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Protein

E3 ubiquitin-protein ligase RNF8

Gene

RNF8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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/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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979). Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity (PubMed:23233665). 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 (PubMed:11322894, PubMed:14981089, PubMed:17724460, PubMed:18001824, PubMed:18001825, PubMed:18006705, PubMed:18077395, PubMed:18337245, PubMed:18948756, PubMed:19015238, PubMed:19124460, PubMed:19202061, PubMed:19203578, PubMed:19203579, PubMed:20550933, PubMed:21558560, PubMed:21857671, PubMed:21911360, PubMed:22266820, PubMed:22373579, PubMed:22531782, PubMed:22705371, PubMed:22865450, PubMed:22980979).25 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.UniRule annotation
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri403 – 441RING-typeUniRule annotationAdd BLAST39

GO - Molecular functioni

  • chromatin binding Source: UniProtKB
  • histone binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via nonhomologous end joining Source: UniProtKB
  • histone exchange Source: UniProtKB
  • histone H2A K63-linked ubiquitination Source: UniProtKB
  • histone H2A ubiquitination Source: UniProtKB
  • histone H2B ubiquitination Source: UniProtKB
  • interstrand cross-link repair Source: UniProtKB
  • isotype switching Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • negative regulation of transcription elongation from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • protein autoubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • spermatid development Source: UniProtKB
  • 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

BioCyciZFISH:ENSG00000112130-MONOMER.
ReactomeiR-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-69473. G2/M DNA damage checkpoint.
SIGNORiO76064.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase RNF8UniRule annotation (EC:6.3.2.-UniRule annotation)
Short name:
hRNF8
Alternative name(s):
RING finger protein 8UniRule annotation
Gene namesi
Name:RNF8UniRule annotation
Synonyms:KIAA0646
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:10071. RNF8.

Subcellular locationi

GO - Cellular componenti

  • chromosome, telomeric region Source: UniProtKB
  • cytoplasm Source: HPA
  • midbody Source: UniProtKB-SubCell
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • site of double-strand break Source: UniProtKB
  • ubiquitin ligase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi42R → A: Abolishes interaction with ATM-phosphorylated MDC1. Abolishes interaction with human herpesvirus 1 ICP0. Abolishes recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent. 4 Publications1
Mutagenesisi403C → S: Marked reduction of E2-dependent ubiquitination of histone H2A. Loss of UBE2E2- and UBE2N-binding. Loss of nuclear localization. 4 Publications1
Mutagenesisi405I → 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. 3 Publications1
Mutagenesisi406C → S: Abolishes ubiquitin-ligase activity. 1 Publication1
Mutagenesisi443D → R: Does not affect the monomeric structure but abolishes ability to monoubiquitinate H2A in nucleosomes. 1 Publication1

Organism-specific databases

DisGeNETi9025.
OpenTargetsiENSG00000112130.
PharmGKBiPA34445.

Polymorphism and mutation databases

BioMutaiRNF8.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000560481 – 485E3 ubiquitin-protein ligase RNF8Add BLAST485

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei157PhosphoserineCombined sources1

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.UniRule annotation1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO76064.
PaxDbiO76064.
PeptideAtlasiO76064.
PRIDEiO76064.

PTM databases

iPTMnetiO76064.
PhosphoSitePlusiO76064.

Expressioni

Tissue specificityi

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.2 Publications

Developmental stagei

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.1 Publication

Gene expression databases

BgeeiENSG00000112130.
CleanExiHS_RNF8.
ExpressionAtlasiO76064. baseline and differential.
GenevisibleiO76064. HS.

Organism-specific databases

HPAiHPA050731.
HPA064925.

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-4827' phosphorylated HERC2 (via C-terminus). Interacts (via FHA domain) with phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8 degradation by the proteasome.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CEP44Q9C0F13EBI-373337,EBI-744115
HEL-S-70V9HW803EBI-373337,EBI-10175326
HOMEZQ8IX15-33EBI-373337,EBI-10172004
MAD1L1Q9Y6D95EBI-373337,EBI-742610
MDC1Q1467611EBI-373337,EBI-495644
PNMA2Q9UL426EBI-373337,EBI-302355
RBFOX2O432513EBI-373337,EBI-746056
SEPT3Q9UH035EBI-373337,EBI-727037
TMEM79Q9BSE25EBI-373337,EBI-8649725
VRK1Q999862EBI-373337,EBI-1769146
WASLO004016EBI-373337,EBI-957615

GO - Molecular functioni

  • histone binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114492. 54 interactors.
DIPiDIP-31265N.
IntActiO76064. 43 interactors.
MINTiMINT-1459889.
STRINGi9606.ENSP00000362578.

