IF2B1_RAT
ID IF2B1_RAT Reviewed; 577 AA.
AC Q8CGX0; B1WBP3;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Insulin-like growth factor 2 mRNA-binding protein 1;
DE Short=IGF2 mRNA-binding protein 1;
DE Short=IMP-1;
DE AltName: Full=B-actin zipcode-binding protein 1;
DE Short=ZBP1;
DE Short=rZBP-1;
DE AltName: Full=IGF-II mRNA-binding protein 1;
DE AltName: Full=VICKZ family member 1;
GN Name=Igf2bp1; Synonyms=Imp1, Vickz1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, SUBCELLULAR LOCATION,
RP AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Embryonic brain;
RX PubMed=14614102; DOI=10.1523/jneurosci.23-32-10433.2003;
RA Eom T., Antar L.N., Singer R.H., Bassell G.J.;
RT "Localization of a beta-actin messenger ribonucleoprotein complex with
RT zipcode-binding protein modulates the density of dendritic filopodia and
RT filopodial synapses.";
RL J. Neurosci. 23:10433-10444(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryonic kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP RNA-BINDING, AND TISSUE SPECIFICITY.
RX PubMed=9178888; DOI=10.1038/sj.onc.1201093;
RA Leeds P., Kren B.T., Boylan J.M., Betz N.A., Steer C.J., Gruppuso P.A.,
RA Ross J.;
RT "Developmental regulation of CRD-BP, an RNA-binding protein that stabilizes
RT c-myc mRNA in vitro.";
RL Oncogene 14:1279-1286(1997).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12716932; DOI=10.1523/jneurosci.23-08-03251.2003;
RA Tiruchinapalli D.M., Oleynikov Y., Kelic S., Shenoy S.M., Hartley A.,
RA Stanton P.K., Singer R.H., Bassell G.J.;
RT "Activity-dependent trafficking and dynamic localization of zipcode binding
RT protein 1 and beta-actin mRNA in dendrites and spines of hippocampal
RT neurons.";
RL J. Neurosci. 23:3251-3261(2003).
RN [6]
RP FUNCTION IN AXONAL REGENERATION.
RX PubMed=21964071; DOI=10.1038/emboj.2011.347;
RA Donnelly C.J., Willis D.E., Xu M., Tep C., Jiang C., Yoo S., Schanen N.C.,
RA Kirn-Safran C.B., van Minnen J., English A., Yoon S.O., Bassell G.J.,
RA Twiss J.L.;
RT "Limited availability of ZBP1 restricts axonal mRNA localization and nerve
RT regeneration capacity.";
RL EMBO J. 30:4665-4677(2011).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 213-LYS-GLU-214; 294-LYS-GLU-295; TYR-396 AND 423-LYS-LYS-424.
RX PubMed=21471362; DOI=10.1523/jneurosci.2387-10.2011;
RA Perycz M., Urbanska A.S., Krawczyk P.S., Parobczak K., Jaworski J.;
RT "Zipcode binding protein 1 regulates the development of dendritic arbors in
RT hippocampal neurons.";
RL J. Neurosci. 31:5271-5285(2011).
RN [8]
RP REVIEW.
RX PubMed=23069990; DOI=10.1007/s00018-012-1186-z;
RA Bell J.L., Wachter K., Muhleck B., Pazaitis N., Kohn M., Lederer M.,
RA Huttelmaier S.;
RT "Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs): post-
RT transcriptional drivers of cancer progression?";
RL Cell. Mol. Life Sci. 70:2657-2675(2013).
