Cytoplasmic
polyadenylation element binding protein (CPEB) provides temporal and
spatial control of protein synthesis required for early development and
neuronal synaptic plasticity. CPEB regulates protein expression by
inhibiting polyadenylation of selected mRNA transcripts, which prevents
binding of the ribosome for protein synthesis. Two RNA recognition motif
domains and a C-terminal binuclear zinc-binding domain are required for
mRNA binding, but the zinc-binding domain is not required for
sequence-specific recognition of the targeted mRNA transcript. The
structure and function of the zinc-binding domain of CPEB are unknown.
The C-terminal region of CPEB may participate in assembly of the
ribonucleoprotein complex that includes the scaffold protein, Symplekin,
and the cleavage and polyadenylation specificity factor. Sumoylation of
Symplekin is required for polyadenylation, and both cleavage and
polyadenylation specificity factor and poly(A) polymerase are
sumoylated. The foreshortened poly(A) tail is maintained by poly(A)
ribonuclease, which associates with CPEB. While zinc-binding domains are
renowned for nucleic acid recognition, binuclear zinc-binding
structural motifs, such as LIM (Lin-11, Isl-1, Mec-3), RING (really
interesting new gene), PHD (plant homeodomain) and ZZ (ZZ-type zinc
finger) domains, participate in protein-protein interactions. Here, we
report the solution structure of the C-terminal zinc-binding domain of
CPEB1 (CPEB1-ZZ), which has a cross-braced zinc binding topology. The
structural similarity to other ZZ domains suggests that the CPEB1-ZZ
domain recruits sumoylated proteins during assembly of the
ribonucleoprotein complex prior to mRNA export from the nucleus.
Otan tämän 2019 uudestaan esiin Nobelin palkinnon kohdistuttua HIF säätelyyn, johon CPEB_ZZ proteiinit osallistuvat HIF1 alfa mRNA-tason säätelyllä. 10.10.2019.
Näitä ryhmiä on
listattuna eräässä artikkelissa kolmekymmentä, kuten juuri mainitsin ja ne ovat
luokiteltuna sinkkisormen rakenteen mukaan. kahdentenatoista ryhmänä
mainitaan ryhmä ZZZ eli "ZZ_ tyyppiset ZNF proteiinit".
Sinkkisormirakenne on C-x-C-x-C-x-C ja siitä annetaan netissä enemmänkin selvitystä.
Tässä ZZZ- ryhmässä
kerrotaan olevan 18 jäsentä ja niistä kolme on
transkriptiotekijää.(Kirjoitin ryhmät edelliseen tekstiin juuri näkyville tänään netistä)
Tärkeimpinä tai
tutkituimpina mainitaan:HERC2, NBR1 ja CREBBP.
Nyt Duodecim, joka on vastikään tullut, kertoo
eräästä proteiinista , joka kuuluu aggresomia muodostaviin ja sen nimi on CPEB. Kun tarkistan sen ryhmän, se näyttää
kuuluvaan erään artikkelin mukaan ZZ_ tyyppisiin ZNF- proteiineihin, joten se on "ZZZ"
nimistä ryhmää, vaikka juuri sen nimisenä en sitä löydä
näistä aiemmin mainituista 18sta.
Ensinnä lisätieto PubMed hakulaitteella tästä geenistä englanniksi. Suomalaisen selityksen saa Duodecimista ja otan siitäkin myöhemmin sitaattia muistiin.
GEENI ”CPEB” : Cytoplasmic polyadenylation
element-binding protein 1 (15q25.2)
Also known as
CPEB; CPEB-1; h-CPEB; CPE-BP1; hCPEB-1
Summary. This gene encodes a member of the cytoplasmic
polyadenylation element binding protein family. This highly
conserved protein binds to a specific RNA sequence, called the
cytoplasmic polyadenylation element, found in the 3' untranslated
region of some mRNAs. The encoded protein functions in both the
cytoplasm and the nucleus. It is involved in the regulation of mRNA
translation, as well as processing of the 3' untranslated region,
and may play a role in cell proliferation and tumorigenesis.
Alternative splicing results in multiple transcript variants.
