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O42254 (IF2B1_CHICK) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Insulin-like growth factor 2 mRNA-binding protein 1

Short name=IGF2 mRNA-binding protein 1
Short name=IMP-1
Alternative name(s):
IGF-II mRNA-binding protein 1
VICKZ family member 1
Zip-code binding polypeptide
Zipcode-binding protein 1
Short name=ZBP-1
Gene names
Name:IGF2BP1
Synonyms:VICKZ1, ZBP1
OrganismGallus gallus (Chicken) [Reference proteome]
Taxonomic identifier9031 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiTestudines + Archosauria groupArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalliformesPhasianidaePhasianinaeGallus

Protein attributes

Sequence length576 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (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, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Promotes the directed movement of 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. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Ref.7 Ref.8

Subunit structure

Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Associates with the cytoskeleton, predominantly with actin filament bundles and occasionnally with microtubules. In a heterologous system, interacts with ELAVL1, DHX9 and HNRNPU. Ref.8

Subcellular location

Nucleus. Cytoplasm. Cytoplasmperinuclear region. Cell projectiongrowth cone. Cell projectionfilopodium. Cell projectionlamellipodium. Note: In the nucleus, located in discrete foci, coinciding with the sites of ACTB transcription. Export from the nucleus is mediated by XPO1. In the cytoplasm, colocalizes with ACTB mRNA at the leading edge, in growth cone filopodia and along neurites. In these locations, also colocalizes with microtubules. 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. In migrating fibroblasts, localizes not only to leading edges, but also to retracting tails. In response to cellular stress, such as oxidative stress or heat shock, recruited to stress granules. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8

Tissue specificity

Expressed in neurons and embryonic fibroblasts (at protein level). Ref.1 Ref.2

Domain

Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute to transcript binding. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full length protein By similarity. Ref.4 Ref.8

Post-translational modification

Phosphorylated by SRC at Tyr-396. This residue is involved in ACTB mRNA binding, its phosphorylation impairs association with ACTB mRNA and hence abolishes translational repression. Phosphorylation occurs in close proximity to filopodia and in the growth cones of differentiated neuroglioblastoma cells. Ref.6

Sequence similarities

Belongs to the RRM IMP/VICKZ family.

Contains 4 KH domains.

Contains 2 RRM (RNA recognition motif) domains.

Ontologies

Keywords
   Biological processmRNA transport
Translation regulation
Transport
   Cellular componentCell projection
Cytoplasm
Nucleus
   DomainRepeat
   LigandRNA-binding
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processCRD-mediated mRNA stabilization

Inferred from electronic annotation. Source: Ensembl

mRNA transport

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of translation

Inferred from electronic annotation. Source: Ensembl

regulation of mRNA stability involved in response to stress

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentCRD-mediated mRNA stability complex

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasmic stress granule

Inferred from electronic annotation. Source: Ensembl

filopodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

growth cone

Inferred from electronic annotation. Source: UniProtKB-SubCell

lamellipodium

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionmRNA 3'-UTR binding

Inferred from sequence or structural similarity. Source: UniProtKB

mRNA 5'-UTR binding

Inferred from electronic annotation. Source: Ensembl

nucleotide binding

Inferred from electronic annotation. Source: InterPro

translation regulator activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 576576Insulin-like growth factor 2 mRNA-binding protein 1
PRO_0000282536

Regions

Domain2 – 7574RRM 1
Domain81 – 15676RRM 2
Domain195 – 26066KH 1
Domain276 – 34368KH 2
Domain404 – 46966KH 3
Domain486 – 55267KH 4

Amino acid modifications

Modified residue3961Phosphotyrosine; by SRC Ref.6

Experimental info

Mutagenesis2131K → E: Decrease in Y RNA binding. Only small decrease in affinity for binding to ACTB and MYC transcripts, some accumulation in the nucleus, and complete loss of formation of higher ordered protein-RNA complexes; when associated with E-294. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and perturbed subcellular location, including accumulation in the nucleus and loss of localization to stress granules; when associated with E-294, 422-E-E-423 and 505-E-E-506. Ref.8
Mutagenesis2941K → E: Decrease in Y RNA binding. Only small decrease in affinity for binding to ACTB and MYC transcripts, some accumulation in the nucleus, and complete loss of formation of higher ordered protein-RNA complexes; when associated with E-213. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, 422-E-E-423 and 505-E-E-506. Ref.8
Mutagenesis3961Y → F: Increases the interaction with ACTB mRNA and its translational repression. Ref.6
Mutagenesis3961Y → Q: Impairs the interaction with beta-actin mRNA and its translation repression. Ref.6
Mutagenesis422 – 4232KK → EE: Almost complete loss of Y RNA binding. About 80-fold decrease in affinity for binding to ACTB transcript, but almost no effect on MYC transcript binding; when associated with 505-E-E-506. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, E-294 and 505-E-E-506.
Mutagenesis504 – 5052KG → EE: Decrease in Y RNA binding. About 80-fold decrease in affinity for binding to ACTB transcript, but almost no effect on MYC transcript binding; when associated with 422-E-E-423. Loss of homo- and heterooligomerization with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC transcript binding, almost complete loss of ELAVL1-, DHX9- and HNRNPU-binding and accumulation in the nucleus; when associated with E-213, E-294 and 422-E-E-423.

