MIU-motiivin merkitys? Vastaus: Motiivi , joka tekee Interaktion Ubikitiinin (monoubikitiinin) kanssa.

Etsin tämän motiivin merkitystä ja tapaan uuden  deubikitinaasiryhmän MINDY jäsenen.
https://www.ncbi.nlm.nih.gov/pubmed/28082312

EMBO Rep. 2017 Mar;18(3):392-402. doi: 10.15252/embr.201643205. Epub 2017 Jan 12.

A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains.

Kristariyanto YA¹, Abdul Rehman SA¹, Weidlich S¹, Knebel A¹, Kulathu Y².  Abstract

The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb.

The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb. We here identify that this linkage-selective binding is mediated by a single MIU motif (MIU2) in MINDY-1. The crystal structure of MIU2 in complex with K48-linked polyubiquitin chains reveals that MIU2 on its own binds to all three Ub moieties in an open conformation that can only be accommodated by K48-linked triUb. The weak Ub binder MIU1 increases overall affinity of the tMIU for polyUb chains without affecting its linkage selectivity. Our analyses reveal new concepts for linkage selectivity and polyUb recognition by UBDs.

© 2017 The Authors.

KEYWORDS:
MINDY deubiquitinase; motif interacting with ubiquitin; polyubiquitin; ubiquitin binding domain; ubiquitin signaling

PMID: 28082312
PMCID: PMC5331195
DOI: 10.15252/embr.201643205
  [Indexed for MEDLINE] Free PMC Article

Myös  E3 uikitiiniligaasi  RING-finger proteiini 168 sisältää  MIU1 ja MIU2- domeenit

RNF168 , RING finger E3 ubikitiiniligaasi

https://www.ncbi.nlm.nih.gov/gene/165918
(RNF168 on mainittu myös toisessa kohtaa, jonka löytää indexistä) 

Official Symbol

RNF168

Official Full Name

ring finger protein 168

Also known as

hRNF168

Summary

This gene encodes an E3 ubiquitin ligase protein that contains a RING finger, a motif present in a variety of functionally distinct proteins and known to be involved in protein-DNA and protein-protein interactions. The protein is involved in DNA double-strand break (DSB) repair. Mutations in this gene result in Riddle syndrome. [provided by RefSeq, Sep 2011]

Expression Broad expression in testis (RPKM 13.5), bone marrow (RPKM 9.5) and 24 other tissues See more

Preferred Names E3 ubiquitin-protein ligase RNF168

Names RING-type E3 ubiquitin transferase RNF168; ring finger protein 168, E3 ubiquitin protein ligase.

 

RING 15-58 "cross -brace"motif 

 x-C-xx-C-x(11)-C-x-H-xx-C-xx-C-x(11)-C-xx-C-x(4)

qCgiCm eilvepvtlp CnHtlCkpCf qstvekaslC CpfCrrrv

 

FEATURES             Location/Qualifiers
     source          1..571
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="3"
                     /map="3q29"
     Protein         1..571
                     /product="E3 ubiquitin-protein ligase RNF168"
                     /EC_number="2.3.2.27"
                     /note="ring finger protein 168, E3 ubiquitin protein
                     ligase; RING-type E3 ubiquitin transferase RNF168"
                     /calculated_mol_wt=64889
     Region          15..58
                     /region_name="RING"
                     /note="RING-finger (Really Interesting New Gene) domain, a
                     specialized type of Zn-finger of 40 to 60 residues that
                     binds two atoms of zinc; defined by the 'cross-brace'
                     motif C-X2-C-X(9-39)-C-X(1-3)-
                     H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved
                     in...; cd00162"
                     /db_xref="CDD:238093"
     Site            order(16,19,31,33,36,39,51,54)
                     /site_type="other"
                     /note="cross-brace motif"
                     /db_xref="CDD:238093"
     Site            70
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:Q80XJ2};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Region          110..128 1 lskpgelrre yeeeiskva
                     /region_name="LR motif 1.
                     {ECO:0000255|HAMAP-Rule:MF_03066}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            134
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Region          143..151    1 eeyiqrlla
                     /region_name="UMI motif.
                     {ECO:0000255|HAMAP-Rule:MF_03066}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Region          168..191      1 meeqlksdee larklsidin nfce 
                     /region_name="MIU motif 1.
                     {ECO:0000255|HAMAP-Rule:MF_03066}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            197
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000250|UniProtKB:B2RYR0};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            362
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphothreonine. {ECO:0000250|UniProtKB:B2RYR0};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            411
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:19690332, ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            414
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:19690332}; propagated from
                     UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            415
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:18669648,
                     ECO:0000244|PubMed:19690332}; propagated from
                     UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Region          439..462        1 rhkqeeqdrl lalqlqkevd keqm
                     /region_name="MIU motif 2.
                     {ECO:0000255|HAMAP-Rule:MF_03066}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Region          466..477 1 rqkgspdeyh lr
                     /region_name="LR motif 2.
                     {ECO:0000255|HAMAP-Rule:MF_03066}"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     Site            470
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (Q8IYW5.1)"
     CDS             1..571
                     /gene="RNF168"
                     /gene_synonym="hRNF168"
                     /coded_by="NM_152617.4:596..2311"
                     /db_xref="CCDS:CCDS3317.1"
                     /db_xref="GeneID:165918"
                     /db_xref="HGNC:HGNC:26661"
                     /db_xref="MIM:612688"
ORIGIN      
        1 malpkdaips lsecqcgicm eilvepvtlp cnhtlckpcf qstvekaslc cpfcrrrvss
       61 wtryhtrrns lvnvelwtii qkhypreckl rasgqeseev addyqpvrll skpgelrrey
      121 eeeiskvaae rraseeeenk aseeyiqrll aeeeeeekrq aekrrramee qlksdeelar
      181 klsidinnfc egsisaspln srksdpvtpk sekksknkqr ntgdiqkylt pksqfgsash
      241 seavqevrkd svskdidssd rksptgqdte iedmptlspq islgvgeqga dssiespmpw
      301 lcacgaewyh egnvktrpsn hgkelcvlsh erpktrvpys ketavmpcgr tesgcaptsg
      361 vtqtngnntg eteneescll iskeiskrkn qessfeavkd pcfsakrrkv spesspdqee
      421 teinftqkli dlehllferh kqeeqdrlla lqlqkevdke qmvpnrqkgs pdeyhlrats
      481 sppdkvlngq rknpkdgnfk rqthtkhptp ergsrdknrq vslkmqlkqs vnrrkmpnst
      541 rdhckvsksa hslqpsisqk svfqmfqrct k
//