Structurei

Secondary structure

1485
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 22Combined sources7
Beta strandi29 – 32Combined sources4
Beta strandi38 – 49Combined sources12
Helixi56 – 58Combined sources3
Beta strandi64 – 68Combined sources5
Beta strandi74 – 78Combined sources5
Beta strandi85 – 87Combined sources3
Beta strandi105 – 109Combined sources5
Beta strandi119 – 128Combined sources10
Helixi129 – 132Combined sources4
Helixi133 – 135Combined sources3
Helixi351 – 400Combined sources50
Turni404 – 406Combined sources3
Beta strandi411 – 416Combined sources6
Beta strandi421 – 423Combined sources3
Helixi424 – 430Combined sources7
Turni431 – 433Combined sources3
Turni438 – 440Combined sources3
Beta strandi447 – 449Combined sources3
Helixi451 – 461Combined sources11
Helixi466 – 480Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CSWNMR-A8-139[»]
2PIEX-ray1.35A13-146[»]
4AYCX-ray1.90A/B351-485[»]
4ORHX-ray4.80C/G/H/K/L345-485[»]
4WHVX-ray8.30C/D/I/J345-485[»]
ProteinModelPortaliO76064.
SMRiO76064.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO76064.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 92FHAUniRule annotationAdd BLAST55

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi276 – 345Gln-richAdd BLAST70

Domaini

The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2 (PubMed:18001824). This domain is required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (PubMed:23233665).2 Publications

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri403 – 441RING-typeUniRule annotationAdd BLAST39

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410INBI. Eukaryota.
ENOG410Z9IW. LUCA.
GeneTreeiENSGT00400000022349.
HOGENOMiHOG000154169.
HOVERGENiHBG023954.
InParanoidiO76064.
KOiK10667.
OMAiIHKGDHI.
OrthoDBiEOG091G0I40.
PhylomeDBiO76064.
TreeFamiTF330957.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
3.30.40.10. 1 hit.
HAMAPiMF_03067. RNF8. 1 hit.
InterProiIPR000253. FHA_dom.
IPR017335. RNF8.
IPR008984. SMAD_FHA_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00498. FHA. 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O76064-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGEPGFFVTG DRAGGRSWCL RRVGMSAGWL LLEDGCEVTV GRGFGVTYQL
60 70 80 90 100
VSKICPLMIS RNHCVLKQNP EGQWTIMDNK SLNGVWLNRA RLEPLRVYSI
110 120 130 140 150
HQGDYIQLGV PLENKENAEY EYEVTEEDWE TIYPCLSPKN DQMIEKNKEL
160 170 180 190 200
RTKRKFSLDE LAGPGAEGPS NLKSKINKVS CESGQPVKSQ GKGEVASTPS
210 220 230 240 250
DNLDPKLTAL EPSKTTGAPI YPGFPKVTEV HHEQKASNSS ASQRSLQMFK
260 270 280 290 300
VTMSRILRLK IQMQEKHEAV MNVKKQTQKG NSKKVVQMEQ ELQDLQSQLC
310 320 330 340 350
AEQAQQQARV EQLEKTFQEE EQHLQGLEIA QGEKDLKQQL AQALQEHWAL
360 370 380 390 400
MEELNRSKKD FEAIIQAKNK ELEQTKEEKE KMQAQKEEVL SHMNDVLENE
410 420 430 440 450
LQCIICSEYF IEAVTLNCAH SFCSYCINEW MKRKIECPIC RKDIKSKTYS
460 470 480
LVLDNCINKM VNNLSSEVKE RRIVLIRERK AKRLF
Length:485
Mass (Da):55,518
Last modified:November 1, 1998 - v1
Checksum:i54650B2FFC9948B1
GO
Isoform 2 (identifier: O76064-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:98
Mass (Da):10,846
Checksum:i0E5E5F3D13560D56
GO
Isoform 3 (identifier: O76064-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:448
Mass (Da):50,829
Checksum:iC20C2E1E5A761106
GO