CC -!- FUNCTION: RNA-binding factor that recruits target transcripts to
CC cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging'
CC into mRNPs allows mRNA transport and transient storage. It also
CC modulates the rate and location at which target transcripts encounter
CC the translational apparatus and shields them from endonuclease attacks
CC or microRNA-mediated degradation. Preferentially binds to N6-
CC methyladenosine (m6A)-containing mRNAs and increases their stability
CC (By similarity). During neuronal development, key regulator of neurite
CC outgrowth, growth cone guidance and neuronal cell migration, presumably
CC through the spatiotemporal fine tuning of protein synthesis, such as
CC that of beta-actin/ACTB (By similarity). May regulate mRNA transport to
CC activated synapses (By similarity). Binds to the 3'-UTR of CD44 mRNA
CC and stabilizes it, hence promotes cell adhesion and invadopodia
CC formation in cancer cells (By similarity). Binds to the oncofetal H19
CC transcript and to the neuron-specific TAU mRNA and regulates their
CC localization (By similarity). Binds to and stabilizes BTRC/FBW1A mRNA
CC (By similarity). Binds to the adenine-rich autoregulatory sequence
CC (ARS) located in PABPC1 mRNA and represses its translation. PABPC1
CC mRNA-binding is stimulated by PABPC1 protein. Prevents BTRC/FBW1A mRNA
CC degradation by disrupting microRNA-dependent interaction with AGO2 (By
CC similarity). During cellular stress, such as oxidative stress or heat
CC shock, stabilizes target mRNAs that are recruited to stress granules,
CC including CD44, IGF2, MAPK4, MYC, PTEN, RAPGEF2 and RPS6KA5 transcripts
CC (By similarity). Binds to the 3'-UTR of IGF2 mRNA by a mechanism of
CC cooperative and sequential dimerization and regulates IGF2 mRNA
CC subcellular localization and translation. Binds to MYC mRNA, in the
CC coding region instability determinant (CRD) of the open reading frame
CC (ORF), hence prevents MYC cleavage by endonucleases and possibly
CC microRNA targeting to MYC-CRD (By similarity). Binding to MYC mRNA is
CC enhanced by m6A-modification of the CRD (By similarity). Binds to and
CC stabilizes ABCB1/MDR-1 mRNA (By similarity). During interstinal wound
CC repair, interacts with and stabilizes PTGS2 transcript. PTGS2 mRNA
CC stabilization may be crucial for colonic mucosal wound healing (By
CC similarity). Interacts with GAP43 transcript and transports it to
CC axons. Regulates localized ACTB mRNA translation, a crucial process for
CC cell polarity, cell migration and neurite outgrowth. Co-
CC transcriptionally associates with the ACTB mRNA in the nucleus. This
CC binding involves a conserved 54-nucleotide element in the ACTB mRNA 3'-
CC UTR, known as the 'zipcode'. The RNP thus formed is exported to the
CC cytoplasm, binds to a motor protein and is transported along the
CC cytoskeleton to the cell periphery. During transport, prevents ACTB
CC mRNA from being translated into protein. When the RNP complex reaches
CC its destination near the plasma membrane, IGF2BP1 is phosphorylated.
CC This releases the mRNA, allowing ribosomal 40S and 60S subunits to
CC assemble and initiate ACTB protein synthesis. Monomeric ACTB then
CC assembles into the subcortical actin cytoskeleton. Plays a direct role
CC in the transport and translation of transcripts required for axonal
CC regeneration in adult sensory neurons. {ECO:0000250|UniProtKB:Q9NZI8,
CC ECO:0000269|PubMed:12716932, ECO:0000269|PubMed:14614102,
CC ECO:0000269|PubMed:21471362, ECO:0000269|PubMed:21964071}.
CC -!- SUBUNIT: Can form homodimers and heterodimers with IGF2BP1 and IGF2BP3
CC (By similarity). Component of the coding region determinant (CRD)-
CC mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1
CC (By similarity). Identification in a mRNP complex, at least composed of
CC DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2,
CC STAU1, STAU2, SYNCRIP and YBX1 (By similarity). Associates with mRNP
CC complex (By similarity). Interacts with FMR1 (By similarity). Component
CC of a multisubunit autoregulatory ribonucleoprotein complex (ARC), at
CC least composed of IGF2BP1, PABPC1 and CSDE1 (By similarity). Interacts
CC through the third and fourth KH domains with PABPC1 in an RNA-
CC independent manner (By similarity). Component of a TAU mRNP complex, at
CC least composed of IGF2BP1, ELAVL4 and G3BP (By similarity). Interacts
CC with ELAVL4 in an RNA-dependent manner (By similarity). Associates with
CC microtubules and polysomes. Interacts with AGO1 and AGO2 (By
CC similarity). Interacts with ELAVL1 and MATR3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZI8}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm. Cytoplasm,
CC perinuclear region {ECO:0000250}. Cytoplasm, P-body
CC {ECO:0000250|UniProtKB:Q9NZI8}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:Q9NZI8}. Cell projection, lamellipodium
CC {ECO:0000250}. Cell projection, dendrite. Cell projection, dendritic
CC spine. Cell projection, growth cone {ECO:0000250}. Cell projection,
CC filopodium. Cell projection, axon. Note=In the nucleus, located in
CC discrete foci, coinciding with the sites of ACTB transcription (By
CC similarity). In the cytoplasm, localizes in cytoplasmic mRNP granules.
