insulin-like growth factor 2 mRNA-binding protein 1 (IGF2 mRNA-binding protein 1, IMP-1, coding region determinant-binding protein, CRD-BP, VICKZ family member 1, IGF2BP1, CRDBP, VICKZ1)

Function: - RNA-binding factor - affects mRNA nuclear export, localization, stability & translation - binds to the 5'-UTR of insulin-like growth factor 2 (IGF2) mRNA & regulates its subcellular localization & translation - binds both to coding region mRNA stability determinant (CRD) & to AU-rich sequences in 3'-UTR of MYC & CD44 mRNAs & stabilizes these mRNAs - binds to 4th & 5th exons of oncofetal H19 & neuron-specific TAU mRNAs & regulates their localizations - binds to adenine-rich autoregulatory sequence (ARS) 5'-UTR of PABPC1 mRNA & is involved in its translational repression - RNA-binding activity to ARS is stimulated by PABPC1 - binds to coding sequence region of BTRC/FBW1A mRNA & mediates stabilization of BTRC/FBW1A & MYC mRNAs in response to beta-catenin signaling - binding to RNA employs a cooperative, sequential mechanism of homo- or heterodimerization - protects the MYC & MDR-1 mRNAs from cleavage by endoribonuclease, thus prolonging their stability - binds to 3'-UTR axonal localization signal of TAU mRNA - binds to conserved 54-nucleotide element in the 3'-UTR of beta actin mRNA known as the 'zipcode' - promotes translocation of the beta-actin mRNA to dendrites - may act as a regulator of mRNA transport to activated synapses in response to synaptic activity - can form homodimers & heterodimers with IGF2BP1 or IGF2BP3 - associates with mRNP complex - found in a RNP granule complex with FMR1 - interacts with FMR1 - component of autoregulatory ribonucleoprotein complex - interacts through 3rd & 4th KH domains with PABPC1 (RNA-independent) - component of a TAU mRNP complex - interacts with ELAVL4 (RNA-dependent) - associates with microtubules & polysomes - phosphorylated - phosphorylation may influence mRNA translation Structure: - belongs to the RRM IMP/VICKZ family - contains 4 KH domains - contains 2 RRM domains (RNA recognition motif) Compartment: - nucleus, cytoplasm - found in lamellipodia of the leading edge, in perinuclear region, & beneath the plasma membrane - subcytoplasmic localization is cell specific & regulated by cell contact & growth - colocalized with H19 RNA at lamellipodia - colocalized with CD44 mRNA in RNP granules - nuclear export is mediated by XPO1/CRM1 - in motile cells, transported towards the leading edge into the cortical region of lamellipodia where it is connected to microfilaments - present in the form of granules & into F-actin-rich protrusion of dendrites, spines & subsynaptic sites - colocalizes with beta-actin mRNA in dendrites & spines - exhibited rapid, bidirectional movements in dendrites & spines - neuronal depolarization by KCl induces its rapid efflux from the cell body into dendrites Alternative splicing: named isoforms=1 Expression: - expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary, gonocytes of testis, oocytes, spermatogonia & semen (at protein level) - expressed in kidney, prostate, trachea - up-regulated in response to beta-catenin activation Pathology: - expressed in testicular cancer & lung cancer (at protein level) - role in growth or survival of lung-cancer cells

General

phosphoprotein RNA-binding protein

Properties

SIZE: MW = 63 kD entity length = 577 aa COMPARTMENT: cytoplasm cell nucleus MOTIF: RNP motif NAME: RNP motif SITE: 2-75 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif RNP motif NAME: RNP motif SITE: 81-156 FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif NAME: ribonucleoprotein-1 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif ribonucleoprotein-2 motif FOR-BINDING-OF: ribonucleic acid MOTIF: ribonucleoprotein-1 motif ribonucleoprotein-2 motif Ser phosphorylation site {S181} Necessary for interaction with ELAVL4 and binding to TAU mRNA {187-570} MOTIF: KH domain SITE: 195-260 FOR-BINDING-OF: ribonucleic acid KH domain SITE: 276-343 FOR-BINDING-OF: ribonucleic acid nuclear export {312-323} KH domain SITE: 405-470 FOR-BINDING-OF: ribonucleic acid domain {485-495} KH domain SITE: 487-553 FOR-BINDING-OF: ribonucleic acid

Database Correlations

UniProt Q9NZI8 PFAM correlations

References

UniProt :accession Q9NZI8