317.1 .
    EF174197 mRNA. Translation: ABO93318.1 .
    EF174198 mRNA. Translation: ABO93319.1 .
    EF174199 mRNA. Translation: ABO93320.1 .
    RefSeqi NP_001128437.1. NM_001134965.1. [B5KFD7-1 ]
    UniGenei Ssc.21857.
    Ssc.95889.

    3D structure databases

    ProteinModelPortali B5KFD7.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9823.ENSSSCP00000016570.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSSSCT00000017025 ; ENSSSCP00000016570 ; ENSSSCG00000015631 . [B5KFD7-4 ]
    ENSSSCT00000031836 ; ENSSSCP00000020573 ; ENSSSCG00000015631 . [B5KFD7-1 ]
    GeneIDi 100188977.
    KEGGi ssc:100188977.

    Organism-specific databases

    CTDi 2887.

    Phylogenomic databases

    eggNOGi NOG307156.
    GeneTreei ENSGT00550000074537.
    HOGENOMi HOG000231904.
    HOVERGENi HBG000468.
    OMAi ESTMGSE.
    OrthoDBi EOG7SFHW7.
    TreeFami TF317511.

    Enzyme and pathway databases

    Reactomei REACT_192916. Signaling by SCF-KIT.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR015042. BPS-dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000159. Ras-assoc.
    IPR000980. SH2.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    Pfami PF08947. BPS. 1 hit.
    PF00169. PH. 1 hit.
    PF00788. RA. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00233. PH. 1 hit.
    SM00314. RA. 1 hit.
    SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 1 hit.
    SSF55550. SSF55550. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS50200. RA. 1 hit.
    PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Pig Grb10 is bi-alleic expressed."
      Nielsen A.L.
      Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4).

    Entry informationi

    Entry nameiGRB10_PIG
    AccessioniPrimary (citable) accession number: B5KFD7
    Secondary accession number(s): B5KFD3, B5KFD4, B5KFD6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 2, 2010
    Last sequence update: October 14, 2008
    Last modified: October 1, 2014
    This is version 41 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3