IF2B2_HUMAN
ID IF2B2_HUMAN Reviewed; 599 AA.
AC Q9Y6M1; A0A4Z0; B3FTN2; B3FTN3; B3FTN4;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Insulin-like growth factor 2 mRNA-binding protein 2;
DE Short=IGF2 mRNA-binding protein 2;
DE Short=IMP-2;
DE AltName: Full=Hepatocellular carcinoma autoantigen p62;
DE AltName: Full=IGF-II mRNA-binding protein 2;
DE AltName: Full=VICKZ family member 2;
GN Name=IGF2BP2; Synonyms=IMP2, VICKZ2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), IDENTIFICATION AS A HEPATOCELLULAR
RP CARCINOMA ANTIGEN, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RC TISSUE=Colon adenocarcinoma;
RX PubMed=10190901; DOI=10.1084/jem.189.7.1101;
RA Zhang J.-Y., Chan E.K.L., Peng X.-X., Tan E.M.;
RT "A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in
RT human hepatocellular carcinoma.";
RL J. Exp. Med. 189:1101-1110(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Pancreatic islet;
RA Prokunina-Olsson L., Hanisch J.J., Jackson A., Chines P.S., Erdos M.R.,
RA Bonnycastle L.L., Swift A., Narisu N., Scott L.J., Morken M., Mohlke K.,
RA Bergman R., Tuomilehto J., Boehnke M., Rotimi C.N., Watanabe R.N.,
RA Collins F.S.;
RT "A novel type 2 diabetes-associated variant of IGF2BP2 gene affects
RT expression of a functional alternative splicing form.";
RL Submitted (JAN-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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 [5]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [6]
RP INTERACTION WITH HNRPD.
RX PubMed=12674497; DOI=10.1515/bc.2003.004;
RA Moraes K.C., Quaresma A.J., Maehnss K., Kobarg J.;
RT "Identification and characterization of proteins that selectively interact
RT with isoforms of the mRNA binding protein AUF1 (hnRNP D).";
RL Biol. Chem. 384:25-37(2003).
RN [7]
RP REVIEW.
RX PubMed=15601260; DOI=10.1042/bc20040151;
RA Yisraeli J.K.;
RT "VICKZ proteins: a multi-talented family of regulatory RNA-binding
RT proteins.";
RL Biol. Cell 97:87-96(2005).
RN [8]
RP SUBCELLULAR LOCATION, 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 [9]
RP INTERACTION WITH IGF2BP1, AND SUBCELLULAR LOCATION.
RX PubMed=17289661; DOI=10.1074/mcp.m600346-mcp200;
RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R.,
RA Johnsen A.H., Christiansen J., Nielsen F.C.;
RT "Molecular composition of IMP1 ribonucleoprotein granules.";
RL Mol. Cell. Proteomics 6:798-811(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162 AND SER-164, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [13]
RP RNA-BINDING, AND DOMAIN.
RX PubMed=20080952; DOI=10.1101/gad.1862910;
RA Chao J.A., Patskovsky Y., Patel V., Levy M., Almo S.C., Singer R.H.;
RT "ZBP1 recognition of beta-actin zipcode induces RNA looping.";
RL Genes Dev. 24:148-158(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-162 AND SER-164, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 6), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [17]
RP ALTERNATIVE INITIATION (ISOFORM 6).
RX PubMed=22427968; DOI=10.1371/journal.pone.0033140;
RA Le H.T., Sorrell A.M., Siddle K.;
RT "Two isoforms of the mRNA binding protein IGF2BP2 are generated by
RT alternative translational initiation.";
RL PLoS ONE 7:E33140-E33140(2012).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 (ISOFORM 6), AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP FUNCTION, RNA-BINDING, OLIGOMERIZATION, INTERACTION WITH ELAVL1; DHX9 AND
RP HNRNPU, SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF LYS-211; LYS-292;
RP 445-LYS-LYS-446 AND 527-LYS-GLY-528.
