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Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

IGF2BP1

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.By similarity7 Publications

GO - Molecular functioni

  1. mRNA 3'-UTR binding Source: UniProtKB
  2. mRNA 5'-UTR binding Source: Ensembl
  3. nucleotide binding Source: InterPro
  4. translation regulator activity Source: Ensembl

GO - Biological processi

  1. CRD-mediated mRNA stabilization Source: Ensembl
  2. mRNA transport Source: UniProtKB-KW
  3. negative regulation of translation Source: Ensembl
  4. regulation of mRNA stability involved in response to stress Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

mRNA transport, Translation regulation, Transport

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:IGF2BP1
Synonyms:VICKZ1, ZBP1
OrganismiGallus gallus (Chicken)
Taxonomic identifieri9031 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiArchelosauriaArchosauriaDinosauriaSaurischiaTheropodaCoelurosauriaAvesNeognathaeGalloanseraeGalliformesPhasianidaePhasianinaeGallus
ProteomesiUP000000539 Componenti: Chromosome 27

Subcellular locationi

  1. Nucleus
  2. Cytoplasm
  3. Cytoplasmperinuclear region
  4. Cell projectiongrowth cone
  5. Cell projectionfilopodium
  6. Cell projectionlamellipodium

  7. 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.

GO - Cellular componenti

  1. CRD-mediated mRNA stability complex Source: UniProtKB
  2. cytoplasmic stress granule Source: Ensembl
  3. filopodium Source: UniProtKB-SubCell
  4. growth cone Source: UniProtKB-SubCell
  5. lamellipodium Source: UniProtKB-SubCell
  6. nucleus Source: UniProtKB-SubCell
  7. perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi213 – 2131K → 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. 1 Publication
Mutagenesisi294 – 2941K → 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. 1 Publication
Mutagenesisi396 – 3961Y → F: Increases the interaction with ACTB mRNA and its translational repression. 1 Publication
Mutagenesisi396 – 3961Y → Q: Impairs the interaction with beta-actin mRNA and its translation repression. 1 Publication
Mutagenesisi422 – 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.
Mutagenesisi504 – 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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 576576Insulin-like growth factor 2 mRNA-binding protein 1PRO_0000282536Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei396 – 3961Phosphotyrosine; by SRC1 Publication

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO42254.

Expressioni

Tissue specificityi

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

Interactioni

Subunit structurei

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.1 Publication

Protein-protein interaction databases

STRINGi9031.ENSGALP00000001973.

Structurei

3D structure databases

ProteinModelPortaliO42254.
SMRiO42254. Positions 1-161.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini2 – 7574RRM 1PROSITE-ProRule annotationAdd
BLAST
Domaini81 – 15676RRM 2PROSITE-ProRule annotationAdd
BLAST
Domaini195 – 26066KH 1PROSITE-ProRule annotationAdd
BLAST
Domaini276 – 34368KH 2PROSITE-ProRule annotationAdd
BLAST
Domaini404 – 46966KH 3PROSITE-ProRule annotationAdd
BLAST
Domaini486 – 55267KH 4PROSITE-ProRule annotationAdd
BLAST

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the RRM IMP/VICKZ family.Curated
Contains 4 KH domains.PROSITE-ProRule annotation
Contains 2 RRM (RNA recognition motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG249985.
GeneTreeiENSGT00530000063171.
HOGENOMiHOG000000675.
HOVERGENiHBG052725.
InParanoidiO42254.
KOiK17391.
OMAiGSIENCC.
OrthoDBiEOG7T7GSK.
PhylomeDBiO42254.
TreeFamiTF320229.

Family and domain databases

Gene3Di3.30.1370.10. 4 hits.
3.30.70.330. 2 hits.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00013. KH_1. 4 hits.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 4 hits.
SM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 4 hits.
PROSITEiPS50084. KH_TYPE_1. 4 hits.
PS50102. RRM. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O42254-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNKLYIGNLN ESVTPADLEK VFNDHKISFS GQFLVKSGYA FVDCPDEQWA
60 70 80 90 100
MKAIETFSGK VELHGKQLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDGL
110 120 130 140 150
LAQYGTVENC EQVNTDSETA VVNVTYTNRE QTRQAIMKLN GHQLENHVLK
160 170 180 190 200
VSYIPDEQSV QGPENGRRGG FGARGAPRQG SPVTAGAPVK QQPVDIPLRL
210 220 230 240 250
LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA EKAISIHSTP
260 270 280 290 300
EGCSAACKMI LEIMQKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK
310 320 330 340 350
KVEQDTETKI TISSLQDLTL YNPERTITVK GSIENCCKAE QEIMKKVREA
360 370 380 390 400
YENDVAAMSL QSHLIPGLNL AAVGLFPASS NAVPPPPSSV SGAAPYSSFM
410 420 430 440 450
PPEQETVHVF IPAQAVGAII GKKGQHIKQL SRFASASIKI APPETPDSKV
460 470 480 490 500
RMVVITGPPE AQFKAQGRIY GKLKEENFFG PKEEVKLETH IRVPASAAGR
510 520 530 540 550
VIGKGGKTVN ELQNLTAAEV VVPRDQTPDE NEQVIVKIIG HFYASQMAQR
560 570
KIRDILAQVK QQHQKGQSGQ LQARRK
Length:576
Mass (Da):63,271
Last modified:January 1, 1998 - v1
Checksum:i01AAF2D1D81C8811
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026527 mRNA. Translation: AAB82295.1.
RefSeqiNP_990402.1. NM_205071.1.
UniGeneiGga.567.

Genome annotation databases

EnsembliENSGALT00000001975; ENSGALP00000001973; ENSGALG00000001293.
GeneIDi395953.
KEGGigga:395953.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026527 mRNA. Translation: AAB82295.1.
RefSeqiNP_990402.1. NM_205071.1.
UniGeneiGga.567.

3D structure databases

ProteinModelPortaliO42254.
SMRiO42254. Positions 1-161.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9031.ENSGALP00000001973.

Proteomic databases

PaxDbiO42254.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSGALT00000001975; ENSGALP00000001973; ENSGALG00000001293.
GeneIDi395953.
KEGGigga:395953.

Organism-specific databases

CTDi10642.

Phylogenomic databases

eggNOGiNOG249985.
GeneTreeiENSGT00530000063171.
HOGENOMiHOG000000675.
HOVERGENiHBG052725.
InParanoidiO42254.
KOiK17391.
OMAiGSIENCC.
OrthoDBiEOG7T7GSK.
PhylomeDBiO42254.
TreeFamiTF320229.

Miscellaneous databases

NextBioi20816018.
PROiO42254.

Family and domain databases

Gene3Di3.30.1370.10. 4 hits.
3.30.70.330. 2 hits.
InterProiIPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF00013. KH_1. 4 hits.
PF00076. RRM_1. 1 hit.
[Graphical view]
SMARTiSM00322. KH. 4 hits.
SM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54791. SSF54791. 4 hits.
PROSITEiPS50084. KH_TYPE_1. 4 hits.
PS50102. RRM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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.

Entry informationi

Entry nameiIF2B1_CHICK
AccessioniPrimary (citable) accession number: O42254
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: January 1, 1998
Last modified: February 4, 2015
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.