Insulin-like growth factor 2 mRNA-binding protein 1

UniProt Q9NZI8 Organism Homo sapiens Gene CRDBP, IGF2BP1, VICKZ1, ZBP1

Also known as: CRDBP, IGF2BP1, VICKZ1, ZBP1

Function

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. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability. 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, 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 (By similarity). 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 ACTB (By similarity). May regulate mRNA transport to activated synapses (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). 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 preventing MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. Binding to MYC mRNA is enhanced by m6A-modification of the CRD. Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to the oncofetal H19 transcript and to the neuron-specific TAU mRNA and regulates their localizations. Binds to and stabilizes BTRC/FBW1A mRNA. 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. Promotes the directed movement of tumor-derived 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. Interacts with Hepatitis C virus (HCV) 5'-UTR and 3'-UTR and specifically enhances translation at the HCV IRES, but not 5'-cap-dependent translation, possibly by recruiting eIF3. Interacts with HIV-1 GAG protein and blocks the formation of infectious HIV-1 particles. Reduces HIV-1 assembly by inhibiting viral RNA packaging, as well as assembly and processing of GAG protein on cellular membranes. 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.

Classification

Family (Pfam): PF00013 KH_1, PF00076 RRM_1
InterPro: IGF2BP1_RRM1, IGF2BP1_RRM2, KH_dom, KH_dom_type_1, KH_dom_type_1_sf, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom
Functional cluster: Protein Serine/Threonine Kinases

Experimental structures · PDB · 2

3KRM X-ray 2.75A
6QEY X-ray 2.20A

A predicted model is available from AlphaFold.

Gene Ontology · 29

Neighborhood · nearest proteins

Nearest neighbours of Insulin-like growth factor 2 mRNA-binding protein 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Insulin-like growth factor 2 mRNA-binding protein 1 4 shared papers
Insulin-like growth factor 2 mRNA-binding protein 1 7 shared papers
Insulin-like growth factor 2 mRNA-binding protein 3 8 shared papers
Insulin-like growth factor 2 mRNA-binding protein 2 6 shared papers
Insulin-like growth factor 2 mRNA-binding protein 3 4 shared papers
Polyadenylate-binding protein 1 7 shared papers
Insulin-like growth factor 2 mRNA-binding protein 2 2 shared papers
Putative RNA-binding regulatory peptide 1 shared papers
Insulin-like growth factor 2 mRNA-binding protein 1 1 shared papers
ELAV-like protein 1 5 shared papers
Cold shock domain-containing protein E1 1 shared papers
Fragile X messenger ribonucleoprotein 1 1 shared papers

Literature · 35 cited papers

An oncopeptide regulates m6A recognition by the m6A reader IGF2BP1 and tumorigenesis. Nat. Commun. · 2020
Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat. Cell Biol. · 2018
Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains. Biol. Chem. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression? Cell. Mol. Life Sci. · 2013
IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling. Genes Dev. · 2012
Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
ZBP1 recognition of beta-actin zipcode induces RNA looping. Genes Dev. · 2010
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
CRD-BP protects the coding region of betaTrCP1 mRNA from miR-183-mediated degradation. Mol. Cell · 2009
IGF2BP1 enhances HCV IRES-mediated translation initiation via the 3'UTR. RNA · 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
… and 23 more in the literature graph

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