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Q8VC56

- RNF8_MOUSE

UniProt

Q8VC56 - RNF8_MOUSE

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Protein

E3 ubiquitin-protein ligase RNF8

Gene

Rnf8

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.5 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri406 – 44439RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. acid-amino acid ligase activity Source: InterPro
  2. chromatin binding Source: UniProtKB
  3. histone binding Source: UniProtKB
  4. protein homodimerization activity Source: UniProtKB
  5. ubiquitin-protein transferase activity Source: UniProtKB
  6. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. cellular response to DNA damage stimulus Source: UniProtKB
  2. double-strand break repair Source: UniProtKB
  3. double-strand break repair via nonhomologous end joining Source: UniProtKB
  4. histone exchange Source: UniProtKB
  5. histone H2A K63-linked ubiquitination Source: UniProtKB
  6. histone H2A ubiquitination Source: UniProtKB
  7. histone H2B ubiquitination Source: UniProtKB
  8. isotype switching Source: UniProtKB
  9. mitotic nuclear division Source: UniProtKB-KW
  10. negative regulation of translational elongation Source: UniProtKB
  11. positive regulation of DNA repair Source: UniProtKB
  12. protein K48-linked ubiquitination Source: UniProtKB
  13. protein K63-linked ubiquitination Source: UniProtKB
  14. response to ionizing radiation Source: UniProtKB
  15. spermatid development Source: UniProtKB
  16. ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Ligase

Keywords - Biological processi

Cell cycle, Cell division, DNA damage, DNA repair, Mitosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF8 (EC:6.3.2.-)
Alternative name(s):
ActA-interacting protein 37
Short name:
AIP37
LaXp180
RING finger protein 8
Gene namesi
Name:Rnf8
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 17

Organism-specific databases

MGIiMGI:1929069. Rnf8.

Subcellular locationi

Nucleus By similarity. Midbody By similarity. Chromosometelomere 2 Publications
Note: Following DNA double-strand breaks, recruited to the sites of damage. During prophase, concomitant with nuclear envelope breakdown, localizes throughout the cell, with a dotted pattern. In telophase, again in the nucleus and also with a discrete dotted pattern in the cytoplasm. In late telophase and during cytokinesis, localizes in the midbody of the tubulin bridge joining the daughter cells. Does not seem to be associated with condensed chromosomes at any time during the cell cycle (By similarity). Recruited at uncapped telomeres.By similarity

GO - Cellular componenti

  1. chromosome, telomeric region Source: UniProtKB
  2. nucleus Source: UniProtKB
  3. site of double-strand break Source: UniProtKB
  4. ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Disruption phenotypei

Male mice are infertile, while females do not show defects. Male mice display defects in histone H2A and H2B ubiquitination in testis cells. While meiotic sex chromosome inactivation in the XY body prior to meiosis is not affected, H4K16ac is decreased, leading to defects in the replacement of histones by protamines during spermiogenesis. Mice lacking both Rnf8 and Chfr develop thymic lymphomas and chromosomes are frequently altered, due to defects in DNA damage response and defects in damage-induced activation of ATM kinase.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 488488E3 ubiquitin-protein ligase RNF8PRO_0000056049Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei157 – 1571PhosphoserineBy similarity

Post-translational modificationi

Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiQ8VC56.

PTM databases

PhosphoSiteiQ8VC56.

Expressioni

Gene expression databases

BgeeiQ8VC56.
CleanExiMM_RNF8.
ExpressionAtlasiQ8VC56. baseline.
GenevestigatoriQ8VC56.

Interactioni

Subunit structurei

Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts (via FHA domain) with ATM-phosphorylated MDC1. Interacts (via FHA domain) with 'Thr-4829' phosphorylated HERC2 (via C-terminus) (By similarity). May interact with the L.monocytogenes protein actA; however, given these errors in the sequence (AJ242721), the relevance of the interaction with actA remains to be confirmed.By similarity1 Publication

Protein-protein interaction databases

BioGridi208404. 1 interaction.
DIPiDIP-59448N.

