ZBED6 (1q32.1), MGR (muscle growth regulator). IFG2 säätelijä. Vaikutusta betasoluun

 https://www.genenames.org/data/genegroup/#!/group/64
KUVA:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606216/figure/pone-0059940-g001/

ZBED6, myös nimi MGR . (1q32.1)  Muscle growth regulating.
Löydän tästä kaksi BED- tyyppistä  ZNF-kohtaa:  ja ne ovat : HHCCHHH ja HCCHHH.
Käsittääkseni tämä geeni siajitsee intronialueessa,  mutta se itse on introniton. Se on johtunut domestikoitneen  DNA:n  transposonista.  Hiiren vastaavassa geenissä on introni tallella ja siitä johtamalla on tehty  ZBED6-muotoa , jota on tutkimuksissa käytetty ja vertailtu.  Eräs alla mainittu  tutkimus luotaa tämän geenin merkitystä betasolujen kehitykselle ja erilaistumiselle. Vuodesta 2009 tätä geeniä on pidetty uutena transkriptiotekijänä, joka säätelee IGF2 ilmenemää ja lihaksen kasvua.  Geenillä on ainakin kymmenen kohdegeeniä, mikä havaittiin  colonkarsinomatutkimuksista.  Lähinnä  ZBED2 vaikutus on  kohdegeenejä vaimentava.  Näistä geeneistä kahdeksan osallistuijoihinkin   seuraavista  signaaliteistä.  Wnt-, Hippo-, TGF-β-, EGF receptori- ja  PI3K signaalitiet.  Geenillä on vaikutusta betasolun tilaan.

 https://www.ncbi.nlm.nih.gov/gene/100381270

Official Symbol

ZBED6provided by HGNC

Official Full Name

zinc finger BED-type containing 6provided by HGNC

Also known as

MGR

Summary:The protein encoded by this transposon-derived intronless gene is a transcriptional repressor that binds to the consensus sequence 5'-GCTCGC-3'. The encoded protein has been shown to repress IGF2 transcription. This gene is located within the first intron of the ZC3H11A gene. [provided by RefSeq, Jul 2016]

 

NM_001174108.2 → NP_001167579.1  zinc finger BED domain-containing protein 6

Conserved Domains (2) summary

smart00614
Location:135 → 182

ZnF_BED; BED zinc finger

pfam05699
Location:868 → 948

Dimer_Tnp_hAT; hAT family C-terminal dimerization region

 

FEATURES             Location/Qualifiers
     source          1..979
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q32.1"
     Protein         1..979
                     /product="zinc finger BED domain-containing protein 6"
                     /calculated_mol_wt=109842
     Region          135..182
                     /region_name="ZnF_BED"
                     /note="BED zinc finger; smart00614"
                     /db_xref="CDD:214746"
     Region          269..315
                     /region_name="ZnF_BED"
                     /note="BED zinc finger; smart00614"
                     /db_xref="CDD:214746"
     Site            381
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:D2EAC2};
                     propagated from UniProtKB/Swiss-Prot (P86452.1)"
     Region          866..948
                     /region_name="HATC (Hobo-Ac-Tam3) domain"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (P86452.1)"
     Region          868..948
                     /region_name="Dimer_Tnp_hAT"
                     /note="hAT family C-terminal dimerization region;
                     pfam05699"
                     /db_xref="CDD:283379"
     CDS             1..979
                     /gene="ZBED6"
                     /gene_synonym="MGR"
                     /coded_by="NM_001174108.2:1..2940"
                     /db_xref="CCDS:CCDS55673.1"
                     /db_xref="GeneID:100381270"
                     /db_xref="HGNC:HGNC:33273"
                     /db_xref="MIM:613512"
ORIGIN      
        1 msvctlsvpv sslspgrrcn tfsdsgilgc vpinsntdee dvveekmvae gvnkeakqpa
       61 kkkrkkglri kgkrrrkkli lakkfskdlg sgrpvadapa llasndpeqd eeslfesnie
      121 kqiylpstra ktsivwhffh vdpqytwrai cnlceksvsr gkpgshlgts tlqrhlqarh
      181 sphwtrankf gvasgeedft ldvslspssg sngsfeyipt dplddnrmgk khdksasdal
      241 raergrflik snivkhalip gtraktsavw nffytdpqhi sravcnickr svsrgrpgsh
      301 lgtstlqrhl qathpihwav ankdsgavan gldeaeters dllsdtlhge kstgsqdlta
      361 edlsdsdsde pmlevenrse spipvaeqgt lmraqerett ccgnpvsshi sqaiiqmive
      421 dmhpynyfst pafqrfmqiv apdyrlpset yfftkavpql ydcvrekifl tlenvqsqki
      481 hltvdiwthd pstdyfivtv hwvsletasf lnngripdfr kwavlcvtgl akdclitnil
      541 qelndqiglw lspnflipsf ivsdnssnvv haikdggfth vpcflhclnm viqdffcehk
      601 sienmlvaar ktchhfshsv karqilqefq ndhqlpwknl kqdetghwis tfymlkwlle
      661 hcysvhhslg rasgvvltsl qwtlmtyvcd ilkpfeeatq kvsvktagln qvlplihhll
      721 lslqklredf qvrgitqaln lvdslslkle tdtllsamlk skpcilatll dpcfknsled
      781 ffpqgadlet ykqflaeevc nymesspeic qiptseascp svtvgadsft sslkegtsss
      841 gsvdssavdn valgsksfmf psavavvdey fkekysefsg gddpliywqr kisiwpaltq
      901 vaiqylscpm cswqsecift knshfhpkqi msldfdnieq lmflkmnlkn vnydystlvl
      961 swdpeqnevv qssekeilp
//