What is known about this protein?

Related articles in PubMed

1. Tumors overexpressing RNF168 show altered DNA repair and responses to genotoxic treatments, genomic instability and resistance to proteotoxic stress. Chroma K, et al. Oncogene, 2017 Apr 27. PMID 27841863
2. RNF168 promotes noncanonical K27 ubiquitination to signal DNA damage. Gatti M, et al. Cell Rep, 2015 Jan 13. PMID 25578731
3. A novel ubiquitin mark at the N-terminal tail of histone H2As targeted by RNF168 ubiquitin ligase. Gatti M, et al. Cell Cycle, 2012 Jul 1. PMID 22713238, Free PMC Article
4. A Novel Reciprocal Crosstalk between RNF168 and PARP1 to Regulate DNA Repair Processes. Kim JJ, et al. Mol Cells, 2018 Aug 31. PMID 30037213, Free PMC ArticleEmerging evidence has suggested that cellular crosstalk between RNF168 and poly(ADP-ribose) polymerase 1 (PARP1) contributes to the precise control of the DNA damage response (DDR). However, the direct and reciprocal functional link between them remains unclear. In this report, we identified that RNF168 ubiquitinates PARP1 via direct interaction and accelerates PARP1 degradation in the presence of poly (ADP-ribose) (PAR) chains, metabolites of activated PARP1. Through mass spectrometric analysis, we revealed that RNF168 ubiquitinated multiple lysine residues on PARP1 via K48-linked ubiquitin chain formation. Consistent with this, micro-irradiation-induced PARP1 accumulation at damaged chromatin was significantly increased by knockdown of endogenous RNF168. In addition, it was confirmed that abnormal changes of HR and HNEJ due to knockdown of RNF168 were restored by overexpression of WT RNF168 but not by reintroduction of mutants lacking E3 ligase activity or PAR binding ability. The comet assay also revealed that both PAR-binding and ubiquitin-conjugation activities are indispensable for the RNF168-mediated DNA repair process. Taken together, our results suggest that RNF168 acts as a counterpart of PARP1 in DDR and regulates the HR/NHEJ repair processes through the ubiquitination of PARP1.
5. Structural insights into two distinct binding modules for Lys63-linked polyubiquitin chains in RNF168. Takahashi TS, et al. Nat Commun, 2018 Jan 12. PMID 29330428, Free PMC Article

See all (83) citations in PubMed

 

USP10 deubikitinaasi hinosäätää NOTC funktiota stabiloimalla NICD1 (16q24.1) . USP10 stabiloi PTEN.

https://www.ncbi.nlm.nih.gov/gene/9100

USP10provided by HGNC

Official Full Name

ubiquitin specific peptidase 10

Also known as

UBPO

Summary

Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]

Expression Ubiquitous expression in placenta (RPKM 15.2), lymph node (RPKM 13.4) and 25 other tissues See more

Related articles in PubMed

1. Deubiquitinase USP10 regulates Notch signaling in the endothelium. Lim R, et al. Science, 2019 Apr 12. PMID 30975888l Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood. We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor. Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs. In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
2. The deubiquitylase USP10 regulates integrin β1 and β5 and fibrotic wound healing. Gillespie SR, et al. J Cell Sci, 2017 Oct 15. PMID 28851806, Free PMC Article
3. USP10 Expression in Normal Adrenal Gland and Various Adrenal Tumors. Zeng Z, et al. Endocr Pathol, 2015 Dec. PMID 26555087
4. USP10 antagonizes c-Myc transcriptional activation through SIRT6 stabilization to suppress tumor formation. Lin Z, et al. Cell Rep, 2013 Dec 26. PMID 24332849, Free PMC Article
5. Over-expression of genes and proteins of ubiquitin specific peptidases (USPs) and proteasome subunits (PSs) in breast cancer tissue observed by the methods of RFDD-PCR and proteomics. Deng S, et al. Breast Cancer Res Treat, 2007 Jul. PMID 17004105

