ID G2HFL3_PANTR Unreviewed; 573 AA.
AC G2HFL3;
DT 16-NOV-2011, integrated into UniProtKB/TrEMBL.
DT 16-NOV-2011, sequence version 1.
DT 24-JAN-2024, entry version 45.
DE RecName: Full=E3 ubiquitin-protein ligase RNF168 {ECO:0000256|HAMAP-Rule:MF_03066};
DE EC=2.3.2.27 {ECO:0000256|HAMAP-Rule:MF_03066};
DE AltName: Full=RING finger protein 168 {ECO:0000256|HAMAP-Rule:MF_03066};
DE AltName: Full=RING-type E3 ubiquitin transferase RNF168 {ECO:0000256|HAMAP-Rule:MF_03066};
GN Name=RNF168 {ECO:0000256|HAMAP-Rule:MF_03066};
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598 {ECO:0000313|EMBL:BAK62521.1};
RN [1] {ECO:0000313|EMBL:BAK62521.1}
RP NUCLEOTIDE SEQUENCE.
RC TISSUE=Testis {ECO:0000313|EMBL:BAK62521.1};
RX PubMed=21484476; DOI=10.1007/s10142-011-0220-9;
RA Kim R.N., Kim D.W., Choi S.H., Chae S.H., Nam S.H., Kim D.W., Kim A.,
RA Kang A., Park K.H., Lee Y.S., Hirai M., Suzuki Y., Sugano S., Hashimoto K.,
RA Kim D.S., Park H.S.;
RT "Major chimpanzee-specific structural changes in sperm development-
RT associated genes.";
RL Funct. Integr. Genomics 11:507-517(2011).
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 H2AX and amplifies the RNF8-dependent H2A
CC ubiquitination, promoting the formation of 'Lys-63'-linked ubiquitin
CC conjugates. This leads to concentrate ubiquitinated histones H2A and
CC H2AX at DNA lesions to the threshold required for recruitment of
CC TP53BP1 and BRCA1. Also recruited at DNA interstrand cross-links (ICLs)
CC sites and promotes accumulation of 'Lys-63'-linked ubiquitination of
CC histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi
CC anemia (FA) complex, followed by interstrand cross-link repair. H2A
CC 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 involved
CC in class switch recombination in immune system, via its role in
CC regulation of DSBs repair. Following DNA damage, promotes the
CC ubiquitination and degradation of JMJD2A/KDM4A in collaboration with
CC RNF8, leading to unmask H4K20me2 mark and promote the recruitment of
CC TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked
CC ubiquitination in vitro; possibly due to partial occlusion of the
CC UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13'
CC and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub,
CC respectively). {ECO:0000256|HAMAP-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:0000256|ARBA:ARBA00000900,
CC ECO:0000256|HAMAP-Rule:MF_03066};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000256|HAMAP-Rule:MF_03066}.
CC -!- SUBUNIT: Monomer. Interacts with UBE2N/UBC13. {ECO:0000256|HAMAP-
CC Rule:MF_03066}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000256|HAMAP-Rule:MF_03066}.
CC Note=Localizes to double-strand breaks (DSBs) sites of DNA damage.
CC {ECO:0000256|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:0000256|HAMAP-
CC Rule:MF_03066}.
CC -!- PTM: Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks
CC (DSBs). {ECO:0000256|HAMAP-Rule:MF_03066}.
CC -!- PTM: Ubiquitinated. {ECO:0000256|HAMAP-Rule:MF_03066}.
CC -!- SIMILARITY: Belongs to the RNF168 family. {ECO:0000256|HAMAP-
CC Rule:MF_03066}.
CC -!- CAUTION: According to a well-established model, RNF168 cannot initiate
CC H2A 'Lys-63'-linked ubiquitination and is recruited following RNF8-
CC dependent histone ubiquitination to amplify H2A 'Lys-63'-linked
CC ubiquitination. However, other data suggest that RNF168 is the priming
CC ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-
CC 15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively).