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-164, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP FUNCTION, INTERACTION WITH ELAVL1; MATR3 AND PABPC1, SUBCELLULAR LOCATION,
RP ROLE OF KH DOMAINS, MUTAGENESIS OF LYS-211; LYS-292; 445-LYS-LYS-446 AND
RP 527-LYS-GLY-528, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=29476152; DOI=10.1038/s41556-018-0045-z;
RA Huang H., Weng H., Sun W., Qin X., Shi H., Wu H., Zhao B.S., Mesquita A.,
RA Liu C., Yuan C.L., Hu Y.C., Huettelmaier S., Skibbe J.R., Su R., Deng X.,
RA Dong L., Sun M., Li C., Nachtergaele S., Wang Y., Hu C., Ferchen K.,
RA Greis K.D., Jiang X., Wei M., Qu L., Guan J.L., He C., Yang J., Chen J.;
RT "Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA
RT stability and translation.";
RL Nat. Cell Biol. 20:285-295(2018).
RN [22]
RP INTERACTION WITH HOXB-AS3 PEPTIDE.
RX PubMed=34457052; DOI=10.3892/ol.2021.12958;
RA Leng F., Miu Y.Y., Zhang Y., Luo H., Lu X.L., Cheng H., Zheng Z.G.;
RT "A micro-peptide encoded by HOXB-AS3 promotes the proliferation and
RT viability of oral squamous cell carcinoma cell lines by directly binding
RT with IGF2BP2 to stabilize c-Myc.";
RL Oncol. Lett. 22:697-697(2021).
RN [23]
RP STRUCTURE BY NMR OF 2-81.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RNA binding domain of IGF-II mRNA-binding
RT protein 2.";
RL Submitted (NOV-2005) to the PDB data bank.
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 (By similarity). Preferentially binds
CC to N6-methyladenosine (m6A)-containing mRNAs and increases their
CC stability (PubMed:29476152). Binds to the 5'-UTR of the insulin-like
CC growth factor 2 (IGF2) mRNAs (PubMed:9891060). Binding is isoform-
CC specific. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC
CC mRNA stability by binding to the coding region instability determinant
CC (CRD) and binding is enhanced by m6A-modification of the CRD
CC (PubMed:29476152). {ECO:0000250, ECO:0000269|PubMed:23640942,
CC ECO:0000269|PubMed:29476152, ECO:0000269|PubMed:9891060}.
CC -!- SUBUNIT: Can form homooligomers and heterooligomers with IGF2BP1 and
CC IGF2BP3 in an RNA-dependent manner (PubMed:23640942). Interacts with
CC HNRPD (PubMed:12674497). Interacts with IGF2BP1 (PubMed:17289661).
CC Interacts with ELAVL1, DHX9, HNRNPU, MATR3 and PABPC1 (PubMed:23640942,
CC PubMed:29476152). Interacts with the HOXB-AS3 peptide; the interaction
CC increases MYC stability (PubMed:34457052).
CC {ECO:0000269|PubMed:12674497, ECO:0000269|PubMed:17289661,
CC ECO:0000269|PubMed:23640942, ECO:0000269|PubMed:29476152,
CC ECO:0000269|PubMed:34457052}.
CC -!- INTERACTION:
CC Q9Y6M1; Q14103-4: HNRNPD; NbExp=4; IntAct=EBI-1024419, EBI-432545;
CC Q9Y6M1; P98179: RBM3; NbExp=6; IntAct=EBI-1024419, EBI-2949699;
CC Q9Y6M1; Q13148: TARDBP; NbExp=3; IntAct=EBI-1024419, EBI-372899;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, P-body
CC {ECO:0000269|PubMed:29476152}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:29476152}. Note=Localized in cytoplasmic mRNP
CC granules containing untranslated mRNAs. Localizes at the connecting
CC piece and the tail of the spermatozoa. In response to cellular stress,
CC such as oxidative stress, recruited to stress granules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=6;
CC Name=1;
CC IsoId=Q9Y6M1-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y6M1-1; Sequence=VSP_036553;
CC Name=3;
CC IsoId=Q9Y6M1-3; Sequence=VSP_036550;
CC Name=4;
CC IsoId=Q9Y6M1-4; Sequence=VSP_036550, VSP_036552;
CC Name=5;
CC IsoId=Q9Y6M1-5; Sequence=VSP_036550, VSP_036553;
CC Name=6;
CC IsoId=Q9Y6M1-6; Sequence=VSP_043699;
CC -!- TISSUE SPECIFICITY: Expressed in oocytes, granulosa cells of small and
CC growing follicles, Leydig cells, spermatogonia and semen (at protein
CC level). Expressed in testicular cancer (at protein level). Expressed
CC weakly in heart, placenta, skeletal muscle, bone marrow, colon, kidney,
CC salivary glands, testis and pancreas. Detected in fetal liver, fetal
CC ovary, gonocytes and interstitial cells of the testis.
