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Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

Igf2bp1

Organism
Mus musculus (Mouse)
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. Regulates localized beta-actin/ACTB mRNA translation, a crucial process for cell polarity, cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The 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, prevents ACTB mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. Monomeric ACTB then assembles into the subcortical actin cytoskeleton (By similarity). During neuronal development, key regulator of neurite outgrowth, growth cone guidance and neuronal cell migration, presumably through the spatiotemporal fine tuning of protein synthesis, such as that of ACTB (By similarity). May regulate mRNA transport to activated synapses (By similarity). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells (By similarity). Binds to the oncofetal H19 transcript and regulates its localization (By similarity). Binds to and stabilizes BTRC/FBW1A mRNA (By similarity). Binds to the adenine-rich autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent interaction with AGO2 (By similarity). During cellular stress, such as oxidative stress or heat shock, stabilizes target mRNAs that are recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts (By similarity). Interacts with GAP43 transcript and transports it to axons. Binds to the 3'-UTR of IGF2 mRNA by a mechanism of cooperative and sequential dimerization and regulates IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA, in the coding region instability determinant (CRD) of the open reading frame (ORF), hence prevents MYC cleavage by endonucleases and possibly microRNA targeting to MYC-CRD. Binds to and stabilizes ABCB1/MDR-1 mRNA. Binds to the neuron-specific TAU mRNA and regulates its localization. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons. During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing.By similarity4 Publications

GO - Molecular functioni

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):
Coding region determinant-binding protein
Short name:
CRD-BP
IGF-II mRNA-binding protein 1
VICKZ family member 1
Zipcode-binding protein 1
Short name:
ZBP-1
Gene namesi
Name:Igf2bp1
Synonyms:Vickz1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:1890357 Igf2bp1

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

Disruption phenotypei

Mutant mice exhibit high perinatal mortality and only 50% are alive 3 days after birth. Early death may be due to intestinal dysfunction. Animals are on average 40% smaller than wild-type and heterozygous sex-matched littermates. Growth retardation, probably due to hypoplasia, appears from 17.5 dpc and remains permanent into adult life. Mutant animals exhibit other stricking features, including impaired development of the intestine, with small and misshapen villi and twisted colon crypts, abnormal kidney architecture and loss of cartilage in the lower extremities. Some animals show signs of neurological damage, including aggressive behavior, restlessness and circular movements.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002825341 – 577Insulin-like growth factor 2 mRNA-binding protein 1Add BLAST577

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei12PhosphoserineBy similarity1
Modified residuei73PhosphoserineBy similarity1
Modified residuei181PhosphoserineCombined sources1
Modified residuei528PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation may impair association with ACTB mRNA and hence abolishes translational repression (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO88477
PaxDbiO88477
PeptideAtlasiO88477
PRIDEiO88477

PTM databases

iPTMnetiO88477
PhosphoSitePlusiO88477

Expressioni

Tissue specificityi

Expressed in zygotes and blastocysts (at protein level). Expressed in brain, skeletal muscle, trophoblasts of placenta, oocytes and spermatogonia (at protein level). Expressed in testis and ovary. Following colon injury, expressed in the wound bed mesenchyme during the first phase of repair, probably by colonic mesenchymal stem cells (at protein level).4 Publications

Developmental stagei

Expressed during embryonic development and expression declines towards birth (at protein level). At 10.5 dpc, mainly expressed in the fore- and hindbrain, the snout, the branchial arches, the developing limb buds, and the tail. At 12.5 dpc, expression increased in the expanding fore- and hindbrain, as well as in the neural tract. Marked expression also observed in the snout, the interdigital mesenchyme of the limb buds, the tail, the branchial arches and somites, and the developing eye, tongue, heart and liver. Expressed in myoblasts and myotubes at 12.5 dpc (at protein level). From 12.5 to 15.5 dpc, expressed at the basal plasma cell membrane in the basal layer of the epidermis of the skin, lung and intestine (at protein level). Expressed in gonads at 12.5 and 14.5 dpc (at protein level). At 14.5 dpc in limb buds, becomes restricted to the future tendons. Expressed in germ cells at 16.5 dpc (at protein level). At 17.5 dpc, expression generally decreases, but remains high in the intestine, in the developing tubules of the kidney, and in the liver. Expressed until P12, although very low levels may remain in some tissues, such as intestines, kidney and brain, throughout adulthood. Following colonic injury, up-regulated in the wound mucosa at days 2 and 4 post-injury and down-regulated at day 6 post-injury, as compared with uninjured mucosa.6 Publications

Gene expression databases

BgeeiENSMUSG00000013415 Expressed in 145 organ(s), highest expression level in brain
GenevisibleiO88477 MM

Interactioni

Subunit structurei

Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3 (By similarity). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (By similarity). Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 (By similarity). Associates with mRNP complex (By similarity). Interacts with FMR1 (By similarity). Component of a multisubunit autoregulatory RNP complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1. Interacts with AGO1 and AGO2 (By similarity). Interacts, through domains KH3 and KH4, with PABPC1 in an RNA-independent manner (By similarity). Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with ELAVL4 in an RNA-dependent manner. Associates with microtubules and polysomes.By similarity1 Publication

Protein-protein interaction databases

BioGridi228260, 7 interactors
ComplexPortaliCPX-1089 CRD-mediated mRNA stability complex
DIPiDIP-48578N
IntActiO88477, 5 interactors
MINTiO88477
STRINGi10090.ENSMUSP00000013559

Structurei

3D structure databases

ProteinModelPortaliO88477
SMRiO88477
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
Domaini405 – 470KH 3PROSITE-ProRule annotationAdd BLAST66
Domaini487 – 553KH 4PROSITE-ProRule annotationAdd BLAST67

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni187 – 570Necessary for interaction with IGF2BP1 and binding to TAU mRNAAdd BLAST384
Regioni312 – 323Sufficient for nuclear exportBy similarityAdd BLAST12
Regioni485 – 495Sufficient for nuclear exportBy similarityAdd BLAST11

Domaini

Domain KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute. 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.

Sequence similaritiesi

Belongs to the RRM IMP/VICKZ family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2193 Eukaryota
ENOG410ZKB4 LUCA
GeneTreeiENSGT00530000063171
HOGENOMiHOG000000675
HOVERGENiHBG052725
InParanoidiO88477
KOiK17391
OMAiEKPISIH
OrthoDBiEOG091G17T1
PhylomeDBiO88477
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.

O88477-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA
60 70 80 90 100
MKAIETFSGK VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL
110 120 130 140 150
LAQYGTVENC EQVNTESETA VVNVTYSNRE QTRQAIMKLN GHQLENHALK
160 170 180 190 200
VSYIPDEQIT QGPENGRRGG FGSRGQPRQG SPVAAGAPAK QQPVDIPLRL
210 220 230 240 250
LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA EKAISVHSTP
260 270 280 290 300
EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK
310 320 330 340 350
KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA
360 370 380 390 400
YENDVAAMSL QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYSSFM
410 420 430 440 450
QAPEQEMVQV FIPAQAVGAI IGKKGQHIKQ LSRFASASIK IAPPETPDSK
460 470 480 490 500
VRMVVITGPP EAQFKAQGRI YGKLKEENFF GPKEEVKLET HIRVPASAAG
510 520 530 540 550
RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII GHFYASQMAQ
560 570
RKIRDILAQV KQQHQKGQSN LAQARRK
Length:577
Mass (Da):63,451
Last modified:November 1, 1998 - v1
Checksum:iEFBB1AF2FF9F0344
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti276E → G in AAH51679 (PubMed:15489334).Curated1
Sequence conflicti406E → G in BAC32119 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061569 mRNA Translation: AAC72743.1
AK044850 mRNA Translation: BAC32119.1
AK013940 mRNA Translation: BAB29071.1
AL603682 Genomic DNA No translation available.
AL606704 Genomic DNA No translation available.
BC051679 mRNA Translation: AAH51679.1
CCDSiCCDS25286.1
RefSeqiNP_034081.1, NM_009951.4
UniGeneiMm.294769
Mm.491157

Genome annotation databases

EnsembliENSMUST00000013559; ENSMUSP00000013559; ENSMUSG00000013415
GeneIDi140486
KEGGimmu:140486
UCSCiuc007lay.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061569 mRNA Translation: AAC72743.1
AK044850 mRNA Translation: BAC32119.1
AK013940 mRNA Translation: BAB29071.1
AL603682 Genomic DNA No translation available.
AL606704 Genomic DNA No translation available.
BC051679 mRNA Translation: AAH51679.1
CCDSiCCDS25286.1
RefSeqiNP_034081.1, NM_009951.4
UniGeneiMm.294769
Mm.491157

3D structure databases

ProteinModelPortaliO88477
SMRiO88477
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228260, 7 interactors
ComplexPortaliCPX-1089 CRD-mediated mRNA stability complex
DIPiDIP-48578N
IntActiO88477, 5 interactors
MINTiO88477
STRINGi10090.ENSMUSP00000013559

PTM databases

iPTMnetiO88477
PhosphoSitePlusiO88477

Proteomic databases

MaxQBiO88477
PaxDbiO88477
PeptideAtlasiO88477
PRIDEiO88477

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000013559; ENSMUSP00000013559; ENSMUSG00000013415
GeneIDi140486
KEGGimmu:140486
UCSCiuc007lay.2 mouse

Organism-specific databases

CTDi10642
MGIiMGI:1890357 Igf2bp1

Phylogenomic databases

eggNOGiKOG2193 Eukaryota
ENOG410ZKB4 LUCA
GeneTreeiENSGT00530000063171
HOGENOMiHOG000000675
HOVERGENiHBG052725
InParanoidiO88477
KOiK17391
OMAiEKPISIH
OrthoDBiEOG091G17T1
PhylomeDBiO88477
TreeFamiTF320229

Miscellaneous databases

PROiPR:O88477
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000013415 Expressed in 145 organ(s), highest expression level in brain
GenevisibleiO88477 MM

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
ProtoNetiSearch...

Entry informationi

Entry nameiIF2B1_MOUSE
AccessioniPrimary (citable) accession number: O88477
Secondary accession number(s): Q80US9, Q8BRH1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: November 1, 1998
Last modified: October 10, 2018
This is version 152 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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