Full text data of RAD51D
RAD51D
(RAD51L3)
[Confidence: low (only semi-automatic identification from reviews)]
DNA repair protein RAD51 homolog 4 (R51H3; RAD51 homolog D; RAD51-like protein 3; TRAD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
DNA repair protein RAD51 homolog 4 (R51H3; RAD51 homolog D; RAD51-like protein 3; TRAD)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
O75771
ID RA51D_HUMAN Reviewed; 328 AA.
AC O75771; B4DJU7; E1P637; O43537; O60355; O75196; O75847; O75848;
read moreAC O76073; O76085; O94908; Q9UFU5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=DNA repair protein RAD51 homolog 4;
DE AltName: Full=R51H3;
DE AltName: Full=RAD51 homolog D;
DE AltName: Full=RAD51-like protein 3;
DE AltName: Full=TRAD;
GN Name=RAD51D; Synonyms=RAD51L3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9512535; DOI=10.1093/nar/26.7.1653;
RA Cartwright R., Dunn A.M., Simpson P.J., Tambini C.E., Thacker J.;
RT "Isolation of novel human and mouse genes of the recA/RAD51
RT recombination-repair gene family.";
RL Nucleic Acids Res. 26:1653-1659(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9570954; DOI=10.1006/geno.1998.5226;
RA Pittman D.L., Weinberg L.R., Schimenti J.C.;
RT "Identification, characterization, and genetic mapping of Rad51d, a
RT new mouse and human RAD51/RecA-related gene.";
RL Genomics 49:103-111(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS 2; 3;
RP 4; 5; 6 AND 7).
RC TISSUE=Brain;
RX PubMed=10092526; DOI=10.1006/bbrc.1999.0413;
RA Kawabata M., Saeki K.;
RT "Multiple alternative transcripts of the human homologue of the mouse
RT TRAD/R51H3/RAD51D gene, a member of the recA/RAD51 gene family.";
RL Biochem. Biophys. Res. Commun. 257:156-162(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-24; GLN-165;
RP THR-225; GLN-232 AND GLY-233.
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RC TISSUE=Thalamus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-328.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND
RP XRCC2.
RX PubMed=11751635; DOI=10.1101/gad.947001;
RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R.,
RA McIlwraith M.J., Benson F.E., West S.C.;
RT "Identification and purification of two distinct complexes containing
RT the five RAD51 paralogs.";
RL Genes Dev. 15:3296-3307(2001).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND
RP XRCC2.
RX PubMed=11842113; DOI=10.1093/nar/30.4.1009;
RA Liu N., Schild D., Thelen M.P., Thompson L.H.;
RT "Involvement of Rad51C in two distinct protein complexes of Rad51
RT paralogs in human cells.";
RL Nucleic Acids Res. 30:1009-1015(2002).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D; XRCC2 AND XRCC3.
RX PubMed=11744692; DOI=10.1074/jbc.M108306200;
RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D.,
RA Albala J.S.;
RT "RAD51C interacts with RAD51B and is central to a larger protein
RT complex in vivo exclusive of RAD51.";
RL J. Biol. Chem. 277:8406-8411(2002).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND XRCC2.
RX PubMed=11842112; DOI=10.1093/nar/30.4.1001;
RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A.,
RA Schild D.;
RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human
RT cells.";
RL Nucleic Acids Res. 30:1001-1008(2002).
RN [14]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [15]
RP INTERACTION WITH ZSWIM7 AND XRCC2.
RX PubMed=16710300; DOI=10.1038/sj.emboj.7601141;
RA Martin V., Chahwan C., Gao H., Blais V., Wohlschlegel J.,
RA Yates J.R. III, McGowan C.H., Russell P.;
RT "Sws1 is a conserved regulator of homologous recombination in
RT eukaryotic cells.";
RL EMBO J. 25:2564-2574(2006).
RN [16]
RP INTERACTION WITH SWSAP1 AND ZSWIM7.
RX PubMed=21965664; DOI=10.1074/jbc.M111.271080;
RA Liu T., Wan L., Wu Y., Chen J., Huang J.;
RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for
RT efficient homologous recombination repair.";
RL J. Biol. Chem. 286:41758-41766(2011).
RN [17]
RP INVOLVEMENT IN BROVCA4.