CC {ECO:0000269|PubMed:10190901, ECO:0000269|PubMed:16049158}.
CC -!- DOMAIN: Domains KH3 and KH4 are the major RNA-binding modules, although
CC KH1 and KH2 may also contribute (PubMed:29476152). The contribution to
CC 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.
CC {ECO:0000269|PubMed:20080952, ECO:0000269|PubMed:23640942,
CC ECO:0000269|PubMed:29476152}.
CC -!- MISCELLANEOUS: Autoantibodies against IGF2BP2 are detected in sera from
CC some patients with hepatocellular carcinoma.
CC -!- MISCELLANEOUS: [Isoform 6]: Generated by alternative initiation at Met-
CC 69. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the RRM IMP/VICKZ family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH21290.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF057352; AAD31596.1; -; mRNA.
DR EMBL; EU408701; ACB86625.1; -; mRNA.
DR EMBL; EU408702; ACB86626.1; -; mRNA.
DR EMBL; EU408703; ACB86627.1; -; mRNA.
DR EMBL; AC016961; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021290; AAH21290.1; ALT_INIT; mRNA.
DR CCDS; CCDS3273.2; -. [Q9Y6M1-2]
DR CCDS; CCDS33903.1; -. [Q9Y6M1-1]
DR CCDS; CCDS77869.1; -. [Q9Y6M1-3]
DR RefSeq; NP_001007226.1; NM_001007225.2. [Q9Y6M1-1]
DR RefSeq; NP_001278801.1; NM_001291872.2. [Q9Y6M1-4]
DR RefSeq; NP_001278802.1; NM_001291873.2. [Q9Y6M1-3]
DR RefSeq; NP_001278803.1; NM_001291874.2. [Q9Y6M1-5]
DR RefSeq; NP_001278804.1; NM_001291875.2.
DR RefSeq; NP_006539.3; NM_006548.5. [Q9Y6M1-2]
DR PDB; 2CQH; NMR; -; A=2-81.
DR PDB; 6ROL; X-ray; 2.10 A; A/B/C/D=426-588.
DR PDBsum; 2CQH; -.
DR PDBsum; 6ROL; -.
DR AlphaFoldDB; Q9Y6M1; -.
DR SMR; Q9Y6M1; -.
DR BioGRID; 115888; 437.
DR DIP; DIP-35539N; -.
DR IntAct; Q9Y6M1; 63.
DR MINT; Q9Y6M1; -.
DR STRING; 9606.ENSP00000371634; -.
DR GlyGen; Q9Y6M1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y6M1; -.
DR PhosphoSitePlus; Q9Y6M1; -.
DR SwissPalm; Q9Y6M1; -.
DR BioMuta; IGF2BP2; -.
DR DMDM; 224471831; -.
DR EPD; Q9Y6M1; -.
DR jPOST; Q9Y6M1; -.
DR MassIVE; Q9Y6M1; -.
DR MaxQB; Q9Y6M1; -.
DR PaxDb; Q9Y6M1; -.
DR PeptideAtlas; Q9Y6M1; -.
DR PRIDE; Q9Y6M1; -.
DR ProteomicsDB; 86724; -. [Q9Y6M1-2]
DR ProteomicsDB; 86725; -. [Q9Y6M1-1]
DR ProteomicsDB; 86726; -. [Q9Y6M1-3]
DR ProteomicsDB; 86727; -. [Q9Y6M1-4]
DR ProteomicsDB; 86728; -. [Q9Y6M1-5]
DR ProteomicsDB; 86729; -. [Q9Y6M1-6]
DR Antibodypedia; 33841; 634 antibodies from 41 providers.
DR DNASU; 10644; -.
DR Ensembl; ENST00000346192.7; ENSP00000320204.5; ENSG00000073792.16. [Q9Y6M1-1]
DR Ensembl; ENST00000382199.7; ENSP00000371634.3; ENSG00000073792.16. [Q9Y6M1-2]
DR Ensembl; ENST00000421047.3; ENSP00000413787.3; ENSG00000073792.16. [Q9Y6M1-3]
DR GeneID; 10644; -.
DR KEGG; hsa:10644; -.