[provided by RefSeq, Jan 2014] Expression. Biased expression in testis (RPKM 19.2), brain (RPKM
6.3) and 8 other tissues See
more Orthologs mouseall
Preferred Names
cytoplasmic polyadenylation element-binding protein 1
Cytoplasmic
polyadenylation element binding protein (CPEB) provides temporal and
spatial control of protein synthesis required for early development
and neuronal synaptic plasticity. CPEB regulates protein expression
by inhibiting polyadenylation of selected mRNA transcripts, which
prevents binding of the ribosome for protein synthesis.
Two RNA recognition
motif domains and a C-terminal binuclear zinc-binding domain are
required for mRNA binding, but the zinc-binding domain is not
required for sequence-specific recognition of the targeted mRNA
transcript.
The structure and
function of the zinc-binding domain of CPEB are unknown (2013).
The C-terminal
region of CPEB may participate in assembly of the ribonucleoprotein
complex that includes the scaffold protein, Symplekin, and the
cleavage and polyadenylation specificity factor. Sumoylation of
Symplekin is required for polyadenylation, and both cleavage and
polyadenylation specificity factor and poly(A) polymerase are
sumoylated.
The foreshortened
poly(A) tail is maintained by poly(A) ribonuclease, which associates
with CPEB.
While zinc-binding
domains are renowned for nucleic acid recognition, binuclear
zinc-binding structural motifs, such as LIM (Lin-11, Isl-1, Mec-3),
RING (really interesting new gene), PHD (plant homeodomain) and ZZ
(ZZ-type zinc finger) domains, participate in protein-protein
interactions.
Here, we report the
solution structure of the C-terminal zinc-binding domain of CPEB1
(CPEB1-ZZ), which has a cross-braced zinc binding topology.
The structural
similarity to other ZZ domains suggests that the CPEB1-ZZ domain
recruits sumoylated proteins during assembly of the ribonucleoprotein
complex prior to mRNA export from the nucleus.
(RAKENNE, HISTORIAPubMed Geenilähteestä Tämä on isoformi2 ja siinä on aminohappoja 491)
LOCUS NP_001073001 491 aa linear PRI 03-JUN-2018
DEFINITION cytoplasmic polyadenylation element-binding protein 1 isoform 2
[Homo sapiens].
ACCESSION NP_001073001
VERSION NP_001073001.1
DBSOURCE REFSEQ: accession NM_001079533.1
KEYWORDS RefSeq.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 491)
AUTHORS Shin J, Paek KY, Ivshina M, Stackpole EE and Richter JD.
TITLE Essential role for non-canonical poly(A) polymerase GLD4 in
cytoplasmic polyadenylation and carbohydrate metabolism
JOURNAL Nucleic Acids Res. 45 (11), 6793-6804 (2017)
PUBMED 28383716
REFERENCE 2 (residues 1 to 491)
AUTHORS Batra R, Stark TJ, Clark E, Belzile JP, Wheeler EC, Yee BA, Huang
H, Gelboin-Burkhart C, Huelga SC, Aigner S, Roberts BT, Bos TJ,
Sathe S, Donohue JP, Rigo F, Ares M Jr, Spector DH and Yeo GW.
TITLE RNA-binding protein CPEB1 remodels host and viral RNA landscapes
JOURNAL Nat. Struct. Mol. Biol. 23 (12), 1101-1110 (2016)
PUBMED 27775709
REMARK GeneRIF: The host RNA-binding protein CPEB1 was highly induced
after cytomegalovirus infection and ectopic expression of CPEB1 in
non-infected cells recapitulated infection-related
post-transcriptional changes. CPEB1 was also required for
poly(A)-tail lengthening of viral RNAs important for productive
infection.
REFERENCE 3 (residues 1 to 491)
AUTHORS Galardi S, Petretich M, Pinna G, D'Amico S, Loreni F, Michienzi A,
Groisman I and Ciafre SA.
TITLE CPEB1 restrains proliferation of Glioblastoma cells through the
regulation of p27(Kip1) mRNA translation
JOURNAL Sci Rep 6, 25219 (2016)
PUBMED 27142352
REMARK GeneRIF: Upon binding to p27(Kip1) 3'UTR, CPEB1 promotes elongation
of poly-A tail and the subsequent translation of p27(Kip1) mRNA.
This leads to higher levels of p27(Kip1) in the cell, in turn
significantly inhibiting cell proliferation, and confers to CPEB1 a
potential value as a tumor suppressor in Glioblastoma.
Publication Status: Online-Only
REFERENCE 4 (residues 1 to 491)
AUTHORS Chen M, Zheng W and Wolynes PG.
TITLE Energy landscapes of a mechanical prion and their implications for
the molecular mechanism of long-term memory
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 113 (18), 5006-5011 (2016)
PUBMED 27091989
REMARK GeneRIF: This mechanical catalysis makes possible a positive
feedback loop that would help localize the formation of CPEB fibers
to active synapse areas and mark those synapses for forming a
long-term memory after the prion form is established. The
functional role of the CPEB helical oligomers in this mechanism
carries with it implications for targeting such species in
neurodegenerative diseases.
REFERENCE 5 (residues 1 to 491)
AUTHORS Kratassiouk G, Pritchard LL, Cuvellier S, Vislovukh A, Meng Q,
Groisman R, Degerny C, Deforzh E, Harel-Bellan A and Groisman I.
TITLE The WEE1 regulators CPEB1 and miR-15b switch from inhibitor to
activators at G2/M
JOURNAL Cell Cycle 15 (5), 667-677 (2016)
PUBMED 27027998
REMARK GeneRIF: WEE1 is regulated at the translational level by CPEB1 and
miR-15b in a coordinated and cell-cycle-dependent manner.
REFERENCE 6 (residues 1 to 491)
AUTHORS Hagele S, Kuhn U, Boning M and Katschinski DM.
TITLE Cytoplasmic polyadenylation-element-binding protein (CPEB)1 and 2
bind to the HIF-1alpha mRNA 3'-UTR and modulate HIF-1alpha protein
expression
JOURNAL Biochem. J. 417 (1), 235-246 (2009)
PUBMED 18752464
REFERENCE 7 (residues 1 to 491)
AUTHORS Sasayama T, Marumoto T, Kunitoku N, Zhang D, Tamaki N, Kohmura E,
Saya H and Hirota T.
TITLE Over-expression of Aurora-A targets cytoplasmic polyadenylation
element binding protein and promotes mRNA polyadenylation of Cdk1
and cyclin B1
JOURNAL Genes Cells 10 (7), 627-638 (2005)
PUBMED 15966895
REFERENCE 8 (residues 1 to 491)
AUTHORS Wilczynska A, Aigueperse C, Kress M, Dautry F and Weil D.
TITLE The translational regulator CPEB1 provides a link between dcp1
bodies and stress granules
JOURNAL J. Cell. Sci. 118 (Pt 5), 981-992 (2005)
PUBMED 15731006
REMARK GeneRIF: CPEB1 has a role in compartmentalization of mRNA
metabolism in the cytoplasm, between dcp1 bodies and stress
granules
REFERENCE 9 (residues 1 to 491)
AUTHORS Mendez R and Richter JD.
TITLE Translational control by CPEB: a means to the end
JOURNAL Nat. Rev. Mol. Cell Biol. 2 (7), 521-529 (2001)
PUBMED 11433366
REMARK Review article
REFERENCE 10 (residues 1 to 491)
AUTHORS Welk JF, Charlesworth A, Smith GD and MacNicol AM.
TITLE Identification and characterization of the gene encoding human
cytoplasmic polyadenylation element binding protein
JOURNAL Gene 263 (1-2), 113-120 (2001)
PUBMED 11223249COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from DA705313.1, AF329403.1,
AC010724.6 and AL832156.1.
Summary: This gene encodes a member of the cytoplasmic
polyadenylation element binding protein family. This highly
conserved protein binds to a specific RNA sequence, called the
cytoplasmic polyadenylation element, found in the 3' untranslated
region of some mRNAs. The encoded protein functions in both the
cytoplasm and the nucleus. It is involved in the regulation of mRNA
translation, as well as processing of the 3' untranslated region,
and may play a role in cell proliferation and tumorigenesis.
Alternative splicing results in multiple transcript variants.
[provided by RefSeq, Jan 2014].
