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Q8CGX0

- IF2B1_RAT

UniProt

Q8CGX0 - IF2B1_RAT

Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

Igf2bp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 87 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      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. During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of beta-actin/ACTB By similarity. May regulate mRNA transport to activated synapses By similarity. Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells By similarity. Binds to the oncofetal H19 transcript and to the neuron-specific TAU mRNA and regulates their localization By similarity. Binds to and stabilizes BTRC/FBW1A mRNA By similarity. Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2 By similarity. During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts By similarity. Binds to the 3'-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD By similarity. Binds to and stabilizes ABCB1/MDR-1 mRNA By similarity. During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing By similarity. Interacts with GAP43 transcript and transports it to axons. Regulates localized ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The 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, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons.By similarity4 Publications

    GO - Molecular functioni

    1. mRNA 3'-UTR binding Source: UniProtKB
    2. mRNA 5'-UTR binding Source: Ensembl
    3. mRNA binding Source: UniProtKB
    4. nucleotide binding Source: InterPro
    5. 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: UniProtKB
    5. RNA localization Source: RGD

    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):
    B-actin zipcode-binding protein 1
    Short name:
    ZBP1
    Short name:
    rZBP-1
    IGF-II mRNA-binding protein 1
    VICKZ family member 1
    Gene namesi
    Name:Igf2bp1
    Synonyms:Imp1, Vickz1
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Chromosome 10

    Organism-specific databases

    RGDi708580. Igf2bp1.

    Subcellular locationi

    Nucleus By similarity. Cytoplasm. Cytoplasmperinuclear region By similarity. Cell projectionlamellipodium By similarity. Cell projectiondendrite. Cell projectiondendritic spine. Cell projectiongrowth cone By similarity. Cell projectionfilopodium. Cell projectionaxon
    Note: In the nucleus, located in discrete foci, coinciding with the sites of ACTB transcription By similarity. In the cytoplasm, localizes in cytoplasmic mRNP granules. Colocalizes with microtubules in growth cone filopodia and along neurites in neuronal cells By similarity. Cytoplasmic colocalization with ACTB mRNA is partially lost at the cell periphery, suggesting release of the transcript By similarity. In cultured hippocampal neurons, predominantly located within dendrites, particularly at dendritic branching points in young cells, compared to axons. In axons, predominantly found in axonal branches and their growth cones. In dendrites, can exhibit different types of movements, from fast retrograde and anterograde movements to stable localization. Dendritic levels are regulated by neuronal activity and glutaminergic signals: they are increased by KCl-induced depolarization, which induces rapid efflux from the cell body into dendrites, and decreased by the NMDA receptor agonist AP-5. In motile cells, such as migrating fibroblasts, localizes to leading edges where it colocalizes with microtubules and microfilaments and to retracting tails By similarity. In motile cells, transported towards the leading edge into the cortical region of the lamellipodia where it is connected to microfilaments By similarity. In response to cellular stress, such as oxidative stress or heat shock, recruited to stress granules, but not to processing bodies By similarity.By similarity

    GO - Cellular componenti

    1. axon Source: UniProtKB-SubCell
    2. CRD-mediated mRNA stability complex Source: UniProtKB
    3. cytoplasmic stress granule Source: UniProtKB
    4. dendrite Source: RGD
    5. dendritic spine Source: UniProtKB-SubCell
    6. filopodium Source: UniProtKB-SubCell
    7. growth cone Source: UniProtKB-SubCell
    8. lamellipodium Source: UniProtKB-SubCell
    9. nucleus Source: UniProtKB-SubCell
    10. perinuclear region of cytoplasm Source: UniProtKB-SubCell
    11. plasma membrane Source: Ensembl
    12. ribonucleoprotein complex Source: UniProtKB

    Keywords - Cellular componenti

    Cell projection, Cytoplasm, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi213 – 2142KE → EL: Loss of function in dendritogenesis; when associated with 294-E-L-295 and 423-E-L-424.
    Mutagenesisi294 – 2952KE → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 423-E-L-424.
    Mutagenesisi396 – 3961Y → F: Loss of function in dendritogenesis. 1 Publication
    Mutagenesisi423 – 4242KK → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 294-E-L-295.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 577577Insulin-like growth factor 2 mRNA-binding protein 1PRO_0000282535Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei181 – 1811PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated. Phosphorylation may impair association with ACTB mRNA and hence abolishes translational repression By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ8CGX0.
    PRIDEiQ8CGX0.

    PTM databases

    PhosphoSiteiQ8CGX0.

    Expressioni

    Tissue specificityi

    Expressed in fetal development and neonatal life, but is undetectable in adult tissues (at protein level). Expressed in embryonic neurons, including in hippocampal (at protein level) and cortical neurons. Also expressed in transformed tissue cultured cell lines derived form adult tissues (at protein level).4 Publications

    Gene expression databases

    GenevestigatoriQ8CGX0.

