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Q8CGX0

- IF2B1_RAT

UniProt

Q8CGX0 - IF2B1_RAT

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Protein

Insulin-like growth factor 2 mRNA-binding protein 1

Gene

Igf2bp1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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. 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 beta-actin/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 to the neuron-specific TAU mRNA and regulates their 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). 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 (By similarity). Binds to and stabilizes ABCB1/MDR-1 mRNA (By similarity). During interstinal wound repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic mucosal wound healing (By similarity). Interacts with GAP43 transcript and transports it to axons. Regulates localized 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. Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons.By similarity4 Publications

GO - Molecular functioni

  1. mRNA 3'-UTR binding Source: UniProtKB
  2. mRNA 5'-UTR binding Source: Ensembl
  3. mRNA binding Source: UniProtKB
  4. nucleotide binding Source: InterPro
  5. 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: UniProtKB
  5. RNA localization Source: RGD
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):
B-actin zipcode-binding protein 1
Short name:
ZBP1
Short name:
rZBP-1
IGF-II mRNA-binding protein 1
VICKZ family member 1
Gene namesi
Name:Igf2bp1
Synonyms:Imp1, Vickz1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 10

Organism-specific databases

RGDi708580. Igf2bp1.

Subcellular locationi

Nucleus By similarity. Cytoplasm. Cytoplasmperinuclear region By similarity. Cell projectionlamellipodium By similarity. Cell projectiondendrite. Cell projectiondendritic spine. Cell projectiongrowth cone By similarity. Cell projectionfilopodium. Cell projectionaxon
Note: In the nucleus, located in discrete foci, coinciding with the sites of ACTB transcription (By similarity). In the cytoplasm, localizes in cytoplasmic mRNP granules. Colocalizes with microtubules in growth cone filopodia and along neurites in neuronal cells (By similarity). Cytoplasmic colocalization with ACTB mRNA is partially lost at the cell periphery, suggesting release of the transcript (By similarity). In cultured hippocampal neurons, predominantly located within dendrites, particularly at dendritic branching points in young cells, compared to axons. In axons, predominantly found in axonal branches and their growth cones. In dendrites, can exhibit different types of movements, from fast retrograde and anterograde movements to stable localization. Dendritic levels are regulated by neuronal activity and glutaminergic signals: they are increased by KCl-induced depolarization, which induces rapid efflux from the cell body into dendrites, and decreased by the NMDA receptor agonist AP-5. In motile cells, such as migrating fibroblasts, localizes to leading edges where it colocalizes with microtubules and microfilaments and to retracting tails (By similarity). In motile cells, transported towards the leading edge into the cortical region of the lamellipodia where it is connected to microfilaments (By similarity). In response to cellular stress, such as oxidative stress or heat shock, recruited to stress granules, but not to processing bodies (By similarity).By similarity

GO - Cellular componenti

  1. CRD-mediated mRNA stability complex Source: UniProtKB
  2. cytoplasmic stress granule Source: UniProtKB
  3. dendrite Source: RGD
  4. nucleus Source: UniProtKB-KW
  5. ribonucleoprotein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi213 – 2142KE → EL: Loss of function in dendritogenesis; when associated with 294-E-L-295 and 423-E-L-424. 1 Publication
Mutagenesisi294 – 2952KE → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 423-E-L-424. 1 Publication
Mutagenesisi396 – 3961Y → F: Loss of function in dendritogenesis. 1 Publication
Mutagenesisi423 – 4242KK → EL: Loss of function in dendritogenesis; when associated with 213-E-L-214 and 294-E-L-295. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 577577Insulin-like growth factor 2 mRNA-binding protein 1PRO_0000282535Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei181 – 1811PhosphoserineBy similarity

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

PaxDbiQ8CGX0.
PRIDEiQ8CGX0.

PTM databases

PhosphoSiteiQ8CGX0.

Expressioni

Tissue specificityi

Expressed in fetal development and neonatal life, but is undetectable in adult tissues (at protein level). Expressed in embryonic neurons, including in hippocampal (at protein level) and cortical neurons. Also expressed in transformed tissue cultured cell lines derived form adult tissues (at protein level).4 Publications

Gene expression databases

ExpressionAtlasiQ8CGX0. baseline.
GenevestigatoriQ8CGX0.

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). Identification 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 ribonucleoprotein complex (ARC), at least composed of IGF2BP1, PABPC1 and CSDE1 (By similarity). Interacts through the third and fourth KH domains with PABPC1 in an RNA-independent manner (By similarity). Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP (By similarity). Interacts with ELAVL4 in an RNA-dependent manner (By similarity). Associates with microtubules and polysomes. Interacts with AGO1 and AGO2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008139.

Structurei

3D structure databases

ProteinModelPortaliQ8CGX0.
SMRiQ8CGX0. 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
Domaini405 – 47066KH 3PROSITE-ProRule annotationAdd
BLAST
Domaini487 – 55367KH 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni187 – 570384Necessary for interaction with ELAVL4 and binding to TAU mRNABy similarityAdd
BLAST
Regioni312 – 32312Sufficient for nuclear exportBy similarityAdd
BLAST
Regioni485 – 49511Sufficient for nuclear exportBy similarityAdd
BLAST

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 (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.
InParanoidiQ8CGX0.
KOiK17391.
OMAiGSIENCC.
OrthoDBiEOG7T7GSK.
PhylomeDBiQ8CGX0.
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. 2 hits.
PF13014. KH_3. 2 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.

