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