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O76064 (RNF8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase RNF8

Short name=hRNF8
EC=6.3.2.-
Alternative name(s):
RING finger protein 8
Gene names
Name:RNF8
Synonyms:KIAA0646
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length485 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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/C1orf86 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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.38 Ref.39

Pathway

Protein modification; protein ubiquitination.

Subunit structure

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-4827' phosphorylated HERC2 (via C-terminus). Interacts (via FHA domain) with phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8 degradation by the proteasome. Ref.2 Ref.10 Ref.11 Ref.12 Ref.14 Ref.18 Ref.21 Ref.33 Ref.35 Ref.39

Subcellular location

Nucleus. Midbody. Chromosometelomere By similarity. Note: Recruited at uncapped telomeres By similarity. 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. Ref.2 Ref.10 Ref.11 Ref.12 Ref.13 Ref.24 Ref.35 Ref.38

Tissue specificity

Ubiquitous. In fetal tissues, highest expression in brain, thymus and liver. In adult tissues, highest levels in brain and testis, lowest levels in peripheral blood cells. Ref.1 Ref.2

Developmental stage

Low levels at the G1-S boundary increase in intensity during S phase and until the end of the G2 phase. Abruptly decreases in late mitosis (at protein level). Barely detectable in anaphase. Ref.15

Domain

The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2. Ref.12

Post-translational modification

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.

Sequence similarities

Belongs to the RNF8 family.

Contains 1 FHA domain.

Contains 1 RING-type zinc finger.

Caution

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 (Ref.22 and Ref.23). 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) (Ref.39). 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 (Ref.39). Additional evidences are however required to confirm these data.

Sequence caution

The sequence BAA31621.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAG60572.1 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.

The sequence EAX03945.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processCell cycle
Cell division
DNA damage
DNA repair
Mitosis
Ubl conjugation pathway
   Cellular componentChromosome
Nucleus
Telomere
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainZinc-finger
   LigandMetal-binding
Zinc
   Molecular functionChromatin regulator
Ligase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to DNA damage stimulus

Inferred from direct assay Ref.27Ref.36Ref.35Ref.31Ref.39. Source: UniProtKB

double-strand break repair

Inferred from direct assay Ref.12Ref.38Ref.39. Source: UniProtKB

double-strand break repair via nonhomologous end joining

Inferred from sequence or structural similarity. Source: UniProtKB

histone H2A K63-linked ubiquitination

Inferred from direct assay Ref.39. Source: UniProtKB

histone H2A ubiquitination

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

histone H2B ubiquitination

Inferred from sequence or structural similarity. Source: UniProtKB

histone exchange

Inferred from sequence or structural similarity. Source: UniProtKB

interstrand cross-link repair

Traceable author statement Ref.34. Source: UniProtKB

isotype switching

Inferred from sequence or structural similarity. Source: UniProtKB

mitosis

Inferred from electronic annotation. Source: UniProtKB-KW

negative regulation of translational elongation

Inferred from mutant phenotype Ref.27. Source: UniProtKB

positive regulation of DNA repair

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

protein K48-linked ubiquitination

Inferred from direct assay Ref.36Ref.35Ref.31. Source: UniProtKB

protein K63-linked ubiquitination

Inferred from direct assay Ref.36. Source: UniProtKB

protein autoubiquitination

Inferred from direct assay Ref.35. Source: UniProtKB

response to ionizing radiation

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

spermatid development

Inferred from sequence or structural similarity. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.35Ref.31. Source: UniProtKB

   Cellular_componentchromosome, telomeric region

Inferred from sequence or structural similarity. Source: UniProtKB

midbody

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

site of double-strand break

Inferred from direct assay Ref.35. Source: UniProtKB

ubiquitin ligase complex

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

   Molecular_functionchromatin binding

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

histone binding

Inferred from direct assay Ref.12Ref.38. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.39. Source: UniProtKB

ubiquitin protein ligase binding

Inferred from physical interaction Ref.35. Source: UniProtKB

ubiquitin-protein ligase activity

Inferred from direct assay Ref.12Ref.38Ref.16Ref.36Ref.35Ref.31Ref.39. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.39. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MDC1Q1467611EBI-373337,EBI-495644