DR MANE-Select; ENST00000382199.7; ENSP00000371634.3; NM_006548.6; NP_006539.3.
DR UCSC; uc003fpo.4; human. [Q9Y6M1-2]
DR CTD; 10644; -.
DR DisGeNET; 10644; -.
DR GeneCards; IGF2BP2; -.
DR HGNC; HGNC:28867; IGF2BP2.
DR HPA; ENSG00000073792; Low tissue specificity.
DR MalaCards; IGF2BP2; -.
DR MIM; 608289; gene.
DR neXtProt; NX_Q9Y6M1; -.
DR OpenTargets; ENSG00000073792; -.
DR PharmGKB; PA128394577; -.
DR VEuPathDB; HostDB:ENSG00000073792; -.
DR eggNOG; KOG2193; Eukaryota.
DR GeneTree; ENSGT00940000154913; -.
DR HOGENOM; CLU_020744_1_0_1; -.
DR InParanoid; Q9Y6M1; -.
DR OMA; SYETQEQ; -.
DR PhylomeDB; Q9Y6M1; -.
DR TreeFam; TF320229; -.
DR PathwayCommons; Q9Y6M1; -.
DR Reactome; R-HSA-428359; Insulin-like Growth Factor-2 mRNA Binding Proteins (IGF2BPs/IMPs/VICKZs) bind RNA.
DR SignaLink; Q9Y6M1; -.
DR BioGRID-ORCS; 10644; 17 hits in 1073 CRISPR screens.
DR ChiTaRS; IGF2BP2; human.
DR EvolutionaryTrace; Q9Y6M1; -.
DR GeneWiki; IGF2BP2; -.
DR GenomeRNAi; 10644; -.
DR Pharos; Q9Y6M1; Tbio.
DR PRO; PR:Q9Y6M1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9Y6M1; protein.
DR Bgee; ENSG00000073792; Expressed in buccal mucosa cell and 175 other tissues.
DR ExpressionAtlas; Q9Y6M1; baseline and differential.
DR Genevisible; Q9Y6M1; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0048027; F:mRNA 5'-UTR binding; IDA:BHF-UCL.
DR GO; GO:0003729; F:mRNA binding; IBA:GO_Central.
DR GO; GO:1990247; F:N6-methyladenosine-containing RNA binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0045182; F:translation regulator activity; ISS:BHF-UCL.
DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR GO; GO:0070934; P:CRD-mediated mRNA stabilization; IDA:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0017148; P:negative regulation of translation; ISS:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; IBA:GO_Central.
DR GO; GO:0001817; P:regulation of cytokine production; IC:BHF-UCL.
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; cd12626; RRM1_IGF2BP2; 1.
DR Gene3D; 3.30.1370.10; -; 2.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR028743; IGF2BP2.
DR InterPro; IPR034843; IGF2BP2_RRM1.
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 PANTHER; PTHR10288:SF93; PTHR10288:SF93; 1.
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; Acetylation; Alternative initiation; Alternative splicing;
KW Cytoplasm; mRNA transport; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; RNA-binding; Translation regulation; Transport.
FT CHAIN 1..599
FT /note="Insulin-like growth factor 2 mRNA-binding protein 2"
FT /id="PRO_0000244496"
FT DOMAIN 3..76
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 82..157
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 193..258
FT /note="KH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 274..341
FT /note="KH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 427..492
FT /note="KH 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT DOMAIN 509..575
FT /note="KH 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00117"
FT REGION 157..188
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 550
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q5SF07"
FT VAR_SEQ 1..80
FT /note="MMNKLYIGNLSPAVTADDLRQLFGDRKLPLAGQVLLKSGYAFVDYPDQNWAI
FT RAIETLSGKVELHGKIMEVDYSVSKKLR -> MFSCPGHYHVDGFLNPG (in
FT isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_036550"
FT VAR_SEQ 1..68
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000305"
FT /id="VSP_043699"
FT VAR_SEQ 113
FT /note="Q -> QVFAFSL (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_036552"
FT VAR_SEQ 358..400
FT /note="Missing (in isoform 2 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:10190901, ECO:0000303|Ref.2"
FT /id="VSP_036553"
FT MUTAGEN 211
FT /note="K->E: Significantly impaired binding to ACTB
FT transcript but little effect on MYC transcript binding,
FT accumulation in the nucleus and partial reduction in
FT interaction with m6A-modified mRNA; when associated with E-
FT 292. Loss of homo- and heterooligomerization with IGF2BP1
FT 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 292; 445-E-E-446 and 526-E-E-527."
FT /evidence="ECO:0000269|PubMed:23640942,
FT ECO:0000269|PubMed:29476152"
FT MUTAGEN 292
FT /note="K->E: Significantly impaired binding to ACTB
FT transcript but little effect on MYC transcript binding,
FT accumulation in the nucleus and partial reduction in
FT interaction with m6A-modified mRNA; when associated with E-
FT 211. Loss of homo- and heterooligomerization with IGF2BP1
FT 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 211; 445-E-E-445 and 526-E-E-527."
FT /evidence="ECO:0000269|PubMed:23640942,
FT ECO:0000269|PubMed:29476152"
FT MUTAGEN 445..446
FT /note="KK->EE: Significantly impaired binding to ACTB and
FT MYC transcripts and loss of interaction with m6A-modified
FT mRNA; when associated with 527-E-E-528. 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 perturbed subcellular location, including accumulation in
FT the nucleus and loss of localization to stress granules;
FT when associated with E-211; E-292 and 527-E-E-528."
FT /evidence="ECO:0000269|PubMed:23640942,
FT ECO:0000269|PubMed:29476152"
FT MUTAGEN 527..528
FT /note="KG->EE: Significantly impaired binding to ACTB and
FT MYC transcripts and loss of interaction with m6A-modified
FT mRNA; when associated with 445-E-E-446. 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 perturbed subcellular location, including accumulation in
FT the nucleus and loss of localization to stress granules;
FT when associated with E-211; E-292 and 445-E-E-446."
FT /evidence="ECO:0000269|PubMed:23640942,
FT ECO:0000269|PubMed:29476152"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:2CQH"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:2CQH"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2CQH"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:2CQH"
FT HELIX 48..58
FT /evidence="ECO:0007829|PDB:2CQH"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:2CQH"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:2CQH"
FT STRAND 428..435
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 439..443
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 448..457
FT /evidence="ECO:0007829|PDB:6ROL"
FT STRAND 459..463
FT /evidence="ECO:0007829|PDB:6ROL"
FT STRAND 472..480
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 482..498
FT /evidence="ECO:0007829|PDB:6ROL"
FT STRAND 510..517
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 518..520
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 521..525
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 527..529
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 530..539
FT /evidence="ECO:0007829|PDB:6ROL"
FT STRAND 542..544
FT /evidence="ECO:0007829|PDB:6ROL"
FT STRAND 555..563
FT /evidence="ECO:0007829|PDB:6ROL"
FT HELIX 565..584
FT /evidence="ECO:0007829|PDB:6ROL"
FT MOD_RES Q9Y6M1-6:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
SQ SEQUENCE 599 AA; 66121 MW; EA656F8733BBB39A CRC64;
MMNKLYIGNL SPAVTADDLR QLFGDRKLPL AGQVLLKSGY AFVDYPDQNW AIRAIETLSG
KVELHGKIME VDYSVSKKLR SRKIQIRNIP PHLQWEVLDG LLAQYGTVEN VEQVNTDTET
AVVNVTYATR EEAKIAMEKL SGHQFENYSF KISYIPDEEV SSPSPPQRAQ RGDHSSREQG
HAPGGTSQAR QIDFPLRILV PTQFVGAIIG KEGLTIKNIT KQTQSRVDIH RKENSGAAEK
PVTIHATPEG TSEACRMILE IMQKEADETK LAEEIPLKIL AHNGLVGRLI GKEGRNLKKI
EHETGTKITI SSLQDLSIYN PERTITVKGT VEACASAEIE IMKKLREAFE NDMLAVNQQA
NLIPGLNLSA LGIFSTGLSV LSPPAGPRGA PPAAPYHPFT THSGYFSSLY PHHQFGPFPH
HHSYPEQEIV NLFIPTQAVG AIIGKKGAHI KQLARFAGAS IKIAPAEGPD VSERMVIITG
PPEAQFKAQG RIFGKLKEEN FFNPKEEVKL EAHIRVPSST AGRVIGKGGK TVNELQNLTS
AEVIVPRDQT PDENEEVIVR IIGHFFASQT AQRKIREIVQ QVKQQEQKYP QGVASQRSK
