IF2B1_MOUSE
ID IF2B1_MOUSE Reviewed; 577 AA.
AC O88477; Q80US9; Q8BRH1;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 172.
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=Coding region determinant-binding protein;
DE Short=CRD-BP;
DE AltName: Full=IGF-II mRNA-binding protein 1;
DE AltName: Full=VICKZ family member 1;
DE AltName: Full=Zipcode-binding protein 1;
DE Short=ZBP-1;
GN Name=Igf2bp1; Synonyms=Vickz1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND RNA-BINDING.
RX PubMed=1559612; DOI=10.1101/gad.6.4.642;
RA Bernstein P.L., Herrick D.J., Prokipcak R.D., Ross J.;
RT "Control of c-myc mRNA half-life in vitro by a protein capable of binding
RT to a coding region stability determinant.";
RL Genes Dev. 6:642-654(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND RNA-BINDING.
RX PubMed=8132663; DOI=10.1016/s0021-9258(17)37102-8;
RA Prokipcak R.D., Herrick D.J., Ross J.;
RT "Purification and properties of a protein that binds to the C-terminal
RT coding region of human c-myc mRNA.";
RL J. Biol. Chem. 269:9261-9269(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8114742; DOI=10.1128/mcb.14.3.2119-2128.1994;
RA Herrick D.J., Ross J.;
RT "The half-life of c-myc mRNA in growing and serum-stimulated cells:
RT influence of the coding and 3' untranslated regions and role of ribosome
RT translocation.";
RL Mol. Cell. Biol. 14:2119-2128(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9801297; DOI=10.1093/nar/26.22.5036;
RA Doyle G.A., Betz N.A., Leeds P.F., Fleisig A.J., Prokipcak R.D., Ross J.;
RT "The c-myc coding region determinant-binding protein: a member of a family
RT of KH domain RNA-binding proteins.";
RL Nucleic Acids Res. 26:5036-5044(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=129/Sv X 129SvCp; TISSUE=Embryonic stem cell;
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 [9]
RP PROTEIN SEQUENCE OF 1-20; 27-52; 302-325; 509-525 AND 555-561,
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A MRNP COMPLEX WITH
RP ELAVL4 AND G3BP, INTERACTION WITH ELAVL4, AND ASSOCIATION WITH POLYSOMES.
RX PubMed=15086518; DOI=10.1111/j.1471-4159.2004.02371.x;
RA Atlas R., Behar L., Elliott E., Ginzburg I.;
RT "The insulin-like growth factor mRNA binding-protein IMP-1 and the Ras-
RT regulatory protein G3BP associate with tau mRNA and HuD protein in
RT differentiated P19 neuronal cells.";
RL J. Neurochem. 89:613-626(2004).
RN [10]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=9891060; DOI=10.1128/mcb.19.2.1262;
RA Nielsen J., Christiansen J., Lykke-Andersen J., Johnsen A.H., Wewer U.M.,
RA Nielsen F.C.;
RT "A family of insulin-like growth factor II mRNA-binding proteins represses
RT translation in late development.";
RL Mol. Cell. Biol. 19:1262-1270(1999).
RN [11]
RP DEVELOPMENTAL STAGE.
RX PubMed=10875929; DOI=10.1074/jbc.m001156200;
RA Runge S., Nielsen F.C., Nielsen J., Lykke-Andersen J., Wewer U.M.,
RA Christiansen J.;
RT "H19 RNA binds four molecules of insulin-like growth factor II mRNA-binding
RT protein.";
RL J. Biol. Chem. 275:29562-29569(2000).
RN [12]
RP ASSOCIATION WITH MICROTUBULES, RNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=11973350; DOI=10.1242/jcs.115.10.2087;
RA Nielsen F.C., Nielsen J., Kristensen M.A., Koch G., Christiansen J.;
RT "Cytoplasmic trafficking of IGF-II mRNA-binding protein by conserved KH
RT domains.";
RL J. Cell Sci. 115:2087-2097(2002).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=12921532; DOI=10.1042/bj20030943;
RA Nielsen J., Adolph S.K., Rajpert-De Meyts E., Lykke-Andersen J., Koch G.,
RA Christiansen J., Nielsen F.C.;
RT "Nuclear transit of human zipcode-binding protein IMP1.";
RL Biochem. J. 376:383-391(2003).