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O76064-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O76064-2)

The sequence of this isoform differs from the canonical sequence as follows:
     81-98: SLNGVWLNRARLEPLRVY → SFPSEKAEDFTAAGERFL
     99-485: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. No experimental confirmation available.
Isoform 3 (identifier: O76064-3)

The sequence of this isoform differs from the canonical sequence as follows:
     413-448: AVTLNCAHSFCSYCINEWMKRKIECPICRKDIKSKT → QRDCSEDRALRAFERLPGSASLRWSGGFSLAVTPLL
     449-485: Missing.
Note: No experimental confirmation available. Gene prediction based on EST data.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 485485E3 ubiquitin-protein ligase RNF8
PRO_0000056048

Regions

Domain38 – 9255FHA
Zinc finger403 – 44139RING-type
Compositional bias276 – 34570Gln-rich

Amino acid modifications

Modified residue1571Phosphoserine Ref.19 Ref.20

Natural variations

Alternative sequence81 – 9818SLNGV…PLRVY → SFPSEKAEDFTAAGERFL in isoform 2.
VSP_036671
Alternative sequence99 – 485387Missing in isoform 2.
VSP_037831
Alternative sequence413 – 44836AVTLN…IKSKT → QRDCSEDRALRAFERLPGSA SLRWSGGFSLAVTPLL in isoform 3.
VSP_054037
Alternative sequence449 – 48537Missing in isoform 3.
VSP_054038
Natural variant1621A → T.
Corresponds to variant rs34338974 [ dbSNP | Ensembl ].
VAR_052096
Natural variant4731I → V.
Corresponds to variant rs1139944 [ dbSNP | Ensembl ].
VAR_052097

Experimental info

Mutagenesis421R → A: Abolishes interaction with ATM-phosphorylated MDC1. Abolishes interaction with human herpesvirus 1 ICP0. Ref.12 Ref.29 Ref.33
Mutagenesis4031C → S: Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization. Ref.2 Ref.10 Ref.11 Ref.12
Mutagenesis4051I → A: Impairs interaction with UBE2L6/UBCH8 and ability to mediate 'Lys-48'-linked ubiquitination E3 ligase activity, while it still catalyzes 'Lys-63'-linked ubiquitination and still interacts with UBE2N/UBC13. Ref.31 Ref.36 Ref.40
Mutagenesis4061C → S: Abolishes ubiquitin-ligase activity. Ref.29
Mutagenesis4431D → R: Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes. Ref.39
Sequence conflict2301V → A in BAD96485. Ref.6
Sequence conflict3341K → R in BAD96485. Ref.6

Secondary structure

....................................... 485
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 54650B2FFC9948B1

FASTA48555,518
        10         20         30         40         50         60 
MGEPGFFVTG DRAGGRSWCL RRVGMSAGWL LLEDGCEVTV GRGFGVTYQL VSKICPLMIS 

        70         80         90        100        110        120 
RNHCVLKQNP EGQWTIMDNK SLNGVWLNRA RLEPLRVYSI HQGDYIQLGV PLENKENAEY 

       130        140        150        160        170        180 
EYEVTEEDWE TIYPCLSPKN DQMIEKNKEL RTKRKFSLDE LAGPGAEGPS NLKSKINKVS 

       190        200        210        220        230        240 
CESGQPVKSQ GKGEVASTPS DNLDPKLTAL EPSKTTGAPI YPGFPKVTEV HHEQKASNSS 

       250        260        270        280        290        300 
ASQRSLQMFK VTMSRILRLK IQMQEKHEAV MNVKKQTQKG NSKKVVQMEQ ELQDLQSQLC 

       310        320        330        340        350        360 
AEQAQQQARV EQLEKTFQEE EQHLQGLEIA QGEKDLKQQL AQALQEHWAL MEELNRSKKD 

       370        380        390        400        410        420 
FEAIIQAKNK ELEQTKEEKE KMQAQKEEVL SHMNDVLENE LQCIICSEYF IEAVTLNCAH 

       430        440        450        460        470        480 
SFCSYCINEW MKRKIECPIC RKDIKSKTYS LVLDNCINKM VNNLSSEVKE RRIVLIRERK 


AKRLF 

« Hide

Isoform 2 [UniParc].

