ID CPEB4_MOUSE Reviewed; 729 AA. AC Q7TN98; A6H6G0; Q69ZD7; DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 12-AUG-2020, entry version 118. DE RecName: Full=Cytoplasmic polyadenylation element-binding protein 4; DE Short=CPE-BP4; DE Short=CPE-binding protein 4; DE Short=mCPEB-4; GN Name=Cpeb4; Synonyms=Kiaa1673; 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] (ISOFORMS 1; 2; 3 AND 4), ALTERNATIVE SPLICING, RP INDUCTION, AND TISSUE SPECIFICITY. RC STRAIN=BALB/cJ; TISSUE=Brain; RX PubMed=12871996; DOI=10.1073/pnas.1133424100; RA Theis M., Si K., Kandel E.R.; RT "Two previously undescribed members of the mouse CPEB family of genes and RT their inducible expression in the principal cell layers of the RT hippocampus."; RL Proc. Natl. Acad. Sci. U.S.A. 100:9602-9607(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RX PubMed=15368895; DOI=10.1093/dnares/11.3.205; RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., RA Nagase T., Ohara O., Koga H.; RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV. RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs RT identified by screening of terminal sequences of cDNA clones randomly RT sampled from size-fractionated libraries."; RL DNA Res. 11:205-218(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17024188; DOI=10.1038/sj.emboj.7601322; RA Huang Y.S., Kan M.C., Lin C.L., Richter J.D.; RT "CPEB3 and CPEB4 in neurons: analysis of RNA-binding specificity and RT translational control of AMPA receptor GluR2 mRNA."; RL EMBO J. 25:4865-4876(2006). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97 AND SER-99, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Kidney, and Spleen; 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 [7] RP FUNCTION. RX PubMed=22138752; DOI=10.1038/nm.2540; RA Ortiz-Zapater E., Pineda D., Martinez-Bosch N., Fernandez-Miranda G., RA Iglesias M., Alameda F., Moreno M., Eliscovich C., Eyras E., Real F.X., RA Mendez R., Navarro P.; RT "Key contribution of CPEB4-mediated translational control to cancer RT progression."; RL Nat. Med. 18:83-90(2011). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION RP PHENOTYPE. RX PubMed=24386439; DOI=10.1371/journal.pone.0084978; RA Tsai L.Y., Chang Y.W., Lin P.Y., Chou H.J., Liu T.J., Lee P.T., Huang W.H., RA Tsou Y.L., Huang Y.S.; RT "CPEB4 knockout mice exhibit normal hippocampus-related synaptic plasticity RT and memory."; RL PLoS ONE 8:E84978-E84978(2013). RN [9] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=27381259; DOI=10.1038/srep29395; RA Shin J., Salameh J.S., Richter J.D.; RT "Impaired neurodevelopment by the low complexity domain of CPEB4 reveals a RT convergent pathway with neurodegeneration."; RL Sci. Rep. 6:29395-29395(2016). RN [10] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION BY ER STRESS, RP AND DISRUPTION PHENOTYPE. RX PubMed=28092655; DOI=10.1038/ncb3461; RA Maillo C., Martin J., Sebastian D., Hernandez-Alvarez M., Garcia-Rocha M., RA Reina O., Zorzano A., Fernandez M., Mendez R.; RT "Circadian- and UPR-dependent control of CPEB4 mediates a translational RT response to counteract hepatic steatosis under ER stress."; RL Nat. Cell Biol. 19:94-105(2017). CC -!