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Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

IGF2BP1

Organism
Gallus gallus (Chicken)
Status
Reviewed-Annotation score: -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

  • mRNA 3'-UTR binding Source: UniProtKB
  • mRNA 5'-UTR binding Source: Ensembl
  • mRNA binding Source: AgBase
  • translation regulator activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionRNA-binding
Biological processmRNA transport, Translation regulation, Transport

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
Proteomesi
  • UP000000539 Componenti: Chromosome 27

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi213K → 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 Publication1
Mutagenesisi294K → 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 Publication1
Mutagenesisi396Y → F: Increases the interaction with ACTB mRNA and its translational repression. 1 Publication1
Mutagenesisi396Y → Q: Impairs the interaction with beta-actin mRNA and its translation repression. 1 Publication1
Mutagenesisi422 – 423KK → 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. 2
Mutagenesisi504 – 505KG → 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. 2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002825361 – 576Insulin-like growth factor 2 mRNA-binding protein 1Add BLAST576

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei396Phosphotyrosine; by SRC1 Publication1

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
PRIDEiO42254

PTM databases

iPTMnetiO42254

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSGALG00000001293

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 occasionally with microtubules. In a heterologous system, interacts with ELAVL1, DHX9 and HNRNPU.1 Publication

Protein-protein interaction databases

STRINGi9031.ENSGALP00000001973

Structurei

Secondary structure

1576
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi404 – 412Combined sources9
Helixi413 – 420Combined sources8
Helixi422 – 424Combined sources3
Helixi426 – 434Combined sources9
Beta strandi436 – 440Combined sources5
Beta strandi449 – 457Combined sources9
Helixi459 – 476Combined sources18
Beta strandi481 – 483Combined sources3
Beta strandi489 – 494Combined sources6
Helixi495 – 501Combined sources7
Beta strandi504 – 506Combined sources3
Helixi508 – 516Combined sources9
Beta strandi518 – 521Combined sources4
Helixi529 – 531Combined sources3
Beta strandi533 – 540Combined sources8
Helixi542 – 560Combined sources19
Helixi561 – 563Combined sources3
Turni565 – 569Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2N8LNMR-A387-573[»]
2N8MNMR-A387-573[»]
ProteinModelPortaliO42254
SMRiO42254
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 75RRM 1PROSITE-ProRule annotationAdd BLAST74
Domaini81 – 156RRM 2PROSITE-ProRule annotationAdd BLAST76
Domaini195 – 260KH 1PROSITE-ProRule annotationAdd BLAST66
Domaini276 – 343KH 2PROSITE-ProRule annotationAdd BLAST68
Domaini404 – 469KH 3PROSITE-ProRule annotationAdd BLAST66
Domaini486 – 552KH 4PROSITE-ProRule annotationAdd BLAST67

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2193 Eukaryota
ENOG410ZKB4 LUCA
GeneTreeiENSGT00530000063171
HOGENOMiHOG000000675
HOVERGENiHBG052725
InParanoidiO42254
KOiK17391
OMAiEKPISIH
OrthoDBiEOG091G17T1
PhylomeDBiO42254
TreeFamiTF320229

Family and domain databases

CDDicd12625 RRM1_IGF2BP1, 1 hit
cd12628 RRM2_IGF2BP1, 1 hit
Gene3Di3.30.1370.10, 2 hits
3.30.70.330, 2 hits
InterProiView protein in InterPro
IPR034837 IGF2BP1_RRM1
IPR034842 IGF2BP1_RRM2
IPR004087 KH_dom
IPR004088 KH_dom_type_1
IPR036612 KH_dom_type_1_sf
IPR012677 Nucleotide-bd_a/b_plait_sf
IPR035979 RBD_domain_sf
IPR000504 RRM_dom
PfamiView protein in Pfam
PF00013 KH_1, 4 hits
PF00076 RRM_1, 2 hits
SMARTiView protein in SMART
SM00322 KH, 4 hits
SM00360 RRM, 2 hits
SUPFAMiSSF54791 SSF54791, 4 hits
SSF54928 SSF54928, 1 hit
PROSITEiView protein in PROSITE
PS50084 KH_TYPE_1, 4 hits
PS50102 RRM, 2 hits

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

EnsembliENSGALT00000052497; ENSGALP00000051506; ENSGALG00000041204
ENSGALT00000080686; ENSGALP00000053168; ENSGALG00000041204
GeneIDi395953
KEGGigga:395953

Similar proteinsi

Entry informationi

Entry nameiIF2B1_CHICK
AccessioniPrimary (citable) accession number: O42254
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: January 1, 1998
Last modified: May 23, 2018
This is version 120 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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