RNF8_DANRE
ID RNF8_DANRE Reviewed; 485 AA.
AC Q803C1; Q6P0F2;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=E3 ubiquitin-protein ligase rnf8 {ECO:0000255|HAMAP-Rule:MF_03067};
DE EC=2.3.2.27 {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=RING finger protein 8 {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=RING-type E3 ubiquitin transferase rnf8;
GN Name=rnf8 {ECO:0000255|HAMAP-Rule:MF_03067}; ORFNames=zgc:55936;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=AB; TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in DNA
CC damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX and promoting the recruitment
CC of DNA repair proteins at double-strand breaks (DSBs) sites, and by
CC catalyzing 'Lys-48'-linked ubiquitination to remove target proteins
CC from DNA damage sites. Following DNA DSBs, it is recruited to the sites
CC of damage by ATM-phosphorylated mdc1 and catalyzes the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX, thereby promoting the
CC formation of tp53bp1 and brca1 ionizing radiation-induced foci (IRIF).
CC H2A ubiquitination also mediates the ATM-dependent transcriptional
CC silencing at regions flanking DSBs in cis, a mechanism to avoid
CC collision between transcription and repair intermediates. Also
CC catalyzes the formation of 'Lys-48'-linked polyubiquitin chains,
CC leading to degradation of substrate proteins. In addition to its
CC function in damage signaling, also plays a role in higher-order
CC chromatin structure by mediating extensive chromatin decondensation.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000255|HAMAP-Rule:MF_03067};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SUBUNIT: Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of
CC the rnf8 homodimer and a E2 heterodimer of ube2n and ube2v2.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067}.
CC Note=Following DNA double-strand breaks, recruited to the sites of
CC damage. {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q803C1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q803C1-2; Sequence=VSP_036672;
CC -!- DOMAIN: The FHA domain specifically recognizes and binds ATM-
CC phosphorylated MDC1. {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SIMILARITY: Belongs to the RNF8 family. {ECO:0000255|HAMAP-
CC Rule:MF_03067}.
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DR EMBL; BC044545; AAH44545.1; -; mRNA.
DR EMBL; BC065643; AAH65643.1; -; mRNA.
DR RefSeq; NP_991116.1; NM_205553.1.
DR RefSeq; NP_991329.1; NM_205766.1. [Q803C1-1]
DR AlphaFoldDB; Q803C1; -.
DR SMR; Q803C1; -.
DR STRING; 7955.ENSDARP00000125628; -.
DR PaxDb; Q803C1; -.
DR GeneID; 404050; -.
DR KEGG; dre:404050; -.
DR CTD; 9025; -.
DR ZFIN; ZDB-GENE-040426-849; rnf8.
DR eggNOG; KOG3872; Eukaryota.
DR InParanoid; Q803C1; -.
DR OrthoDB; 1585372at2759; -.
DR PhylomeDB; Q803C1; -.
DR Reactome; R-DRE-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-DRE-5693571; Nonhomologous End-Joining (NHEJ).
DR Reactome; R-DRE-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-DRE-69473; G2/M DNA damage checkpoint.
DR UniPathway; UPA00143; -.
DR PRO; PR:Q803C1; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0000151; C:ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0043486; P:histone exchange; ISS:UniProtKB.
DR GO; GO:0070535; P:histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; ISS:UniProtKB.
DR GO; GO:0033523; P:histone H2B ubiquitination; ISS:UniProtKB.
DR GO; GO:0045190; P:isotype switching; ISS:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR HAMAP; MF_03067; RNF8; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR017335; RNF8.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR018957; Znf_C3HC4_RING-type.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR PIRSF; PIRSF037950; E3_ubiquit_lig_RNF8; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Chromatin regulator; DNA damage; DNA repair;
KW Metal-binding; Nucleus; Reference proteome; Transferase;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..485
FT /note="E3 ubiquitin-protein ligase rnf8"
FT /id="PRO_0000367278"
FT DOMAIN 43..97
FT /note="FHA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT ZN_FING 392..430
FT /note="RING-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT REGION 150..232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..175
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 471..485
FT /note="ERSKSESISSSGGNK -> LKVRASPAVVVINDDSDSEDSSSSDGDTFLQSN
FT SSIFPDSSGSDDSLILEDSSWTEEDDYL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_036672"
FT CONFLICT 134
FT /note="D -> N (in Ref. 1; AAH65643)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="W -> R (in Ref. 1; AAH65643)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 485 AA; 55325 MW; 088A192AB2AE4706 CRC64;
MEKTEEPPSS NNEEDSPAKE KIWCLQRVGR DSDWLRLFED SEVSVGRGLN VTHQILSSSC
PLMISRIHCV FKLNEGRQWT VTDNKSLNGV WVNGKRIPPS TPCILHQSDS VRLGVPLDGN
PVEFDYILVQ KNFDDVKSFL SGNLGKDSGA ASLSQKLKNS KRKFDGGDES EPCPTQHSKS
KLYRSSAPDK SRAQPCPSGE RRETLKLSSR PLEEDRDKAG SSSSTCSDSS QHLATLHRYN
RSLMVLKGRV GDTQKRAAEL EQQQTQTPER EKEMQDLQTQ LEALRGQLRS QQEQALRRME
TLEKSFCEEE RRLETEKAQQ NEVGLKKQLE EALKEHRKVI EELKHAWQGF KEVLQAKDKE
LEVTKEEKEK AKAQKEEVVT QMTEVLESEL QCSICSELFI EAVTLNCAHS FCQHCISEWR
NRKDKCPMCW QNITSQTRSL VLDNCIDRMV ENLSADMRER RLVLINERKG ERSKSESISS
SGGNK