See all (92) citations in PubMed

GeneRIFs: Gene References Into Functions

1. USP10 silencing demonstrated the inverse effects, and these effects induced by USP10 silencing were significantly blocked by EGF. USP10 overexpression promoted Raf-1 protein expression, but not mRNA expression, through deubiquitination... these results suggest that USP10 promotes proliferation and migration and inhibits apoptosis of endometrial stromal cells in endometriosis through activating the Raf-1/MEK/ERK pathway
2. USP10 functions as an NOTCH1 intracellular domain (NICD1) deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
3. USP10 inhibits hepatic steatosis, insulin resistance, and inflammation through Sirt6.
4. USP10 was expressed primarily in the cytoplasm of prostate cancer tissues. High levels of USP10 expression were strongly correlated with high levels of AR, G3BP2, and p53 in the cytoplasm. High expression of USP10 was significantly associated with poor prognosis of patients with prostate cancer.
5. By using a genome wide siRNA screen for deubiquitinating enzymes, we identified USP10 as a deubiquitinase for Slug in cancer cells. USP10 interacts with Slug and mediates its degradation by the proteasome. Importantly, USP10 is concomitantly highly expressed with Slug in cancer biopsies.
6. Loss of USP10 expression is associated with small intestinal adenocarcinoma.
7. One of the USP10 targets is TP53. Wildtype TP53 is usually rescued from proteasomal degradation by USP10. As most KMT2A leukemias display wildtype p53 alleles, one might argue that the disruption of an USP10 allele can be classified as a pro-oncogenic event.
8. Deubiquitylase USP10 interacts with RNF168 and TOP2alpha, and restrains ubiquitylation of TOP2alpha as well as its chromatin binding.
9. USP10 directly interacted with and stabilized PTEN via deubiquitination.  Mol Cell Biochem. 2018 Apr;441(1-2):1-7. doi: 10.1007/s11010-017-3170-2. Epub 2017 Aug 29. USP10 inhibits lung cancer cell growth and invasion by upregulating PTEN. Sun J¹, Li T¹, Zhao Y¹, Huang L¹, Sun H¹, Wu H¹, Jiang X².To determine the potential tumor suppressor functions of ubiquitin-specific protease 10 (USP10) in lung cancer and elucidate underlying molecular mechanism. The relative expression of USP10 was determined by real-time PCR and immunoblotting. The inhibitory effect of USP10 on tumor growth was demonstrated on allograft mice with Lewis carcinoma cell inoculation. The relative cell proliferation was measured with Cell Counting Kit-8 (CCK-8). The invasive capacity was evaluated by transwell assay. The interaction between USP10 and Phosphatase And Tensin Homolog (PTEN) was examined by co-immunoprecipitation. Ubiquitination/deubiquitination was analyzed by immunoprecipitation followed by immunoblotting. USP10 was down-regulated in lung cancer. Knockdown of USP10 promotes tumor growth and invasion both in vitro and in vivo. We further demonstrated that USP10 directly interacted with and stabilized PTEN via deubiquitination. The pro-cancerous effect of USP10 deficiency was abolished by re-introduction of PTEN. We suggested a tumor suppressor function of USP10 in lung cancer via deubiquitinating and stabilizing PTEN.

 
1. A controlling role for USP10 after wounding in determining myofibroblast development and activation of fibrotic TGFbeta signaling..

Submit: New GeneRIF Correction See all GeneRIFs (26)

Soluvälisignalointisysteemien setti: Notch, EGF, FGF, TGFbeta, Hedgehog ja Wnt. , kuusi signaalinjohtosysteemiä :

Six signal transduction system, notch, EGF, FGF, TGFbeta, Hedgehog, and Wnt, are utilized to provide spatial inputs in a myriad of diverse subcircuits in the development of any bilaterian, and in different contents  in different bilaterians. Though in their internal biochemical interactions these signal transduction cassetes are higly conserved across the bilateria, they are indeed "plugged in" at all levels of gene regulatory networks, in all sorts of regulatory spatial  specification processes.

Lähde:
Eric H. Davidson. 2006.
The Regulatory genome:Gene regulatory network in Development and Evolution.  p. 194.

S. 138:
.. a small set of intercellular signal systems used in developmental, specification processes: for example throughout the bilaterian world Hedgehog, TGFbeta, Wnt, FGF and Notch signaling cassettes are utilized and reutilized in diverse developmental contexts.

The cassette includes in each case  the genes  ( and their regulatory  modules) encoding ligands, the receptors, and the transcription factors which provide the immediaty early responses used to  transduce the intercellular signal at the transcription level in the cell expressing the receptor.

In each of these signaling systems  the cassettes are largely  invariant in their orthologous molecular constitutions, as they appear in different bilaterians, but their target cis-regulatory modules occur in as great variety as the diversity of the jobs they do.  Thus the distinction  betwen the plug-in and the device into  which it is plugged is not in the least obscure.


esim: :

NOTCH modulista
DUB USP 10  hienosäätää  NOTCH:in intrasellularisen NICD1 fraktiota jarruttamalla  ubikitinoitumista  ja täten vaikuttaa  angiogeneesiä .

Deubiquitinase USP10 regulates Notch signaling in the endothelium.Abstract
Notch signaling is a core patterning module for vascular morphogenesis that codetermines the sprouting behavior of endothelial cells (ECs). Tight quantitative and temporal control of Notch activity is essential for vascular development, yet the details of Notch regulation in ECs are incompletely understood.
We found that ubiquitin-specific peptidase 10 (USP10) interacted with the NOTCH1 intracellular domain (NICD1) to slow the ubiquitin-dependent turnover of this short-lived form of the activated NOTCH1 receptor.
 Accordingly, inactivation of USP10 reduced NICD1 abundance and stability and diminished Notch-induced target gene expression in ECs.
 In mice, the loss of endothelial Usp10 increased vessel sprouting and partially restored the patterning defects caused by ectopic expression of NICD1. Thus, USP10 functions as an NICD1 deubiquitinase that fine-tunes endothelial Notch responses during angiogenic sprouting.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S.