- FUNCTION: Sequence-specific RNA-binding protein that binds to the CC cytoplasmic polyadenylation element (CPE), an uridine-rich sequence CC element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR CC (PubMed:17024188). RNA binding results in a clear conformational change CC analogous to the Venus fly trap mechanism (By similarity). Regulates CC activation of unfolded protein response (UPR) in the process of CC adaptation to ER stress in liver, by maintaining translation of CPE- CC regulated mRNAs in conditions in which global protein synthesis is CC inhibited (PubMed:28092655). Required for cell cycle progression, CC specifically for cytokinesis and chromosomal segregation (By CC similarity). Plays a role as an oncogene promoting tumor growth and CC progression by positively regulating translation of t-plasminogen CC activator/PLAT (PubMed:22138752). Stimulates proliferation of CC melanocytes (By similarity). In contrast to CPEB1 and CPEB3, does not CC play role in synaptic plasticity, learning and memory CC (PubMed:24386439). {ECO:0000250|UniProtKB:Q17RY0, CC ECO:0000269|PubMed:17024188, ECO:0000269|PubMed:22138752, CC ECO:0000269|PubMed:24386439, ECO:0000269|PubMed:28092655}. CC -!- SUBUNIT: Interacts with TOB1. {ECO:0000250|UniProtKB:Q17RY0}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27381259}. Cell CC projection, dendrite {ECO:0000269|PubMed:17024188, CC ECO:0000269|PubMed:24386439}. Cell projection, dendritic spine CC {ECO:0000269|PubMed:24386439}. Cell junction, synapse, postsynaptic CC density {ECO:0000269|PubMed:17024188}. Cell projection, axon CC {ECO:0000269|PubMed:27381259}. Cell projection, growth cone CC {ECO:0000269|PubMed:27381259}. Endoplasmic reticulum CC {ECO:0000269|PubMed:28092655}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:28092655}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=mCPEB-4a; CC IsoId=Q7TN98-1; Sequence=Displayed; CC Name=2; Synonyms=mCPEB-4b; CC IsoId=Q7TN98-2; Sequence=VSP_022046; CC Name=3; Synonyms=mCPEB-4c; CC IsoId=Q7TN98-3; Sequence=VSP_022044; CC Name=4; Synonyms=mCPEB-4d; CC IsoId=Q7TN98-4; Sequence=VSP_022043; CC Name=5; CC IsoId=Q7TN98-5; Sequence=VSP_022045; CC -!- TISSUE SPECIFICITY: Highly expressed in brain, including hippocampus, CC amygdala, granule and Purkinje cells of the cerebellum (at protein CC level) (PubMed:17024188, PubMed:24386439). Expressed in spinal cord (at CC protein level) (PubMed:27381259). Expressed in kidney, lung and heart CC (at protein level) (PubMed:12871996, PubMed:27381259, PubMed:24386439). CC Expressed in liver (at protein level) (PubMed:28092655, CC PubMed:12871996, PubMed:27381259, PubMed:24386439). Expressed in spleen CC and testis (at protein level) (PubMed:24386439, PubMed:12871996). CC Weakly expressed in ovary and in granular cells of dentate gyrus and CC the pyramidal cells of CA3 and CA1 of the hippocampus CC (PubMed:12871996). {ECO:0000269|PubMed:12871996, CC ECO:0000269|PubMed:17024188, ECO:0000269|PubMed:24386439, CC ECO:0000269|PubMed:27381259, ECO:0000269|PubMed:28092655}. CC -!- DEVELOPMENTAL STAGE: Highly expressed in developing brain, spinal cord CC and attached dorsal root ganglia (DRG) (at protein level). At embryonic CC day 18.5 expressed in gray matter of spinal cord, diencephalons, CC hippocampus and parts of midbrain and hindbrain. At postnatal day 20 CC expression persists in spinal cord and brain. Expressed in embryonic CC heart. {ECO:0000269|PubMed:27381259}. CC -!- INDUCTION: Up-regulated in granular cells of the dentate gyrus of CA1 CC and CA3 after kainate-induced seizures (PubMed:12871996). Up-regulated CC by high-fat-diet and aging-induced endoplasmic reticulum stress CC (PubMed:28092655). Expression level fluctuation follows the circadian CC clock amplitude (PubMed:28092655). {ECO:0000269|PubMed:12871996, CC ECO:0000269|PubMed:28092655}. CC -!