InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IGF2BP1

Summary

InnateDB Protein

IDBP-57433.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

IGF2BP1

Protein Name

insulin-like growth factor 2 mRNA binding protein 1

Synonyms

CRD-BP; CRDBP; IMP-1; IMP1; VICKZ1; ZBP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000290341

InnateDB Gene

IDBG-57431 (IGF2BP1)

Protein Structure

UniProt Annotation

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. 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 prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-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. {ECO:0000250, ECO:0000269PubMed:10875929, ECO:0000269PubMed:16356927, ECO:0000269PubMed:16541107, ECO:0000269PubMed:16778892, ECO:0000269PubMed:17101699, ECO:0000269PubMed:17255263, ECO:0000269PubMed:17893325, ECO:0000269PubMed:18385235, ECO:0000269PubMed:19029303, ECO:0000269PubMed:19541769, ECO:0000269PubMed:19647520, ECO:0000269PubMed:20080952, ECO:0000269PubMed:22279049, ECO:0000269PubMed:8132663, ECO:0000269PubMed:9891060}.

Subcellular Localization

Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Cell projection, lamellipodium. Cell projection, dendrite {ECO:0000250}. Cell projection, dendritic spine {ECO:0000250}. Cell projection, growth cone. Cell projection, filopodium {ECO:0000250}. Cell projection, axon {ECO:0000250}. 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. In neuronal processes, exhibits fast retrograde and anterograde movements, when associated with ACTB mRNA; this motility is lost when the association is inhibited (By similarity). In hippocampal neurons, predominantly located within dendrites, particularly at dendritic branching points in young cells, compared to axons (By similarity). In axons, predominantly found in axonal branches and their growth cones (By similarity). In motile cells, such as migrating fibroblasts, localizes to leading edges where it colocalizes with microtubules and microfilaments and to retracting tails (By similarity). 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 (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. {ECO:0000250}.

Disease Associations

Tissue Specificity

Mainly expressed in the embryo, including in fetal liver, fetal lung, fetal kidney, fetal thymus (at protein level). Also expressed follicles of ovary, as well as in gonocytes of testis, spermatogonia, semen, oocytes and placenta (at protein level). Expressed in various cancers, including testis and lung cancers (at protein level), as well as kidney, prostate and trachea cancers. {ECO:0000269PubMed:12921532, ECO:0000269PubMed:16049158, ECO:0000269PubMed:17255263, ECO:0000269PubMed:9891060}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 63 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	63 [view]
Protein-Protein	63 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0003676	nucleic acid binding
GO:0003723	RNA binding
GO:0003729	mRNA binding
GO:0003730	mRNA 3'-UTR binding
GO:0005515	protein binding
GO:0044822	poly(A) RNA binding
GO:0045182	translation regulator activity
GO:0048027	mRNA 5'-UTR binding

Biological Process

GO:0006403	RNA localization
GO:0010467	gene expression
GO:0010610	regulation of mRNA stability involved in response to stress
GO:0017148	negative regulation of translation
GO:0042035	regulation of cytokine biosynthetic process
GO:0051028	mRNA transport
GO:0070934	CRD-mediated mRNA stabilization

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0010494	cytoplasmic stress granule
GO:0030027	lamellipodium
GO:0030175	filopodium
GO:0030424	axon
GO:0030425	dendrite
GO:0030426	growth cone
GO:0030529	ribonucleoprotein complex
GO:0043197	dendritic spine
GO:0048471	perinuclear region of cytoplasm
GO:0070937	CRD-mediated mRNA stability complex