RX PubMed=21822267; DOI=10.1038/ng.893;
RA Loveday C., Turnbull C., Ramsay E., Hughes D., Ruark E., Frankum J.R.,
RA Bowden G., Kalmyrzaev B., Warren-Perry M., Snape K., Adlard J.W.,
RA Barwell J., Berg J., Brady A.F., Brewer C., Brice G., Chapman C.,
RA Cook J., Davidson R., Donaldson A., Douglas F., Greenhalgh L.,
RA Henderson A., Izatt L., Kumar A., Lalloo F., Miedzybrodzka Z.,
RA Morrison P.J., Paterson J., Porteous M., Rogers M.T., Shanley S.,
RA Walker L., Eccles D., Evans D.G., Renwick A., Seal S., Lord C.J.,
RA Ashworth A., Reis-Filho J.S., Antoniou A.C., Rahman N.;
RT "Germline mutations in RAD51D confer susceptibility to ovarian
RT cancer.";
RL Nat. Genet. 43:879-882(2011).
RN [18]
RP STRUCTURE BY NMR OF 1-83, AND DNA-BINDING.
RX PubMed=21111057; DOI=10.1016/j.biocel.2010.11.014;
RA Kim Y.M., Choi B.S.;
RT "Structural and functional characterization of the N-terminal domain
RT of human Rad51D.";
RL Int. J. Biochem. Cell Biol. 43:416-422(2011).
CC -!- FUNCTION: Involved in the homologous recombination repair (HRR)
CC pathway of double-stranded DNA breaks arising during DNA
CC replication or induced by DNA-damaging agents. The BCDX2 complex
CC binds single-stranded DNA, single-stranded gaps in duplex DNA and
CC specifically to nicks in duplex DNA.
CC -!- SUBUNIT: Part of a BCDX2 complex consisting of RAD51B, RAD51C,
CC RAD51D and XRCC2. Part of a complex consisting of RAD51B, RAD51C,
CC RAD51D, XRCC2 and XRCC3. Interacts with SWSAP1 and ZSWIM7;
CC involved in homologous recombination repair.
CC -!- INTERACTION:
CC Q6NVH7:SWSAP1; NbExp=2; IntAct=EBI-1055693, EBI-5281637;
CC O43543:XRCC2; NbExp=2; IntAct=EBI-1055693, EBI-3918457;
CC -!- SUBCELLULAR LOCATION: Nucleus (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=TRAD;
CC IsoId=O75771-1; Sequence=Displayed;
CC Name=2; Synonyms=TRAD-D1, D2;
CC IsoId=O75771-2; Sequence=VSP_005558, VSP_005559;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3; Synonyms=TRAD-D3;
CC IsoId=O75771-3; Sequence=VSP_005560;
CC Name=4; Synonyms=TRAD-D4;
CC IsoId=O75771-4; Sequence=VSP_005561;
CC Name=5; Synonyms=TRAD-D5;
CC IsoId=O75771-5; Sequence=VSP_005562;
CC Name=6; Synonyms=TRAD-D6, D7;
CC IsoId=O75771-6; Sequence=VSP_005563, VSP_005564;
CC Name=7; Synonyms=TRAD-D8;
CC IsoId=O75771-7; Sequence=VSP_005565, VSP_005566;
CC Name=8;
CC IsoId=O75771-8; Sequence=VSP_043658;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in colon, prostate, spleen, testis,
CC ovary, thymus and small intestine. Weakly expressed in leukocytes.
CC -!- DISEASE: Breast-ovarian cancer, familial, 4 (BROVCA4)
CC [MIM:614291]: A condition associated with familial predisposition
CC to cancer of the breast and ovaries. Characteristic features in
CC affected families are an early age of onset of breast cancer
CC (often before age 50), increased chance of bilateral cancers
CC (cancer that develop in both breasts, or both ovaries,
CC independently), frequent occurrence of breast cancer among men,
CC increased incidence of tumors of other specific organs, such as
CC the prostate. Note=Disease susceptibility is associated with
CC variations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad51l3/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RAD51L3ID347ch17q12.html";
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DR EMBL; Y15572; CAA75681.1; -; mRNA.
DR EMBL; AF034956; AAC39719.1; -; mRNA.
DR EMBL; AB013341; BAA25914.1; -; mRNA.
DR EMBL; AB016223; BAA31747.1; -; mRNA.
DR EMBL; AB016224; BAA31748.1; -; mRNA.
DR EMBL; AB016225; BAA31749.1; -; mRNA.
DR EMBL; AB018360; BAA33779.1; -; mRNA.
DR EMBL; AB018361; BAA33780.1; -; mRNA.
