ID F7DJH7_HORSE Unreviewed; 573 AA.
AC F7DJH7;
DT 27-JUL-2011, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 2.
DT 27-MAR-2024, entry version 72.
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,
GN ECO:0000313|Ensembl:ENSECAP00000005109.2,
GN ECO:0000313|VGNC:VGNC:22451};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000005109.2, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000005109.2, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000005109.2,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000005109.2}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000005109.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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 RefSeq; XP_001501246.1; XM_001501196.3.
DR AlphaFoldDB; F7DJH7; -.
DR SMR; F7DJH7; -.
DR STRING; 9796.ENSECAP00000005109; -.
DR PaxDb; 9796-ENSECAP00000005109; -.
DR Ensembl; ENSECAT00000007069.3; ENSECAP00000005109.2; ENSECAG00000007003.3.
DR GeneID; 100069836; -.
DR KEGG; ecb:100069836; -.
DR CTD; 165918; -.
DR VGNC; VGNC:22451; RNF168.
DR GeneTree; ENSGT00940000153680; -.
DR HOGENOM; CLU_030653_1_0_1; -.
DR InParanoid; F7DJH7; -.
DR OMA; RTLNRQK; -.
DR OrthoDB; 2919223at2759; -.
DR TreeFam; TF332796; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000002281; Chromosome 19.
DR Bgee; ENSECAG00000007003; Expressed in inner cell mass and 23 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0035861; C:site of double-strand break; IBA:GO_Central.
DR GO; GO:0000151; C:ubiquitin ligase complex; IEA:UniProtKB-UniRule.
DR GO; GO:0042393; F:histone binding; IEA:UniProtKB-UniRule.
DR GO; GO:0140858; F:histone H2AK15 ubiquitin ligase activity; IEA:Ensembl.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IEA:Ensembl.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IEA:Ensembl.
DR GO; GO:0040029; P:epigenetic regulation of gene expression; IEA:Ensembl.
DR GO; GO:0034244; P:negative regulation of transcription elongation by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0045739; P:positive regulation of DNA repair; IEA:UniProtKB-UniRule.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IEA:Ensembl.
DR GO; GO:0010212; P:response to ionizing radiation; IEA:UniProtKB-UniRule.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:Ensembl.
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 3: Inferred from homology;
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 Reference proteome {ECO:0000313|Proteomes:UP000002281};
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..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..268
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 455..573
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 110..128
FT /note="LR motif 1"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 143..151
FT /note="UMI motif"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 439..462
FT /note="MIU motif 2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT MOTIF 466..477
FT /note="LR motif 2"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_03066"
FT COMPBIAS 213..247
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..573
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 573 AA; 65711 MW; 7F8275EA676F054A CRC64;
MAGPKDAIPS LSECQCPICV EILIEPVTLP CNHTLCNPCF QSTVEKASLC CPFCRRRVSS
WTRYHTRRNS LINMELWEII QKHYPKECKL RASGQESEEI VDDYQPVRLL SKPGELRREY
EEEISKVEAE RRANEEEENK ASEEYIQRLL AEEEEEEKRQ AEKRQREMAE QLKNDEELAR
MLSININNFC ERSILASPLN SRKSDPVTIK SQKKSKNKQT NTGDIQKYLS PKSQFGSASQ
SEVVQEGRRN SISKETDSSD VKSPTWQDTE IEEDMPTLSP QVCLEIQDQG TQSSVESPMP
QLCANGTERC LEGKVITSPS NHDKELCVTN HEEPDARAPC SGEAADKPSG KTENGCTVSD
TTQTLGNNTV ETENEESHLL INKDISKRKN QESSFETVKD PCFSAKRRKM FPKGSLDQEE
TETNFTQKLI DLEHLLFERH KQEEEDRLLA LQLQKEVDKE QMKPNRQKGS PDEYQLRAAS
SPPDRLLNGQ KKNSKDRNLK RQTDREHLKP RRGSKNENWQ PALKIQLKHS VNVNGRKVPN
SARDNCNVSK STHSRQPSKS QKSIFQMFQR YTK
//
