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)
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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