CC Colocalizes with microtubules in growth cone filopodia and along
CC neurites in neuronal cells (By similarity). Cytoplasmic colocalization
CC with ACTB mRNA is partially lost at the cell periphery, suggesting
CC release of the transcript (By similarity). In cultured hippocampal
CC neurons, predominantly located within dendrites, particularly at
CC dendritic branching points in young cells, compared to axons. In axons,
CC predominantly found in axonal branches and their growth cones. In
CC dendrites, can exhibit different types of movements, from fast
CC retrograde and anterograde movements to stable localization. Dendritic
CC levels are regulated by neuronal activity and glutaminergic signals:
CC they are increased by KCl-induced depolarization, which induces rapid
CC efflux from the cell body into dendrites, and decreased by the NMDA
CC receptor agonist AP-5. In motile cells, such as migrating fibroblasts,
CC localizes to leading edges where it colocalizes with microtubules and
CC microfilaments and to retracting tails (By similarity). In motile
CC cells, transported towards the leading edge into the cortical region of
CC the lamellipodia where it is connected to microfilaments (By
CC similarity). In response to cellular stress, such as oxidative stress
CC or heat shock, recruited to stress granules, but not to processing
CC bodies (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in fetal development and neonatal life,
CC but is undetectable in adult tissues (at protein level). Expressed in
CC embryonic neurons, including in hippocampal (at protein level) and
CC cortical neurons. Also expressed in transformed tissue cultured cell
CC lines derived form adult tissues (at protein level).
CC {ECO:0000269|PubMed:12716932, ECO:0000269|PubMed:14614102,
CC ECO:0000269|PubMed:21471362, ECO:0000269|PubMed:9178888}.
CC -!- DOMAIN: Domains KH3 and KH4 are the major RNA-binding modules, although
CC KH1 and KH2 may also contribute. KH1 and KH2, and possibly KH3 and KH4,
CC promote the formation of higher ordered protein-RNA complexes, which
CC may be essential for IGF2BP1 cytoplasmic retention. KH domains are
CC required for RNA-dependent homo- and heterooligomerization and for
CC localization to stress granules. KH3 and KH4 mediate association with
CC the cytoskeleton. Two nuclear export signals (NES) have been identified
CC in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent.
CC Both NES may be redundant, since individual in vitro mutations do not
CC affect subcellular location of the full-length protein (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZI8}.
CC -!- PTM: Phosphorylated. Phosphorylation may impair association with ACTB
CC mRNA and hence abolishes translational repression (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the RRM IMP/VICKZ family. {ECO:0000305}.
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DR EMBL; AF541940; AAO16210.1; -; mRNA.
DR EMBL; CH473948; EDM05776.1; -; Genomic_DNA.
DR EMBL; BC161831; AAI61831.1; -; mRNA.
DR RefSeq; NP_783184.1; NM_175594.2.
DR AlphaFoldDB; Q8CGX0; -.
DR SMR; Q8CGX0; -.
DR BioGRID; 257545; 4.
DR STRING; 10116.ENSRNOP00000008139; -.
DR iPTMnet; Q8CGX0; -.
DR PhosphoSitePlus; Q8CGX0; -.
DR PaxDb; Q8CGX0; -.
DR PRIDE; Q8CGX0; -.
DR Ensembl; ENSRNOT00000008139; ENSRNOP00000008139; ENSRNOG00000006122.
DR GeneID; 303477; -.
DR KEGG; rno:303477; -.
DR UCSC; RGD:708580; rat.
DR CTD; 10642; -.
DR RGD; 708580; Igf2bp1.
DR eggNOG; KOG2193; Eukaryota.
DR GeneTree; ENSGT00940000160427; -.
DR HOGENOM; CLU_020744_1_0_1; -.
DR InParanoid; Q8CGX0; -.
DR OMA; XAIMKLN; -.
DR OrthoDB; 286875at2759; -.
DR PhylomeDB; Q8CGX0; -.
DR TreeFam; TF320229; -.
DR PRO; PR:Q8CGX0; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Proteomes; UP000234681; Chromosome 10.
DR Bgee; ENSRNOG00000006122; Expressed in stomach and 1 other tissue.
DR Genevisible; Q8CGX0; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0070937; C:CRD-mediated mRNA stability complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0030175; C:filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISS:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:RGD.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0045182; F:translation regulator activity; ISO:RGD.
DR GO; GO:0070934; P:CRD-mediated mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0140059; P:dendrite arborization; IMP:RGD.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:1900152; P:negative regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; ISO:RGD.
DR GO; GO:0017148; P:negative regulation of translation; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:RGD.
DR GO; GO:0022013; P:pallium cell proliferation in forebrain; ISO:RGD.
DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0010610; P:regulation of mRNA stability involved in response to stress; ISS:UniProtKB.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IBA:GO_Central.
DR GO; GO:0006403; P:RNA localization; IMP:RGD.
DR CDD; cd12625; RRM1_IGF2BP1; 1.
DR CDD; cd12628; RRM2_IGF2BP1; 1.
DR Gene3D; 3.30.1370.10; -; 2.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR034837; IGF2BP1_RRM1.
DR InterPro; IPR034842; IGF2BP1_RRM2.
DR InterPro; IPR004087; KH_dom.
DR InterPro; IPR004088; KH_dom_type_1.
DR InterPro; IPR036612; KH_dom_type_1_sf.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR000504; RRM_dom.
DR Pfam; PF00013; KH_1; 4.
DR Pfam; PF00076; RRM_1; 2.
DR SMART; SM00322; KH; 4.
DR SMART; SM00360; RRM; 2.
DR SUPFAM; SSF54791; SSF54791; 4.
DR SUPFAM; SSF54928; SSF54928; 1.
DR PROSITE; PS50084; KH_TYPE_1; 4.
DR PROSITE; PS50102; RRM; 2.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; mRNA transport; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; RNA-binding; Synapse; Translation regulation;
KW Transport.
FT CHAIN 1..577
FT /note="Insulin-like growth factor 2 mRNA-binding protein 1"
FT /id="PRO_0000282535"
FT DOMAIN 2..75
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 81..156
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 195..260
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 276..343
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 405..470
FT /note="KH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 487..553
FT /note="KH 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 160..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..570
FT /note="Necessary for interaction with ELAVL4 and binding to
FT TAU mRNA"
FT /evidence="ECO:0000250"
FT REGION 312..323
FT /note="Sufficient for nuclear export"
FT /evidence="ECO:0000250"
FT REGION 485..495
FT /note="Sufficient for nuclear export"
FT /evidence="ECO:0000250"
FT MOD_RES 12
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI8"
FT MOD_RES 73
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI8"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI8"
FT MOD_RES 528
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI8"
FT MUTAGEN 213..214
FT /note="KE->EL: Loss of function in dendritogenesis; when
FT associated with 294-E-L-295 and 423-E-L-424."
FT /evidence="ECO:0000269|PubMed:21471362"
FT MUTAGEN 294..295
FT /note="KE->EL: Loss of function in dendritogenesis; when
FT associated with 213-E-L-214 and 423-E-L-424."
FT /evidence="ECO:0000269|PubMed:21471362"
FT MUTAGEN 396
FT /note="Y->F: Loss of function in dendritogenesis."
FT /evidence="ECO:0000269|PubMed:21471362"
FT MUTAGEN 423..424
FT /note="KK->EL: Loss of function in dendritogenesis; when
FT associated with 213-E-L-214 and 294-E-L-295."
FT /evidence="ECO:0000269|PubMed:21471362"
SQ SEQUENCE 577 AA; 63437 MW; 0647676128FBD1EE CRC64;
MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA MKAIETFSGK
VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL LAQYGTVENC EQVNTESETA
VVNVTYSNRE QTRQAIMKLN GHQLENHALK VSYIPDEQIA QGPENGRRGG FGSRGQPRQG
SPVAAGAPAK QQQVDIPLRL LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA
EKAISVHSTP EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK
KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA YENDVAAMSL
QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYGSFM QAPEQEMVQV FIPAQAVGAI
IGKKGQHIKQ LSRFASASIK IAPPETPDSK VRMVVITGPP EAQFKAQGRI YGKLKEENFF
GPKEEVKLET HIRVPASAAG RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII
GHFYASQMAQ RKIRDILAQV KQQHQKGQSN QAQARRK