USP10, (16q24.1), https://www.ncbi.nlm.nih.gov/gene/9100, UBPO (cofactor of DNA-bound androgenreceptor complex);

ZBTB48 (1p36.31), HKR3, TZAP, ZNF855 . Telomeerin ylläpito. Transkriptiotekijä.

ZBTB48, https://www.ncbi.nlm.nih.gov/gene/3104

  zinc finger and BTB domain containing 48 [ Homo sapiens (human) ]

Gene ID: 3104, updated on 7-Jul-2019

Official Symbol ZBTB48.

Official Full Name zinc finger and BTB domain containing 48.

Also known as HKR3; TZAP; ZNF855; pp9964

Expression: Ubiquitous expression in testis (RPKM 9.3), spleen (RPKM 7.4) and 25 other tissues See 

Preferred Names

telomere zinc finger-associated protein

Names

GLI-Kruppel family member HKR3

krueppel-related zinc finger protein 3

telomeric zinc finger-associated protein

zinc finger and BTB domain-containing protein 48

zinc finger protein 855

NM_001278647.2 → NP_001265576.1  telomere zinc finger-associated protein

Conserved Domains (6) summary

COG5048
Location:464 → 612

COG5048; FOG: Zn-finger [General function prediction only]

COG5189
Location:374 → 459

SFP1; Putative transcriptional repressor regulating G2/M transition [Transcription / Cell division and chromosome partitioning]

sd00017
Location:467 → 487

ZF_C2H2; C2H2 Zn finger [structural motif]

sd00019
Location:409 → 425

ZF_C2H2; C2H2 Zn finger [structural motif]

pfam00651
Location:16 → 119

BTB; BTB/POZ domain. The BTB (for BR-C, ttk and bab) or POZ (for Pox virus and Zinc finger) domain is present near the N-terminus of a fraction of zinc finger (pfam00096) proteins and in proteins that contain the pfam01344 motif such as Kelch and a family of pox virus proteins. The BTB/POZ domain mediates homomeric dimerisation and in some instances heteromeric dimerisation. The structure of the dimerized PLZF BTB/POZ domain has been solved and consists of a tightly intertwined homodimer. The central scaffolding of the protein is made up of a cluster of alpha-helices flanked by short beta-sheets at both the top and bottom of the molecule. POZ domains from several zinc finger proteins have been shown to mediate transcriptional repression and to interact with components of histone deacetylase co-repressor complexes including N-CoR and SMRT. The POZ or BTB domain is also known as BR-C/Ttk or ZiN.

pfam13465
Location:305 → 328

zf-H2C2_2; Zinc-finger double domain

                             
FEATURES             Location/Qualifiers
     source          1..688
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p36.31"
     Protein         1..688
                     /product="telomere zinc finger-associated protein"
                     /note="GLI-Kruppel family member HKR3; zinc finger and BTB
                     domain-containing protein 48; krueppel-related zinc finger
                     protein 3; zinc finger protein 855; telomeric zinc
                     finger-associated protein"
                     /calculated_mol_wt=76923
     Region          16..119
                     /region_name="BTB"
                     /note="BTB/POZ domain; pfam00651"
                     /db_xref="CDD:306997"
     Site            169
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (P10074.2)"
     Site            171
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (P10074.2)"
     Site            179
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:24275569};
                     propagated from UniProtKB/Swiss-Prot (P10074.2)"
     Region          293..313
                     /region_name="C2H2 Zn finger"
                     /note="C2H2 Zn finger [structural motif]"
                     /db_xref="CDD:275368"
     Site            order(293,296,309,313)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:275368"
     Site            order(298,300,302,304..305,308..309,312,326,359,363..364,
                     367..368,371,385,387,389,391..392,395..396,400)
                     /site_type="other"
                     /note="putative nucleic acid binding site [nucleotide
                     binding]"
                     /db_xref="CDD:275368"
     Region          305..328
                     /region_name="zf-H2C2_2"
                     /note="Zinc-finger double domain; pfam13465"
                     /db_xref="CDD:316026"
     Region          321..372
                     /region_name="C2H2 Zn finger"
                     /note="C2H2 Zn finger [structural motif]"
                     /db_xref="CDD:275368"
     Site            order(321,324,368,372)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:275368"
     Region          <374 ..459="" cdd="" cddsrv.cgi="" db_xref="CDD:<a href=" https:="" note="Putative transcriptional repressor regulating G2/M
                     transition [Transcription / Cell division and chromosome
                     partitioning]; COG5189" region_name="SFP1" tructure="" uid="227516" www.ncbi.nlm.nih.gov="">227516

