RFWD3_MOUSE
ID RFWD3_MOUSE Reviewed; 774 AA.
AC Q8CIK8; Q3UV90; Q6PJA8; Q8R2T9; Q8R351;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 160.
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;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=28691929; DOI=10.1172/jci92069;
RA Knies K., Inano S., Ramirez M.J., Ishiai M., Surralles J., Takata M.,
RA Schindler D.;
RT "Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia.";
RL J. Clin. Invest. 127:3013-3027(2017).
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-59 and Ser-75 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}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and do not show overt phenotypic
CC abnormalities, although there is some evidence for increased embryonic
CC lethality, earlier death, and subfertility, associated with testicular
CC and ovarian atrophy in mutant. Mutant mice embryonic fibroblasts are
CC hypersensitive to DNA cross-linking agents and show increased
CC chromosomal breakage compared to controls.
CC {ECO:0000269|PubMed:28691929}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH27246.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK137499; BAE23381.1; -; mRNA.
DR EMBL; AK137698; BAE23467.1; -; mRNA.
DR EMBL; BC018533; AAH18533.2; -; mRNA.
DR EMBL; BC023694; AAH23694.1; -; mRNA.
DR EMBL; BC026603; AAH26603.1; -; mRNA.
DR EMBL; BC027246; AAH27246.1; ALT_INIT; mRNA.
DR EMBL; BC096602; AAH96602.1; -; mRNA.
DR CCDS; CCDS22672.1; -.
DR RefSeq; NP_666330.2; NM_146218.4.
DR AlphaFoldDB; Q8CIK8; -.
DR SMR; Q8CIK8; -.
DR BioGRID; 231573; 4.
DR STRING; 10090.ENSMUSP00000043780; -.
DR iPTMnet; Q8CIK8; -.
DR PhosphoSitePlus; Q8CIK8; -.
DR EPD; Q8CIK8; -.
DR MaxQB; Q8CIK8; -.
DR PaxDb; Q8CIK8; -.
DR PeptideAtlas; Q8CIK8; -.
DR PRIDE; Q8CIK8; -.
DR ProteomicsDB; 255187; -.
DR Antibodypedia; 30261; 123 antibodies from 25 providers.
DR DNASU; 234736; -.
DR Ensembl; ENSMUST00000038739; ENSMUSP00000043780; ENSMUSG00000033596.
DR GeneID; 234736; -.
DR KEGG; mmu:234736; -.
DR UCSC; uc009nmb.1; mouse.
DR CTD; 55159; -.
DR MGI; MGI:2384584; Rfwd3.
DR VEuPathDB; HostDB:ENSMUSG00000033596; -.
DR eggNOG; KOG1645; Eukaryota.
DR GeneTree; ENSGT00390000008931; -.
DR HOGENOM; CLU_021009_1_0_1; -.
DR InParanoid; Q8CIK8; -.
DR OMA; FWEQKTD; -.
DR OrthoDB; 1451258at2759; -.
DR PhylomeDB; Q8CIK8; -.
DR TreeFam; TF323359; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 234736; 9 hits in 109 CRISPR screens.
DR ChiTaRS; Rfwd3; mouse.
DR PRO; PR:Q8CIK8; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q8CIK8; protein.
DR Bgee; ENSMUSG00000033596; Expressed in dorsal pancreas and 254 other tissues.
DR Genevisible; Q8CIK8; MM.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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; ISO:MGI.
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; ISO:MGI.
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 2: Evidence at transcript level;
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..774
FT /note="E3 ubiquitin-protein ligase RFWD3"
FT /id="PRO_0000278235"
FT REPEAT 493..535
FT /note="WD 1"
FT REPEAT 536..568
FT /note="WD 2"
FT REPEAT 583..628
FT /note="WD 3"
FT ZN_FING 288..332
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 32..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 358..403
FT /evidence="ECO:0000255"
FT COMPBIAS 103..126
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 59
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:Q6PCD5"
FT MOD_RES 75
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000250|UniProtKB:Q6PCD5"
FT CONFLICT 63
FT /note="A -> T (in Ref. 2; AAH18533)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="N -> S (in Ref. 2; AAH18533)"
FT /evidence="ECO:0000305"
FT CONFLICT 413
FT /note="A -> V (in Ref. 2; AAH18533)"
FT /evidence="ECO:0000305"
FT CONFLICT 459
FT /note="L -> M (in Ref. 1; BAE23381)"
FT /evidence="ECO:0000305"
FT CONFLICT 724
FT /note="Q -> H (in Ref. 2; AAH18533)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="S -> N (in Ref. 2; AAH18533)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 774 AA; 84312 MW; C17DC43CC8422E14 CRC64;
MAEVAVGQAS DLVPSEMDHE VIYSHLQGPL EGTIEPATPT EVVSNGAPLQ PAPAELANSQ
GGAHVQPAPA EVVSSQDGLP TLQPLPPASI DLTEEVQPSE ENMEVVNPGT SEEPSQGSGA
NPTAGAARSV SMNNFISGLQ RLHNMLELLR PPPADHSVGP IRTRRRMAPI LRARAGESQR
QDNGRYVPHT PLYAYFQVSR SQPYPLPAAH DSETRNPPSG TDSDSDGSAE DEEVVVQAEE
PEANIPEQGV IATDQEATSV TGDDAVPKES PQKPNMLSAM EDEEGETCTI CLEQWTNAGD
HRISALRCGH LFGFRCISKW LKGQTRKCPQ CNKKAKHSDI VVIYARSLRA LDTSEQERMK
SDLLNEQMLR KQAELESAQC RLQLQVLIDK CTKLNSRVQD LEKFVVRHQN SAAQQCSRSK
ALCGKCLSSS QSPGKYSSEK TFTISQTGKC RILAYCDGLS CLVASQPSPQ ASFLPGFGVK
MLSTANMKSS QYIPMHNKQI RGLSFSSQSK GLLLSASLDC TIKLTSLETN TVVQTYNTGR
PVWSCCWCLD ENNYVYAGLA SGSILIYDLR NTNTYIQELV PQKARCPLVS LSYLPKAAVA
AFPYGGVLAG TLENASFWEL KSDFSHKPHV LSLEPGGFVD FQTESSTRHC LVTYRPDKSH
NTVRTVLLEM SYKLDDAGEP VCSCLPVQTF LGGPTCKLLT KSAIFQSPEN NGNVLVCTGD
EASQSTLLWN AGSGLLLQNL KAGEPVLDIC PFETNQNSYL ATLTEKTVHM YKWE