Transcript Variant: This variant (2), also known as short, contains
a distinct 5' UTR, lacks an in-frame portion of the 5' coding
region, and uses an alternate in-frame splice site in the central
coding region, compared to variant 1. The resulting isoform (2) has
a shorter N-terminus and lacks a central 5 aa segment, compared to
isoform 1.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the Gene
record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AF329403.1, SRR1660807.143381.1
[ECO:0000332]
RNAseq introns :: mixed/partial sample support
SAMEA1965299, SAMEA1966682
[ECO:0000350]
##Evidence-Data-END##
FEATURES Location/Qualifiers
source 1..491
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="15"
/map="15q25.2"
Protein 1..491
/product="cytoplasmic polyadenylation element-binding
protein 1 isoform 2"
/note="CPE-binding protein 1"
/calculated_mol_wt=54032
Region <1 ..232="" cdd="" cddsrv.cgi="" db_xref="CDD:<a href=" https:="" note="Cytoplasmic polyadenylation element-binding protein
1 N-terminus; pfam16368" region_name="CEBP1_N" tructure="" uid="292978" www.ncbi.nlm.nih.gov="">292978
"
Region 234..341
/region_name="RRM1_CPEB1"
/note="RNA recognition motif 1 in cytoplasmic
polyadenylation element-binding protein 1 (CPEB-1) and
similar proteins; cd12723"
/db_xref="CDD:241167" Region 352..437
/region_name="RRM2_CPEB1"
/note="RNA recognition motif 2 in cytoplasmic
polyadenylation element-binding protein 1 (CPEB-1) and
similar proteins; cd12725"
/db_xref="CDD:241169" Region 429..484
/region_name="CEBP_ZZ"
/note="Cytoplasmic polyadenylation element-binding protein
ZZ domain; pfam16366"
/db_xref="CDD:292976"
CDS 1..491
/gene="CPEB1"
/gene_synonym="CPE-BP1; CPEB; CPEB-1; h-CPEB; hCPEB-1"
/coded_by="NM_001079533.1:226..1701"
/note="isoform 2 is encoded by transcript variant 2"
/db_xref="CCDS:CCDS42072.2"
/db_xref="GeneID:64506"
/db_xref="HGNC:HGNC:21744"
/db_xref="MIM:607342"
(Kliinisempää tekstiä löytää PubMed artikkeleista. Merkel et al. kirjoittamaan koetan asettaa suomennosta , koska se kuvaa ZZZ ryhmään kuuluvan proteiinin rakennetta).
The mouse cytoplasmic polyadenylation element-binding protein 3
(CPEB3) is a translational regulator implicated in long-term memory
maintenance. Invertebrate orthologs of CPEB3 in Aplysia and
Drosophila are functional prions that are physiologically active in
the aggregated state. To determine if this principle applies to the
mammalian CPEB3, we expressed it in yeast and found that it forms
heritable aggregates that are the hallmark of known prions. In
addition, we confirm in the mouse the importance of CPEB3's prion
formation for CPEB3 function. Interestingly, deletion analysis of the
CPEB3 prion domain uncovered a tripartite organization: two
aggregation-promoting domains surround a regulatory module that
affects interaction with the actin cytoskeleton. In all, our data
provide direct evidence that CPEB3 is a functional prion in the
mammalian brain and underline the potential importance of an
actin/CPEB3 feedback loop for the synaptic plasticity underlying the
persistence of long-term memory.
PMID:26074072
(CPEB4:n circadinen ja UPR kontrolli välittää translationaalista vastetta, joka vastavaikuttaa maksan rasvoittumiseen ER-stressin aikana, kun on suuri vaatimus ER-proteiinien laskostamisest). .
Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress
The cytoplasmic polyadenylation element-binding (CPEB) proteins
regulate pre-mRNA processing and translation of CPE-containing
mRNAs in early embryonic development and synaptic activity.
However, specific functions in adult organisms are poorly
understood. Here we show that CPEB4 is required for adaptation
to high-fat-diet- and ageing-induced endoplasmic reticulum (ER)
stress, and subsequent hepatosteatosis. Stress-activated liver
CPEB4 expression is dual-mode regulated. First, Cpeb4 mRNA
transcription is controlled by the circadian clock, and then its
translation is regulated by the unfolded protein response (UPR)
through upstream open reading frames within the 5′UTR. Thus, the
CPEB4 protein is synthesized only following ER stress but the
induction amplitude is circadian. In turn, CPEB4 activates a second
wave of UPR translation required to maintain ER and mitochondrial
homeostasis. Our results suggest that combined transcriptional and
translational Cpeb4 regulation generates a ‘circadian
mediator’, which coordinates hepatic UPR activity with periods of
high ER-protein-folding demand. Accordingly, CPEB4 deficiency
results in non-alcoholic fatty liver disease.