Sequences

Sequence LengthMass (Da)Tools
O42254 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 01AAF2D1D81C8811

FASTA57663,271
        10         20         30         40         50         60 
MNKLYIGNLN ESVTPADLEK VFNDHKISFS GQFLVKSGYA FVDCPDEQWA MKAIETFSGK 

        70         80         90        100        110        120 
VELHGKQLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDGL LAQYGTVENC EQVNTDSETA 

       130        140        150        160        170        180 
VVNVTYTNRE QTRQAIMKLN GHQLENHVLK VSYIPDEQSV QGPENGRRGG FGARGAPRQG 

       190        200        210        220        230        240 
SPVTAGAPVK QQPVDIPLRL LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA 

       250        260        270        280        290        300 
EKAISIHSTP EGCSAACKMI LEIMQKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK 

       310        320        330        340        350        360 
KVEQDTETKI TISSLQDLTL YNPERTITVK GSIENCCKAE QEIMKKVREA YENDVAAMSL 

       370        380        390        400        410        420 
QSHLIPGLNL AAVGLFPASS NAVPPPPSSV SGAAPYSSFM PPEQETVHVF IPAQAVGAII 

       430        440        450        460        470        480 
GKKGQHIKQL SRFASASIKI APPETPDSKV RMVVITGPPE AQFKAQGRIY GKLKEENFFG 

       490        500        510        520        530        540 
PKEEVKLETH IRVPASAAGR VIGKGGKTVN ELQNLTAAEV VVPRDQTPDE NEQVIVKIIG 

       550        560        570 
HFYASQMAQR KIRDILAQVK QQHQKGQSGQ LQARRK 

« Hide

References

[1]"Characterization of a beta-actin mRNA zipcode-binding protein."
Ross A.F., Oleynikov Y., Kislauskis E.H., Taneja K.L., Singer R.H.
Mol. Cell. Biol. 17:2158-2165(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, TISSUE SPECIFICITY.
Tissue: Embryonic fibroblast.
[2]"Neurotrophin-induced transport of a beta-actin mRNP complex increases beta-actin levels and stimulates growth cone motility."
Zhang H.L., Eom T., Oleynikov Y., Shenoy S.M., Liebelt D.A., Dictenberg J.B., Singer R.H., Bassell G.J.
Neuron 31:261-275(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"Real-time visualization of ZBP1 association with beta-actin mRNA during transcription and localization."
Oleynikov Y., Singer R.H.
Curr. Biol. 13:199-207(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, SUBCELLULAR LOCATION.
[4]"Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule formation, and cytoskeletal attachment."
Farina K.L., Huttelmaier S., Musunuru K., Darnell R., Singer R.H.
J. Cell Biol. 160:77-87(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, SUBCELLULAR LOCATION, DOMAIN.
[5]"ZBP1 regulates mRNA stability during cellular stress."
Stoehr N., Lederer M., Reinke C., Meyer S., Hatzfeld M., Singer R.H., Huettelmaier S.
J. Cell Biol. 175:527-534(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[6]"Spatial regulation of beta-actin translation by Src-dependent phosphorylation of ZBP1."
Huttelmaier S., Zenklusen D., Lederer M., Dictenberg J., Lorenz M., Meng X., Bassell G.J., Condeelis J., Singer R.H.
Nature 438:512-515(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-396, MUTAGENESIS OF TYR-396, SUBCELLULAR LOCATION.
[7]"IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling."
Stohr N., Kohn M., Lederer M., Glass M., Reinke C., Singer R.H., Huttelmaier S.
Genes Dev. 26:176-189(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL MIGRATION.
[8]"Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding proteins) is modulated by distinct RNA-binding domains."
Wachter K., Kohn M., Stohr N., Huttelmaier S.
Biol. Chem. 394:1077-1090(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, RNA-BINDING, OLIGOMERIZATION, INTERACTION WITH ELAVL1; DHX9 AND HNRNPU, SUBCELLULAR LOCATION, DOMAIN, MUTAGENESIS OF LYS-213; LYS-294; 423-LYS-LYS-424 AND 505-LYS-GLY-506.
[9]"Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of cancer progression?"
Bell J.L., Wachter K., Muhleck B., Pazaitis N., Kohn M., Lederer M., Huttelmaier S.
Cell. Mol. Life Sci. 70:2657-2675(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF026527 mRNA. Translation: AAB82295.1.
RefSeqNP_990402.1. NM_205071.1.
UniGeneGga.567.

3D structure databases

ProteinModelPortalO42254.
SMRO42254. Positions 1-161.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9031.ENSGALP00000001973.

Proteomic databases

PaxDbO42254.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSGALT00000001975; ENSGALP00000001973; ENSGALG00000001293.
GeneID395953.
KEGGgga:395953.

Organism-specific databases

CTD10642.

Phylogenomic databases

eggNOGNOG249985.
GeneTreeENSGT00530000063171.
HOGENOMHOG000000675.
HOVERGENHBG052725.
InParanoidO42254.
KOK17391.
OMAITQGPEN.
OrthoDBEOG7T7GSK.
PhylomeDBO42254.
TreeFamTF320229.

Family and domain databases

Gene3D3.30.1370.10. 4 hits.
3.30.70.330. 2 hits.
InterProIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamPF00013. KH_1. 4 hits.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTSM00322. KH. 4 hits.
SM00360. RRM. 2 hits.
[Graphical view]
SUPFAMSSF54791. SSF54791. 4 hits.
PROSITEPS50084. KH_TYPE_1. 4 hits.
PS50102. RRM. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio20816018.
PROO42254.

Entry information

Entry nameIF2B1_CHICK
AccessionPrimary (citable) accession number: O42254
Entry history
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families