Structurei

3D structure databases

ProteinModelPortaliQ8VC56.
SMRiQ8VC56. Positions 8-140, 348-486.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini38 – 9255FHAPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi299 – 35153Gln-richAdd
BLAST

Domaini

The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4829' phosphorylated HERC2.By similarity

Sequence similaritiesi

Belongs to the RNF8 family.Curated
Contains 1 FHA domain.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri406 – 44439RING-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

GeneTreeiENSGT00400000022349.
HOGENOMiHOG000154169.
HOVERGENiHBG023954.
InParanoidiQ8VC56.
KOiK10667.
TreeFamiTF330957.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR017335. E3_Ub_ligase_RNF8.
IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00498. FHA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
PIRSFiPIRSF037950. E3_ubiquit_lig_RNF8. 1 hit.
SMARTiSM00240. FHA. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS50006. FHA_DOMAIN. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VC56-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MGEPDPLVSG QLAARRSWCL RRLGMDCEWL QLEAGTEVTI GRGLSVTYQL
60 70 80 90 100
ISKVCPLMIS RSHCVLKQNP EGQWTIMDNK SLNGVWLNRE RLAPLQGYCI
110 120 130 140 150
RKGDHIQLGV PLESRETAEY EYEVIEEDWE SLAPCLAPKN DQRMEKHKGS
160 170 180 190 200
RTKRKFSSPG LENLPAEGSS DLRCPLANVA SKPIEPEKLH GKGDASSQSL
210 220 230 240 250
GCLCPGLTSL KASERAAGPH ACSALPKVLE LSCPKKQKAC RPSASQNSLE
260 270 280 290 300
LFKVTMSRML KLKTQMQEKQ IAVLNVKRQT RKGSSKKIVR MEKELRNLQS
310 320 330 340 350
QLYAEQAQQQ ARVEQLEKTF QEEAHYLQGL EKEQGECDLK QQLVQALQEH
360 370 380 390 400
QALMEELNCS KKDFEKIIQA KNKELEQTKE EKDKVQAQKE EVLSHMNDLL
410 420 430 440 450
ENELQCIICS EYFIEAVTLN CAHSFCSFCI NEWMKRKVEC PICRKDIESR
460 470 480
TNSLVLDNCI SKMVDNLSSD VKERRSVLIR ERRAKRLS
Length:488
Mass (Da):55,517
Last modified:March 1, 2002 - v1
Checksum:i428242204EBC44A1
GO

Sequence cautioni

The sequence CAB92239.1 differs from that shown. Reason: Frameshift at positions 219, 266 and 283.
The sequence CAB92239.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AK076180 mRNA. Translation: BAC36236.1.
AK147168 mRNA. Translation: BAE27732.1.
CT010295 mRNA. Translation: CAJ18503.1.
BC021778 mRNA. Translation: AAH21778.1.
AJ242721 mRNA. Translation: CAB92239.1. Frameshift.
CCDSiCCDS37538.1.
RefSeqiNP_067394.1. NM_021419.1.
UniGeneiMm.305994.

Genome annotation databases

EnsembliENSMUST00000024817; ENSMUSP00000024817; ENSMUSG00000090083.
GeneIDi58230.
KEGGimmu:58230.
UCSCiuc008btf.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AK076180 mRNA. Translation: BAC36236.1 .
AK147168 mRNA. Translation: BAE27732.1 .
CT010295 mRNA. Translation: CAJ18503.1 .
BC021778 mRNA. Translation: AAH21778.1 .
AJ242721 mRNA. Translation: CAB92239.1 . Frameshift.
CCDSi CCDS37538.1.
RefSeqi NP_067394.1. NM_021419.1.
UniGenei Mm.305994.

3D structure databases

ProteinModelPortali Q8VC56.
SMRi Q8VC56. Positions 8-140, 348-486.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 208404. 1 interaction.
DIPi DIP-59448N.

