RNF8A_XENLA
ID RNF8A_XENLA Reviewed; 540 AA.
AC Q7ZX20;
DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=E3 ubiquitin-protein ligase rnf8-A {ECO:0000255|HAMAP-Rule:MF_03067};
DE EC=2.3.2.27 {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=RING finger protein 8-A {ECO:0000255|HAMAP-Rule:MF_03067};
DE AltName: Full=RING-type E3 ubiquitin transferase rnf8-A;
GN Name=rnf8-A {ECO:0000255|HAMAP-Rule:MF_03067};
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=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in DNA
CC damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX and promoting the recruitment
CC of DNA repair proteins at double-strand breaks (DSBs) sites, and by
CC catalyzing 'Lys-48'-linked ubiquitination to remove target proteins
CC from DNA damage sites. Following DNA DSBs, it is recruited to the sites
CC of damage by ATM-phosphorylated mdc1 and catalyzes the 'Lys-63'-linked
CC ubiquitination of histones H2A and H2AX, thereby promoting the
CC formation of tp53bp1 and brca1 ionizing radiation-induced foci (IRIF).
CC H2A 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
CC catalyzes the formation of 'Lys-48'-linked polyubiquitin chains,
CC leading to degradation of substrate proteins. In addition to its
CC function in damage signaling, also plays a role in higher-order
CC chromatin structure by mediating extensive chromatin decondensation.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
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_03067};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SUBUNIT: Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of
CC the rnf8 homodimer and a E2 heterodimer of ube2n and ube2v2.
CC {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03067}.
CC Note=Following DNA double-strand breaks, recruited to the sites of
CC damage. {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- DOMAIN: The FHA domain specifically recognizes and binds ATM-
CC phosphorylated MDC1. {ECO:0000255|HAMAP-Rule:MF_03067}.
CC -!- SIMILARITY: Belongs to the RNF8 family. {ECO:0000255|HAMAP-
CC Rule:MF_03067}.
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DR EMBL; BC046256; AAH46256.1; -; mRNA.
DR RefSeq; NP_001080384.1; NM_001086915.1.
DR AlphaFoldDB; Q7ZX20; -.
DR SMR; Q7ZX20; -.
DR PRIDE; Q7ZX20; -.
DR DNASU; 380076; -.
DR GeneID; 380076; -.
DR KEGG; xla:380076; -.
DR CTD; 380076; -.
DR Xenbase; XB-GENE-6254223; rnf8.S.
DR OMA; YCIKQWR; -.
DR OrthoDB; 1585372at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000186698; Chromosome 5S.
DR Bgee; 380076; Expressed in testis and 19 other tissues.
DR GO; GO:0000781; C:chromosome, telomeric region; ISS:UniProtKB.
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:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0043486; P:histone exchange; ISS:UniProtKB.
DR GO; GO:0070535; P:histone H2A K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0033522; P:histone H2A ubiquitination; ISS:UniProtKB.
DR GO; GO:0033523; P:histone H2B 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:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:0007286; P:spermatid development; ISS:UniProtKB.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR HAMAP; MF_03067; RNF8; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR017335; RNF8.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00498; FHA; 1.
DR PIRSF; PIRSF037950; E3_ubiquit_lig_RNF8; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00518; ZF_RING_1; 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..540
FT /note="E3 ubiquitin-protein ligase rnf8-A"
FT /id="PRO_0000367279"
FT DOMAIN 30..84
FT /note="FHA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT ZN_FING 382..420
FT /note="RING-type"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03067"
FT REGION 128..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 135..150
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 167..181
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 522..540
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 540 AA; 61925 MW; A504B796022A1D94 CRC64;
MTDEGPGMCW CLRRCGRNTE DLLLPDGEEV TLGRGLGVTY QLKPTLCPLM ISRTHCLFKQ
NTGGEWTVTD NKSLNGVWRN KERLEPHKAY TLSEGALIQL GVPPPNMESA EFEYMLVREH
LEKLSGSLIR PLPDKTKATR TKRKFTSEDT DASGNEGPSN FSIPKFYRVS REDEDSAKSS
HTTDLYKQPT VEPTASGTES RLNDSVEAEV VAPTQQQCRS TLQLSRVRQT MEEIRRLNVQ
MQEKQMEMQE KLNSPLENQV GANSVLAVQK ELRALHNHLS NEQEQHMQSV KELKEIFEEE
QQSMGSRKQV EEEHLKEQLA QALQEHTQLM QELNRSKNDF EQIIEAKNKE LQETKEEKEK
VFAQKEEVLN HMNDVLDNEL QCIICSEHFI EAVTLNCAHS FCSYCIKSWK KRKEECPICR
QEIVTETRSL VLDNCIDSMV DKLSPEMKNR RAALILERKE MVQAEESNPV LVVSDSSSFL
SDTFYISSSS SDSDELGNDF WMRSEEEEYE ETLFGCGTDE LDSSDFESDD DEEEDSFLII