DR EMBL; AB018362; BAA33781.1; -; mRNA.
DR EMBL; AB018363; BAA33782.1; -; mRNA.
DR EMBL; AB020412; BAA34690.1; -; mRNA.
DR EMBL; AY623116; AAT38112.1; -; Genomic_DNA.
DR EMBL; AK296241; BAG58959.1; -; mRNA.
DR EMBL; AC022916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471147; EAW80181.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80184.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80196.1; -; Genomic_DNA.
DR EMBL; BC014422; AAH14422.1; -; mRNA.
DR EMBL; AL117459; CAB55937.1; -; mRNA.
DR PIR; T17247; T17247.
DR RefSeq; NP_001136043.1; NM_001142571.1.
DR RefSeq; NP_002869.3; NM_002878.3.
DR RefSeq; NP_598332.1; NM_133629.2.
DR UniGene; Hs.631757; -.
DR PDB; 2KZ3; NMR; -; A=1-83.
DR PDBsum; 2KZ3; -.
DR ProteinModelPortal; O75771; -.
DR SMR; O75771; 1-304.
DR DIP; DIP-24265N; -.
DR IntAct; O75771; 7.
DR MINT; MINT-127795; -.
DR PhosphoSite; O75771; -.
DR PaxDb; O75771; -.
DR PRIDE; O75771; -.
DR DNASU; 5892; -.
DR Ensembl; ENST00000335858; ENSP00000338408; ENSG00000185379.
DR Ensembl; ENST00000345365; ENSP00000338790; ENSG00000185379.
DR Ensembl; ENST00000357906; ENSP00000350581; ENSG00000185379.
DR Ensembl; ENST00000360276; ENSP00000353417; ENSG00000185379.
DR Ensembl; ENST00000394589; ENSP00000378090; ENSG00000185379.
DR Ensembl; ENST00000586044; ENSP00000465584; ENSG00000185379.
DR Ensembl; ENST00000587977; ENSP00000466587; ENSG00000185379.
DR Ensembl; ENST00000588594; ENSP00000465366; ENSG00000185379.
DR Ensembl; ENST00000590016; ENSP00000466399; ENSG00000185379.
DR GeneID; 5892; -.
DR KEGG; hsa:5892; -.
DR UCSC; uc002hir.2; human.
DR CTD; 5892; -.
DR GeneCards; GC17M033427; -.
DR HGNC; HGNC:9823; RAD51D.
DR MIM; 602954; gene.
DR MIM; 614291; phenotype.
DR neXtProt; NX_O75771; -.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR PharmGKB; PA34179; -.
DR eggNOG; COG0468; -.
DR HOGENOM; HOG000049134; -.
DR HOVERGEN; HBG057455; -.
DR KO; K10871; -.
DR OMA; CSLSYKA; -.
DR PhylomeDB; O75771; -.
DR GeneWiki; RAD51L3; -.
DR GenomeRNAi; 5892; -.
DR NextBio; 22920; -.
DR PRO; PR:O75771; -.
DR ArrayExpress; O75771; -.
DR Bgee; O75771; -.
DR Genevestigator; O75771; -.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0008094; F:DNA-dependent ATPase activity; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C.
DR InterPro; IPR016467; DNA_recomb/repair_RecA-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR020588; RecA_ATP-bd.
DR Pfam; PF08423; Rad51; 1.
DR PIRSF; PIRSF005856; Rad51; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50162; RECA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome;
KW DNA damage; DNA recombination; DNA repair; DNA-binding;
KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome.
FT CHAIN 1 328 DNA repair protein RAD51 homolog 4.
FT /FTId=PRO_0000122942.
FT NP_BIND 107 114 ATP (Potential).
FT REGION 1 83 Preferencially binds ssDNA.
FT COMPBIAS 200 205 Poly-Val.
FT VAR_SEQ 49 88 ALVALRRVLLAQFSAFPVNGADLYEELKTSTAILSTGIGS
FT -> TWRAHSSGNLGGLQLPQVPAGRSWSGVRNALKKAGLGH
FT GGTDGLSLNAFDERGTAVSTSR (in isoform 8).
FT /FTId=VSP_043658.
FT VAR_SEQ 49 49 A -> S (in isoform 2).
FT /FTId=VSP_005558.
FT VAR_SEQ 50 328 Missing (in isoform 2).
FT /FTId=VSP_005559.
FT VAR_SEQ 50 161 Missing (in isoform 3).
FT /FTId=VSP_005560.
