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onsdag 20 juni 2018

CPEB1-ZZ on oma ainutlaatuinen c-terminaalisen ZZ- Zf omaava ryhmä

ZZ_tyyppiset sinkkisormiproteiinit (ZZZ)

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) 

ZZZ ryhmä:


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 mouse all
  • Preferred Names
  • cytoplasmic polyadenylation element-binding protein 1
  • Names
  • CPE-binding protein 1"

(Peptidisekvenssistä ja historiasta. Isoformi 2)

(Konservoidut domeenit)

Konserved Domains (4) summary
cd12723
Location:234 → 341
RRM1_CPEB1; RNA recognition motif 1 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
cd12725
Location:352 → 437
RRM2_CPEB1; RNA recognition motif 2 in cytoplasmic polyadenylation element-binding protein 1 (CPEB-1) and similar proteins
pfam16366
Location:429 → 484
CEBP_ZZ; Cytoplasmic polyadenylation element-binding protein ZZ domain
pfam16368
Location:1 → 232
CEBP1_N; Cytoplasmic polyadenylation element-binding protein 1 N-terminus




(Suom) CPEB-proteiinin C-terminaalinen alue on ZZ-_domeeni, jolla on kyky tehdä proteiini-proteiini-interaktioita.



  • 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.

PMID:
23500490
DOI:

(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   11223249
COMMENT     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"

 ORIGIN 1 mlfptsaqes srglpdandl clglqslslt gwdrpwstqd sdssaqssth svlsmlhnpl 61 gnvlgkppls flpldplgsd lvdkfpapsv rgsrldtrpi ldsrssspsd sdtsgfssgs 121 dhlsdlissl rispplpfls lsgggprdpl kmgvgsrmdq eqaalaavtp sptsaskrwp 181 gasvwpswdl leapkdpfsi erearlhrqa aavneatctw sgqlpprnyk npiysckvfl 241 ggvpwditea glvntfrvfg slsvewpgkd gkhprcppkg nmpkgyvylv feleksvrsl 301 lqacshdpls pdglseyyfk mssrrmrcke vqvipwvlad snfvrspsqr ldpsrtvfvg 361 alhgmlnaea laailndlfg gvvyagidtd khkypigsgr vtfnnqrsyl kavsaafvei 421 kttkftkkvq idpyledslc hicssqpgpf fcrdqvcfky fcrscwhwrh smeglrhhsp 481 lmrnqknrds s //



(Kliinisempää tekstiä löytää PubMed artikkeleista. Merkel et al. kirjoittamaan koetan asettaa suomennosta , koska  se kuvaa ZZZ ryhmään kuuluvan  proteiinin rakennetta).

Related articles in PubMed ( About CPEB1)

  1. RNA-binding protein CPEB1 remodels host and viral RNA landscapes. Batra R, et al. Nat Struct Mol Biol, 2016 Dec. PMID 27775709, Free PMC Article
  2. Specificity factors in cytoplasmic polyadenylation. Charlesworth A, et al. Wiley Interdiscip Rev RNA, 2013 Jul-Aug. PMID 23776146, Free PMC Article
  3. Translational control of cell growth and malignancy by the CPEBs. D'Ambrogio A, et al. Nat Rev Cancer, 2013 Apr. PMID 23446545
See all (48) citations in PubMed

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

  1. Results suggest that CPEB1-mediated translational control is essential for the differentiation of GSCs.



(Onkohan CPEB 2,3,4 myös ZZZ? Onkohan nämä neuronivälittäjäaineita? Otan vain linkit esiin tähän musitakin. 

About CPEB2


CPBE2  näyttää toimivan CPEB1:n vahvistajana.

About CPEB3


CPEB3 Funktionaalinen prioni, josta on  hyötyä.
Abstract 
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
DOI:10.1016/j.celrep.2015.04.060
[Indexed for MEDLINE] Free full text

About CPEB4

(CPEB4:n  circadinen ja UPR kontrolli  välittää  translationaalista vastetta, joka vastavaikuttaa maksan rasvoittumiseen  ER-stressin aikana, kun on suuri vaatimus ER-proteiinien laskostamisest). .

Alla oleva linkki käsittää tekstiä CPB4.stä
ticle | Published:

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.


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