RN [14]
RP FUNCTION.
RX PubMed=15355996; DOI=10.1074/jbc.m405853200;
RA Liao B., Patel M., Hu Y., Charles S., Herrick D.J., Brewer G.;
RT "Targeted knockdown of the RNA-binding protein CRD-BP promotes cell
RT proliferation via an insulin-like growth factor II-dependent pathway in
RT human K562 leukemia cells.";
RL J. Biol. Chem. 279:48716-48724(2004).
RN [15]
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=15121863; DOI=10.1128/mcb.24.10.4448-4464.2004;
RA Hansen T.V., Hammer N.A., Nielsen J., Madsen M., Dalbaeck C., Wewer U.M.,
RA Christiansen J., Nielsen F.C.;
RT "Dwarfism and impaired gut development in insulin-like growth factor II
RT mRNA-binding protein 1-deficient mice.";
RL Mol. Cell. Biol. 24:4448-4464(2004).
RN [16]
RP DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RX PubMed=16049158; DOI=10.1530/rep.1.00664;
RA Hammer N.A., Hansen T.O., Byskov A.G., Rajpert-De Meyts E., Groendahl M.L.,
RA Bredkjaer H.E., Wewer U.M., Christiansen J., Nielsen F.C.;
RT "Expression of IGF-II mRNA-binding proteins (IMPs) in gonads and testicular
RT cancer.";
RL Reproduction 130:203-212(2005).
RN [17]
RP FUNCTION, AND RNA-BINDING.
RX PubMed=17264115; DOI=10.1093/nar/gkl1148;
RA Sparanese D., Lee C.H.;
RT "CRD-BP shields c-myc and MDR-1 RNA from endonucleolytic attack by a
RT mammalian endoribonuclease.";
RL Nucleic Acids Res. 35:1209-1221(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [20]
RP FUNCTION IN AXONAL REGENERATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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 [21]
RP FUNCTION IN INTESTINAL WOUND REPAIR, RNA-BINDING, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=22465430; DOI=10.1053/j.gastro.2012.03.037;
RA Manieri N.A., Drylewicz M.R., Miyoshi H., Stappenbeck T.S.;
RT "Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic
RT mesenchymal stem cells in mice.";
RL Gastroenterology 143:110-121(2012).
RN [22]
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). Regulates localized beta-actin/ACTB mRNA translation,
CC a crucial process for cell polarity, cell migration and neurite
CC outgrowth. Co-transcriptionally associates with the ACTB mRNA in the
CC nucleus. This binding involves a conserved 54-nucleotide element in the
CC ACTB mRNA 3'-UTR, known as the 'zipcode'. The RNP thus formed is
CC exported to the cytoplasm, binds to a motor protein and is transported
CC along the cytoskeleton to the cell periphery. During transport,
CC prevents ACTB mRNA from being translated into protein. When the RNP
CC complex reaches its destination near the plasma membrane, IGF2BP1 is
CC phosphorylated. This releases the mRNA, allowing ribosomal 40S and 60S
CC subunits to assemble and initiate ACTB protein synthesis. Monomeric
CC ACTB then assembles into the subcortical actin cytoskeleton (By
CC 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 ACTB (By similarity). May regulate mRNA transport to activated
CC synapses (By similarity). Binds to the 3'-UTR of CD44 mRNA and
CC stabilizes it, hence promotes cell adhesion and invadopodia formation
CC in cancer cells (By similarity). Binds to the oncofetal H19 transcript
CC and regulates its localization (By similarity). Binds to and stabilizes
CC BTRC/FBW1A mRNA (By similarity). Binds to the adenine-rich
CC autoregulatory sequence (ARS) located in PABPC1 mRNA and represses its
CC translation. PABPC1 mRNA-binding is stimulated by PABPC1 protein.
