IF2B1_CHICK
ID IF2B1_CHICK Reviewed; 576 AA.
AC O42254;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 140.
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=IGF-II mRNA-binding protein 1;
DE AltName: Full=VICKZ family member 1;
DE AltName: Full=Zip-code binding polypeptide;
DE AltName: Full=Zipcode-binding protein 1;
DE Short=ZBP-1;
GN Name=IGF2BP1; Synonyms=VICKZ1, ZBP1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, RNA-BINDING, AND TISSUE SPECIFICITY.
RC TISSUE=Embryonic fibroblast;
RX PubMed=9121465; DOI=10.1128/mcb.17.4.2158;
RA Ross A.F., Oleynikov Y., Kislauskis E.H., Taneja K.L., Singer R.H.;
RT "Characterization of a beta-actin mRNA zipcode-binding protein.";
RL Mol. Cell. Biol. 17:2158-2165(1997).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11502257; DOI=10.1016/s0896-6273(01)00357-9;
RA Zhang H.L., Eom T., Oleynikov Y., Shenoy S.M., Liebelt D.A.,
RA Dictenberg J.B., Singer R.H., Bassell G.J.;
RT "Neurotrophin-induced transport of a beta-actin mRNP complex increases
RT beta-actin levels and stimulates growth cone motility.";
RL Neuron 31:261-275(2001).
RN [3]
RP FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12573215; DOI=10.1016/s0960-9822(03)00044-7;
RA Oleynikov Y., Singer R.H.;
RT "Real-time visualization of ZBP1 association with beta-actin mRNA during
RT transcription and localization.";
RL Curr. Biol. 13:199-207(2003).
RN [4]
RP FUNCTION, RNA-BINDING, ASSOCIATION WITH CYTOSKELETON, SUBCELLULAR LOCATION,
RP AND DOMAIN.
RX PubMed=12507992; DOI=10.1083/jcb.200206003;
RA Farina K.L., Huttelmaier S., Musunuru K., Darnell R., Singer R.H.;
RT "Two ZBP1 KH domains facilitate beta-actin mRNA localization, granule
RT formation, and cytoskeletal attachment.";
RL J. Cell Biol. 160:77-87(2003).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=17101699; DOI=10.1083/jcb.200608071;
RA Stoehr N., Lederer M., Reinke C., Meyer S., Hatzfeld M., Singer R.H.,
RA Huettelmaier S.;
RT "ZBP1 regulates mRNA stability during cellular stress.";
RL J. Cell Biol. 175:527-534(2006).
RN [6]
RP FUNCTION, PHOSPHORYLATION AT TYR-396, MUTAGENESIS OF TYR-396, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16306994; DOI=10.1038/nature04115;
RA Huttelmaier S., Zenklusen D., Lederer M., Dictenberg J., Lorenz M.,
RA Meng X., Bassell G.J., Condeelis J., Singer R.H.;
RT "Spatial regulation of beta-actin translation by Src-dependent
RT phosphorylation of ZBP1.";
RL Nature 438:512-515(2005).
RN [7]
RP FUNCTION IN CELL MIGRATION.
RX PubMed=22279049; DOI=10.1101/gad.177642.111;
RA Stohr N., Kohn M., Lederer M., Glass M., Reinke C., Singer R.H.,
RA Huttelmaier S.;
RT "IGF2BP1 promotes cell migration by regulating MK5 and PTEN signaling.";
RL Genes Dev. 26:176-189(2012).
RN [8]
RP FUNCTION, RNA-BINDING, OLIGOMERIZATION, INTERACTION WITH ELAVL1; DHX9 AND
RP HNRNPU, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-213; LYS-294;
RP 423-LYS-LYS-424 AND 505-LYS-GLY-506.
RX PubMed=23640942; DOI=10.1515/hsz-2013-0111;
RA Wachter K., Kohn M., Stohr N., Huttelmaier S.;
RT "Subcellular localization and RNP formation of IGF2BPs (IGF2 mRNA-binding
RT proteins) is modulated by distinct RNA-binding domains.";
RL Biol. Chem. 394:1077-1090(2013).