Related articles in PubMed

1. Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells. Akhtar Ali M, et al. Proc Natl Acad Sci U S A, 2015 Jun 23. PMID 26056301, Free PMC Articlethe..  view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.
2. Studying phenotypic evolution in domestic animals: a walk in the footsteps of Charles Darwin. Andersson L. Cold Spring Harb Symp Quant Biol, 2009. PMID 20375320
3. ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth. Markljung E, et al. PLoS Biol, 2009 Dec. PMID 20016685, Free PMC Article
4. Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells. Wang X, et al. Proc Natl Acad Sci U S A, 2013 Oct 1. PMID 24043816, Free PMC Article
   Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):15997-6002. doi: 10.1073/pnas.1303625110. Epub 2013 Sep 16. Abstract
   We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function.
   ZBED6 was translated from a ZC3H11A transcript in which the ZBED6-containing intron was retained.
   ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which lacked N-terminal nuclear localization signals (NLS).
   We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function - i.e., insulin production - because
    (i) the nuclear ZBED6 were the predominant forms in rapidly proliferating βTC-6 cells, but not in human islet cells;
    (ii) down-regulation of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis;
    (iii) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (iv) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis.
    Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.
   PMID: 24043816PMCID: PMC3791784DOI:10.1073/pnas.1303625110 [Indexed for MEDLINE] Free PMC Article
5. A domesticated transposon mediates the effects of a single-nucleotide polymorphism responsible for enhanced muscle growth. Butter F, et al. EMBO Rep, 2010 Apr. PMID 20134481, Free PMC Article Single-nucleotide polymorphisms (SNPs) in the regulatory regions of the genome can have a profound impact on phenotype. The G3072A polymorphism in intron 3 of insulin-like growth factor 2 (IGF2) is implicated in higher muscle content and reduced fat in European pigs and is bound by a putative repressor. Here, we identify this repressor--which we call muscle growth regulator (MGR)--by using a DNA protein interaction screen based on quantitative mass spectrometry. MGR has a bipartite nuclear localization signal, two BED-type zinc fingers and is highly conserved between placental mammals. Surprisingly, the gene is located in an intron and belongs to the hobo-Ac-Tam3 transposase superfamily, suggesting regulatory use of a formerly parasitic element. In transactivation assays, MGR differentially represses the expression of the two SNP variants. Knockdown of MGR in C2C12 myoblast cells upregulates Igf2 expression and mild overexpression retards growth. Thus, MGR is the repressor responsible for enhanced muscle growth in the IGF2 G3072A polymorphism in commercially bred pigs.

See all (10) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes
2. Mouse MGR (Zbed6) is a repressor of Igf2.
3. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation.