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Protein

Cytoplasmic polyadenylation element-binding protein 3

Gene

CPEB3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator (By similarity). In contrast to CPEB1, does not bind to the cytoplasmic polyadenylation element (CPE), a uridine-rich sequence element within the mRNA 3'-UTR, but binds to a U-rich loop within a stem-loop structure (By similarity). Required for the consolidation and maintenance of hippocampal-based long term memory (By similarity). In the basal state, binds to the mRNA 3'-UTR of the glutamate receptors GRIA2/GLUR2 mRNA and negatively regulates their translation (By similarity). Also represses the translation of DLG4, GRIN1, GRIN2A and GRIN2B (By similarity). When activated, acts as a translational activator of GRIA1 and GRIA2 (By similarity). In the basal state, suppresses SUMO2 translation but activates it following neuronal stimulation (By similarity). Binds to the 3'-UTR of TRPV1 mRNA and represses TRPV1 translation which is required to maintain normal thermoception (By similarity). Binds actin mRNA, leading to actin translational repression in the basal state and to translational activation following neuronal stimulation (By similarity). Negatively regulates target mRNA levels by binding to TOB1 which recruits CNOT7/CAF1 to a ternary complex and this leads to target mRNA deadenylation and decay (PubMed:21336257). In addition to its role in translation, binds to and inhibits the transcriptional activation activity of STAT5B without affecting its dimerization or DNA-binding activity. This, in turn, represses transcription of the STAT5B target gene EGFR which has been shown to play a role in enhancing learning and memory performance (PubMed:20639532). In contrast to CPEB1, CPEB2 and CPEB4, not required for cell cycle progression (PubMed:26398195).By similarity3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei444Required for RNA-binding activity1 Publication1
Sitei488Required for RNA-binding activity1 Publication1

GO - Molecular functioni

  • mRNA 3'-UTR AU-rich region binding Source: UniProtKB
  • mRNA 3'-UTR binding Source: UniProtKB
  • nucleotide binding Source: InterPro
  • poly(A) RNA binding Source: UniProtKB
  • ribosome binding Source: GO_Central
  • RNA binding Source: UniProtKB
  • RNA stem-loop binding Source: UniProtKB
  • translation factor activity, RNA binding Source: UniProtKB
  • translation repressor activity, nucleic acid binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Translation regulation

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cytoplasmic polyadenylation element-binding protein 3
Short name:
CPE-BP3
Short name:
CPE-binding protein 3
Short name:
hCPEB-3
Gene namesi
Name:CPEB3
Synonyms:KIAA0940
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:21746. CPEB3.

Subcellular locationi

GO - Cellular componenti

  • apical dendrite Source: UniProtKB
  • CCR4-NOT complex Source: UniProtKB
  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: UniProtKB
  • dendrite Source: UniProtKB
  • messenger ribonucleoprotein complex Source: GO_Central
  • neuron projection Source: UniProtKB
  • nucleus Source: UniProtKB
  • postsynaptic density Source: UniProtKB-SubCell
  • postsynaptic membrane Source: UniProtKB-KW
  • synapse Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi349L → A: Abolishes nuclear export; when associated with A-353. 1 Publication1
Mutagenesisi353L → A: Abolishes nuclear export; when associated with A-349. 1 Publication1
Mutagenesisi441R → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi444F → A or N: Abolishes RNA binding. 1 Publication1
Mutagenesisi444F → Y: Does not impair RNA binding. 1 Publication1
Mutagenesisi446G → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi463R → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi470D → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi474K → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi479S → A: Does not impair RNA binding. 1 Publication1
Mutagenesisi488F → A: Reduced RNA binding. 1 Publication1
Mutagenesisi488F → Y: Does not impair RNA binding. 1 Publication1
Mutagenesisi528R → A: Does not impair RNA binding. 1 Publication1

Organism-specific databases

DisGeNETi22849.
OpenTargetsiENSG00000107864.
PharmGKBiPA134903478.

Polymorphism and mutation databases

BioMutaiCPEB3.
DMDMi119368633.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002692611 – 698Cytoplasmic polyadenylation element-binding protein 3Add BLAST698

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei192PhosphoserineCombined sources1
Modified residuei195PhosphoserineBy similarity1
Modified residuei290PhosphoserineBy similarity1
Modified residuei308Asymmetric dimethylarginineBy similarity1

Post-translational modificationi

Activated by NEURL1-mediated monoubiquitination, resulting in the growth of new dendritic spines and increased levels of GRIA1 and GRIA2. NEURL1-mediated monoubiquitination facilitates synaptic plasticity and hippocampal-dependent memory storage.By similarity
Under basal unstimulated conditions when CPEB3 is mainly unaggregated, sumoylated and acts as a translational repressor. Following neuronal stimulation, becomes desumoylated and aggregated which is required for the translation of mRNA targets and for dendritic filopodia formation.By similarity
Following neuronal stimulation, cleaved by CAPN2 which abolishes its translational repressor activity, leading to translation of CPEB3 target mRNAs.By similarity
Phosphorylation is enhanced by neuronal stimulation.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei441 – 442Cleavage; by CAPN2By similarity2

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8NE35.
PaxDbiQ8NE35.
PeptideAtlasiQ8NE35.
PRIDEiQ8NE35.

PTM databases

iPTMnetiQ8NE35.
PhosphoSitePlusiQ8NE35.

Expressioni

Gene expression databases

BgeeiENSG00000107864.
CleanExiHS_CPEB3.
ExpressionAtlasiQ8NE35. baseline and differential.
GenevisibleiQ8NE35. HS.

Interactioni

Subunit structurei

Following synaptic activity, forms amyloid-like oligomers (By similarity). Aggregation requires an intact actin cytoskeleton (By similarity). Interacts with STAT5B; this inhibits STAT5B-mediated transcriptional activation (PubMed:20639532). Interacts with E3 ubiquitin-protein ligase NEURL1; this leads to monoubiquitination and activation of CPEB3 (By similarity). Interacts with CAPN2; this leads to cleavage of CPEB3 (By similarity). Interacts (via C-terminal RNA-binding region) with TOB1; TOB1 also binds CNOT7/CAF1 and recruits it to CPEB3 to form a ternary complex (PubMed:21336257). Interacts with SUMO-conjugating enzyme UBC9 (By similarity). Interacts with IPO5; the interaction is enhanced in a RAN-regulated manner following neuronal stimulation and mediates CPEB3 nuclear import (PubMed:22730302). Interacts with exportin XPO1/CRM1 (PubMed:22730302).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TOB1P506167EBI-8596191,EBI-723281

Protein-protein interaction databases

BioGridi116521. 1 interactor.
IntActiQ8NE35. 7 interactors.
STRINGi9606.ENSP00000265997.

Structurei

Secondary structure

1698
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi443 – 446Combined sources4
Helixi454 – 460Combined sources7
Turni461 – 464Combined sources4
Beta strandi467 – 470Combined sources4
Beta strandi474 – 477Combined sources4
Beta strandi478 – 481Combined sources4
Beta strandi485 – 489Combined sources5
Helixi494 – 503Combined sources10
Beta strandi504 – 507Combined sources4
Beta strandi510 – 515Combined sources6
Beta strandi518 – 520Combined sources3
Beta strandi522 – 528Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DNLNMR-A440-540[»]
2RUGNMR-A440-540[»]
ProteinModelPortaliQ8NE35.
SMRiQ8NE35.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8NE35.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini441 – 532RRM 1PROSITE-ProRule annotationAdd BLAST92
Domaini549 – 631RRM 2PROSITE-ProRule annotationAdd BLAST83

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi13 – 27Gln-richAdd BLAST15
Compositional biasi26 – 200Pro-richAdd BLAST175
Compositional biasi170 – 238Ala-richAdd BLAST69

Domaini

The N-terminal Gln-rich region is required for the formation of amyloid-like oligomers and for the stability of long-term potentiation and spatial memory.By similarity

Sequence similaritiesi

Belongs to the RRM CPEB family.Curated
Contains 2 RRM (RNA recognition motif) domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0129. Eukaryota.
ENOG410Y1XZ. LUCA.
GeneTreeiENSGT00390000012886.
HOGENOMiHOG000290660.
HOVERGENiHBG058010.
InParanoidiQ8NE35.
KOiK02602.
OMAiKGRMGIN.
OrthoDBiEOG091G0AO9.
PhylomeDBiQ8NE35.
TreeFamiTF317658.

Family and domain databases

Gene3Di3.30.70.330. 2 hits.
InterProiIPR032296. CEBP_ZZ.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF16366. CEBP_ZZ. 1 hit.
PF16367. RRM_7. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NE35-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MQDDLLMDKS KTQPQPQQQQ RQQQQPQPES SVSEAPSTPL SSETPKPEEN
60 70 80 90 100
SAVPALSPAA APPAPNGPDK MQMESPLLPG LSFHQPPQQP PPPQEPAAPG
110 120 130 140 150
ASLSPSFGST WSTGTTNAVE DSFFQGITPV NGTMLFQNFP HHVNPVFGGT
160 170 180 190 200
FSPQIGLAQT QHHQQPPPPA PAPQPAQPAQ PPQAQPPQQR RSPASPSQAP
210 220 230 240 250
YAQRSAAAAY GHQPIMTSKP SSSSAVAAAA AAAAASSASS SWNTHQSVNA
260 270 280 290 300
AWSAPSNPWG GLQAGRDPRR AVGVGVGVGV GVPSPLNPIS PLKKPFSSNV
310 320 330 340 350
IAPPKFPRAA PLTSKSWMED NAFRTDNGNN LLPFQDRSRP YDTFNLHSLE
360 370 380 390 400
NSLMDMIRTD HEPLKGKHYP PSGPPMSFAD IMWRNHFAGR MGINFHHPGT
410 420 430 440 450
DNIMALNNAF LDDSHGDQAL SSGLSSPTRC QNGERVERYS RKVFVGGLPP
460 470 480 490 500
DIDEDEITAS FRRFGPLVVD WPHKAESKSY FPPKGYAFLL FQEESSVQAL
510 520 530 540 550
IDACLEEDGK LYLCVSSPTI KDKPVQIRPW NLSDSDFVMD GSQPLDPRKT
560 570 580 590 600
IFVGGVPRPL RAVELAMIMD RLYGGVCYAG IDTDPELKYP KGAGRVAFSN
610 620 630 640 650
QQSYIAAISA RFVQLQHNDI DKRVEVKPYV LDDQMCDECQ GTRCGGKFAP
660 670 680 690
FFCANVTCLQ YYCEYCWASI HSRAGREFHK PLVKEGGDRP RHVPFRWS
Length:698
Mass (Da):76,014
Last modified:December 12, 2006 - v2
Checksum:i0E67DCB7F8A40C96
GO
Isoform 2 (identifier: Q8NE35-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     366-388: Missing.
     408-408: N → SRSSLFPFED

Show »
Length:684
Mass (Da):74,440
Checksum:i7CD47A66E821AE71
GO

Sequence cautioni

The sequence BAA76784 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti519Missing in AAH36444 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_029776324R → W.1 PublicationCorresponds to variant rs17853616dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_022034366 – 388Missing in isoform 2. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_022035408N → SRSSLFPFED in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023157 mRNA. Translation: BAA76784.2. Different initiation.
AL158040, AL365398 Genomic DNA. Translation: CAI13636.1.
AL365398, AL158040 Genomic DNA. Translation: CAI14104.1.
BC036444 mRNA. Translation: AAH36444.1.
CCDSiCCDS31246.1. [Q8NE35-1]
CCDS53553.1. [Q8NE35-2]
RefSeqiNP_001171608.1. NM_001178137.1. [Q8NE35-2]
NP_055727.3. NM_014912.4. [Q8NE35-1]
XP_005269687.1. XM_005269630.4. [Q8NE35-2]
UniGeneiHs.131683.
Hs.701732.

Genome annotation databases

EnsembliENST00000265997; ENSP00000265997; ENSG00000107864. [Q8NE35-1]
ENST00000412050; ENSP00000398310; ENSG00000107864. [Q8NE35-2]
ENST00000614585; ENSP00000482128; ENSG00000107864. [Q8NE35-1]
GeneIDi22849.
KEGGihsa:22849.
UCSCiuc001khv.3. human. [Q8NE35-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023157 mRNA. Translation: BAA76784.2. Different initiation.
AL158040, AL365398 Genomic DNA. Translation: CAI13636.1.
AL365398, AL158040 Genomic DNA. Translation: CAI14104.1.
BC036444 mRNA. Translation: AAH36444.1.
CCDSiCCDS31246.1. [Q8NE35-1]
CCDS53553.1. [Q8NE35-2]
RefSeqiNP_001171608.1. NM_001178137.1. [Q8NE35-2]
NP_055727.3. NM_014912.4. [Q8NE35-1]
XP_005269687.1. XM_005269630.4. [Q8NE35-2]
UniGeneiHs.131683.
Hs.701732.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DNLNMR-A440-540[»]
2RUGNMR-A440-540[»]
ProteinModelPortaliQ8NE35.
SMRiQ8NE35.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116521. 1 interactor.
IntActiQ8NE35. 7 interactors.
STRINGi9606.ENSP00000265997.

PTM databases

iPTMnetiQ8NE35.
PhosphoSitePlusiQ8NE35.

Polymorphism and mutation databases

BioMutaiCPEB3.
DMDMi119368633.

Proteomic databases

MaxQBiQ8NE35.
PaxDbiQ8NE35.
PeptideAtlasiQ8NE35.
PRIDEiQ8NE35.

Protocols and materials databases

DNASUi22849.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265997; ENSP00000265997; ENSG00000107864. [Q8NE35-1]
ENST00000412050; ENSP00000398310; ENSG00000107864. [Q8NE35-2]
ENST00000614585; ENSP00000482128; ENSG00000107864. [Q8NE35-1]
GeneIDi22849.
KEGGihsa:22849.
UCSCiuc001khv.3. human. [Q8NE35-1]

Organism-specific databases

CTDi22849.
DisGeNETi22849.
GeneCardsiCPEB3.
HGNCiHGNC:21746. CPEB3.
MIMi610606. gene.
neXtProtiNX_Q8NE35.
OpenTargetsiENSG00000107864.
PharmGKBiPA134903478.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0129. Eukaryota.
ENOG410Y1XZ. LUCA.
GeneTreeiENSGT00390000012886.
HOGENOMiHOG000290660.
HOVERGENiHBG058010.
InParanoidiQ8NE35.
KOiK02602.
OMAiKGRMGIN.
OrthoDBiEOG091G0AO9.
PhylomeDBiQ8NE35.
TreeFamiTF317658.

Miscellaneous databases

ChiTaRSiCPEB3. human.
EvolutionaryTraceiQ8NE35.
GenomeRNAii22849.
PROiQ8NE35.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107864.
CleanExiHS_CPEB3.
ExpressionAtlasiQ8NE35. baseline and differential.
GenevisibleiQ8NE35. HS.

Family and domain databases

Gene3Di3.30.70.330. 2 hits.
InterProiIPR032296. CEBP_ZZ.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]
PfamiPF16366. CEBP_ZZ. 1 hit.
PF16367. RRM_7. 1 hit.
[Graphical view]
SMARTiSM00360. RRM. 2 hits.
[Graphical view]
SUPFAMiSSF54928. SSF54928. 1 hit.
PROSITEiPS50102. RRM. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCPEB3_HUMAN
AccessioniPrimary (citable) accession number: Q8NE35
Secondary accession number(s): Q5T389, Q9NQJ7, Q9Y2E9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: December 12, 2006
Last modified: November 30, 2016
This is version 119 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The CPEB3 gene contains an intron-encoded self-cleaving ribozyme which is structurally and biochemically related to human hepatitis delta virus ribozymes and which may play a role in the regulation of CPEB3 translation (PubMed:16990549). A polymorphism in the ribozyme sequence which influences cleavage activity of the ribozyme may play a role in episodic memory with carriers of a rare C allele-containing ribozyme showing significantly poorer memory recall performance than T allele carriers (PubMed:19503753).2 Publications

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.