" Region 380..401 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Site order(380,383,396,401) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:275368" Region 409..425 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275370" Region 438..459 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Site order(438,441,454,459) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:275368" Region <464 ..612="" cdd="" cddsrv.cgi="" db_xref="CDD:<a href=" https:="" note="FOG: Zn-finger [General function prediction only]" region_name="COG5048" tructure="" uid="227381" www.ncbi.nlm.nih.gov="">227381" Region 467..487 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Site order(467,470,483,487) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:275368" Site order(472,474,476,478..479,482..483,486,500,502,506..507, 510..511,514,528,530,532,534..535,538..539) /site_type="other" /note="putative nucleic acid binding site [nucleotide binding]" /db_xref="CDD:275368" Region 495..515 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Site order(495,498,511,515) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:275368" Region 523..540 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Region 555..572 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Region 580..600 /region_name="C2H2 Zn finger" /note="C2H2 Zn finger [structural motif]" /db_xref="CDD:275368" Site order(580,583,596,600) /site_type="other" /note="Zn binding site [ion binding]" /db_xref="CDD:275368" CDS 1..688 /gene="ZBTB48" /gene_synonym="HKR3; pp9964; TZAP; ZNF855" /coded_by="NM_001278647.2:126..2192" /db_xref="CCDS:CCDS84.1" /db_xref="GeneID:3104" /db_xref="HGNC:HGNC:4930" /db_xref="MIM:165270" ORIGIN 1 mdgsfvqhsv rvlqelnkqr ekgqycdatl dvgglvfkah wsvlaccshf fqslygdgsg 61 gsvvlpagfa eifgllldff ytghlaltsg nrdqvllaar elrvpeavel cqsfkpktsv 121 gqaaggqsgl gppasqnvns hvkepaglee eevsrtlglv prdqeprgsh spqrpqlhsp 181 aqsegpsslc gklkqalkpc pledkkpedc kvpprpleae gaqlqggsne wevvvqvedd 241 gdgdymsepe avltrrksnv irkpcaaepa lsagslaaep aenrkgtavp vecptchkkf 301 lskyylkvhn rkhtgekpfe cpkcgkcyfr kenllehear ncmnrseqvf tcsvcqetfr 361 rrmelrvhmv shtgempykc sscsqqfmqk kdlqshmikl hgapkphacp tcakcflsrt 421 elqlheafkh rgeklfvcee cghrassrng lqmhikakhr nerphvcefc shaftqkanl 481 nmhlrthtge kpfqchlcgk tfrtqasldk hnrthtgerp fscefceqrf tekgpllrhv 541 asrhqegrph fcqicgktfk aveqlrvhvr rhkgvrkfec tecgykftrq ahlrrhmeih 601 drvenynprq rklrnliied ekmvvvalqp paelevgsae viveslaqgg lasqlpgqrl 661 caeesftgpg vlepsliita avpedcdt //

Related articles in PubMed

1. TZAP or not to zap telomeres. Lossaint G, et al. Science, 2017 Feb 10. PMID 28183935
2. Human Krüppel-related 3 (HKR3): a candidate for the 1p36 neuroblastoma tumour suppressor gene? Maris JM, et al. Eur J Cancer, 1997 Oct. PMID 9516840
3. Cloning, chromosomal localization, physical mapping, and genomic characterization of HKR3. Maris JM, et al. Genomics, 1996 Jul 15. PMID 8661141
4. A factor that regulates the class II major histocompatibility complex gene DPA is a member of a subfamily of zinc finger proteins that includes a Drosophila developmental control protein. Sugawara M, et al. Mol Cell Biol, 1994 Dec. PMID 7969177, Free PMC Article
5. ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator. Jahn A, et al. EMBO Rep, 2017 Jun. PMID 28500257, Free PMC Article

See all (24) citations in PubMed

GeneRIFs: Gene References Into Functions

1. study demonstrate through a combination of RNAseq, ChIPseq and expression proteomics experiments that ZBTB48 acts as a transcriptional activator on a small set of target genes, including mitochondrial fission process 1 (MTFP1). This discovery places ZBTB48 at the interface of telomere length regulation, transcriptional control and mitochondrial metabolism
2. this study describes a specific telomere-associated protein: TZAP (telomeric zinc finger-associated protein). Binding of TZAP to long telomeres represents the switch that triggers telomere trimming, setting the upper limit of telomere length.
3. HKR3 potently activated the transcription of the tumor suppressor gene ARF by acting on the proximal promoter region (bp, -149 approximately +53), which contains Sp1 and FBI-1 binding elements (FREs).

Submit: New GeneRIF Correction

 

 

 

PARP tyyppinen sinkkisormiproteiini LIG3(17q12) , DNA ligaasi 3 alfa

PARP-tyyppisiä sinkkisormirakenteita (C-x-C-x-H-x-C)  esiintyy ainakin kahdella geenituottella LIG3 ja PARP1, joista toinen on transkriptiotekijä.
https://www.ncbi.nlm.nih.gov/gene/3980

LIG3 ( 17q129

Official Symbol LIG3

Official Full Name; DNA ligase 3

Also known as LIG2; LIG3alpha

Summary: This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Expression: Ubiquitous expression in testis (RPKM 7.0), thyroid (RPKM 4.6) and 25 other tissues See more

Preferred Names

DNA ligase 3

Names

ligase II, DNA, ATP-dependent

ligase III, DNA, ATP-dependent

polydeoxyribonucleotide synthase [ATP] 3

 

Conserved Domains (5) summary

cd07967
Location:686 → 824

OBF_DNA_ligase_III; The Oligonucleotide/oligosaccharide binding (OB)-fold domain of ATP-dependent DNA ligase III is a DNA-binding module that is part of the catalytic core unit

cd07902
Location:468 → 680

Adenylation_DNA_ligase_III; Adenylation domain of DNA Ligase III

TIGR00574
Location:318 → 830

dnl1; DNA ligase I, ATP-dependent (dnl1)

pfam00645
Location:97 → 179

zf-PARP; Poly(ADP-ribose) polymerase and DNA-Ligase Zn-finger regionPoly(ADP-ribose) polymerase is an important regulatory component of the cellular response to DNA damage. The amino-terminal region of Poly(ADP-ribose) polymerase consists of two PARP-type zinc fingers. This region acts as a DNA nick sensor.

pfam04675
Location:264 → 429

DNA_ligase_A_N; DNA ligase N terminus

 

https://www.ncbi.nlm.nih.gov/protein/NP_002302.2 

Region          97..179
                     /region_name="zf-PARP"
                     /note="Poly(ADP-ribose) polymerase and DNA-Ligase
                     Zn-finger region; pfam00645"
                     /db_xref="CDD:279039"

ORIGIN      
        1 mslafkiffp qtlralsrke lclfrkhhwr dvrqfsqwse tdllhghplf lrrkpvlsfq
       61 gshlrsraty lvflpglhvg lCsgpCemae qrfCvdyakr gtagCkkCke kivkgvCrig
      121 kvvpnpfses ggdmkewyhi kCmfeklera rattkkiedl telegweele dnekeqitqh
      181 iadlsskaag tpkkkavvqa kltttgqvts pvkgasfvts tnprkfsgfs akpnnsgeap
      241 ssptpkrsls sskcdprhkd cllrefrklc amvadnpsyn tktqiiqdfl rkgsagdgfh
      301 gdvyltvkll lpgviktvyn lndkqivklf srifncnpdd mardleqgdv setirvffeq
      361 sksfppaaks lltiqevdef llrlskltke deqqqalqdi asrctandlk ciirlikhdl
      421 kmnsgakhvl daldpnayea fkasrnlqdv vervlhnaqe vekepgqrra lsvqaslmtp
      481 vqpmlaeack sveyamkkcp ngmfseikyd gervqvhkng dhfsyfsrsl kpvlphkvah
      541 fkdyipqafp gghsmildse vllidnktgk plpfgtlgvh kkaafqdanv clfvfdciyf
      601 ndvslmdrpl cerrkflhdn mveipnrimf semkrvtkal dladmitrvi qegleglvlk
      661 dvkgtyepgk rhwlkvkkdy lnegamadta dlvvlgafyg qgskggmmsi flmgcydpgs
      721 qkwctvtkca gghddatlar lqneldmvki skdpskipsw lkvnkiyypd fivpdpkkaa
      781 vweitgaefs kseahtadgi sirfprctri rddkdwksat nlpqlkelyq lskekadftv
      841 vagdegsstt ggsseenkgp sgsavsrkap skpsastkka egklsnsnsk dgnmqtakps
      901 amkvgeklat ksspvkvgek rkaadetlcq tkrrpaseqr grtvpagrr

Related articles in PubMed

1. LIG3 gene polymorphisms and risk of gastric cancer in a Southern Chinese population. Hua RX, et al. Gene, 2019 Jul 15. PMID 31034940
2. Polymorphism rs1052536 in Base Excision Repair Gene Is a Risk Factor in a High-Risk Area of Neural Tube Defects in China. Li G, et al. Med Sci Monit, 2018 Jul 19. PMID 30022792, Free PMC Article
3. Human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining. Kukshal V, et al. Nucleic Acids Res, 2015 Aug 18. PMID 26130724, Free PMC Article
4. Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy. Synowiec E, et al. Cell Mol Biol (Noisy-le-grand), 2015 Mar 28. PMID 25817347
5. Escape from telomere-driven crisis is DNA ligase III dependent. Jones RE, et al. Cell Rep, 2014 Aug 21. PMID 25127141

See all (129) citations in PubMed

GeneRIFs: Gene References Into Functions

1. MM express elevated MALAT1 and involve in alternative non-homozygous end joining (A-NHEJ) pathway by binding to PARP1 and LIG3, two key components of the A-NHEJ protein complex.
2. Data report that polymorphisms in LIG3 gene are not associated with the susceptibility to gastric cancer. The study helps to provide novel insight into the role of LIG3 polymorphisms in gastric cancer risk.
3. High lig3 expression is associated with multiple myeloma.
4. The homozygotes of rs1052536 TT were associated with an increased risk for NTDs than CC, and variants of rs1052536 T were associated with an increased risk of Neural Tube Defects. The stratified analysis showed that TT genotype of rs1052536 increased the risk of anencephaly and the T allele significantly increased the risk of cranial Neural Tube Defects.
5. single-stranded break repair by human DNA ligase III isoforms reveal biochemical differences from DNA ligase I
6. The g.29661G>A and g.29059C>T polymorphisms of LIG3 may play a role in the keratoconus and Fuchs endothelial corneal dystrophy pathogenesis and can be considered as markers in these diseases.
7. A computational approach to determine susceptibility to cancer by evaluating the deleterious effect of nsSNP in XRCC1 gene on binding interaction of XRCC1 protein with ligase III.
8. In the context of tyrosine kinase-activated leukemias, c-MYC contributes to aberrant DNA repair through downstream targets LIG3 and PARP1 up-regulation.

 

ZBED5, ZBED7, ZBED8, ZBED9 fylogeneettisesti toista haaraa kuin edelliset

 https://www.genenames.org/data/genegroup/#!/group/64
"Buster"- haaran ZBED geenit.

