RFWD3_AILME
ID RFWD3_AILME Reviewed; 773 AA.
AC D2HWM5;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 09-FEB-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=E3 ubiquitin-protein ligase RFWD3;
DE EC=2.3.2.27;
DE AltName: Full=RING finger and WD repeat domain-containing protein 3;
DE AltName: Full=RING finger protein 201;
GN Name=RFWD3; Synonyms=RNF201; ORFNames=PANDA_016934;
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
CC -!- FUNCTION: E3 ubiquitin-protein ligase required for the repair of DNA
CC interstrand cross-links (ICL) in response to DNA damage. Plays a key
CC role in RPA-mediated DNA damage signaling and repair. Acts by mediating
CC ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and
CC RAD51 at stalled replication forks, leading to remove them from DNA
CC damage sites and promote homologous recombination. Also mediates the
CC ubiquitination of p53/TP53 in the late response to DNA damage, and acts
CC as a positive regulator of p53/TP53 stability, thereby regulating the
CC G1/S DNA damage checkpoint. May act by catalyzing the formation of
CC short polyubiquitin chains on p53/TP53 that are not targeted to the
CC proteasome. In response to ionizing radiation, interacts with MDM2 and
CC enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from
CC extending polyubiquitin chains on ubiquitinated p53/TP53.
CC {ECO:0000250|UniProtKB:Q6PCD5}.
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:0000250|UniProtKB:Q6PCD5};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000250|UniProtKB:Q6PCD5}.
CC -!- SUBUNIT: Interacts with MDM2 and p53/TP53. Binds to the RPA complex via
CC direct interaction with RPA2. Interacts with RAD51.
CC {ECO:0000250|UniProtKB:Q6PCD5}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q6PCD5}. Nucleus,
CC PML body {ECO:0000250|UniProtKB:Q6PCD5}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q6PCD5}. Note=In undamaged cells, found both in
CC the cytoplasm and in the nucleus, partially associated with PML nuclear
CC bodies. In response to replication block, such as that caused by
CC hydroxyurea treatment, or to DNA damage caused by ionizing radiations
CC or doxorubicin, recruited to the nucleus, to stalled replication forks
CC or to sites of DNA repair. This recruitment depends upon RPA2.
CC {ECO:0000250|UniProtKB:Q6PCD5}.
CC -!- DOMAIN: The coiled coil domain may be involved in RPA2-binding.
CC {ECO:0000250|UniProtKB:Q6PCD5}.
CC -!- PTM: Phosphorylated at Ser-46 and Ser-63 upon DNA damage by ATM or ATR.
CC ATM phosphorylation occurs at early times upon DNA damage, while ATR is
CC the major kinase at later times. Phosphorylation by ATM and ATR is
CC required to stabilize p53/TP53. Part of the phosphorylation depends
CC upon RPA2 presence. {ECO:0000250|UniProtKB:Q6PCD5}.
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DR EMBL; GL193557; EFB22419.1; -; Genomic_DNA.
DR RefSeq; XP_011232989.1; XM_011234687.2.
DR AlphaFoldDB; D2HWM5; -.
DR SMR; D2HWM5; -.
DR STRING; 9646.ENSAMEP00000001391; -.
DR Ensembl; ENSAMET00000001443; ENSAMEP00000001391; ENSAMEG00000001323.
DR GeneID; 100478259; -.
DR KEGG; aml:100478259; -.
DR CTD; 55159; -.
DR eggNOG; KOG1645; Eukaryota.
DR HOGENOM; CLU_021009_1_0_1; -.
DR InParanoid; D2HWM5; -.
DR OrthoDB; 1451258at2759; -.
DR UniPathway; UPA00143; -.
DR Proteomes; UP000008912; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IEA:Ensembl.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; ISS:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; ISS:UniProtKB.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IEA:Ensembl.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR037381; RFWD3.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR PANTHER; PTHR16047; PTHR16047; 1.
DR Pfam; PF13639; zf-RING_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00320; WD40; 2.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 3: Inferred from homology;
KW Coiled coil; Cytoplasm; DNA damage; DNA repair; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transferase;
KW Ubl conjugation pathway; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..773
FT /note="E3 ubiquitin-protein ligase RFWD3"
FT /id="PRO_0000394253"
FT REPEAT 494..536
FT /note="WD 1"
FT REPEAT 538..576
FT /note="WD 2"
FT REPEAT 582..627
FT /note="WD 3"
FT ZN_FING 287..331
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 18..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 92..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 361..403
FT /evidence="ECO:0000255"
FT COMPBIAS 92..109
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 261..275
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 47
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:Q6PCD5"
FT MOD_RES 64
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:Q6PCD5"
SQ SEQUENCE 773 AA; 84945 MW; 1336647E0E02ABE5 CRC64;
MAQEAMEYNV DEQLEHRVAE QPVPAEVVST QGGPPPLQPL PTEVVSSQGA PPLLQPAPAE
GTSSQVGPHL LQPAAQLSVD LTEEVELLGE DRVENINPGA SEEHRQPSRV NRPIPVSSLD
SMNSFISGLQ RLHGMLEFLR PPSDHNVGPV RSRRRRGSAS RRSRTVGSQR TDSARSRAPL
DAYFQVSRTQ PHLPSMSQDS ETRNPVSEDL QVSSSSSSDS ESSAEYEEVV VQAEDTRAVV
SEEQGGTAAE QEVTCVGGGE TLPKQSPQKT NPLLPSVSKD DEEGDTCTIC FEHWTNAGDH
RLSALRCGHL FGYKCISKWL KGQARKCPQC NKKAKHSDIV VLYARTLRAL DTSEHERMKS
SLLKEQMLRK QAELESAQCR LQLQVLTDEC SKLHSRVQDL QKLTVQHRDQ ISQSPSGSQA
RSLNCLPSSQ NQRKYHFQKT FTVSPTGNCR IMTYCDALSC LVVSQPSPQA SFLPGFGVKM
LSTANMKSSQ YVPMHGKQIR GLAFSSRSKG LLLSASLDST VKLTSLETNT VVQTYNAGRP
VWSCCWCLDE SNHIYAGLVN GSILVYDLRN TSSHIQELVP QKARCPLVSL SYIPRAASAA
FPYGGVLAGT LENASFWELK MGFSHWPHVL PMEPGGCVDF QTESSTRHCL VTYRPDKNHN
TLRSVLMEMS YKLNDAGEPV CSCRPVQTFL GGPTCKLLTK SAIFQNPEND GSILVCTGDE
ASNSALLWDA GSGSLLQELQ ADQPVLDICP FEANHSSCLA TLTEKMVHIY RWE