- DOMAIN: The 2 RRM domains and the C-terminal region mediate interaction CC with CPE-containing RNA. The interdomain linker (564-579) acts as a CC hinge to fix the relative orientation of the 2 RRMs. The ZZ domain CC (509-566) coordinates 2 Zn ions and is probably implicated in mediating CC interactions with other proteins in addition to increasing the affinity CC of the RRMs for the CPEs. Unlike in CPEB1, a continuous polar interface CC is formed between the 2 RRMs. {ECO:0000250|UniProtKB:Q17RY0, CC ECO:0000250|UniProtKB:Q9BZB8}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype at young age or under CC unchallenged conditions (PubMed:24386439, PubMed:28092655). At 80 weeks CC or under high fat diet feeding conditions, mutant mice develop CC hepatosteatosis with excessive liver weight and accumulation of CC cytosolic lipid droplets sometimes accompanied by fibrosis CC (PubMed:28092655). {ECO:0000269|PubMed:24386439, CC ECO:0000269|PubMed:28092655}. CC -!- SIMILARITY: Belongs to the RRM CPEB family. {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; AY313775; AAQ20844.1; -; mRNA. DR EMBL; AK173229; BAD32507.1; -; mRNA. DR EMBL; BC115430; AAI15431.1; -; mRNA. DR EMBL; BC115431; AAI15432.1; -; mRNA. DR EMBL; BC145863; AAI45864.1; -; mRNA. DR EMBL; BC145865; AAI45866.1; -; mRNA. DR CCDS; CCDS24514.1; -. [Q7TN98-1] DR RefSeq; NP_001277607.1; NM_001290678.1. [Q7TN98-5] DR RefSeq; NP_080528.2; NM_026252.4. [Q7TN98-1] DR SMR; Q7TN98; -. DR BioGRID; 212288; 1. DR STRING; 10090.ENSMUSP00000020543; -. DR iPTMnet; Q7TN98; -. DR PhosphoSitePlus; Q7TN98; -. DR jPOST; Q7TN98; -. DR PaxDb; Q7TN98; -. DR PRIDE; Q7TN98; -. DR Antibodypedia; 28980; 148 antibodies. DR Ensembl; ENSMUST00000020543; ENSMUSP00000020543; ENSMUSG00000020300. [Q7TN98-1] DR GeneID; 67579; -. DR KEGG; mmu:67579; -. DR UCSC; uc007iir.2; mouse. [Q7TN98-2] DR UCSC; uc007iis.2; mouse. [Q7TN98-5] DR UCSC; uc007iit.2; mouse. [Q7TN98-1] DR CTD; 80315; -. DR MGI; MGI:1914829; Cpeb4. DR eggNOG; KOG0129; Eukaryota. DR GeneTree; ENSGT00940000154998; -. DR InParanoid; Q7TN98; -. DR KO; K02602; -. DR OMA; SHRNPAF; -. DR PhylomeDB; Q7TN98; -. DR TreeFam; TF317658; -. DR BioGRID-ORCS; 67579; 0 hits in 18 CRISPR screens. DR ChiTaRS; Cpeb4; mouse. DR PRO; PR:Q7TN98; -. DR Proteomes; UP000000589; Chromosome 11. DR RNAct; Q7TN98; protein. DR Bgee; ENSMUSG00000020300; Expressed in liver and 286 other tissues. DR ExpressionAtlas; Q7TN98; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0030425; C:dendrite; IDA:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:1990124; C:messenger ribonucleoprotein complex; IBA:GO_Central. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0098794; C:postsynapse; ISO:MGI. DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB. DR GO; GO:0045202; C:synapse; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003730; F:mRNA 3'-UTR binding; IBA:GO_Central. DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central. DR GO; GO:0003723; F:RNA binding; IDA:MGI. DR GO; GO:0008135; F:translation factor activity, RNA binding; IBA:GO_Central. DR GO; GO:0000900; F:translation repressor activity, mRNA regulatory element binding; IBA:GO_Central. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:UniProtKB. DR GO; GO:0036294; P:cellular response to decreased oxygen levels; ISS:UniProtKB. DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB. DR GO; GO:0035235; P:ionotropic glutamate receptor signaling pathway; ISS:UniProtKB. DR GO; GO:2000766; P:negative regulation of cytoplasmic translation; IBA:GO_Central. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:0002931; P:response to ischemia; IDA:UniProtKB. DR Gene3D; 3.30.40.130; -; 1. DR Gene3D; 3.30.70.330; -; 2. DR InterPro; IPR032296; CEBP_ZZ. DR InterPro; IPR038446; CEBP_ZZ_sf. DR InterPro; IPR034819; CPEB. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR PANTHER; PTHR12566; PTHR12566; 1. DR Pfam; PF16366; CEBP_ZZ; 1. DR Pfam; PF16367; RRM_7; 1. DR SMART; SM00360; RRM; 2. DR SUPFAM; SSF54928; SSF54928; 1. DR PROSITE; PS50102; RRM; 2. PE 1: Evidence at protein level; KW Alternative splicing; Cell junction; Cell projection; Cytoplasm; KW Endoplasmic reticulum; Metal-binding; Phosphoprotein; Reference proteome; KW Repeat; RNA-binding; Synapse; Zinc. FT CHAIN 1..729 FT /note="Cytoplasmic polyadenylation element-binding protein FT 4" FT /id="PRO_0000269265" FT DOMAIN 472..563 FT /note="RRM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 580..662 FT /note="RRM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT REGION 1..375 FT /note="Low complexity region" FT /evidence="ECO:0000303|PubMed:27381259" FT REGION 541..543 FT /note="RNA-binding" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT COMPBIAS 232..246 FT /note="His-rich" FT COMPBIAS 302..310 FT /note="Poly-Gly" FT METAL 667 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 675 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 684 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 689 FT /note="Zinc 2" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 694 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 697 FT /note="Zinc 1" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 702 FT /note="Zinc 2; via tele nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT METAL 710 FT /note="Zinc 2; via pros nitrogen" FT /evidence="ECO:0000250|UniProtKB:Q9BZB8" FT SITE 473 FT /note="RNA-binding" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT SITE 561 FT /note="Important for the positionning of RRM1 relative to FT RRM2" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 97 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:19144319, FT ECO:0000244|PubMed:21183079" FT MOD_RES 99 FT /note="Phosphoserine" FT /evidence="ECO:0000244|PubMed:21183079" FT MOD_RES 137 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 252 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 255 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 326 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 330 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT MOD_RES 332 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q17RY0" FT VAR_SEQ 402..427 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:12871996" FT /id="VSP_022043" FT VAR_SEQ 402..419 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12871996" FT /id="VSP_022044" FT VAR_SEQ 404..428 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15368895, FT ECO:0000303|PubMed:15489334" FT /id="VSP_022045" FT VAR_SEQ 420..427 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12871996" FT /id="VSP_022046" SQ SEQUENCE 729 AA; 80122 MW; 7CB042EDE4B7C0CA CRC64; MGDYGFGVLV QSNTGNKSAF PVRFHPHLQP PHHHQNATPN PAAFINNNTA ANGSSAGSAW LFPAPATHNI QDEILGSEKA KSQQQEQQDP LEKQQLSPSP GQEAGILPET EKAKAEENPG DSSSENSNGK EKLRIESPVL TGFDYQEATG LGTSTQPLTS SASSLTGFSN WSAAIAPSSS TIINEDASFF HQGGVPGASA NNGALLFQNF PHHVSPGFGG SFSPQIGPLS QHHPHHPHFQ HHHSQHQQQR RSPASPHPPP FTHRSAAFNQ LPHLANNLNK PPSPWSSYQS PSPTPSSSWS PGGGGYGGWG ASQGRDHRRG LNGGITPLNS ISPLKKNFAS NHIQLQKYAR PSSAFAPKSW MEDSLNRADN IFPFPERPRT FDMHSLESSL IDIMRAENDS IKGRLNYSYP GSDSSLLINA RTYGRRRGQS SLFPMEDGFL DDGRGDQPLH SGLGSPHCFT HQNGERVERY SRKVFVGGLP PDIDEDEITA SFRRFGPLIV DWPHKAESKS YFPPKGYAFL LFQDESSVQA LIDACIEEDG KLYLCVSSPT IKDKPVQIRP WNLSDSDFVM DGSQPLDPRK TIFVGGVPRP LRAVELAMIM DRLYGGVCYA GIDTDPELKY PKGAGRVAFS NQQSYIAAIS ARFVQLQHGE IDKRVEVKPY VLDDQLCDEC QGARCGGKFA PFFCANVTCL QYYCEYCWAA IHSRAGREFH KPLVKEGGDR PRHISFRWN //