RN [9]
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). Plays a direct role in the transport and translation
CC of transcripts required for axonal regeneration in adult sensory
CC neurons (By similarity). Regulates localized beta-actin/ACTB mRNA
CC translation in polarized cells, a crucial process for cell migration
CC and neurite outgrowth. Co-transcriptionally associates with the ACTB
CC mRNA in the nucleus. This binding involves by a conserved 54-nucleotide
CC element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The
CC ribonucleoparticle (RNP) thus formed is exported to the cytoplasm,
CC binds to a motor protein and is transported along the cytoskeleton to
CC the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA
CC from being translated into protein. When the RNP complex reaches its
CC destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC.
CC This releases the mRNA, allowing ribosomal 40S and 60S subunits to
CC assemble and initiate ACTB protein synthesis. The monomeric ACTB
CC protein then assembles into the subcortical actin cytoskeleton, which
CC pushes the leading edge onwards. Binds MYC mRNA. Binding to MYC mRNA is
CC enhanced by m6A-modification of the CRD (By similarity). Promotes the
CC directed movement of cells by fine-tuning intracellular signaling
CC networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts
CC with PTEN transcript open reading frame (ORF) and prevents mRNA decay.
CC This combined action on MAPK4 (down-regulation) and PTEN (up-
CC regulation) antagonizes HSPB1 phosphorylation, consequently it prevents
CC G-actin sequestration by phosphorylated HSPB1, allowing F-actin
CC polymerization. Hence enhances the velocity of cell migration and
CC stimulates directed cell migration by PTEN-modulated polarization.
CC {ECO:0000250|UniProtKB:Q9NZI8, ECO:0000269|PubMed:11502257,
CC ECO:0000269|PubMed:12507992, ECO:0000269|PubMed:12573215,
CC ECO:0000269|PubMed:16306994, ECO:0000269|PubMed:22279049,
CC ECO:0000269|PubMed:23640942, ECO:0000269|PubMed:9121465}.
CC -!- SUBUNIT: Can form homooligomers and heterooligomers with IGF2BP1 and
CC IGF2BP3 in an RNA-dependent manner. Associates with the cytoskeleton,
CC predominantly with actin filament bundles and occasionally with
CC microtubules. In a heterologous system, interacts with ELAVL1, DHX9 and
CC HNRNPU. {ECO:0000269|PubMed:23640942}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear
CC region. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9NZI8}. Cytoplasm,
CC Stress granule {ECO:0000250|UniProtKB:Q9NZI8}. Cell projection, growth
CC cone. Cell projection, filopodium. Cell projection, lamellipodium.
CC Note=In the nucleus, located in discrete foci, coinciding with the
CC sites of ACTB transcription. Export from the nucleus is mediated by
CC XPO1. In the cytoplasm, colocalizes with ACTB mRNA at the leading edge,
CC in growth cone filopodia and along neurites. In these locations, also
CC colocalizes with microtubules. Colocalization with ACTB mRNA is
CC partially lost at the cell periphery, suggesting release of the
CC transcript. In neuronal processes, exhibits fast retrograde and
CC anterograde movements, when associated with ACTB mRNA; this motility is
CC lost when the association is inhibited. In migrating fibroblasts,
CC localizes not only to leading edges, but also to retracting tails. In
CC response to cellular stress, such as oxidative stress or heat shock,
CC recruited to stress granules.
CC -!- TISSUE SPECIFICITY: Expressed in neurons and embryonic fibroblasts (at
CC protein level). {ECO:0000269|PubMed:11502257,
CC ECO:0000269|PubMed:9121465}.
