IGF2BP3
Domain
All KH domains contribute to binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute (PubMed:29476152). The KH domains are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules.
Function
RNA-binding factor that may recruit 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 (PubMed:29476152). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.
Sequence Similarities
Belongs to the RRM IMP/VICKZ family.
Tissue Specificity
Expressed in fetal liver, fetal lung, fetal kidney, fetal thymus, fetal placenta, fetal follicles of ovary and gonocytes of testis, growing oocytes, spermatogonia and semen (at protein level). Expressed in cervix adenocarcinoma, in testicular, pancreatic and renal-cell carcinomas (at protein level). Expressed ubiquitously during fetal development at 8 and 14 weeks of gestation. Expressed in ovary, testis, brain, placenta, pancreatic cancer tissues and pancreatic cancer cell lines.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasm
- P-body
- Cytoplasm
- Stress granule
- Found in lamellipodia of the leading edge, in the perinuclear region, and beneath the plasma membrane. The subcytoplasmic localization is cell specific and regulated by cell contact and growth. Localized at the connecting piece and the tail of the spermatozoa. Colocalized with CD44 mRNA in RNP granules. In response to cellular stress, such as oxidative stress, recruited to stress granules.
Alternative names
IMP3, KOC1, VICKZ3, IGF2BP3, Insulin-like growth factor 2 mRNA-binding protein 3, IGF2 mRNA-binding protein 3, IMP-3, IGF-II mRNA-binding protein 3, KH domain-containing protein overexpressed in cancer, VICKZ family member 3, hKOC