Sequence cautioni

The sequence BAA31621 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAG60572 differs from that shown. Reason: Erroneous translation. Wrong choice of CDS.Curated
The sequence EAX03945 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti230V → A in BAD96485 (Ref. 6) Curated1
Sequence conflicti334K → R in BAD96485 (Ref. 6) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052096162A → T.Corresponds to variant rs34338974dbSNPEnsembl.1
Natural variantiVAR_052097473I → V.Corresponds to variant rs1139944dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03667181 – 98SLNGV…PLRVY → SFPSEKAEDFTAAGERFL in isoform 2. 1 PublicationAdd BLAST18
Alternative sequenceiVSP_03783199 – 485Missing in isoform 2. 1 PublicationAdd BLAST387
Alternative sequenceiVSP_054037413 – 448AVTLN…IKSKT → QRDCSEDRALRAFERLPGSA SLRWSGGFSLAVTPLL in isoform 3. CuratedAdd BLAST36
Alternative sequenceiVSP_054038449 – 485Missing in isoform 3. CuratedAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4833.1. [O76064-3]
CCDS4834.1. [O76064-1]
RefSeqiNP_003949.1. NM_003958.3. [O76064-1]
NP_898901.1. NM_183078.2. [O76064-3]
UniGeneiHs.485278.

Genome annotation databases

EnsembliENST00000229866; ENSP00000229866; ENSG00000112130. [O76064-2]
ENST00000373479; ENSP00000362578; ENSG00000112130. [O76064-1]
ENST00000469731; ENSP00000418879; ENSG00000112130. [O76064-3]
GeneIDi9025.
KEGGihsa:9025.
UCSCiuc003onq.4. human. [O76064-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS4833.1. [O76064-3]
CCDS4834.1. [O76064-1]
RefSeqiNP_003949.1. NM_003958.3. [O76064-1]
NP_898901.1. NM_183078.2. [O76064-3]
UniGeneiHs.485278.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CSWNMR-A8-139[»]
2PIEX-ray1.35A13-146[»]
4AYCX-ray1.90A/B351-485[»]
4ORHX-ray4.80C/G/H/K/L345-485[»]
4WHVX-ray8.30C/D/I/J345-485[»]
ProteinModelPortaliO76064.
SMRiO76064.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114492. 54 interactors.
DIPiDIP-31265N.
IntActiO76064. 43 interactors.
MINTiMINT-1459889.
STRINGi9606.ENSP00000362578.

PTM databases

iPTMnetiO76064.
PhosphoSitePlusiO76064.

Polymorphism and mutation databases

BioMutaiRNF8.

Proteomic databases

MaxQBiO76064.
PaxDbiO76064.
PeptideAtlasiO76064.
PRIDEiO76064.

Protocols and materials databases

DNASUi9025.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000229866; ENSP00000229866; ENSG00000112130. [O76064-2]
ENST00000373479; ENSP00000362578; ENSG00000112130. [O76064-1]
ENST00000469731; ENSP00000418879; ENSG00000112130. [O76064-3]
GeneIDi9025.
KEGGihsa:9025.
UCSCiuc003onq.4. human. [O76064-1]

Organism-specific databases

CTDi9025.
DisGeNETi9025.
GeneCardsiRNF8.
HGNCiHGNC:10071. RNF8.
HPAiHPA050731.
HPA064925.
MIMi611685. gene.
neXtProtiNX_O76064.
OpenTargetsiENSG00000112130.
PharmGKBiPA34445.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INBI. Eukaryota.
ENOG410Z9IW. LUCA.
GeneTreeiENSGT00400000022349.
HOGENOMiHOG000154169.
HOVERGENiHBG023954.
InParanoidiO76064.
KOiK10667.
OMAiIHKGDHI.
OrthoDBiEOG091G0I40.
PhylomeDBiO76064.
TreeFamiTF330957.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000112130-MONOMER.
ReactomeiR-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-69473. G2/M DNA damage checkpoint.
SIGNORiO76064.

Miscellaneous databases

ChiTaRSiRNF8. human.
EvolutionaryTraceiO76064.
GeneWikiiRNF8.
GenomeRNAii9025.
PROiO76064.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112130.
CleanExiHS_RNF8.
ExpressionAtlasiO76064. baseline and differential.
GenevisibleiO76064. HS.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
3.30.40.10. 1 hit.
HAMAPiMF_03067. RNF8. 1 hit.
InterProiIPR000253. FHA_dom.
IPR017335. RNF8.
IPR008984. SMAD_FHA_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00498. FHA. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiRNF8_HUMAN
AccessioniPrimary (citable) accession number: O76064
Secondary accession number(s): A6NN24
, A8MYC0, B4DPG0, Q53H16, Q5NKW5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 165 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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 (PubMed:19203578 and PubMed:19203579). 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) (PubMed:22980979). 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 (PubMed:22980979). Additional evidences are however required to confirm these data.UniRule annotation1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.