CC -!- DOMAIN: Domains KH3 and KH4 are the major RNA-binding modules, although
CC KH1 and KH2 may also contribute to transcript binding. The contribution
CC to RNA-binding of individual KH domains may be target-specific. KH1 and
CC KH2, and possibly KH3 and KH4, promote the formation of higher ordered
CC protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic
CC retention. KH domains are required for RNA-dependent homo- and
CC heterooligomerization and for localization to stress granules. KH3 and
CC KH4 mediate association with the cytoskeleton. Two nuclear export
CC signals (NES) have been identified in KH2 and KH4 domains,
CC respectively. Only KH2 NES is XPO1-dependent. Both NES may be
CC redundant, since individual in vitro mutations do not affect
CC subcellular location of the full length protein.
CC {ECO:0000250|UniProtKB:Q9NZI8}.
CC -!- PTM: Phosphorylated by SRC at Tyr-396. This residue is involved in ACTB
CC mRNA binding, its phosphorylation impairs association with ACTB mRNA
CC and hence abolishes translational repression. Phosphorylation occurs in
CC close proximity to filopodia and in the growth cones of differentiated
CC neuroglioblastoma cells. {ECO:0000269|PubMed:16306994}.
CC -!- SIMILARITY: Belongs to the RRM IMP/VICKZ family. {ECO:0000305}.
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DR EMBL; AF026527; AAB82295.1; -; mRNA.
DR RefSeq; NP_990402.1; NM_205071.1.
DR PDB; 2N8L; NMR; -; A=387-573.
DR PDB; 2N8M; NMR; -; A=387-573.
DR PDBsum; 2N8L; -.
DR PDBsum; 2N8M; -.
DR AlphaFoldDB; O42254; -.
DR BMRB; O42254; -.
DR SMR; O42254; -.
DR STRING; 9031.ENSGALP00000001973; -.
DR iPTMnet; O42254; -.
DR PaxDb; O42254; -.
DR GeneID; 395953; -.
DR KEGG; gga:395953; -.
DR CTD; 10642; -.
DR VEuPathDB; HostDB:geneid_395953; -.
DR eggNOG; KOG2193; Eukaryota.
DR HOGENOM; CLU_020744_1_0_1; -.
DR InParanoid; O42254; -.
DR OrthoDB; 286875at2759; -.
DR PhylomeDB; O42254; -.
DR TreeFam; TF320229; -.
DR PRO; PR:O42254; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0070937; C:CRD-mediated mRNA stability complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030175; C:filopodium; IDA:AgBase.
DR GO; GO:0030426; C:growth cone; IDA:AgBase.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IMP:AgBase.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; ISS:UniProtKB.
DR GO; GO:0070934; P:CRD-mediated mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; IDA:AgBase.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:AgBase.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0051252; P:regulation of RNA metabolic process; IBA:GO_Central.
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 3D-structure; Cell projection; Cytoplasm; mRNA transport; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding;
KW Translation regulation; Transport.
FT CHAIN 1..576
FT /note="Insulin-like growth factor 2 mRNA-binding protein 1"
FT /id="PRO_0000282536"
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 404..469
FT /note="KH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 486..552
FT /note="KH 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 158..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 396
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:16306994"
FT MUTAGEN 213
FT /note="K->E: Decrease in Y RNA binding. Only small decrease
FT in affinity for binding to ACTB and MYC transcripts, some
FT accumulation in the nucleus, and complete loss of formation
FT of higher ordered protein-RNA complexes; when associated
FT with E-294. Loss of homo- and heterooligomerization with
FT IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC
FT transcript binding, almost complete loss of ELAVL1-,
FT DHX9- and HNRNPU-binding and perturbed subcellular
FT location, including accumulation in the nucleus and loss of
FT localization to stress granules; when associated with E-
FT 294, 422-E-E-423 and 505-E-E-506."
