Reviewed, UniProtKB/Swiss-Prot O76064 (RNF8_HUMAN)

Names and origin

Protein names

Recommended name:
    E3 ubiquitin-protein ligase RNF8
    EC=6.3.2.-
Alternative name(s):
    RING finger protein 8

Gene names

Name:	RNF8
Synonyms:	KIAA0646

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	485 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	E3 ubiquitin-protein ligase required for assembly of repair proteins to sites of DNA damage. Catalyzes the 'Lys-63'-linked ubiquitination of histone H2A and H2AX. Following DNA double-strand breaks (DSBs), it is recruited to the sites of damage by ATM-phosphorylated MDC1, mediates the ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Promotes the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating UBC13 (UBE2N). Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Enforces the G2/M DNA damage checkpoint. Controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites following DNA double-strand breaks (DSBs). Ubiquitination of histone H2A requires UBC13 but not MMS2 (UBE2V2). May also ubiquitinate histone H2B. Catalyzes the 'Lys-63'-linked ubiquitination of PCNA. 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.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.26
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts with ATM-phosphorylated MDC1. Ref.10 Ref.11 Ref.12 Ref.14 Ref.2 Ref.18
Subcellular location	Nucleus. 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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.22 Ref.26 Ref.2
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.2 Ref.1
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.
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.
Sequence caution	The sequence EAX03945.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cell cycle Cell division DNA damage DNA repair Mitosis Ubl conjugation pathway
Cellular component	Chromosomal protein Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell division Inferred from electronic annotation. Source: UniProtKB-KW double-strand break repair Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB histone H2A ubiquitination Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB histone H2B ubiquitination Inferred from sequence or structural similarity. Source: UniProtKB mitosis Inferred from electronic annotation. Source: UniProtKB-KW modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB response to ionizing radiation Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-KW nucleus Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB ubiquitin ligase complex Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB
Molecular function	chromatin binding Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB histone binding Ref.12 Ref.26 Inferred from direct assay. Source: UniProtKB ubiquitin-protein ligase activity Ref.12 Ref.16 Ref.26 Inferred from direct assay. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EXOSC2	Q13868	1	EBI-373337,EBI-301735
MDC1	Q14676	5	EBI-373337,EBI-495644
ORC2L	Q13416	1	EBI-373337,EBI-374957

Alternative products

This entry describes 2 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:
     1-80: MGEPGFFVTG...EGQWTIMDNK → MKLISSFFHFPQ

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 485

485

E3 ubiquitin-protein ligase RNF8

PRO_0000056048

Regions

Domain

38 – 92

55

FHA

Zinc finger

403 – 441

39

RING-type

Compositional bias

276 – 345

70

Gln-rich

Amino acid modifications

Modified residue

157

1

Phosphoserine Ref.19

Natural variations

Alternative sequence

1 – 80

80

MGEPG…IMDNK → MKLISSFFHFPQ in isoform 2.

VSP_036671

Natural variant

162

1

A → T: dbSNP rs34338974.

VAR_052096

Natural variant

473

1

I → V: dbSNP rs1139944.

VAR_052097

Experimental info

Mutagenesis

42

1

R → A: Abolishes interaction with ATM-phosphorylated MDC1. Ref.12

Mutagenesis

403

1

C → S: Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization. Ref.10 Ref.11 Ref.12 Ref.2

Sequence conflict

230

1

V → A in BAD96485. Ref.6

Sequence conflict

334

1

K → R in BAD96485. Ref.6

Secondary structure

1

.

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485

Helix Strand Turn

Details...

