ID   RN168_XENLA             Reviewed;         557 AA.
AC   Q6INS5;
DT   24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 99.
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};
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Ovary;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (JUN-2004) 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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; BC072198; AAH72198.1; -; mRNA.
DR   RefSeq; NP_001085123.1; NM_001091654.1.
DR   AlphaFoldDB; Q6INS5; -.
DR   SMR; Q6INS5; -.
DR   PRIDE; Q6INS5; -.
DR   DNASU; 432198; -.
DR   GeneID; 432198; -.
DR   KEGG; xla:432198; -.
DR   CTD; 432198; -.
DR   Xenbase; XB-GENE-5765277; rnf168.L.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000186698; Chromosome 5L.
DR   Bgee; 432198; Expressed in ovary and 19 other tissues.
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: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; IPR018957; Znf_C3HC4_RING-type.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Pfam; PF00097; zf-C3HC4; 1.
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..557
FT                   /note="E3 ubiquitin-protein ligase rnf168"
FT                   /id="PRO_0000367284"
FT   ZN_FING         16..55
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   REGION          482..543
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           112..130
FT                   /note="LR motif 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   MOTIF           145..153
FT                   /note="UMI motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   MOTIF           170..193
FT                   /note="MIU motif 1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   MOTIF           422..445
FT                   /note="MIU motif 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   MOTIF           449..460
FT                   /note="LR motif 2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT   COMPBIAS        518..539
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   557 AA;  62890 MW;  AB0FD6DEFBDC94E8 CRC64;
     MTKEKTLPLP RSECICPICQ EILLEPVTLP CKHTLCNPCF QMTVEKASLC CPFCRKRVST
     WARLHSRTRT LVNTELWERI QKQYPKECQR RASGQESDDL ADELASCPAP LLCQPGEIRQ
     EYEAEVSKIE AERLAQEEAE RKASEDYIQK LLAEEAAQDR LHSEAVQREM EEQLKIDEEL
     ARTLSVDLDV SNASCSSVSS VTSKKVVVSK SSKNVKNKQR VSGDIERFLT PRAVAVVGID
     ESMNSDSSEC FIVFDEGEDE MPELSPQCPS TSLIQERGVE LIMPYLSDCY KVESNTTSQQ
     DRCSERSQVC NGTYSSCSDS IDMEESMAIK KQSTTAGLFP ERGYHSPENG MESNTMNCST
     PKHLGMTGTL KRKCEDCSID LEEKAGSCRN VKKKKLSLTE DCPVPSVHAG KLIELEENLY
     ERRRQEEQDR LLALQLQREL DKELKQVNRG KGSPDEYELR TKRGLKLQEC LKLQECQDSP
     LPLRKEIPVQ DNSRNTQSEY SPDENKKPSR KNSVRSARVR QSRAVANTEG SSDGINVLKP
     INKQPTILDL FQRSAGK