CPEB_APLCA
ID CPEB_APLCA Reviewed; 687 AA.
AC Q967R6; Q967R5;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Cytoplasmic polyadenylation element-binding protein {ECO:0000303|PubMed:12480159};
DE Short=CPE-binding protein {ECO:0000303|PubMed:12480159};
DE Short=CPEB {ECO:0000303|PubMed:14697205};
OS Aplysia californica (California sea hare).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda;
OC Heterobranchia; Euthyneura; Tectipleura; Aplysiida; Aplysioidea;
OC Aplysiidae; Aplysia.
OX NCBI_TaxID=6500 {ECO:0000312|EMBL:AAK52834.1};
RN [1] {ECO:0000312|EMBL:AAK52834.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=12480159; DOI=10.1016/s0006-8993(02)03729-0;
RA Liu J., Schwartz J.H.;
RT "The cytoplasmic polyadenylation element binding protein and
RT polyadenylation of messenger RNA in Aplysia neurons.";
RL Brain Res. 959:68-76(2003).
RN [2] {ECO:0000305}
RP FUNCTION, AND DOMAIN.
RX PubMed=14697205; DOI=10.1016/s0092-8674(03)01020-1;
RA Si K., Lindquist S., Kandel E.R.;
RT "A neuronal isoform of the Aplysia CPEB has prion-like properties.";
RL Cell 115:879-891(2003).
RN [3] {ECO:0000305}
RP FUNCTION, AND INDUCTION BY SEROTONIN.
RX PubMed=14697206; DOI=10.1016/s0092-8674(03)01021-3;
RA Si K., Giustetto M., Etkin A., Hsu R., Janisiewicz A.M., Miniaci M.C.,
RA Kim J.H., Zhu H., Kandel E.R.;
RT "A neuronal isoform of CPEB regulates local protein synthesis and
RT stabilizes synapse-specific long-term facilitation in Aplysia.";
RL Cell 115:893-904(2003).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=16687512; DOI=10.1523/jneurosci.4917-05.2006;
RA Liu J., Hu J.Y., Wu F., Schwartz J.H., Schacher S.;
RT "Two mRNA-binding proteins regulate the distribution of syntaxin mRNA in
RT Aplysia sensory neurons.";
RL J. Neurosci. 26:5204-5214(2006).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=18817739; DOI=10.1016/j.neuron.2008.07.036;
RA Miniaci M.C., Kim J.H., Puthanveettil S.V., Si K., Zhu H., Kandel E.R.,
RA Bailey C.H.;
RT "Sustained CPEB-dependent local protein synthesis is required to stabilize
RT synaptic growth for persistence of long-term facilitation in Aplysia.";
RL Neuron 59:1024-1036(2008).
RN [6] {ECO:0000305}
RP SUBUNIT.
RX PubMed=20144764; DOI=10.1016/j.cell.2010.01.008;
RA Si K., Choi Y.B., White-Grindley E., Majumdar A., Kandel E.R.;
RT "Aplysia CPEB can form prion-like multimers in sensory neurons that
RT contribute to long-term facilitation.";
RL Cell 140:421-435(2010).
RN [7] {ECO:0000305}
RP SUBCELLULAR LOCATION.
RX PubMed=19887896; DOI=10.3858/emm.2010.42.1.003;
RA Chae Y.S., Lee S.H., Cheang Y.H., Lee N., Rim Y.S., Jang D.J., Kaang B.K.;
RT "Neuronal RNA granule contains ApCPEB1, a novel cytoplasmic polyadenylation
RT element binding protein, in Aplysia sensory neuron.";
RL Exp. Mol. Med. 42:30-37(2010).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=21270333; DOI=10.1073/pnas.1019368108;
RA Heinrich S.U., Lindquist S.;
RT "Protein-only mechanism induces self-perpetuating changes in the activity
RT of neuronal Aplysia cytoplasmic polyadenylation element binding protein
RT (CPEB).";
RL Proc. Natl. Acad. Sci. U.S.A. 108:2999-3004(2011).
RN [9] {ECO:0000305}
RP SUBUNIT.
RX PubMed=23435382; DOI=10.1038/nsmb.2503;
RA Raveendra B.L., Siemer A.B., Puthanveettil S.V., Hendrickson W.A.,
RA Kandel E.R., McDermott A.E.;
RT "Characterization of prion-like conformational changes of the neuronal
RT isoform of Aplysia CPEB.";
RL Nat. Struct. Mol. Biol. 20:495-501(2013).
RN [10] {ECO:0000305}
RP FUNCTION, AND INDUCTION.
RX PubMed=26095361; DOI=10.1016/j.celrep.2015.05.034;
RA Fiumara F., Rajasethupathy P., Antonov I., Kosmidis S., Sossin W.S.,
RA Kandel E.R.;
RT "MicroRNA-22 gates long-term heterosynaptic plasticity in Aplysia through
RT presynaptic regulation of CPEB and downstream targets.";
RL Cell Rep. 11:1866-1875(2015).
RN [11]
RP SUBUNIT.
RX PubMed=27091989; DOI=10.1073/pnas.1602702113;
RA Chen M., Zheng W., Wolynes P.G.;
RT "Energy landscapes of a mechanical prion and their implications for the
RT molecular mechanism of long-term memory.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:5006-5011(2016).
CC -!- FUNCTION: Sequence-specific RNA-binding protein that regulates mRNA
CC cytoplasmic polyadenylation and translation initiation
CC (PubMed:14697205). In its amyloid-like oligomeric form, acts as a
CC translational activator (PubMed:14697205, PubMed:21270333). Up-
CC regulated at activated synapses where it is required for the late phase
CC of memory-related long-term synaptic facilitation (PubMed:14697206).
CC Sustained CPEB-mediated protein synthesis for at least 72 hours after
CC neuronal stimulation is required for the persistance of synaptic
CC facilitation (PubMed:18817739). Activates translation of atypical
CC protein kinase C (PubMed:26095361). Required for the relocalization of
CC syntaxin mRNA to the axon hillock from the opposite pole in the cell
CC body of sensory neurons during long-term facilitation
CC (PubMed:16687512). {ECO:0000269|PubMed:14697205,
CC ECO:0000269|PubMed:14697206, ECO:0000269|PubMed:16687512,
CC ECO:0000269|PubMed:18817739, ECO:0000269|PubMed:21270333,
CC ECO:0000269|PubMed:26095361}.
CC -!- SUBUNIT: Exists in 2 different conformational states, a soluble alpha-
CC helix-rich form and an insoluble beta-sheet-rich amyloid form
CC (PubMed:23435382). Stable self-sustaining active amyloid-like oligomers
CC are formed upon neuronal stimulation and contribute to long-term
CC facilitation in sensory neurons (PubMed:20144764). More than 80% of the
CC soluble form is found in high molecular weight oligomers, the majority
CC of which have the size of a decamer or larger oligomer
CC (PubMed:23435382). The insoluble form binds RNA with significantly
CC greater affinity than the soluble form (PubMed:23435382). A mechanical
CC pulling force can facilitate the alpha-helix to beta-sheet transition
CC by lowering the free energy barrier between the two forms and
CC interactions with the cytoskeleton may provide the necessary mechanical
CC force (PubMed:27091989). {ECO:0000269|PubMed:20144764,
CC ECO:0000269|PubMed:23435382, ECO:0000303|PubMed:27091989}.
CC -!- INTERACTION:
CC Q967R6; Q967R6: -; NbExp=6; IntAct=EBI-16038339, EBI-16038339;
CC -!- SUBCELLULAR LOCATION: Synapse, synaptosome
CC {ECO:0000269|PubMed:12480159}. Cytoplasmic granule
CC {ECO:0000269|PubMed:19887896}. Note=In sensory neurons, detected in
CC cytoplasmic granules composed of proteins and RNA.
CC {ECO:0000269|PubMed:19887896}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=ApCPEB77 {ECO:0000303|PubMed:12480159};
CC IsoId=Q967R6-1; Sequence=Displayed;
CC Name=2; Synonyms=ApCPEB49 {ECO:0000303|PubMed:12480159};
CC IsoId=Q967R6-2; Sequence=VSP_058507;
CC -!- TISSUE SPECIFICITY: Isoform 1: Enriched in nervous tissue. Isoform 2:
CC Predominates in ovotestis and is only weakly expressed in nervous
CC tissue. {ECO:0000269|PubMed:12480159}.
CC -!- INDUCTION: By neuronal stimulation with serotonin (at protein level)
CC (PubMed:14697206). MicroRNA-22 (miR-22) binds to the 3'-UTR of CPEB
CC mRNA and inhibits its translation while serotonin triggers down-
CC regulation of miR22, thereby up-regulating CPEB expression
CC (PubMed:26095361). {ECO:0000269|PubMed:14697206,
CC ECO:0000269|PubMed:26095361}.
CC -!- DOMAIN: The N-terminal Gln-rich domain can confer two distinct
CC functional states, a dominant active prion-like aggregated state and a
CC soluble state. {ECO:0000269|PubMed:14697205}.
CC -!- SIMILARITY: Belongs to the RRM CPEB family. {ECO:0000305}.
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DR EMBL; AF367844; AAK52834.1; -; mRNA.
DR EMBL; AF367845; AAK52835.1; -; mRNA.
DR RefSeq; NP_001191467.1; NM_001204538.1. [Q967R6-1]
DR AlphaFoldDB; Q967R6; -.
DR SMR; Q967R6; -.
DR DIP; DIP-60237N; -.
DR GeneID; 100533221; -.
DR CTD; 100533221; -.
DR OrthoDB; 1075356at2759; -.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0071598; C:neuronal ribonucleoprotein granule; IDA:UniProtKB.
DR GO; GO:0099154; C:serotonergic synapse; IMP:SynGO.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IEA:InterPro.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0008494; F:translation activator activity; IDA:UniProtKB.
DR GO; GO:0045182; F:translation regulator activity; IMP:SynGO.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IMP:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB.
DR GO; GO:0099547; P:regulation of translation at synapse, modulating synaptic transmission; IMP:SynGO.
DR Gene3D; 3.30.70.330; -; 2.
DR Gene3D; 4.10.640.40; -; 1.
DR InterPro; IPR032292; CEBP1_N.
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; PF16368; CEBP1_N; 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 Activator; Alternative splicing; Amyloid; Coiled coil; Repeat; RNA-binding;
KW Synapse; Synaptosome; Translation regulation.
FT CHAIN 1..687
FT /note="Cytoplasmic polyadenylation element-binding protein"
FT /id="PRO_0000437255"
FT DOMAIN 450..529
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 551..628
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 139..159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..246
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 55..144
FT /evidence="ECO:0000255"
FT COMPBIAS 221..244
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..246
FT /note="Missing (in isoform 2)"
FT /id="VSP_058507"
SQ SEQUENCE 687 AA; 77218 MW; 1BF7387AE7418C51 CRC64;
MSQSPQTVDQ AISVKTDYED NQQEHIPSNF EIFRRINALL DNSLEANNVS CSQSQSQQQQ
QQTQQQQQQQ QQQQQQQHLQ QVQQQQLLKQ QQQQAQQQQI QQQLLQQQQQ KQQLQQQQQQ
EQLQQQQLQL QQQLQQQLQH IQKEPSSHTY TPGPSPELQS VLNYANVPLS KSAAFNCNNS
SSYSVGPTPV QSPVTPSPAA SAVTVNSPSY GNFQLFGENA FDSTTPFQSD GTSQSHSRSL
ANDSDPMVVM SPGRDSIIPL SPTEKILYQN FLLSKQAQGE NTALPPSPPH EIMPLSPLEK
KLYSNLLSKH TQGMRAINST SPLQTPLTPP RSPQEVLYAS MPAAQVGESS SVIDMMSRMD
LSGRNQQADY SGTLAFLDAH NVLRRRTPSS SRSRSVMERS APSSYFANLD PYAIDRAARL
HRNAAAVGEA SCTWSGHLPP RNHENPVYSP KVFLGGVPWD ITESGLQAAF SKYGHLKIEW
PGKDGYVHLL FDVEKSVRSL LQACTHDFSN GDYFYKISSR RMRSKEVQVI PWVLADSNHV
FQPSQRLESN KTVFVGALHG MITAEALGRI MSDLFGNVVY AGIDTDKHKY PIGSGRVTFS
SRKSYMKAVQ AAFVEIKTPK FTKKLQVDPY LGDAICSLCN SHQGNYFCRD LLCFKYLCRS
CWYWQHAPDS MRQHRPLTRN TKSSLSL