ZBED5, Buster1 ( 11p15.4)  transposonijohdannainen,  Buster1 transposaasin  kaltainen proteiini

 https://www.ncbi.nlm.nih.gov/gene/58486#gene-expression

Official Symbol

ZBED5provided by HGNC

Official Full Name

zinc finger BED-type containing 5provided by HGNC

Also known as

Buster1

Summary

This gene is unusual in that its coding sequence is mostly derived from Charlie-like DNA transposon; however, it does not appear to be an active DNA transposon as it is not flanked by terminal inverted repeats. The encoded protein is conserved among the mammalian Laurasiatheria branch. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2009]

Expression: Ubiquitous expression in lymph node (RPKM 23.1), endometrium (RPKM 21.4) and 25 other tissues See more

Preferred Names

zinc finger BED domain-containing protein 5

Names

transposon-derived Buster1 transposase-like protein

 NM_001143667.2 → NP_001137139.1  zinc finger BED domain-containing protein 5

 Conserved Domains (1) summary

smart00614
Location:117 → 160

ZnF_BED; BED zinc finger

ORIGIN      
        1 miapllcils ynfntfailn vyskltmfct tnslpmdlll kqgslkqeve sfcyqivses
       61 ndqkvgilqs edkqlqpsvs kksegelsrv kfisnsnkit fskkpkrrky desylsfgft
      121 yfgnrdapha qcvlckkils nsslapsklr rhletkhaay kdkdisffkq hldspennkp
      181 ptpkivntdn esateasynv syhialsgea htigellikp cakdvvmrmf deqyskkida
      241 vqlsnstvar rikdlaadie eelvcrlkic dgfslqldes advsglavll vfvryrfnks
      301 ieedlllces lqsnatgeei fncinsfmqk heiewekcvd vcsdasravd gkiaeavtli
      361 kyvapestss hcllyrhala vkimptslkn vldqavqiin yikarphqsr llkilceemg
      421 aqhtalllnt evrwlsrgkv lvrlfelrre llvfmdsafr lsdcltnssw llrlayladi
      481 ftklnevnls mqgknvtvft vfdkmssllr klefwassve eenfdcfptl sdflteinst
      541 vdkdicsaiv qhlrglratl lkyfpvtndn nawvrnpftv tvkpaslvar dyeslidlts
      601 dsqvkqnfse lslndfwssl iqeypsiarr avrvllpfat mhlcetgfsy yaatktkyrk
      661 rldaaphmri rlsnitpnik ricdkktqkh csh
//

Related articles in PubMed

1. Comparative analysis of the recently discovered hAT transposon TcBuster in human cells. Woodard LE, et al. PLoS One, 2012. PMID 23166581, Free PMC Article
2. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Smit AF. Curr Opin Genet Dev, 1999 Dec. PMID 10607616
3. ZBED evolution: repeated utilization of DNA transposons as regulators of diverse host functions. Hayward A, et al. PLoS One, 2013. PMID 23533661, Free PMC Article
4. Genome-scale RNAi screen for host factors required for HIV replication. Zhou H, et al. Cell Host Microbe, 2008 Nov 13. PMID 18976975
5. Functional proteomics mapping of a human signaling pathway. Colland F, et al. Genome Res, 2004 Jul. PMID 15231748, Free PMC Article

See all (12) citations in PubMed

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

 

GeneRIFs: Gene References Into Functions

1. Observational study of gene-disease association. (HuGE Navigator)
2. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)

Submit: New GeneRIF Correction

 https://www.ncbi.nlm.nih.gov/pubmed/26838027 
 https://www.ncbi.nlm.nih.gov/pubmed/23166581

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.

ZBED4 (22q13.33) Verkkokalvon tappien valoreseptoreissa mRNA ZBED4,

 https://www.genenames.org/data/genegroup/#!/group/64

ZBED4 (22q13.33) geeni ilmentyy eniten luuytimessä ja paksusuolessa. Sen mRNA:ta on retinan tapeissa valoreseptoreissa ja  Müllerin gliasoluissa.  Proteiinilla on 1171 aminohappoa ja sen N-tgerminaalisessa domeenissa ilmenee neljä BED tyyppistä  sinkkisormea. C-terminaalissa on lisäksi katalyyttinen aluea,  alfa-helikaalinen domeeni ja imeerisoitumiskohta.

Katson sen neljää BED ZNF domeenia ja niissä olevat  H ja C kombinaatiot ovat seuraavat:
HCCHH, HHCCHH, HHCCCCHH, HCCHCCHH .

 https://www.ncbi.nlm.nih.gov/gene/9889
KUVA: 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606216/figure/pone-0059940-g001/

Official Symbol

ZBED4provided by HGNC

Official Full Name

zinc finger BED-type containing 4provided by HGNC

Expression: Ubiquitous expression in bone marrow (RPKM 4.8), colon (RPKM 4.3) and 25 other tissues See more

Preferred Names

zinc finger BED domain-containing protein 4

Names

zinc finger, BED domain containing 4

 NM_014838.3 → NP_055653.2  zinc finger BED domain-containing protein 4

 