Q8CGX0-1 [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
VSYIPDEQIA QGPENGRRGG FGSRGQPRQG SPVAAGAPAK QQQVDIPLRL
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 TGAAPYGSFM
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 QAQARRK
Length:577
Mass (Da):63,437
Last modified:March 1, 2003 - v1
Checksum:i0647676128FBD1EE
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF541940 mRNA. Translation: AAO16210.1.
CH473948 Genomic DNA. Translation: EDM05776.1.
BC161831 mRNA. Translation: AAI61831.1.
RefSeqiNP_783184.1. NM_175594.2.
UniGeneiRn.77572.

Genome annotation databases

EnsembliENSRNOT00000008139; ENSRNOP00000008139; ENSRNOG00000006122.
GeneIDi303477.
KEGGirno:303477.
UCSCiRGD:708580. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF541940 mRNA. Translation: AAO16210.1 .
CH473948 Genomic DNA. Translation: EDM05776.1 .
BC161831 mRNA. Translation: AAI61831.1 .
RefSeqi NP_783184.1. NM_175594.2.
UniGenei Rn.77572.

3D structure databases

ProteinModelPortali Q8CGX0.
SMRi Q8CGX0. Positions 1-161.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000008139.

PTM databases

PhosphoSitei Q8CGX0.

Proteomic databases

PaxDbi Q8CGX0.
PRIDEi Q8CGX0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000008139 ; ENSRNOP00000008139 ; ENSRNOG00000006122 .
GeneIDi 303477.
KEGGi rno:303477.
UCSCi RGD:708580. rat.

Organism-specific databases

CTDi 10642.
RGDi 708580. Igf2bp1.

Phylogenomic databases

eggNOGi NOG249985.
GeneTreei ENSGT00530000063171.
HOGENOMi HOG000000675.
HOVERGENi HBG052725.
InParanoidi Q8CGX0.
KOi K17391.
OMAi GSIENCC.
OrthoDBi EOG7T7GSK.
PhylomeDBi Q8CGX0.
TreeFami TF320229.

Miscellaneous databases

NextBioi 651402.
PROi Q8CGX0.

Gene expression databases

ExpressionAtlasi Q8CGX0. baseline.
Genevestigatori Q8CGX0.

Family and domain databases

Gene3Di 3.30.1370.10. 4 hits.
3.30.70.330. 2 hits.
InterProi IPR004087. KH_dom.
IPR004088. KH_dom_type_1.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view ]
Pfami PF00013. KH_1. 2 hits.
PF13014. KH_3. 2 hits.
PF00076. RRM_1. 1 hit.
[Graphical view ]
SMARTi SM00322. KH. 4 hits.
SM00360. RRM. 2 hits.
[Graphical view ]
SUPFAMi SSF54791. SSF54791. 4 hits.
PROSITEi PS50084. KH_TYPE_1. 4 hits.
PS50102. RRM. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Localization of a beta-actin messenger ribonucleoprotein complex with zipcode-binding protein modulates the density of dendritic filopodia and filopodial synapses."
    Eom T., Antar L.N., Singer R.H., Bassell G.J.
    J. Neurosci. 23:10433-10444(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Strain: Sprague-Dawley.
    Tissue: Embryonic brain.
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Embryonic kidney.
  4. "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes c-myc mRNA in vitro."
    Leeds P., Kren B.T., Boylan J.M., Betz N.A., Steer C.J., Gruppuso P.A., Ross J.
    Oncogene 14:1279-1286(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: RNA-BINDING, TISSUE SPECIFICITY.
  5. "Activity-dependent trafficking and dynamic localization of zipcode binding protein 1 and beta-actin mRNA in dendrites and spines of hippocampal neurons."
    Tiruchinapalli D.M., Oleynikov Y., Kelic S., Shenoy S.M., Hartley A., Stanton P.K., Singer R.H., Bassell G.J.
    J. Neurosci. 23:3251-3261(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "Limited availability of ZBP1 restricts axonal mRNA localization and nerve regeneration capacity."
    Donnelly C.J., Willis D.E., Xu M., Tep C., Jiang C., Yoo S., Schanen N.C., Kirn-Safran C.B., van Minnen J., English A., Yoon S.O., Bassell G.J., Twiss J.L.
    EMBO J. 30:4665-4677(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN AXONAL REGENERATION.
  7. "Zipcode binding protein 1 regulates the development of dendritic arbors in hippocampal neurons."
    Perycz M., Urbanska A.S., Krawczyk P.S., Parobczak K., Jaworski J.
    J. Neurosci. 31:5271-5285(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF 213-LYS-GLU-214; 294-LYS-GLU-295; TYR-396 AND 423-LYS-LYS-424.
  8. "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_RAT
AccessioniPrimary (citable) accession number: Q8CGX0
Secondary accession number(s): B1WBP3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: March 1, 2003
Last modified: October 29, 2014
This is version 88 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