CC These data suggest that RNF168 might be recruited to DSBs sites in a
CC RNF8-dependent manner by binding to non-histone proteins ubiquitinated
CC via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is
CC then amplified by RNF8. Additional evidences are however required to
CC confirm these data. {ECO:0000256|HAMAP-Rule:MF_03066}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|HAMAP-Rule:MF_03066}.
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DR EMBL; AK305527; BAK62521.1; -; mRNA.
DR RefSeq; NP_001315235.1; NM_001328306.1.
DR AlphaFoldDB; G2HFL3; -.
DR GeneID; 743342; -.
DR KEGG; ptr:743342; -.
DR CTD; 165918; -.
DR OrthoDB; 2919223at2759; -.
DR UniPathway; UPA00143; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:UniProtKB-UniRule.
DR GO; GO:0003682; F:chromatin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0042393; F:histone binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043130; F:ubiquitin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IEA:UniProtKB-UniRule.
DR GO; GO:0045739; P:positive regulation of DNA repair; IEA:UniProtKB-UniRule.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0010212; P:response to ionizing radiation; IEA:UniProtKB-UniRule.
DR CDD; cd21952; MIU2_RNF168; 1.
DR CDD; cd16550; RING-HC_RNF168; 1.
DR CDD; cd22265; UDM1_RNF168; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR23328:SF1; E3 UBIQUITIN-PROTEIN LIGASE RNF168; 1.
DR PANTHER; PTHR23328; UNCHARACTERIZED; 1.
DR Pfam; PF00097; zf-C3HC4; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator {ECO:0000256|HAMAP-Rule:MF_03066};
KW DNA damage {ECO:0000256|HAMAP-Rule:MF_03066};
KW DNA repair {ECO:0000256|HAMAP-Rule:MF_03066};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_03066};
KW Nucleus {ECO:0000256|ARBA:ARBA00023242, ECO:0000256|HAMAP-Rule:MF_03066};
KW Transferase {ECO:0000256|HAMAP-Rule:MF_03066};
KW Ubl conjugation {ECO:0000256|HAMAP-Rule:MF_03066};
KW Ubl conjugation pathway {ECO:0000256|HAMAP-Rule:MF_03066};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|HAMAP-Rule:MF_03066};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|HAMAP-
KW Rule:MF_03066}.
FT DOMAIN 16..55
FT /note="RING-type"
FT /evidence="ECO:0000259|PROSITE:PS50089"
FT REGION 153..176
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 461..558
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 112..130
FT /note="LR motif 1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 145..153
FT /note="UMI motif"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 170..193
FT /note="MIU motif 1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 468..479
FT /note="LR motif 2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT COMPBIAS 193..207
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..223
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 224..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..270
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 271..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..524
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 573 AA; 65263 MW; 18E64AFA5BA8C482 CRC64;
MALPKDAIPS LSECQCGICM EILVEPVTLP CNHTLCKPCF QSTVEKASLC CPFCRRRVSS
WTRYHTRRNS LVNVELWKII QKHYPRECKL RASGQESEEV EIADDYQPVR LLSKPGELRR
EYEEEISKVA AERRASEEEE NKASEEYIQR LLAEEEEEEK RQAEKRRRAM EEQLKSDEEL
ARKLSIDINN FCEGSISASP LNSRKSDPVT PKSEKKSKNK QRNTGDIQKY LTPKSQFGSA
SHSEAVQEVR KNSVSKDIDS SDRKSPTGQD TEIEDMPTLS PQISLGIGEQ GADSSIESPM
PWLCACGAEW YHEGNVKTRP SNHGKELCVL SHERPKTRVP YSKETAVMPC GRTESGCAPT
SGVTQTNGNN TGETENEESC LLISKEISKR KNQESSFEAV KDPCFSAKRR KMSPESSPDQ
EETEINFTQK LIDLEHLLFE SHKQEEQDRL LALQLQKEVD KEQMVPNRQK GSPDEYHLRA
ASSPPDKVLN GQRKNPKDGN FKRQTHTKHP TPERGSRDKN RQVSLKMQLK QSVNRRKMPN
STRDHCKVSR SAHSLQPSIS QKSVFQMFQR CTK
//