    Interactioni

    Subunit structurei

    Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3 By similarity. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 By similarity. Identification in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 By similarity. Associates with mRNP complex By similarity. Interacts with FMR1 By similarity. Component of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1 By similarity. Interacts through the third and fourth KH domains with PABPC1 in an RNA-independent manner By similarity. Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP By similarity. Interacts with ELAVL4 in an RNA-dependent manner By similarity. Associates with microtubules and polysomes. Interacts with AGO1 and AGO2 By similarity.By similarity

    Protein-protein interaction databases

    STRINGi10116.ENSRNOP00000008139.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8CGX0.
    SMRiQ8CGX0. 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
    Domaini405 – 47066KH 3PROSITE-ProRule annotationAdd
    BLAST
    Domaini487 – 55367KH 4PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni187 – 570384Necessary for interaction with ELAVL4 and binding to TAU mRNABy similarityAdd
    BLAST
    Regioni312 – 32312Sufficient for nuclear exportBy similarityAdd
    BLAST
    Regioni485 – 49511Sufficient for nuclear exportBy similarityAdd
    BLAST

    Domaini

    Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. 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.
    InParanoidiQ8CGX0.
    KOiK17391.
    OMAiGSIENCC.
    OrthoDBiEOG7T7GSK.
    PhylomeDBiQ8CGX0.
    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. 2 hits.
    PF13014. KH_3. 2 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.

    Q8CGX0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA    50
    MKAIETFSGK VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL 100
    LAQYGTVENC EQVNTESETA VVNVTYSNRE QTRQAIMKLN GHQLENHALK 150
    VSYIPDEQIA QGPENGRRGG FGSRGQPRQG SPVAAGAPAK QQQVDIPLRL 200
    LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA EKAISVHSTP 250
    EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK 300
    KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA 350
    YENDVAAMSL QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYGSFM 400
    QAPEQEMVQV FIPAQAVGAI IGKKGQHIKQ LSRFASASIK IAPPETPDSK 450
    VRMVVITGPP EAQFKAQGRI YGKLKEENFF GPKEEVKLET HIRVPASAAG 500
    RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII GHFYASQMAQ 550
    RKIRDILAQV KQQHQKGQSN QAQARRK 577
    Length:577
    Mass (Da):63,437
    Last modified:March 1, 2003 - v1
    Checksum:i0647676128FBD1EE
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF541940 mRNA. Translation: AAO16210.1.
    CH473948 Genomic DNA. Translation: EDM05776.1.
    BC161831 mRNA. Translation: AAI61831.1.
    RefSeqiNP_783184.1. NM_175594.2.
    UniGeneiRn.77572.

    Genome annotation databases

    EnsembliENSRNOT00000008139; ENSRNOP00000008139; ENSRNOG00000006122.
    GeneIDi303477.
    KEGGirno:303477.
    UCSCiRGD:708580. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF541940 mRNA. Translation: AAO16210.1 .
    CH473948 Genomic DNA. Translation: EDM05776.1 .
    BC161831 mRNA. Translation: AAI61831.1 .
    RefSeqi NP_783184.1. NM_175594.2.
    UniGenei Rn.77572.

    3D structure databases

    ProteinModelPortali Q8CGX0.
    SMRi Q8CGX0. Positions 1-161.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10116.ENSRNOP00000008139.

    PTM databases

    PhosphoSitei Q8CGX0.

    Proteomic databases

    PaxDbi Q8CGX0.
    PRIDEi Q8CGX0.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSRNOT00000008139 ; ENSRNOP00000008139 ; ENSRNOG00000006122 .
    GeneIDi 303477.
    KEGGi rno:303477.
    UCSCi RGD:708580. rat.

    Organism-specific databases

    CTDi 10642.
    RGDi 708580. Igf2bp1.

    Phylogenomic databases

    eggNOGi NOG249985.
    GeneTreei ENSGT00530000063171.
    HOGENOMi HOG000000675.
    HOVERGENi HBG052725.
    InParanoidi Q8CGX0.
    KOi K17391.
    OMAi GSIENCC.
    OrthoDBi EOG7T7GSK.
    PhylomeDBi Q8CGX0.
    TreeFami TF320229.

    Miscellaneous databases

    NextBioi 651402.
    PROi Q8CGX0.

    Gene expression databases

    Genevestigatori Q8CGX0.

    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. 2 hits.
    PF13014. KH_3. 2 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. "Localization of a beta-actin messenger ribonucleoprotein complex with zipcode-binding protein modulates the density of dendritic filopodia and filopodial synapses."
      Eom T., Antar L.N., Singer R.H., Bassell G.J.
      J. Neurosci. 23:10433-10444(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
      Strain: Sprague-Dawley.
      Tissue: Embryonic brain.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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].
      Tissue: Embryonic kidney.
    4. "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro."
      Leeds P., Kren B.T., Boylan J.M., Betz N.A., Steer C.J., Gruppuso P.A., Ross J.
      Oncogene 14:1279-1286(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: RNA-BINDING, TISSUE SPECIFICITY.
    5. "Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons."
      Tiruchinapalli D.M., Oleynikov Y., Kelic S., Shenoy S.M., Hartley A., Stanton P.K., Singer R.H., Bassell G.J.
      J. Neurosci. 23:3251-3261(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    6. "Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity."
      Donnelly C.J., Willis D.E., Xu M., Tep C., Jiang C., Yoo S., Schanen N.C., Kirn-Safran C.B., van Minnen J., English A., Yoon S.O., Bassell G.J., Twiss J.L.
      EMBO J. 30:4665-4677(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN AXONAL REGENERATION.
    7. "Zipcode binding protein 1 regulates the development of dendritic arbors in hippocampal neurons."
      Perycz M., Urbanska A.S., Krawczyk P.S., Parobczak K., Jaworski J.
      J. Neurosci. 31:5271-5285(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 213-LYS-GLU-214; 294-LYS-GLU-295; TYR-396 AND 423-LYS-LYS-424.
    8. "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_RAT
    AccessioniPrimary (citable) accession number: Q8CGX0
    Secondary accession number(s): B1WBP3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 3, 2007
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 87 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