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O42254

- IF2B1_CHICK

UniProt

O42254 - IF2B1_CHICK

Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

IGF2BP1

Organism
Gallus gallus (Chicken)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 94 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons By similarity. Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.By similarity7 Publications

    GO - Molecular functioni

    1. mRNA 3'-UTR binding Source: UniProtKB
    2. mRNA 5'-UTR binding Source: Ensembl
    3. nucleotide binding Source: InterPro
    4. translation regulator activity Source: Ensembl

    GO - Biological processi

    1. CRD-mediated mRNA stabilization Source: Ensembl
    2. mRNA transport Source: UniProtKB-KW
    3. negative regulation of translation Source: Ensembl
    4. regulation of mRNA stability involved in response to stress Source: Ensembl

    Keywords - Biological processi

    mRNA transport, Translation regulation, Transport

    Keywords - Ligandi

    RNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Insulin-like growth factor 2 mRNA-binding protein 1
    Short name:
    IGF2 mRNA-binding protein 1
    Short name:
    IMP-1
    Alternative name(s):
    IGF-II mRNA-binding protein 1
    VICKZ family member 1
    Zip-code binding polypeptide
    Zipcode-binding protein 1
    Short name:
    ZBP-1
    Gene namesi
    Name:IGF2BP1
    Synonyms:VICKZ1, ZBP1
    OrganismiGallus gallus (Chicken)
    Taxonomic identifieri9031 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus
    ProteomesiUP000000539: Chromosome 27

    Subcellular locationi

    Nucleus. Cytoplasm. Cytoplasmperinuclear region. Cell projectiongrowth cone. Cell projectionfilopodium. Cell projectionlamellipodium
    Note: In the nucleus, located in discrete foci, coinciding with the sites of ACTB transcription. Export from the nucleus is mediated by XPO1. In the cytoplasm, colocalizes with ACTB mRNA at the leading edge, in growth cone filopodia and along neurites. In these locations, also colocalizes with microtubules. Colocalization with ACTB mRNA is partially lost at the cell periphery, suggesting release of the transcript. In neuronal processes, exhibits fast retrograde and anterograde movements, when associated with ACTB mRNA; this motility is lost when the association is inhibited. In migrating fibroblasts, localizes not only to leading edges, but also to retracting tails. In response to cellular stress, such as oxidative stress or heat shock, recruited to stress granules.

    GO - Cellular componenti

    1. CRD-mediated mRNA stability complex Source: UniProtKB
    2. cytoplasmic stress granule Source: Ensembl
    3. filopodium Source: UniProtKB-SubCell
    4. growth cone Source: UniProtKB-SubCell
    5. lamellipodium Source: UniProtKB-SubCell
    6. nucleus Source: UniProtKB-SubCell
    7. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    8. plasma membrane Source: Ensembl

    Keywords - Cellular componenti

    Cell projection, Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi213 – 2131K → E: Decrease in Y RNA binding. Only small decrease in affinity for binding to ACTB and MYC transcripts, some accumulation in the nucleus, and complete loss of formation of higher ordered protein-RNA complexes; when associated with E-294. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and perturbed subcellular location, including accumulation in the nucleus and loss of localization to stress granules; when associated with E-294, 422-E-E-423 and 505-E-E-506. 1 Publication
    Mutagenesisi294 – 2941K → E: Decrease in Y RNA binding. Only small decrease in affinity for binding to ACTB and MYC transcripts, some accumulation in the nucleus, and complete loss of formation of higher ordered protein-RNA complexes; when associated with E-213. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, 422-E-E-423 and 505-E-E-506. 1 Publication
    Mutagenesisi396 – 3961Y → F: Increases the interaction with ACTB mRNA and its translational repression. 1 Publication
    Mutagenesisi396 – 3961Y → Q: Impairs the interaction with beta-actin mRNA and its translation repression. 1 Publication
    Mutagenesisi422 – 4232KK → EE: Almost complete loss of Y RNA binding. About 80-fold decrease in affinity for binding to ACTB transcript, but almost no effect on MYC transcript binding; when associated with 505-E-E-506. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, E-294 and 505-E-E-506.
    Mutagenesisi504 – 5052KG → EE: Decrease in Y RNA binding. About 80-fold decrease in affinity for binding to ACTB transcript, but almost no effect on MYC transcript binding; when associated with 422-E-E-423. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, E-294 and 422-E-E-423.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 576576Insulin-like growth factor 2 mRNA-binding protein 1PRO_0000282536Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei396 – 3961Phosphotyrosine; by SRC1 Publication

    Post-translational modificationi

    Phosphorylated by SRC at Tyr-396. This residue is involved in ACTB mRNA binding, its phosphorylation impairs association with ACTB mRNA and hence abolishes translational repression. Phosphorylation occurs in close proximity to filopodia and in the growth cones of differentiated neuroglioblastoma cells.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiO42254.

    Expressioni

    Tissue specificityi

    Expressed in neurons and embryonic fibroblasts (at protein level).2 Publications

    Interactioni

    Subunit structurei

    Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Associates with the cytoskeleton, predominantly with actin filament bundles and occasionnally with microtubules. In a heterologous system, interacts with ELAVL1, DHX9 and HNRNPU.1 Publication

    Protein-protein interaction databases

    STRINGi9031.ENSGALP00000001973.

    Structurei

    3D structure databases

    ProteinModelPortaliO42254.
    SMRiO42254. Positions 1-161.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini2 – 7574RRM 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini81 – 15676RRM 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini195 – 26066KH 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini276 – 34368KH 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini404 – 46966KH 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini486 – 55267KH 4PROSITE-ProRule annotationAdd
    BLAST

    Domaini

    Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute to transcript binding. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full length protein By similarity.By similarity

    Sequence similaritiesi

    Belongs to the RRM IMP/VICKZ family.Curated
    Contains 4 KH domains.PROSITE-ProRule annotation
    Contains 2 RRM (RNA recognition motif) domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG249985.
    GeneTreeiENSGT00530000063171.
    HOGENOMiHOG000000675.
    HOVERGENiHBG052725.
    InParanoidiO42254.
    KOiK17391.
    OMAiGSIENCC.
    OrthoDBiEOG7T7GSK.
    PhylomeDBiO42254.
    TreeFamiTF320229.

    Family and domain databases

    Gene3Di3.30.1370.10. 4 hits.
    3.30.70.330. 2 hits.
    InterProiIPR004087. KH_dom.
    IPR004088. KH_dom_type_1.
    IPR012677. Nucleotide-bd_a/b_plait.
    IPR000504. RRM_dom.
    [Graphical view]
    PfamiPF00013. KH_1. 4 hits.
    PF00076. RRM_1. 1 hit.
    [Graphical view]
    SMARTiSM00322. KH. 4 hits.
    SM00360. RRM. 2 hits.
    [Graphical view]
    SUPFAMiSSF54791. SSF54791. 4 hits.
    PROSITEiPS50084. KH_TYPE_1. 4 hits.
    PS50102. RRM. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O42254-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNKLYIGNLN ESVTPADLEK VFNDHKISFS GQFLVKSGYA FVDCPDEQWA    50
    MKAIETFSGK VELHGKQLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDGL 100
    LAQYGTVENC EQVNTDSETA VVNVTYTNRE QTRQAIMKLN GHQLENHVLK 150
    VSYIPDEQSV QGPENGRRGG FGARGAPRQG SPVTAGAPVK QQPVDIPLRL 200
    LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA EKAISIHSTP 250
    EGCSAACKMI LEIMQKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK 300
    KVEQDTETKI TISSLQDLTL YNPERTITVK GSIENCCKAE QEIMKKVREA 350
    YENDVAAMSL QSHLIPGLNL AAVGLFPASS NAVPPPPSSV SGAAPYSSFM 400
    PPEQETVHVF IPAQAVGAII GKKGQHIKQL SRFASASIKI APPETPDSKV 450
    RMVVITGPPE AQFKAQGRIY GKLKEENFFG PKEEVKLETH IRVPASAAGR 500
    VIGKGGKTVN ELQNLTAAEV VVPRDQTPDE NEQVIVKIIG HFYASQMAQR 550
    KIRDILAQVK QQHQKGQSGQ LQARRK 576
    Length:576
    Mass (Da):63,271
    Last modified:January 1, 1998 - v1
    Checksum:i01AAF2D1D81C8811
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026527 mRNA. Translation: AAB82295.1.
    RefSeqiNP_990402.1. NM_205071.1.
    UniGeneiGga.567.

    Genome annotation databases

    EnsembliENSGALT00000001975; ENSGALP00000001973; ENSGALG00000001293.
    GeneIDi395953.
    KEGGigga:395953.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026527 mRNA. Translation: AAB82295.1 .
    RefSeqi NP_990402.1. NM_205071.1.
    UniGenei Gga.567.

    3D structure databases

    ProteinModelPortali O42254.
    SMRi O42254. Positions 1-161.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9031.ENSGALP00000001973.

    Proteomic databases

    PaxDbi O42254.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSGALT00000001975 ; ENSGALP00000001973 ; ENSGALG00000001293 .
    GeneIDi 395953.
    KEGGi gga:395953.

    Organism-specific databases

    CTDi 10642.

    Phylogenomic databases

    eggNOGi NOG249985.
    GeneTreei ENSGT00530000063171.
    HOGENOMi HOG000000675.
    HOVERGENi HBG052725.
    InParanoidi O42254.
    KOi K17391.
    OMAi GSIENCC.
    OrthoDBi EOG7T7GSK.
    PhylomeDBi O42254.
    TreeFami TF320229.

    Miscellaneous databases

    NextBioi 20816018.
    PROi O42254.

    Family and domain databases

    Gene3Di 3.30.1370.10. 4 hits.
    3.30.70.330. 2 hits.
    InterProi IPR004087. KH_dom.
    IPR004088. KH_dom_type_1.
    IPR012677. Nucleotide-bd_a/b_plait.
    IPR000504. RRM_dom.
    [Graphical view ]
    Pfami PF00013. KH_1. 4 hits.
    PF00076. RRM_1. 1 hit.
    [Graphical view ]
    SMARTi SM00322. KH. 4 hits.
    SM00360. RRM. 2 hits.
    [Graphical view ]
    SUPFAMi SSF54791. SSF54791. 4 hits.
    PROSITEi PS50084. KH_TYPE_1. 4 hits.
    PS50102. RRM. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of a beta-actin mRNA zipcode-binding protein."
      Ross A.F., Oleynikov Y., Kislauskis E.H., Taneja K.L., Singer R.H.
      Mol. Cell. Biol. 17:2158-2165(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, TISSUE SPECIFICITY.
      Tissue: Embryonic fibroblast.
    2. "Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility."
      Zhang H.L., Eom T., Oleynikov Y., Shenoy S.M., Liebelt D.A., Dictenberg J.B., Singer R.H., Bassell G.J.
      Neuron 31:261-275(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    3. "Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization."
      Oleynikov Y., Singer R.H.
      Curr. Biol. 13:199-207(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, SUBCELLULAR LOCATION.
    4. "Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment."
      Farina K.L., Huttelmaier S., Musunuru K., Darnell R., Singer R.H.
      J. Cell Biol. 160:77-87(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, SUBCELLULAR LOCATION, DOMAIN.
    5. Cited for: SUBCELLULAR LOCATION.
    6. "Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1."
      Huttelmaier S., Zenklusen D., Lederer M., Dictenberg J., Lorenz M., Meng X., Bassell G.J., Condeelis J., Singer R.H.
      Nature 438:512-515(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION AT TYR-396, MUTAGENESIS OF TYR-396, SUBCELLULAR LOCATION.
    7. "IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling."
      Stohr N., Kohn M., Lederer M., Glass M., Reinke C., Singer R.H., Huttelmaier S.
      Genes Dev. 26:176-189(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CELL MIGRATION.
    8. "Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains."
      Wachter K., Kohn M., Stohr N., Huttelmaier S.
      Biol. Chem. 394:1077-1090(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, RNA-BINDING, OLIGOMERIZATION, INTERACTION WITH ELAVL1; DHX9 AND HNRNPU, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF LYS-213; LYS-294; 423-LYS-LYS-424 AND 505-LYS-GLY-506.
    9. "Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?"
      Bell J.L., Wachter K., Muhleck B., Pazaitis N., Kohn M., Lederer M., Huttelmaier S.
      Cell. Mol. Life Sci. 70:2657-2675(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.

    Entry informationi

    Entry nameiIF2B1_CHICK
    AccessioniPrimary (citable) accession number: O42254
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 3, 2007
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 94 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