Beta strand

15 – 20

6

Beta strand

29 – 31

3

Beta strand

38 – 43

6

Beta strand

46 – 49

4

Helix

56 – 58

3

Beta strand

64 – 68

5

Beta strand

74 – 80

7

Beta strand

85 – 89

5

Beta strand

106 – 109

4

Beta strand

124 – 128

5

Helix

129 – 132

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 54650B2FFC9948B1	FASTA	485	55,518
	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
	Isoform 2. Checksum: C810A0DE8DD7D6A7	FASTA	417	48,137
	10 20 30 40 50 60 MKLISSFFHF PQSLNGVWLN RARLEPLRVY SIHQGDYIQL GVPLENKENA EYEYEVTEED 70 80 90 100 110 120 WETIYPCLSP KNDQMIEKNK ELRTKRKFSL DELAGPGAEG PSNLKSKINK VSCESGQPVK 130 140 150 160 170 180 SQGKGEVAST PSDNLDPKLT ALEPSKTTGA PIYPGFPKVT EVHHEQKASN SSASQRSLQM 190 200 210 220 230 240 FKVTMSRILR LKIQMQEKHE AVMNVKKQTQ KGNSKKVVQM EQELQDLQSQ LCAEQAQQQA 250 260 270 280 290 300 RVEQLEKTFQ EEEQHLQGLE IAQGEKDLKQ QLAQALQEHW ALMEELNRSK KDFEAIIQAK 310 320 330 340 350 360 NKELEQTKEE KEKMQAQKEE VLSHMNDVLE NELQCIICSE YFIEAVTLNC AHSFCSYCIN 370 380 390 400 410 EWMKRKIECP ICRKDIKSKT YSLVLDNCIN KMVNNLSSEV KERRIVLIRE RKAKRLF

References

	« Hide 'large scale' referencesShow '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: 9852682] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], 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: 16215985] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 9734811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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].
[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]. 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. , 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: 14574404] [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. , 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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: 11322894] [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: 14981089] [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: 18001824] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH MDC1, 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: 18077395] [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: 18006705] [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: 17724460] [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: 18948756] [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: 18337245] [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: 18678647] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157, MASS SPECTROMETRY.
[20]	"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: 19203578] [Abstract] Cited for: FUNCTION.
[21]	"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: 19203579] [Abstract] Cited for: FUNCTION.
[22]	"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: 19124460] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[23]	"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: 19015238] [Abstract] Cited for: FUNCTION.
[24]	"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: 19202061] [Abstract] Cited for: FUNCTION.
[25]	"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.
[26]	"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: 18001825] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 13-146 IN COMPLEX WITH PHOSPHOPEPTIDE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF334675 mRNA. Translation: AAQ14887.1.
AB012770 Genomic DNA. Translation: BAA33557.1.
AB014546 mRNA. Translation: BAA31621.2. Different initiation.
AK298319 mRNA. Translation: BAG60572.1.
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.

IPI

IPI00022561.
IPI00923427.

RefSeq

NP_003949.1.
NP_898901.1.

UniGene

Hs.485278

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CSW	NMR	-	A	8-139	[»]
2PIE	X-ray	1.35	A	13-146	[»]

SMR

O76064. Positions 8-140.

ModBase

Search...

Protein-protein interaction databases

IntAct

O76064. 13 interactions.

PTM databases

PhosphoSite

O76064.

Proteomic databases

PRIDE

O76064.

Genome annotation databases

Ensembl

ENSG00000112130. Homo sapiens. [Contig view]

GeneID

9025.

KEGG

hsa:9025.

Organism-specific databases

GeneCards

GC06P037429.

H-InvDB

HIX0005839.

HGNC

HGNC:10071. RNF8.

MIM

611685. gene.

PharmGKB

PA34445.

HUGE

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GenAtlas

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Phylogenomic databases

HOGENOM

O76064.

HOVERGEN

O76064.

OMA

O76064. VGMSAGW.

Gene expression databases

ArrayExpress

O76064.

Bgee

O76064.

CleanEx

HS_RNF8.

GermOnline

ENSG00000112130. Homo sapiens.

Family and domain databases

InterPro

IPR017335. E3_Ub_ligase_RNF8.
IPR000253. FHA.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:2.60.200.20. FHA. 1 hit.

Pfam

PF00498. FHA. 1 hit.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]

PIRSF

PIRSF037950. E3_ubiquit_lig_RNF8. 1 hit.

SMART

SM00240. FHA. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS50006. FHA_DOMAIN. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

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Other Resources

NextBio

33813.

SOURCE

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Entry information

Entry name

RNF8_HUMAN

Accession

Primary (citable) accession number: O76064
Secondary accession number(s): A6NN24 , A8MYC0, B4DPG0, Q53H16, Q5NKW5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 6, 2002
Last sequence update:	November 1, 1998
Last modified:	June 16, 2009
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)