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 27-MAR-2024, entry version 194. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7Q98; X-ray; 2.50 A; C/F/I/L/O=367-376. DR PDB; 7Q99; X-ray; 2.55 A; C=367-376. DR PDBsum; 2CQH; -. DR PDBsum; 6ROL; -. DR PDBsum; 7Q98; -. DR PDBsum; 7Q99; -. DR AlphaFoldDB; Q9Y6M1; -. DR SMR; Q9Y6M1; -. DR BioGRID; 115888; 478. DR DIP; DIP-35539N; -. DR IntAct; Q9Y6M1; 74. DR MINT; Q9Y6M1; -. DR STRING; 9606.ENSP00000410242; -. 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; 9606-ENSP00000371634; -. DR PeptideAtlas; 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 Pumba; Q9Y6M1; -. DR Antibodypedia; 33841; 717 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 AGR; HGNC:28867; -. 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 OrthoDB; 3035007at2759; -. 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; 18 hits in 1151 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 176 other cell types or tissues. DR ExpressionAtlas; Q9Y6M1; baseline and differential. 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:1990247; F:N6-methyladenosine-containing RNA reader activity; 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:0090079; F:translation regulator activity, nucleic acid binding; IEA:Ensembl. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0106106; P:cold-induced thermogenesis; IEA:Ensembl. DR GO; GO:0070934; P:CRD-mediated mRNA stabilization; IDA:UniProtKB. DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl. 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 CDD; cd22491; KH-I_IGF2BP2_rpt1; 1. DR CDD; cd22494; KH-I_IGF2BP2_rpt2; 1. DR CDD; cd22497; KH-I_IGF2BP2_rpt3; 1. DR CDD; cd22500; KH-I_IGF2BP2_rpt4; 1. DR CDD; cd12626; RRM1_IGF2BP2; 1. DR CDD; cd12629; RRM2_IGF2BP2; 1. DR Gene3D; 3.30.310.210; -; 1. DR Gene3D; 3.30.70.330; -; 2. DR Gene3D; 3.30.1370.10; K Homology domain, type 1; 2. 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; INSULIN-LIKE GROWTH FACTOR 2 MRNA-BINDING PROTEIN 2; 1. DR PANTHER; PTHR10288; KH DOMAIN CONTAINING RNA BINDING PROTEIN; 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; Eukaryotic type KH-domain (KH-domain type I); 4. DR SUPFAM; SSF54928; RNA-binding domain, RBD; 1. DR PROSITE; PS50084; KH_TYPE_1; 4. DR PROSITE; PS50102; RRM; 2. DR Genevisible; Q9Y6M1; HS. 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 FT E-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 FT E-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 FT E-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 FT E-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 370..372 FT /evidence="ECO:0007829|PDB:7Q98" 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 //