FT /evidence="ECO:0000269|PubMed:23640942"
FT MUTAGEN 294
FT /note="K->E: Decrease in Y RNA binding. Only small decrease
FT in affinity for binding to ACTB and MYC transcripts, some
FT accumulation in the nucleus, and complete loss of formation
FT of higher ordered protein-RNA complexes; when associated
FT with E-213. Loss of homo- and heterooligomerization with
FT IGF2BP1 and IGF2BP2, almost complete loss of ACTB and MYC
FT transcript binding, almost complete loss of ELAVL1-,
FT DHX9- and HNRNPU-binding and accumulation in the nucleus;
FT when associated with E-213, 422-E-E-423 and 505-E-E-506."
FT /evidence="ECO:0000269|PubMed:23640942"
FT MUTAGEN 396
FT /note="Y->F: Increases the interaction with ACTB mRNA and
FT its translational repression."
FT /evidence="ECO:0000269|PubMed:16306994"
FT MUTAGEN 396
FT /note="Y->Q: Impairs the interaction with beta-actin mRNA
FT and its translation repression."
FT /evidence="ECO:0000269|PubMed:16306994"
FT MUTAGEN 422..423
FT /note="KK->EE: Almost complete loss of Y RNA binding. About
FT 80-fold decrease in affinity for binding to ACTB
FT transcript, but almost no effect on MYC transcript binding;
FT when associated with 505-E-E-506. Loss of homo- and
FT heterooligomerization with IGF2BP1 and IGF2BP2, almost
FT complete loss of ACTB and MYC transcript binding, almost
FT complete loss of ELAVL1-, DHX9- and HNRNPU-binding and
FT accumulation in the nucleus; when associated with E-213, E-
FT 294 and 505-E-E-506."
FT MUTAGEN 504..505
FT /note="KG->EE: Decrease in Y RNA binding. About 80-fold
FT decrease in affinity for binding to ACTB transcript, but
FT almost no effect on MYC transcript binding; when associated
FT with 422-E-E-423. Loss of homo- and heterooligomerization
FT with IGF2BP1 and IGF2BP2, almost complete loss of ACTB and
FT MYC transcript binding, almost complete loss of ELAVL1-,
FT DHX9- and HNRNPU-binding and accumulation in the nucleus;
FT when associated with E-213, E-294 and 422-E-E-423."
FT STRAND 404..412
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 413..420
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 422..424
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 426..434
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 436..440
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 449..457
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 459..476
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 489..494
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 495..501
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 504..506
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 508..516
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 518..521
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 529..531
FT /evidence="ECO:0007829|PDB:2N8L"
FT STRAND 533..540
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 542..560
FT /evidence="ECO:0007829|PDB:2N8L"
FT HELIX 561..563
FT /evidence="ECO:0007829|PDB:2N8L"
FT TURN 565..569
FT /evidence="ECO:0007829|PDB:2N8M"
SQ SEQUENCE 576 AA; 63271 MW; 01AAF2D1D81C8811 CRC64;
MNKLYIGNLN ESVTPADLEK VFNDHKISFS GQFLVKSGYA FVDCPDEQWA MKAIETFSGK
VELHGKQLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDGL LAQYGTVENC EQVNTDSETA
VVNVTYTNRE QTRQAIMKLN GHQLENHVLK VSYIPDEQSV QGPENGRRGG FGARGAPRQG
SPVTAGAPVK QQPVDIPLRL LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA
EKAISIHSTP EGCSAACKMI LEIMQKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK
KVEQDTETKI TISSLQDLTL YNPERTITVK GSIENCCKAE QEIMKKVREA YENDVAAMSL
QSHLIPGLNL AAVGLFPASS NAVPPPPSSV SGAAPYSSFM PPEQETVHVF IPAQAVGAII
GKKGQHIKQL SRFASASIKI APPETPDSKV RMVVITGPPE AQFKAQGRIY GKLKEENFFG
PKEEVKLETH IRVPASAAGR VIGKGGKTVN ELQNLTAAEV VVPRDQTPDE NEQVIVKIIG
HFYASQMAQR KIRDILAQVK QQHQKGQSGQ LQARRK
