RN168_DANRE
ID RN168_DANRE Reviewed; 474 AA.
AC Q7T308;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=E3 ubiquitin-protein ligase rnf168 {ECO:0000255|HAMAP-Rule:MF_03066};
DE EC=2.3.2.27 {ECO:0000255|HAMAP-Rule:MF_03066};
DE AltName: Full=RING finger protein 168 {ECO:0000255|HAMAP-Rule:MF_03066};
DE AltName: Full=RING-type E3 ubiquitin transferase rnf168;
GN Name=rnf168 {ECO:0000255|HAMAP-Rule:MF_03066}; ORFNames=zgc:64185;
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].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase required for accumulation of
CC repair proteins to sites of DNA damage. Acts with ube2n/ubc13 to
CC amplify the rnf8-dependent histone ubiquitination. Recruited to sites
CC of DNA damage at double-strand breaks (DSBs) by binding to
CC ubiquitinated histone H2A and ubiquitinates histone H2A and H2AX,
CC leading to amplify the rnf8-dependent H2A ubiquitination and promoting
CC the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to
CC concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the
CC threshold required for recruitment of tp53bp1 and brca1. Catalyzes
CC monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A
CC (H2AK13Ub and H2AK15Ub, respectively). {ECO:0000255|HAMAP-
CC Rule:MF_03066}.
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_03066};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|HAMAP-Rule:MF_03066}.
CC -!- SUBUNIT: Monomer. {ECO:0000255|HAMAP-Rule:MF_03066}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03066}.
CC Note=Localizes to double-strand breaks (DSBs) sites of DNA damage.
CC {ECO:0000255|HAMAP-Rule:MF_03066}.
CC -!- DOMAIN: The MIU motif (motif interacting with ubiquitin) mediates the
CC interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains.
CC The UMI motif mediates interaction with ubiquitin with a preference for
CC 'Lys-63'-linked ubiquitin. The specificity for different types of
CC ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU
CC and UMI motifs) with LR motifs (LRMs). {ECO:0000255|HAMAP-
CC Rule:MF_03066}.
CC -!- SIMILARITY: Belongs to the RNF168 family. {ECO:0000255|HAMAP-
CC Rule:MF_03066}.
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DR EMBL; BC053301; AAH53301.1; -; mRNA.
DR RefSeq; NP_956149.1; NM_199855.1.
DR AlphaFoldDB; Q7T308; -.
DR SMR; Q7T308; -.
DR STRING; 7955.ENSDARP00000037364; -.
DR PaxDb; Q7T308; -.
DR GeneID; 334081; -.
DR KEGG; dre:334081; -.
DR CTD; 165918; -.
DR ZFIN; ZDB-GENE-030131-6013; rnf168.
DR eggNOG; KOG4159; Eukaryota.
DR InParanoid; Q7T308; -.
DR PhylomeDB; Q7T308; -.
DR Reactome; R-DRE-3108214; SUMOylation of DNA damage response and repair proteins.
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:Q7T308; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031491; F:nucleosome binding; IBA:GO_Central.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0070535; P:histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0035518; P:histone H2A monoubiquitination; ISS:UniProtKB.
DR GO; GO:0036351; P:histone H2A-K13 ubiquitination; ISS:UniProtKB.
DR GO; GO:0036352; P:histone H2A-K15 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:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR Gene3D; 3.30.40.10; -; 1.
DR HAMAP; MF_03066; RNF168; 1.
DR InterPro; IPR034725; RNF168.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; DNA damage; DNA repair; Metal-binding; Nucleus;
KW Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..474
FT /note="E3 ubiquitin-protein ligase rnf168"
FT /id="PRO_0000367283"
FT ZN_FING 26..65
FT /note="RING-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 192..259
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..474
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 119..137
FT /note="LR motif 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT MOTIF 152..160
FT /note="UMI motif"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT MOTIF 174..195
FT /note="MIU motif 1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT MOTIF 353..376
FT /note="MIU motif 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT MOTIF 379..390
FT /note="LR motif 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT COMPBIAS 231..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 367..386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..419
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..434
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 442..474
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 474 AA; 53248 MW; E6C858B63EA0EDA7 CRC64;
MPPVSEVDRG PVEESSGGLK RSDCVCPVCL EIFLEPVTLP CMHTFCKPCF LETVDKSNMC
CPLCRKRVST WARLNSRNKT LVNMELWRRI QDAFPSQCER RVQGIDDDEE AVMIPKPRVC
QPGELRKEYE DQISKLVEEK RALEEAERRA SEEYIQRLLA EEEERLEEER RRREEQQLEN
DEKLARLLSL ELNSGPASES TCNIKPAEAT PAKKKPSVGD IEKFLRPVPH RQPSSSDSSP
DSSLMANKEN ILSPPKPLSA LSAEDCGKLT VHMLECNGKP STSSFNPSTS EHTFVFNTPK
SSSVKRKSSE IELQSEVDLH SKRPCALLRF DSSSEDSPFL SEVAVHEEAL RSRWQQEEED
RRLALRIQKE LDRENSVDRR KGSADSYQLR QKNTSVSTTT SPDVEGTKKG SNTTTAKNCT
GRRGEEKTEK RLSGTTPGKR PGVKTPVSST AVSSTVKKGT KQTTLTEMFP NMGS
