Q8CGX0 (IF2B1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 85. History...
Names and origin
|Protein names||Recommended name:|
Insulin-like growth factor 2 mRNA-binding protein 1
Short name=IGF2 mRNA-binding protein 1
B-actin zipcode-binding protein 1
IGF-II mRNA-binding protein 1
VICKZ family member 1
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||577 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. Ref.1 Ref.5 Ref.6 Ref.7
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.
Nucleus By similarity. Cytoplasm. Cytoplasm › perinuclear region By similarity. Cell projection › lamellipodium By similarity. Cell projection › dendrite. Cell projection › dendritic spine. Cell projection › growth cone By similarity. Cell projection › filopodium. Cell projection › axon. 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. Ref.1 Ref.5 Ref.7
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). Ref.1 Ref.4 Ref.5 Ref.7
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.
Phosphorylated. Phosphorylation may impair association with ACTB mRNA and hence abolishes translational repression By similarity.
Belongs to the RRM IMP/VICKZ family.
Contains 4 KH domains.
Contains 2 RRM (RNA recognition motif) domains.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 577||577||Insulin-like growth factor 2 mRNA-binding protein 1||PRO_0000282535|
|Domain||2 – 75||74||RRM 1|
|Domain||81 – 156||76||RRM 2|
|Domain||195 – 260||66||KH 1|
|Domain||276 – 343||68||KH 2|
|Domain||405 – 470||66||KH 3|
|Domain||487 – 553||67||KH 4|
|Region||187 – 570||384||Necessary for interaction with ELAVL4 and binding to TAU mRNA By similarity|
|Region||312 – 323||12||Sufficient for nuclear export By similarity|
|Region||485 – 495||11||Sufficient for nuclear export By similarity|
Amino acid modifications
|Modified residue||181||1||Phosphoserine By similarity|
|Mutagenesis||213 – 214||2||KE → EL: Loss of function in dendritogenesis; when associated with 294-E-L-295 and 423-E-L-424.|
|Mutagenesis||294 – 295||2||KE → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 423-E-L-424.|
|Mutagenesis||396||1||Y → F: Loss of function in dendritogenesis. Ref.7|
|Mutagenesis||423 – 424||2||KK → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 294-E-L-295.|
|||"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.
Tissue: Embryonic brain.
|||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].
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|||"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.
|AF541940 mRNA. Translation: AAO16210.1.|
CH473948 Genomic DNA. Translation: EDM05776.1.
BC161831 mRNA. Translation: AAI61831.1.
|RefSeq||NP_783184.1. NM_175594.2. |
3D structure databases
|SMR||Q8CGX0. Positions 1-161. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000008139; ENSRNOP00000008139; ENSRNOG00000006122. |
|UCSC||RGD:708580. rat. |
|RGD||708580. Igf2bp1. |
Gene expression databases
Family and domain databases
|Gene3D||3.30.1370.10. 4 hits. |
18.104.22.1680. 2 hits.
|InterPro||IPR004087. KH_dom. |
|Pfam||PF00013. KH_1. 2 hits. |
PF13014. KH_3. 2 hits.
PF00076. RRM_1. 1 hit.
|SMART||SM00322. KH. 4 hits. |
SM00360. RRM. 2 hits.
|SUPFAM||SSF54791. SSF54791. 4 hits. |
|PROSITE||PS50084. KH_TYPE_1. 4 hits. |
PS50102. RRM. 2 hits.
|Accession||Primary (citable) accession number: Q8CGX0|
Secondary accession number(s): B1WBP3
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families