PTM databases

PhosphoSitei Q8VC56.

Proteomic databases

PRIDEi Q8VC56.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000024817 ; ENSMUSP00000024817 ; ENSMUSG00000090083 .
GeneIDi 58230.
KEGGi mmu:58230.
UCSCi uc008btf.1. mouse.

Organism-specific databases

CTDi 9025.
MGIi MGI:1929069. Rnf8.

Phylogenomic databases

GeneTreei ENSGT00400000022349.
HOGENOMi HOG000154169.
HOVERGENi HBG023954.
InParanoidi Q8VC56.
KOi K10667.
TreeFami TF330957.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

NextBioi 314253.
PROi Q8VC56.
SOURCEi Search...

Gene expression databases

Bgeei Q8VC56.
CleanExi MM_RNF8.
ExpressionAtlasi Q8VC56. baseline.
Genevestigatori Q8VC56.

Family and domain databases

Gene3Di 2.60.200.20. 1 hit.
3.30.40.10. 1 hit.
InterProi IPR017335. E3_Ub_ligase_RNF8.
IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view ]
Pfami PF00498. FHA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view ]
PIRSFi PIRSF037950. E3_ubiquit_lig_RNF8. 1 hit.
SMARTi SM00240. FHA. 1 hit.
SM00184. RING. 1 hit.
[Graphical view ]
SUPFAMi SSF49879. SSF49879. 1 hit.
PROSITEi PS50006. FHA_DOMAIN. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Extraembryonic tissue, Liver and Placenta.
  2. "Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
    Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Kidney.
  4. "LaXp180, a mammalian ActA-binding protein, identified with the yeast two-hybrid system co-localizes with intracellular Listeria monocytogenes."
    Pfeuffer T., Goebel W., Laubinger J., Bachmann M., Kuhn M.
    Cell. Microbiol. 2:101-114(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-283, INTERACTION WITH ACTA.
    Strain: CD-1.
    Tissue: Embryo.
  5. "RNF8-dependent histone modifications regulate nucleosome removal during spermatogenesis."
    Lu L.Y., Wu J., Ye L., Gavrilina G.B., Saunders T.L., Yu X.
    Dev. Cell 18:371-384(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  6. Cited for: FUNCTION.
  7. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  8. "DNA-damage response and repair activities at uncapped telomeres depend on RNF8."
    Peuscher M.H., Jacobs J.J.
    Nat. Cell Biol. 13:1139-1145(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  9. "The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection."
    Rai R., Li J.M., Zheng H., Lok G.T., Deng Y., Huen M.S., Chen J., Jin J., Chang S.
    Nat. Struct. Mol. Biol. 18:1400-1407(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  10. "The E3 ligase RNF8 regulates KU80 removal and NHEJ repair."
    Feng L., Chen J.
    Nat. Struct. Mol. Biol. 19:201-206(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiRNF8_MOUSE
AccessioniPrimary (citable) accession number: Q8VC56
Secondary accession number(s): Q4FJV7, Q9JK13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: March 1, 2002
Last modified: October 29, 2014
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

The precise role of Rnf8 at telomeres is subject to debate. 2 publications reported recruitment of Rnf8 at uncapped telomeres followed by regulation of non-homologous end joining (NHEJ), however the 2 publications reported different data and conclusions. According to a report, Rnf8 promotes telomere end protection and inhibits NHEJ by mediating ubiquitination via 'Lys-63'-linked ubiquitin and stabilization of Tpp1 at uncapped telomeres (PubMed:22101936). According to another report, Rnf8 recruitment at uncapped telomeres leads to promote NHEJ and the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that Rnf8 may have a detrimental role in case of telomeric crisis and enhance cancer development by aggravating telomere-induced genome instability (PubMed:21857671).2 Publications
According to a well-established model, RNF8 initiate H2A 'Lys-63'-linked ubiquitination leading to recruitment of RNF168 to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidences are however required to confirm these data.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3