RN168_XENTR
ID RN168_XENTR Reviewed; 535 AA.
AC B0BLU1;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2008) 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; BC158160; AAI58161.1; -; mRNA.
DR RefSeq; NP_001119969.1; NM_001126497.1.
DR AlphaFoldDB; B0BLU1; -.
DR SMR; B0BLU1; -.
DR STRING; 8364.ENSXETP00000006779; -.
DR PaxDb; B0BLU1; -.
DR GeneID; 100144920; -.
DR KEGG; xtr:100144920; -.
DR CTD; 165918; -.
DR Xenbase; XB-GENE-5765249; rnf168.
DR eggNOG; KOG4159; Eukaryota.
DR InParanoid; B0BLU1; -.
DR OrthoDB; 458276at2759; -.
DR Reactome; R-XTR-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-XTR-5693571; Nonhomologous End-Joining (NHEJ).
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008143; Chromosome 5.
DR Proteomes; UP000790000; 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; 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..535
FT /note="E3 ubiquitin-protein ligase rnf168"
FT /id="PRO_0000367285"
FT ZN_FING 16..55
FT /note="RING-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT REGION 429..535
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 406..429
FT /note="MIU motif 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT MOTIF 433..444
FT /note="LR motif 2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03066"
FT COMPBIAS 429..451
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 457..481
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 490..527
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 535 AA; 60590 MW; 6DB5B3D5F46E928B CRC64;
MAKVQKLPLP WSECICPICQ EILLEPVTLP CKHTLCNPCF QMTVEKASLC CPFCRKRVST
WARQHSRTRT LVNKELWEVI QKQYPKQCQR RASGQESDDL SDELTSCPVP VLCKPGEIRQ
EYEAEVSKIE AERTAQEEAE RKASEDYIQK LLAEEEAEEN LHAEASQREI EEQLKRDEEL
ARLLSGDMDL SNASCTSVSP VTSKKVVSKS SKIVKSKQRV SGDIERFLSP KPRRALAAFG
INESRNSDTS GSCILLDEDE DEIPDLSPQC PSTSLIQERD VELPMPYLPN CYKLESDAAS
QQDSCSERND ICNGTYSCSD SIDVEVSKTM EQQRATADSQ EYRMETNAMS YSTPKRKCEE
CYLDIEEKAG SCQSVKKKKL SLSEDSPVLS VHAGKFIELE ENLYERRKQE EHDRLFALQL
QRELDKELKQ VNRGKGSPDE YQLRPKRGLK LQECNDSPLP HNEQTPVQDK GGNTQSGYSP
DENKKPSRKK SITSSQVRQS RAVTNTERSS EGMNVLKPSN KQPTILDLFQ RSAGK