Conserved Domains (2) summary

pfam02892
Location:118 → 166

zf-BED; BED zinc finger

pfam05699
Location:1088 → 1164

Dimer_Tnp_hAT; hAT family C-terminal dimerisation region

FEATURES             Location/Qualifiers
     source          1..1171
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="22"
                     /map="22q13.33"
     Protein         1..1171
                     /product="zinc finger BED domain-containing protein 4"
                     /note="zinc finger, BED domain containing 4"
                     /calculated_mol_wt=130192
     Region          118..166
                     /region_name="zf-BED"
                     /note="BED zinc finger; pfam02892"
                     /db_xref="CDD:308506"
     Region          288..336
                     /region_name="zf-BED"
                     /note="BED zinc finger; pfam02892"
                     /db_xref="CDD:308506"
     Region          459..506
                     /region_name="zf-BED"
                     /note="BED zinc finger; pfam02892"
                     /db_xref="CDD:308506"
     Region          561..609
                     /region_name="zf-BED"
                     /note="BED zinc finger; pfam02892"
                     /db_xref="CDD:308506"
     Site            624
                     /site_type="phosphorylation"
                     /experiment="experimental evidence, no additional details
                     recorded"
                     /note="Phosphoserine. {ECO:0000244|PubMed:23186163};
                     propagated from UniProtKB/Swiss-Prot (O75132.2)"
     Region          1088..1164
                     /region_name="Dimer_Tnp_hAT"
                     /note="hAT family C-terminal dimerisation region;
                     pfam05699"
                     /db_xref="CDD:310361"
     CDS             1..1171
                     /gene="ZBED4"
                     /coded_by="NM_014838.3:476..3991"
                     /db_xref="CCDS:CCDS33677.1"
                     /db_xref="GeneID:9889"
                     /db_xref="HGNC:HGNC:20721"
                     /db_xref="MIM:612552"
ORIGIN      
        1 mennlktcpk edgdfvsdki kfkieeeddd gippdslerm dfkseqedmk qtdsggerag
       61 lggtgcsckp pgkylsaese ddygalfsqy sstlydvame avtqsllssr nmssrkkspa
      121 wkhffisprd stkaicmycv kefsrgknek dlstsclmrh vrrahptvli qengsvsavs
      181 sfpspslllp pqpadagdls tilspiklvq kvaskipspd riteesvsvv sseeissdms
      241 vsekcgreea lvgssphlpa lhydepaenl aekslplpks tsgsrrrsav wkhfylspld
      301 nskavcihcm nefsrgkngk dlgtsclirh mwrahraivl qenggtgipp lystpptllp
      361 sllppegels svssspvkpv respsasssp drltedlqsh lnpgdglmed vaafsssddi
      421 geasasspek qqadglsprl fesgaifqqn kkvmkrlkse vwhhfslapm dslkaecryc
      481 gcaisrgkkg dvgtsclmrh lyrrhpevvg sqkgflgasl anspyatlas aesssskltd
      541 lptvvtknnq vmfpvnskkt sklwnhfsic sadstkvvcl hcgrtisrgk kptnlgtscl
      601 lrhlqrfhsn vlktevseta rpsspdtrvp rgtelsgass fddtnekfyd shpvakkits
      661 liaemialdl qpysfvdnvg fnrlleylkp qyslpapsyf srtaipgmyd nvkqiimshl
      721 keaesgvihf tsgiwmsnqt reyltltahw vsfesparpr cddhhcsall dvsqvdcdys
      781 gnsiqkqlec wweawvtstg lqvgitvtdn asigktlneg ehssvqcfsh tvnlivseai
      841 ksqrmvqnll slarkicerv hrspkakekl aelqreyalp qhhliqdvps kwstsfhmle
      901 rlieqkrain emsvecnfre liscdqwevm qsvcralkpf eaasremstq mstlsqvipm
      961 vhilnrkvem lfeetmgidt mlrslkeamv srlsatlhdp ryvfatlldp rykaslftee
     1021 eaeqykqdli relelmnsts edvaashrcd agspskdsaa eenlwslvak vkkkdprekl
     1081 peamvlayle eevlehscdp ltywnlkkas wpglsalavr flgcppsivp seklfntpte
     1141 ngslgqsrlm mehfeklifl kvnlpliyfq y
//

Related articles in PubMed

1. ZBED4, a novel retinal protein expressed in cones and Müller cells. Farber DB, et al. Adv Exp Med Biol, 2010. PMID 20238005
2. Human DNA replication-related element binding factor (hDREF) self-association via hATC domain is necessary for its nuclear accumulation and DNA binding. Yamashita D, et al. J Biol Chem, 2007 Mar 9. PMID 17209048
3. ZBED4, a BED-type zinc-finger protein in the cones of the human retina. Saghizadeh M, et al. Invest Ophthalmol Vis Sci, 2009 Aug. PMID 19369242, Free PMC Article RESULTS: One of 80 cDNAs differentially expressed in normal and cd dog retinas corresponded to a novel gene, ZBED4, which is also expressed in human and mouse retinas. ZBED4 mRNA was found to be present in cone photoreceptors. When ZBED4 cDNA was transfected into HEK293 cells, the expressed protein showed nuclear localization. However, in human retinas, ZBED4 was localized to cone nuclei, inner segments, and pedicles, as well as to Müller cell endfeet. Confirming these immunohistochemical results, the 135-kDa ZBED4 was found in both the nuclear and cytosolic extracts of human retinas. ZBED4 has four predicted DNA-binding domains, a dimerization domain, and two LXXLL motifs characteristic of coactivators/corepressors of nuclear hormone receptors.  CONCLUSIONS:
   ZBED4 cellular/subcellular localization and domains suggest a regulatory role for this protein, which may exert its effects in cones and Müller cells through multiple ways of action.
   

See all (19) citations in PubMed

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

 

GeneRIFs: Gene References Into Functions

1. There was no association between SNPs in the BRD1 and ZBED4 genes and schizophrenia in the Chinese population.
2. ZBED4, a novel protein that in human retina is localized to cone photoreceptors and glial Muller cells.
3. Observational study of gene-disease association. (HuGE Navigator)
4. ZBED4 cellular/subcellular localization and domains suggest a regulatory role for this protein, which may exert its effects in cones and Muller cells through multiple ways of action.