CC Prevents BTRC/FBW1A mRNA degradation by disrupting microRNA-dependent
CC interaction with AGO2 (By similarity). During cellular stress, such as
CC oxidative stress or heat shock, stabilizes target mRNAs that are
CC recruited to stress granules, including CD44, IGF2, MAPK4, MYC, PTEN,
CC RAPGEF2 and RPS6KA5 transcripts (By similarity). Interacts with GAP43
CC transcript and transports it to axons. Binds to the 3'-UTR of IGF2 mRNA
CC by a mechanism of cooperative and sequential dimerization and regulates
CC IGF2 mRNA subcellular localization and translation. Binds to MYC mRNA,
CC in the coding region instability determinant (CRD) of the open reading
CC frame (ORF), hence prevents MYC cleavage by endonucleases and possibly
CC microRNA targeting to MYC-CRD. Binding to MYC mRNA is enhanced by m6A-
CC modification of the CRD (By similarity). Binds to and stabilizes
CC ABCB1/MDR-1 mRNA. Binds to the neuron-specific TAU mRNA and regulates
CC its localization. Plays a direct role in the transport and translation
CC of transcripts required for axonal regeneration in adult sensory
CC neurons. During interstinal wound repair, interacts with and stabilizes
CC PTGS2 transcript. PTGS2 mRNA stabilization may be crucial for colonic
CC mucosal wound healing. {ECO:0000250, ECO:0000250|UniProtKB:Q9NZI8,
CC ECO:0000269|PubMed:15355996, ECO:0000269|PubMed:17264115,
CC ECO:0000269|PubMed:21964071, ECO:0000269|PubMed:22465430}.
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). Identified 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 RNP complex (ARC), at least composed
CC of IGF2BP1, PABPC1 and CSDE1. Interacts with AGO1 and AGO2 (By
CC similarity). Interacts, through domains KH3 and KH4, with PABPC1 in an
CC RNA-independent manner (By similarity). Component of a TAU mRNP
CC complex, at least composed of IGF2BP1, ELAVL4 and G3BP. Interacts with
CC ELAVL4 in an RNA-dependent manner. Associates with microtubules and
CC polysomes. Interacts with ELAVL1 and MATR3 (By similarity).
CC {ECO:0000250|UniProtKB:Q9NZI8, ECO:0000269|PubMed:15086518}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear region
CC {ECO:0000250}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q9NZI8}.
CC Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q9NZI8}. Cell
CC projection, lamellipodium {ECO:0000250}. Cell projection, dendrite
CC {ECO:0000250}. Cell projection, dendritic spine {ECO:0000250}. Cell
CC projection, growth cone {ECO:0000250}. Cell projection, filopodium
CC {ECO:0000250}. Cell projection, axon {ECO:0000250}. Note=In the
CC nucleus, located in discrete foci, coinciding with the sites of ACTB
CC transcription (By similarity). In the cytoplasm, localizes in
CC cytoplasmic mRNP granules. Colocalizes with microtubules in growth cone
CC filopodia and along neurites in neuronal cells (By similarity).
CC Cytoplasmic colocalization with ACTB mRNA is partially lost at the cell
CC periphery, suggesting release of the transcript (By similarity). In
CC hippocampal neurons, predominantly located within dendrites,
CC particularly at dendritic branching points in young cells, compared to
CC axons (By similarity). In axons, predominantly found in axonal branches
CC and their growth cones (By similarity). In neuronal processes, exhibits
CC fast retrograde and anterograde movements, when associated with ACTB
CC mRNA; this motility is lost when the association is inhibited (By
CC similarity). Dendritic levels are regulated by neuronal activity and
CC glutaminergic signals: they are increased by KCl-induced
CC depolarization, which induces rapid efflux from the cell body into
CC dendrites, and decreased by NMDA receptor agonists (By similarity). In
CC motile cells, such as migrating fibroblasts, localizes to leading edges
CC where it colocalizes with microtubules and microfilaments and to
CC retracting tails (By similarity). In motile cells, transported towards
CC the leading edge into the cortical region of the lamellipodia where it
CC is connected to microfilaments (By similarity). In response to cellular
CC stress, such as oxidative stress or heat shock, recruited to stress
CC granules, but not to processing bodies (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in zygotes and blastocysts (at protein
CC level). Expressed in brain, skeletal muscle, trophoblasts of placenta,
CC oocytes and spermatogonia (at protein level). Expressed in testis and
CC ovary. Following colon injury, expressed in the wound bed mesenchyme
CC during the first phase of repair, probably by colonic mesenchymal stem
CC cells (at protein level). {ECO:0000269|PubMed:16049158,
CC ECO:0000269|PubMed:21964071, ECO:0000269|PubMed:22465430,
CC ECO:0000269|PubMed:9891060}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryonic development and
CC expression declines towards birth (at protein level). At 10.5 dpc,
CC mainly expressed in the fore- and hindbrain, the snout, the branchial
CC arches, the developing limb buds, and the tail. At 12.5 dpc, expression
CC increased in the expanding fore- and hindbrain, as well as in the
CC neural tract. Marked expression also observed in the snout, the
CC interdigital mesenchyme of the limb buds, the tail, the branchial
CC arches and somites, and the developing eye, tongue, heart and liver.
CC Expressed in myoblasts and myotubes at 12.5 dpc (at protein level).
CC From 12.5 to 15.5 dpc, expressed at the basal plasma cell membrane in
CC the basal layer of the epidermis of the skin, lung and intestine (at
CC protein level). Expressed in gonads at 12.5 and 14.5 dpc (at protein
CC level). At 14.5 dpc in limb buds, becomes restricted to the future
CC tendons. Expressed in germ cells at 16.5 dpc (at protein level). At
CC 17.5 dpc, expression generally decreases, but remains high in the
CC intestine, in the developing tubules of the kidney, and in the liver.
CC Expressed until P12, although very low levels may remain in some
CC tissues, such as intestines, kidney and brain, throughout adulthood.
CC Following colonic injury, up-regulated in the wound mucosa at days 2
CC and 4 post-injury and down-regulated at day 6 post-injury, as compared
CC with uninjured mucosa. {ECO:0000269|PubMed:10875929,
CC ECO:0000269|PubMed:15121863, ECO:0000269|PubMed:16049158,
CC ECO:0000269|PubMed:21964071, ECO:0000269|PubMed:22465430,
CC ECO:0000269|PubMed:9891060}.
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.
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 -!- DISRUPTION PHENOTYPE: Mutant mice exhibit high perinatal mortality and
CC only 50% are alive 3 days after birth. Early death may be due to
CC intestinal dysfunction. Animals are on average 40% smaller than wild-
CC type and heterozygous sex-matched littermates. Growth retardation,
CC probably due to hypoplasia, appears from 17.5 dpc and remains permanent
CC into adult life. Mutant animals exhibit other stricking features,
CC including impaired development of the intestine, with small and
CC misshapen villi and twisted colon crypts, abnormal kidney architecture
CC and loss of cartilage in the lower extremities. Some animals show signs
CC of neurological damage, including aggressive behavior, restlessness and
CC circular movements. {ECO:0000269|PubMed:15121863}.
CC -!- SIMILARITY: Belongs to the RRM IMP/VICKZ family. {ECO:0000305}.
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DR EMBL; AF061569; AAC72743.1; -; mRNA.
DR EMBL; AK044850; BAC32119.1; -; mRNA.
DR EMBL; AK013940; BAB29071.1; -; mRNA.
DR EMBL; AL603682; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL606704; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051679; AAH51679.1; -; mRNA.
DR CCDS; CCDS25286.1; -.
DR RefSeq; NP_034081.1; NM_009951.4.
DR AlphaFoldDB; O88477; -.
DR SMR; O88477; -.
DR BioGRID; 228260; 20.
DR ComplexPortal; CPX-1089; CRD-mediated mRNA stability complex.
DR DIP; DIP-48578N; -.
DR IntAct; O88477; 4.
DR STRING; 10090.ENSMUSP00000013559; -.
DR iPTMnet; O88477; -.
DR PhosphoSitePlus; O88477; -.
DR MaxQB; O88477; -.
DR PaxDb; O88477; -.
DR PeptideAtlas; O88477; -.
DR PRIDE; O88477; -.
DR ProteomicsDB; 267196; -.
DR Antibodypedia; 17915; 333 antibodies from 37 providers.
DR DNASU; 140486; -.
DR Ensembl; ENSMUST00000013559; ENSMUSP00000013559; ENSMUSG00000013415.
DR GeneID; 140486; -.
DR KEGG; mmu:140486; -.
DR UCSC; uc007lay.2; mouse.
DR CTD; 10642; -.
DR MGI; MGI:1890357; Igf2bp1.
DR VEuPathDB; HostDB:ENSMUSG00000013415; -.
DR eggNOG; KOG2193; Eukaryota.
DR GeneTree; ENSGT00940000160427; -.
DR HOGENOM; CLU_020744_1_0_1; -.
DR InParanoid; O88477; -.
DR OMA; XAIMKLN; -.
DR OrthoDB; 286875at2759; -.
DR PhylomeDB; O88477; -.
DR TreeFam; TF320229; -.
DR BioGRID-ORCS; 140486; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Igf2bp1; mouse.
DR PRO; PR:O88477; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O88477; protein.
DR Bgee; ENSMUSG00000013415; Expressed in embryonic post-anal tail and 125 other tissues.
DR Genevisible; O88477; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0070937; C:CRD-mediated mRNA stability complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISO:MGI.
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:MGI.
DR GO; GO:0070934; P:CRD-mediated mRNA stabilization; ISS:UniProtKB.
DR GO; GO:0140059; P:dendrite arborization; ISO:MGI.
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:MGI.
DR GO; GO:0017148; P:negative regulation of translation; ISO:MGI.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IMP:MGI.
DR GO; GO:0022013; P:pallium cell proliferation in forebrain; IMP:MGI.
DR GO; GO:2000767; P:positive regulation of cytoplasmic translation; ISO:MGI.
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; ISO:MGI.
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; Direct protein sequencing; mRNA transport;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; RNA-binding; Synapse;
KW Translation regulation; Transport.
FT CHAIN 1..577
FT /note="Insulin-like growth factor 2 mRNA-binding protein 1"
FT /id="PRO_0000282534"
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 156..190
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..570
FT /note="Necessary for interaction with IGF2BP1 and binding
FT to TAU mRNA"
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:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 528
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZI8"
FT CONFLICT 276
FT /note="E -> G (in Ref. 8; AAH51679)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="E -> G (in Ref. 6; BAC32119)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 577 AA; 63451 MW; EFBB1AF2FF9F0344 CRC64;
MNKLYIGNLN ESVTPADLEK VFAEHKISYS GQFLVKSGYA FVDCPDEHWA MKAIETFSGK
VELQGKRLEI EHSVPKKQRS RKIQIRNIPP QLRWEVLDSL LAQYGTVENC EQVNTESETA
VVNVTYSNRE QTRQAIMKLN GHQLENHALK VSYIPDEQIT QGPENGRRGG FGSRGQPRQG
SPVAAGAPAK QQPVDIPLRL LVPTQYVGAI IGKEGATIRN ITKQTQSKID VHRKENAGAA
EKAISVHSTP EGCSSACKMI LEIMHKEAKD TKTADEVPLK ILAHNNFVGR LIGKEGRNLK
KVEQDTETKI TISSLQDLTL YNPERTITVK GAIENCCRAE QEIMKKVREA YENDVAAMSL
QSHLIPGLNL AAVGLFPASS SAVPPPPSSV TGAAPYSSFM QAPEQEMVQV FIPAQAVGAI
IGKKGQHIKQ LSRFASASIK IAPPETPDSK VRMVVITGPP EAQFKAQGRI YGKLKEENFF
GPKEEVKLET HIRVPASAAG RVIGKGGKTV NELQNLTAAE VVVPRDQTPD ENDQVIVKII
GHFYASQMAQ RKIRDILAQV KQQHQKGQSN LAQARRK