Checksum: 0E5E5F3D13560D56
Show »

FASTA9810,846
Isoform 3 [UniParc].

Checksum: C20C2E1E5A761106
Show »

FASTA44850,829

References

« Hide 'large scale' references
[1]"Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif."
Seki N., Hattori A., Sugano S., Suzuki Y., Nakagawara A., Ohhira M., Muramatsu M., Hori T., Saito T.
J. Hum. Genet. 43:272-274(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Brain.
[2]"The RING finger protein RNF8 recruits UBC13 for lysine 63-based self polyubiquitylation."
Plans V., Scheper J., Soler M., Loukili N., Okano Y., Thomson T.M.
J. Cell. Biochem. 97:572-582(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH UBE2E2 AND UBE2N, AUTOUBIQUITINATION, MUTAGENESIS OF CYS-403.
Tissue: Fetal brain.
[3]"Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Kidney.
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Hepatoma.
[7]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] (ISOFORM 1).
Tissue: Muscle.
[10]"N-terminally extended human ubiquitin-conjugating enzymes (E2s) mediate the ubiquitination of RING-finger proteins, ARA54 and RNF8."
Ito K., Adachi S., Iwakami R., Yasuda H., Muto Y., Seki N., Okano Y.
Eur. J. Biochem. 268:2725-2732(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH UBE2E1; UBE2E2 AND UBE2E3, MUTAGENESIS OF CYS-403.
[11]"The RING finger protein, RNF8, interacts with retinoid X receptor alpha and enhances its transcription-stimulating activity."
Takano Y., Adachi S., Okuno M., Muto Y., Yoshioka T., Matsushima-Nishiwaki R., Tsurumi H., Ito K., Friedman S.L., Moriwaki H., Kojima S., Okano Y.
J. Biol. Chem. 279:18926-18934(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RXRA, MUTAGENESIS OF CYS-403.
[12]"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins."
Mailand N., Bekker-Jensen S., Faustrup H., Melander F., Bartek J., Lukas C., Lukas J.
Cell 131:887-900(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH MDC1, DOMAIN, MUTAGENESIS OF ARG-42 AND CYS-403.
[13]"Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage."
Wang B., Elledge S.J.
Proc. Natl. Acad. Sci. U.S.A. 104:20759-20763(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[14]"Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase."
Kolas N.K., Chapman J.R., Nakada S., Ylanko J., Chahwan R., Sweeney F.D., Panier S., Mendez M., Wildenhain J., Thomson T.M., Pelletier L., Jackson S.P., Durocher D.
Science 318:1637-1640(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MDC1.
[15]"Regulation of mitotic exit by the RNF8 ubiquitin ligase."
Plans V., Guerra-Rebollo M., Thomson T.M.
Oncogene 27:1355-1365(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[16]"PCNA is ubiquitinated by RNF8."
Zhang S., Chea J., Meng X., Zhou Y., Lee E.Y.C., Lee M.Y.W.T.
Cell Cycle 7:3399-3404(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[17]"RNF8-dependent and RNF8-independent regulation of 53BP1 in response to DNA damage."
Sakasai R., Tibbetts R.
J. Biol. Chem. 283:13549-13555(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[18]"Noncanonical E2 variant-independent function of UBC13 in promoting checkpoint protein assembly."
Huen M.S.Y., Huang J., Yuan J., Yamamoto M., Akira S., Ashley C., Xiao W., Chen J.
Mol. Cell. Biol. 28:6104-6112(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE2N.
[19]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[20]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[21]"HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes."
Bekker-Jensen S., Rendtlew Danielsen J., Fugger K., Gromova I., Nerstedt A., Lukas C., Bartek J., Lukas J., Mailand N.
Nat. Cell Biol. 12:80-86(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HERC2.
[22]"The RIDDLE syndrome protein mediates a ubiquitin-dependent signaling cascade at sites of DNA damage."
Stewart G.S., Panier S., Townsend K., Al-Hakim A.K., Kolas N.K., Miller E.S., Nakada S., Ylanko J., Olivarius S., Mendez M., Oldreive C., Wildenhain J., Tagliaferro A., Pelletier L., Taubenheim N., Durandy A., Byrd P.J., Stankovic T., Taylor A.M.R., Durocher D.
Cell 136:420-434(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins."
Doil C., Mailand N., Bekker-Jensen S., Menard P., Larsen D.H., Pepperkok R., Ellenberg J., Panier S., Durocher D., Bartek J., Lukas J., Lukas C.
Cell 136:435-446(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"Accumulation of Pax2 transactivation domain interaction protein (PTIP) at sites of DNA breaks via RNF8-dependent pathway is required for cell survival after DNA damage."
Gong Z., Cho Y.-W., Kim J.-E., Ge K., Chen J.
J. Biol. Chem. 284:7284-7293(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[25]"Histone ubiquitination associates with BRCA1-dependent DNA damage response."
Wu J., Huen M.S.Y., Lu L.-Y., Ye L., Dou Y., Ljungman M., Chen J., Yu X.
Mol. Cell. Biol. 29:849-860(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[26]"The Rap80-BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8-Ubc13-dependent ubiquitination events at DNA double strand breaks."
Shao G., Lilli D.R., Patterson-Fortin J., Coleman K.A., Morrissey D.E., Greenberg R.A.
Proc. Natl. Acad. Sci. U.S.A. 106:3166-3171(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[27]"ATM-dependent chromatin changes silence transcription in cis to DNA double-strand breaks."
Shanbhag N.M., Rafalska-Metcalf I.U., Balane-Bolivar C., Janicki S.M., Greenberg R.A.
Cell 141:970-981(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[28]"Critical roles of ring finger protein RNF8 in replication stress responses."
Sy S.M., Jiang J., Dong S.S., Lok G.T., Wu J., Cai H., Yeung E.S., Huang J., Chen J., Deng Y., Huen M.S.
J. Biol. Chem. 286:22355-22361(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[29]"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, MUTAGENESIS OF ARG-42 AND CYS-406.
[30]"RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of BRCA1 and 53BP1."
Nakada S., Yonamine R.M., Matsuo K.
Cancer Res. 72:4974-4983(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[31]"RNF8- and RNF168-dependent degradation of KDM4A/JMJD2A triggers 53BP1 recruitment to DNA damage sites."
Mallette F.A., Mattiroli F., Cui G., Young L.C., Hendzel M.J., Mer G., Sixma T.K., Richard S.
EMBO J. 31:1865-1878(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN UBIQUITINATION OF KDM4A, MUTAGENESIS OF ILE-405.
[32]"A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure."
Luijsterburg M.S., Acs K., Ackermann L., Wiegant W.W., Bekker-Jensen S., Larsen D.H., Khanna K.K., van Attikum H., Mailand N., Dantuma N.P.
EMBO J. 31:2511-2527(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[33]"Viral E3 ubiquitin ligase-mediated degradation of a cellular E3: viral mimicry of a cellular phosphorylation mark targets the RNF8 FHA domain."
Chaurushiya M.S., Lilley C.E., Aslanian A., Meisenhelder J., Scott D.C., Landry S., Ticau S., Boutell C., Yates J.R. III, Schulman B.A., Hunter T., Weitzman M.D.
Mol. Cell 46:79-90(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN HERPESVIRUS 1 ICP0, MUTAGENESIS OF ARG-42.
[34]"A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network."
Yan Z., Guo R., Paramasivam M., Shen W., Ling C., Fox D. III, Wang Y., Oostra A.B., Kuehl J., Lee D.Y., Takata M., Hoatlin M.E., Schindler D., Joenje H., de Winter J.P., Li L., Seidman M.M., Wang W.
Mol. Cell 47:61-75(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[35]"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, SUBCELLULAR LOCATION, INTERACTION WITH UBE2N.
[36]"Differential regulation of RNF8-mediated Lys48- and Lys63-based poly-ubiquitylation."
Lok G.T., Sy S.M., Dong S.S., Ching Y.P., Tsao S.W., Thomson T.M., Huen M.S.
Nucleic Acids Res. 40:196-205(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ILE-405.
[37]"Solution structure of the FHA domain of human ubiquitin ligase protein RNF8."
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 8-139.
[38]"RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly."
Huen M.S.Y., Grant R., Manke I., Minn K., Yu X., Yaffe M.B., Chen J.
Cell 131:901-914(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 13-146 IN COMPLEX WITH PHOSPHOPEPTIDE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
[39]"RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA Damage signaling."
Mattiroli F., Vissers J.H., van Dijk W.J., Ikpa P., Citterio E., Vermeulen W., Marteijn J.A., Sixma T.K.
Cell 150:1182-1195(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 351-483 IN COMPLEX WITH ZINC, SUBUNIT, FUNCTION, MUTAGENESIS OF ASP-443.
[40]"Molecular insights into the function of RING Finger (RNF)-containing proteins hRNF8 and hRNF168 in Ubc13/Mms2-dependent ubiquitylation."
Campbell S.J., Edwards R.A., Leung C.C., Neculai D., Hodge C.D., Dhe-Paganon S., Glover J.N.
J. Biol. Chem. 287:23900-23910(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (4.8 ANGSTROMS) OF 345-485 IN COMPLEX WITH UBE2N, MUTAGENESIS OF ILE-405.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB012770 Genomic DNA. Translation: BAA33557.1.
AF334675 mRNA. Translation: AAQ14887.1.
AB014546 mRNA. Translation: BAA31621.2. Different initiation.
AK298319 mRNA. Translation: BAG60572.1. Sequence problems.
BT007446 mRNA. Translation: AAP36114.1.
AK222765 mRNA. Translation: BAD96485.1.
AL096712 Genomic DNA. Translation: CAB75689.1.
CH471081 Genomic DNA. Translation: EAX03944.1.
CH471081 Genomic DNA. Translation: EAX03945.1. Sequence problems.
BC007517 mRNA. Translation: AAH07517.1.
RefSeqNP_003949.1. NM_003958.3.
NP_898901.1. NM_183078.2.
UniGeneHs.485278.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CSWNMR-A8-139[»]
2PIEX-ray1.35A13-146[»]
4AYCX-ray1.90A/B351-485[»]
4ORHX-ray4.80C/G/H/K/L345-485[»]
ProteinModelPortalO76064.
SMRO76064. Positions 13-140, 351-483.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114492. 41 interactions.
DIPDIP-31265N.
IntActO76064. 21 interactions.
MINTMINT-1459889.
STRING9606.ENSP00000362578.

PTM databases

PhosphoSiteO76064.

Proteomic databases

PaxDbO76064.
PRIDEO76064.

Protocols and materials databases

DNASU9025.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229866; ENSP00000229866; ENSG00000112130. [O76064-2]
ENST00000373479; ENSP00000362578; ENSG00000112130. [O76064-1]
ENST00000394443; ENSP00000377961; ENSG00000112130. [O76064-2]
GeneID9025.
KEGGhsa:9025.
UCSCuc003onq.4. human. [O76064-1]

Organism-specific databases

CTD9025.
GeneCardsGC06P037321.
HGNCHGNC:10071. RNF8.
HPAHPA050731.
MIM611685. gene.
neXtProtNX_O76064.
PharmGKBPA34445.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG242257.
HOGENOMHOG000154169.
HOVERGENHBG023954.
KOK10667.
OMAIHKGDHI.
OrthoDBEOG75J0N0.
PhylomeDBO76064.
TreeFamTF330957.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressO76064.
BgeeO76064.
CleanExHS_RNF8.
GenevestigatorO76064.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
3.30.40.10. 1 hit.
InterProIPR017335. E3_Ub_ligase_RNF8.
IPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERPTHR15067:SF3. PTHR15067:SF3. 1 hit.
PfamPF00498. FHA. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
PIRSFPIRSF037950. E3_ubiquit_lig_RNF8. 1 hit.
SMARTSM00240. FHA. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
PROSITEPS50006. FHA_DOMAIN. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO76064.
GeneWikiRNF8.
GenomeRNAi9025.
NextBio33813.
PROO76064.
SOURCESearch...

Entry information

Entry nameRNF8_HUMAN
AccessionPrimary (citable) accession number: O76064
Secondary accession number(s): A6NN24 expand/collapse secondary AC list , A8MYC0, B4DPG0, Q53H16, Q5NKW5
Entry history
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM