RFWD3_HUMAN
ID RFWD3_HUMAN Reviewed; 774 AA.
AC Q6PCD5; A8K585; B2RE35; D3DUJ8; Q5XKR3; Q9H9Q3; Q9NVT4;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=E3 ubiquitin-protein ligase RFWD3 {ECO:0000305};
DE EC=2.3.2.27 {ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658};
DE AltName: Full=RING finger and WD repeat domain-containing protein 3;
DE AltName: Full=RING finger protein 201;
GN Name=RFWD3 {ECO:0000312|HGNC:HGNC:25539};
GN Synonyms=RNF201 {ECO:0000312|HGNC:HGNC:25539};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Teratocarcinoma, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-564.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS LYS-392 AND THR-770.
RC TISSUE=Brain, and Testis;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP FUNCTION, INTERACTION WITH MDM2 AND TP53, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-46 AND SER-63, AND MUTAGENESIS OF SER-46; SER-63 AND
RP CYS-315.
RX PubMed=20173098; DOI=10.1073/pnas.0912094107;
RA Fu X., Yucer N., Liu S., Li M., Yi P., Mu J.J., Yang T., Chu J., Jung S.Y.,
RA O'Malley B.W., Gu W., Qin J., Wang Y.;
RT "RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in
RT response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4579-4584(2010).
RN [7]
RP FUNCTION, INTERACTION WITH RPA2, AND SUBCELLULAR LOCATION.
RX PubMed=21504906; DOI=10.1074/jbc.m111.222869;
RA Gong Z., Chen J.;
RT "E3 ligase RFWD3 participates in replication checkpoint control.";
RL J. Biol. Chem. 286:22308-22313(2011).
RN [8]
RP FUNCTION, INTERACTION WITH RPA2, SUBCELLULAR LOCATION, PHOSPHORYLATION,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF CYS-315.
RX PubMed=21558276; DOI=10.1074/jbc.m111.222802;
RA Liu S., Chu J., Yucer N., Leng M., Wang S.Y., Chen B.P., Hittelman W.N.,
RA Wang Y.;
RT "RING finger and WD repeat domain 3 (RFWD3) associates with replication
RT protein A (RPA) and facilitates RPA-mediated DNA damage response.";
RL J. Biol. Chem. 286:22314-22322(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26474068; DOI=10.1016/j.molcel.2015.09.011;
RA Elia A.E., Wang D.C., Willis N.A., Boardman A.P., Hajdu I., Adeyemi R.O.,
RA Lowry E., Gygi S.P., Scully R., Elledge S.J.;
RT "RFWD3-dependent ubiquitination of RPA regulates repair at stalled
RT replication forks.";
RL Mol. Cell 60:280-293(2015).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-46 AND SER-63, INVOLVEMENT IN FANCW, VARIANT FANCW LYS-639,
RP CHARACTERIZATION OF VARIANT FANCW LYS-639, AND MUTAGENESIS OF CYS-315;
RP GLN-499; LEU-518 AND TRP-543.
RX PubMed=28575657; DOI=10.1016/j.molcel.2017.04.021;
RA Feeney L., Munoz I.M., Lachaud C., Toth R., Appleton P.L., Schindler D.,
RA Rouse J.;
RT "RPA-mediated recruitment of the E3 ligase RFWD3 is vital for interstrand
RT crosslink repair and human health.";
RL Mol. Cell 66:610-621(2017).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INVOLVEMENT IN FANCW, VARIANT FANCW
RP LYS-639, AND CHARACTERIZATION OF VARIANT FANCW LYS-639.
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).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-46 AND SER-63, AND
RP MUTAGENESIS OF 36-LEU--PRO-38; 53-LEU--PRO-55; 70-LEU--PRO-72 AND CYS-315.
RX PubMed=28575658; DOI=10.1016/j.molcel.2017.04.022;
RA Inano S., Sato K., Katsuki Y., Kobayashi W., Tanaka H., Nakajima K.,
RA Nakada S., Miyoshi H., Knies K., Takaori-Kondo A., Schindler D., Ishiai M.,
RA Kurumizaka H., Takata M.;
RT "RFWD3-mediated ubiquitination promotes timely removal of both RPA and
RT RAD51 from dna damage sites to facilitate homologous recombination.";
RL Mol. Cell 66:622-634(2017).
CC -!- FUNCTION: E3 ubiquitin-protein ligase required for the repair of DNA
CC interstrand cross-links (ICL) in response to DNA damage
CC (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657,
CC PubMed:28575658). Plays a key role in RPA-mediated DNA damage signaling
CC and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068,
CC PubMed:28575657, PubMed:28575658, PubMed:28691929). 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 (PubMed:26474068,
CC PubMed:28575657, PubMed:28575658). Also mediates the ubiquitination of
CC p53/TP53 in the late response to DNA damage, and acts as a positive
CC regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage
CC checkpoint (PubMed:20173098). May act by catalyzing the formation of
CC short polyubiquitin chains on p53/TP53 that are not targeted to the
CC proteasome (PubMed:20173098). In response to ionizing radiation,
CC interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by
CC restricting MDM2 from extending polyubiquitin chains on ubiquitinated
CC p53/TP53 (PubMed:20173098). {ECO:0000269|PubMed:20173098,
CC ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276,
CC ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575657,
CC ECO:0000269|PubMed:28575658, ECO:0000269|PubMed:28691929}.
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:0000269|PubMed:26474068,
CC ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575657,
CC ECO:0000269|PubMed:28575658}.
CC -!- SUBUNIT: Interacts with MDM2 and p53/TP53 (PubMed:20173098). Binds to
CC the RPA complex via direct interaction with RPA2 (PubMed:21504906,
CC PubMed:21558276, PubMed:26474068, PubMed:28575658). Interacts with
CC RAD51 (PubMed:28575658). {ECO:0000269|PubMed:20173098,
CC ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276,
CC ECO:0000269|PubMed:26474068, ECO:0000269|PubMed:28575658}.
CC -!- INTERACTION:
CC Q6PCD5; Q00987: MDM2; NbExp=2; IntAct=EBI-2129159, EBI-389668;
CC Q6PCD5; Q00987-11: MDM2; NbExp=5; IntAct=EBI-2129159, EBI-5279149;
CC Q6PCD5; P15927: RPA2; NbExp=3; IntAct=EBI-2129159, EBI-621404;
CC Q6PCD5; P04637: TP53; NbExp=5; IntAct=EBI-2129159, EBI-366083;
CC Q6PCD5; P61088: UBE2N; NbExp=2; IntAct=EBI-2129159, EBI-1052908;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20173098,
CC ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:21558276,
CC ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28691929}. Nucleus, PML
CC body {ECO:0000269|PubMed:21558276}. Cytoplasm
CC {ECO:0000269|PubMed:21558276, ECO:0000269|PubMed:28691929}. Note=In
CC undamaged cells, found both in the cytoplasm and in the nucleus,
CC partially associated with PML nuclear bodies (PubMed:21558276). In
CC response to replication block, such as that caused by hydroxyurea
CC treatment, or to DNA damage caused by ionizing radiations or
CC doxorubicin, recruited to the nucleus, to stalled replication forks or
CC to sites of DNA repair (PubMed:21504906, PubMed:28575657). This
CC recruitment depends upon RPA2 (PubMed:21504906).
CC {ECO:0000269|PubMed:21504906, ECO:0000269|PubMed:28575657}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated in the S-G2 phase.
CC {ECO:0000269|PubMed:21558276}.
CC -!- DOMAIN: The coiled coil domain may be involved in RPA2-binding.
CC {ECO:0000269|PubMed:21558276}.
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:0000269|PubMed:20173098,
CC ECO:0000269|PubMed:21558276, ECO:0000269|PubMed:28575657,
CC ECO:0000269|PubMed:28575658}.
CC -!- DISEASE: Fanconi anemia, complementation group W (FANCW) [MIM:617784]:
CC A form of Fanconi anemia, a disorder affecting all bone marrow elements
CC and resulting in anemia, leukopenia and thrombopenia. It is associated
CC with cardiac, renal and limb malformations, dermal pigmentary changes,
CC and a predisposition to the development of malignancies. At the
CC cellular level it is associated with hypersensitivity to DNA-damaging
CC agents, chromosomal instability (increased chromosome breakage) and
CC defective DNA repair. {ECO:0000269|PubMed:28575657,
CC ECO:0000269|PubMed:28691929}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA91662.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAF83889.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG38132.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK001382; BAA91662.1; ALT_INIT; mRNA.
DR EMBL; AK022673; BAB14169.1; -; mRNA.
DR EMBL; AK291200; BAF83889.1; ALT_INIT; mRNA.
DR EMBL; AK315786; BAG38132.1; ALT_INIT; mRNA.
DR EMBL; AC109599; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471114; EAW95680.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95681.1; -; Genomic_DNA.
DR EMBL; BC002574; AAH02574.2; -; mRNA.
DR EMBL; BC059371; AAH59371.2; -; mRNA.
DR CCDS; CCDS32486.1; -.
DR RefSeq; NP_060594.3; NM_018124.3.
DR RefSeq; XP_005256078.1; XM_005256021.4.
DR RefSeq; XP_005256079.1; XM_005256022.4.
DR RefSeq; XP_011521493.1; XM_011523191.2.
DR RefSeq; XP_016878880.1; XM_017023391.1.
DR PDB; 6CVZ; X-ray; 1.80 A; A/B/C=425-774.
DR PDBsum; 6CVZ; -.
DR AlphaFoldDB; Q6PCD5; -.
DR SMR; Q6PCD5; -.
DR BioGRID; 120460; 78.
DR DIP; DIP-52688N; -.
DR IntAct; Q6PCD5; 50.
DR MINT; Q6PCD5; -.
DR STRING; 9606.ENSP00000354361; -.
DR iPTMnet; Q6PCD5; -.
DR PhosphoSitePlus; Q6PCD5; -.
DR BioMuta; RFWD3; -.
DR DMDM; 126253679; -.
DR EPD; Q6PCD5; -.
DR jPOST; Q6PCD5; -.
DR MassIVE; Q6PCD5; -.
DR MaxQB; Q6PCD5; -.
DR PaxDb; Q6PCD5; -.
DR PeptideAtlas; Q6PCD5; -.
DR PRIDE; Q6PCD5; -.
DR ProteomicsDB; 67062; -.
DR Antibodypedia; 30261; 123 antibodies from 25 providers.
DR DNASU; 55159; -.
DR Ensembl; ENST00000361070.9; ENSP00000354361.4; ENSG00000168411.14.
DR Ensembl; ENST00000571750.5; ENSP00000460049.1; ENSG00000168411.14.
DR GeneID; 55159; -.
DR KEGG; hsa:55159; -.
DR MANE-Select; ENST00000361070.9; ENSP00000354361.4; NM_018124.4; NP_060594.3.
DR UCSC; uc002fda.4; human.
DR CTD; 55159; -.
DR DisGeNET; 55159; -.
DR GeneCards; RFWD3; -.
DR GeneReviews; RFWD3; -.
DR HGNC; HGNC:25539; RFWD3.
DR HPA; ENSG00000168411; Tissue enhanced (bone).
DR MalaCards; RFWD3; -.
DR MIM; 614151; gene.
DR MIM; 617784; phenotype.
DR neXtProt; NX_Q6PCD5; -.
DR OpenTargets; ENSG00000168411; -.
DR Orphanet; 84; Fanconi anemia.
DR PharmGKB; PA134960063; -.
DR VEuPathDB; HostDB:ENSG00000168411; -.
DR eggNOG; KOG1645; Eukaryota.
DR GeneTree; ENSGT00390000008931; -.
DR HOGENOM; CLU_021009_1_0_1; -.
DR InParanoid; Q6PCD5; -.
DR OMA; FWEQKTD; -.
DR OrthoDB; 1451258at2759; -.
DR PhylomeDB; Q6PCD5; -.
DR TreeFam; TF323359; -.
DR PathwayCommons; Q6PCD5; -.
DR SignaLink; Q6PCD5; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55159; 103 hits in 1120 CRISPR screens.
DR ChiTaRS; RFWD3; human.
DR GenomeRNAi; 55159; -.
DR Pharos; Q6PCD5; Tbio.
DR PRO; PR:Q6PCD5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q6PCD5; protein.
DR Bgee; ENSG00000168411; Expressed in oocyte and 141 other tissues.
DR ExpressionAtlas; Q6PCD5; baseline and differential.
DR Genevisible; Q6PCD5; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; IMP:UniProtKB.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:2000001; P:regulation of DNA damage checkpoint; IMP:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB.
DR GO; GO:0010212; P:response to ionizing radiation; IDA: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; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Disease variant; DNA damage;
KW DNA repair; Fanconi anemia; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transferase; Ubl conjugation pathway;
KW WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..774
FT /note="E3 ubiquitin-protein ligase RFWD3"
FT /id="PRO_0000278234"
FT REPEAT 495..537
FT /note="WD 1"
FT REPEAT 539..577
FT /note="WD 2"
FT REPEAT 583..628
FT /note="WD 3"
FT ZN_FING 287..331
FT /note="RING-type; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 95..116
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 257..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 361..413
FT /evidence="ECO:0000255"
FT COMPBIAS 187..223
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 46
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:20173098,
FT ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658"
FT MOD_RES 63
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:20173098,
FT ECO:0000269|PubMed:28575657, ECO:0000269|PubMed:28575658"
FT VARIANT 90
FT /note="T -> N (in dbSNP:rs8058922)"
FT /id="VAR_030700"
FT VARIANT 392
FT /note="R -> K (in dbSNP:rs17854997)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030701"
FT VARIANT 564
FT /note="I -> V (in dbSNP:rs7193541)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_030702"
FT VARIANT 639
FT /note="I -> K (in FANCW; abolishes interaction with the RPA
FT complex and subsequent recruitment of the protein at DNA
FT damage sites; decreased function in double-strand break
FT repair via homologous recombination; dbSNP:rs1555524842)"
FT /evidence="ECO:0000269|PubMed:28575657,
FT ECO:0000269|PubMed:28691929"
FT /id="VAR_078953"
FT VARIANT 770
FT /note="I -> T (in dbSNP:rs17854996)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030703"
FT MUTAGEN 36..38
FT /note="LQP->AAA: Decreased interaction with RAD51; when
FT associated with 53-A--A-55 and 70-A--A-72."
FT /evidence="ECO:0000269|PubMed:28575658"
FT MUTAGEN 46
FT /note="S->A: Markedly decreases phosphorylation following
FT ionizing radiation and abolishes ability to stimulate
FT p53/TP53 ubiquitination; when associated with A-63."
FT /evidence="ECO:0000269|PubMed:20173098"
FT MUTAGEN 53..55
FT /note="LQP->AAA: Decreased interaction with RAD51; when
FT associated with 36-A--A-38 and 70-A--A-72."
FT /evidence="ECO:0000269|PubMed:28575658"
FT MUTAGEN 63
FT /note="S->A: Markedly decreases phosphorylation following
FT ionizing radiation and abolishes ability to stimulate
FT p53/TP53 ubiquitination; when associated with A-46."
FT /evidence="ECO:0000269|PubMed:20173098"
FT MUTAGEN 70..72
FT /note="LQP->AAA: Decreased interaction with RAD51; when
FT associated with 36-A--A-38 and 53-A--A-55."
FT /evidence="ECO:0000269|PubMed:28575658"
FT MUTAGEN 315
FT /note="C->A: Abolishes ability to stimulate p53/TP53
FT ubiquitination. No effect on nuclear localization in
FT response to DNA damage."
FT /evidence="ECO:0000269|PubMed:20173098,
FT ECO:0000269|PubMed:21558276, ECO:0000269|PubMed:28575657,
FT ECO:0000269|PubMed:28575658"
FT MUTAGEN 499
FT /note="Q->A: Does not affect interaction with the RPA
FT complex and subsequent recruitment at DNA damage sites."
FT /evidence="ECO:0000269|PubMed:28575657"
FT MUTAGEN 518
FT /note="L->A: Does not affect interaction with the RPA
FT complex and subsequent recruitment at DNA damage sites."
FT /evidence="ECO:0000269|PubMed:28575657"
FT MUTAGEN 543
FT /note="W->A: Abolishes interaction with the RPA complex and
FT subsequent recruitment at DNA damage sites."
FT /evidence="ECO:0000269|PubMed:28575657"
FT CONFLICT 221
FT /note="S -> P (in Ref. 1; BAF83889)"
FT /evidence="ECO:0000305"
FT CONFLICT 552
FT /note="A -> T (in Ref. 1; BAA91662)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="A -> V (in Ref. 1; BAA91662)"
FT /evidence="ECO:0000305"
FT CONFLICT 741
FT /note="Q -> R (in Ref. 1; BAB14169)"
FT /evidence="ECO:0000305"
FT STRAND 435..443
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 457..460
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 461..467
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 470..472
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 475..483
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 484..487
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 491..498
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 500..505
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 507..509
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 512..517
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 520..526
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 527..530
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 531..537
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 542..547
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 550..552
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 554..559
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 564..568
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 572..574
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 576..579
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 588..594
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 606..611
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 614..620
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 626..630
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 635..644
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 645..648
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 649..660
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 664..674
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 680..691
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 703..706
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 714..718
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 725..730
FT /evidence="ECO:0007829|PDB:6CVZ"
FT TURN 731..733
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 736..741
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 748..754
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 757..763
FT /evidence="ECO:0007829|PDB:6CVZ"
FT STRAND 765..774
FT /evidence="ECO:0007829|PDB:6CVZ"
SQ SEQUENCE 774 AA; 85094 MW; EF6E0E186FD2E580 CRC64;
MAHEAMEYDV QVQLNHAEQQ PAPAGMASSQ GGPALLQPVP ADVVSSQGVP SILQPAPAEV
ISSQATPPLL QPAPQLSVDL TEVEVLGEDT VENINPRTSE QHRQGSDGNH TIPASSLHSM
TNFISGLQRL HGMLEFLRPS SSNHSVGPMR TRRRVSASRR ARAGGSQRTD SARLRAPLDA
YFQVSRTQPD LPATTYDSET RNPVSEELQV SSSSDSDSDS SAEYGGVVDQ AEESGAVILE
EQLAGVSAEQ EVTCIDGGKT LPKQPSPQKS EPLLPSASMD EEEGDTCTIC LEQWTNAGDH
RLSALRCGHL FGYRCISTWL KGQVRKCPQC NKKARHSDIV VLYARTLRAL DTSEQERMKS
SLLKEQMLRK QAELESAQCR LQLQVLTDKC TRLQRRVQDL QKLTSHQSQN LQQPRGSQAW
VLSCSPSSQG QHKHKYHFQK TFTVSQAGNC RIMAYCDALS CLVISQPSPQ ASFLPGFGVK
MLSTANMKSS QYIPMHGKQI RGLAFSSYLR GLLLSASLDN TIKLTSLETN TVVQTYNAGR
PVWSCCWCLD EANYIYAGLA NGSILVYDVR NTSSHVQELV AQKARCPLVS LSYMPRAASA
AFPYGGVLAG TLEDASFWEQ KMDFSHWPHV LPLEPGGCID FQTENSSRHC LVTYRPDKNH
TTIRSVLMEM SYRLDDTGNP ICSCQPVHTF FGGPTCKLLT KNAIFQSPEN DGNILVCTGD
EAANSALLWD AASGSLLQDL QTDQPVLDIC PFEVNRNSYL ATLTEKMVHI YKWE