FT VAR_SEQ 88 118 SLDKLLDAGLYTGEVTEIVGGPGSGKTQVCL -> RHGGRT
FT QVGTWEDCSCLRSPQGDRGVGSGML (in isoform 6).
FT /FTId=VSP_005563.
FT VAR_SEQ 88 101 SLDKLLDAGLYTGE -> RQKLSGGSRWCMHL (in
FT isoform 5).
FT /FTId=VSP_005562.
FT VAR_SEQ 116 160 Missing (in isoform 4).
FT /FTId=VSP_005561.
FT VAR_SEQ 119 328 Missing (in isoform 6).
FT /FTId=VSP_005564.
FT VAR_SEQ 193 212 VTGSSGTVKVVVVDSVTAVV -> DGIPEHLNHIPHCLHVH
FT LPC (in isoform 7).
FT /FTId=VSP_005565.
FT VAR_SEQ 213 328 Missing (in isoform 7).
FT /FTId=VSP_005566.
FT VARIANT 24 24 R -> S (in dbSNP:rs28363257).
FT /FTId=VAR_020560.
FT VARIANT 165 165 R -> Q (in dbSNP:rs4796033).
FT /FTId=VAR_020561.
FT VARIANT 225 225 A -> T (in dbSNP:rs28363282).
FT /FTId=VAR_020562.
FT VARIANT 232 232 R -> Q (in dbSNP:rs28363283).
FT /FTId=VAR_020563.
FT VARIANT 233 233 E -> G (in dbSNP:rs28363284).
FT /FTId=VAR_020564.
FT CONFLICT 231 231 A -> V (in Ref. 9; CAB55937).
FT HELIX 14 22
FT HELIX 28 31
FT HELIX 36 43
FT HELIX 47 61
SQ SEQUENCE 328 AA; 35049 MW; 6038DA9356DF354A CRC64;
MGVLRVGLCP GLTEEMIQLL RSHRIKTVVD LVSADLEEVA QKCGLSYKAL VALRRVLLAQ
FSAFPVNGAD LYEELKTSTA ILSTGIGSLD KLLDAGLYTG EVTEIVGGPG SGKTQVCLCM
AANVAHGLQQ NVLYVDSNGG LTASRLLQLL QAKTQDEEEQ AEALRRIQVV HAFDIFQMLD
VLQELRGTVA QQVTGSSGTV KVVVVDSVTA VVSPLLGGQQ REGLALMMQL ARELKTLARD
LGMAVVVTNH ITRDRDSGRL KPALGRSWSF VPSTRILLDT IEGAGASGGR RMACLAKSSR
QPTGFQEMVD IGTWGTSEQS ATLQGDQT
//
ID RA51D_HUMAN Reviewed; 328 AA.
AC O75771; B4DJU7; E1P637; O43537; O60355; O75196; O75847; O75848;
read moreAC O76073; O76085; O94908; Q9UFU5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=DNA repair protein RAD51 homolog 4;
DE AltName: Full=R51H3;
DE AltName: Full=RAD51 homolog D;
DE AltName: Full=RAD51-like protein 3;
DE AltName: Full=TRAD;
GN Name=RAD51D; Synonyms=RAD51L3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9512535; DOI=10.1093/nar/26.7.1653;
RA Cartwright R., Dunn A.M., Simpson P.J., Tambini C.E., Thacker J.;
RT "Isolation of novel human and mouse genes of the recA/RAD51
RT recombination-repair gene family.";
RL Nucleic Acids Res. 26:1653-1659(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9570954; DOI=10.1006/geno.1998.5226;
RA Pittman D.L., Weinberg L.R., Schimenti J.C.;
RT "Identification, characterization, and genetic mapping of Rad51d, a
RT new mouse and human RAD51/RecA-related gene.";
RL Genomics 49:103-111(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS 2; 3;
RP 4; 5; 6 AND 7).
RC TISSUE=Brain;
RX PubMed=10092526; DOI=10.1006/bbrc.1999.0413;
RA Kawabata M., Saeki K.;
RT "Multiple alternative transcripts of the human homologue of the mouse
RT TRAD/R51H3/RAD51D gene, a member of the recA/RAD51 gene family.";
RL Biochem. Biophys. Res. Commun. 257:156-162(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-24; GLN-165;
RP THR-225; GLN-232 AND GLY-233.
RG NIEHS SNPs program;
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 8).
RC TISSUE=Thalamus;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R.,
RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N.,
RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B.,
RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J.,
RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E.,
RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J.,
RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C.,
RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in
RT the human lineage.";
RL Nature 440:1045-1049(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 156-328.
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [10]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND
RP XRCC2.
RX PubMed=11751635; DOI=10.1101/gad.947001;
RA Masson J.Y., Tarsounas M.C., Stasiak A.Z., Stasiak A., Shah R.,
RA McIlwraith M.J., Benson F.E., West S.C.;
RT "Identification and purification of two distinct complexes containing
RT the five RAD51 paralogs.";
RL Genes Dev. 15:3296-3307(2001).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND
RP XRCC2.
RX PubMed=11842113; DOI=10.1093/nar/30.4.1009;
RA Liu N., Schild D., Thelen M.P., Thompson L.H.;
RT "Involvement of Rad51C in two distinct protein complexes of Rad51
RT paralogs in human cells.";
RL Nucleic Acids Res. 30:1009-1015(2002).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D; XRCC2 AND XRCC3.
RX PubMed=11744692; DOI=10.1074/jbc.M108306200;
RA Miller K.A., Yoshikawa D.M., McConnell I.R., Clark R., Schild D.,
RA Albala J.S.;
RT "RAD51C interacts with RAD51B and is central to a larger protein
RT complex in vivo exclusive of RAD51.";
RL J. Biol. Chem. 277:8406-8411(2002).
RN [13]
RP IDENTIFICATION IN A COMPLEX WITH RAD51C; RAD51D AND XRCC2.
RX PubMed=11842112; DOI=10.1093/nar/30.4.1001;
RA Wiese C., Collins D.W., Albala J.S., Thompson L.H., Kronenberg A.,
RA Schild D.;
RT "Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human
RT cells.";
RL Nucleic Acids Res. 30:1001-1008(2002).
RN [14]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [15]
RP INTERACTION WITH ZSWIM7 AND XRCC2.
RX PubMed=16710300; DOI=10.1038/sj.emboj.7601141;
RA Martin V., Chahwan C., Gao H., Blais V., Wohlschlegel J.,
RA Yates J.R. III, McGowan C.H., Russell P.;
RT "Sws1 is a conserved regulator of homologous recombination in
RT eukaryotic cells.";
RL EMBO J. 25:2564-2574(2006).
RN [16]
RP INTERACTION WITH SWSAP1 AND ZSWIM7.
RX PubMed=21965664; DOI=10.1074/jbc.M111.271080;
RA Liu T., Wan L., Wu Y., Chen J., Huang J.;
RT "hSWS1.SWSAP1 is an evolutionarily conserved complex required for
RT efficient homologous recombination repair.";
RL J. Biol. Chem. 286:41758-41766(2011).
RN [17]
RP INVOLVEMENT IN BROVCA4.
RX PubMed=21822267; DOI=10.1038/ng.893;
RA Loveday C., Turnbull C., Ramsay E., Hughes D., Ruark E., Frankum J.R.,
RA Bowden G., Kalmyrzaev B., Warren-Perry M., Snape K., Adlard J.W.,
RA Barwell J., Berg J., Brady A.F., Brewer C., Brice G., Chapman C.,
RA Cook J., Davidson R., Donaldson A., Douglas F., Greenhalgh L.,
RA Henderson A., Izatt L., Kumar A., Lalloo F., Miedzybrodzka Z.,
RA Morrison P.J., Paterson J., Porteous M., Rogers M.T., Shanley S.,
RA Walker L., Eccles D., Evans D.G., Renwick A., Seal S., Lord C.J.,
RA Ashworth A., Reis-Filho J.S., Antoniou A.C., Rahman N.;
RT "Germline mutations in RAD51D confer susceptibility to ovarian
RT cancer.";
RL Nat. Genet. 43:879-882(2011).
RN [18]
RP STRUCTURE BY NMR OF 1-83, AND DNA-BINDING.
RX PubMed=21111057; DOI=10.1016/j.biocel.2010.11.014;
RA Kim Y.M., Choi B.S.;
RT "Structural and functional characterization of the N-terminal domain
RT of human Rad51D.";
RL Int. J. Biochem. Cell Biol. 43:416-422(2011).
CC -!- FUNCTION: Involved in the homologous recombination repair (HRR)
CC pathway of double-stranded DNA breaks arising during DNA
CC replication or induced by DNA-damaging agents. The BCDX2 complex
CC binds single-stranded DNA, single-stranded gaps in duplex DNA and
CC specifically to nicks in duplex DNA.
CC -!- SUBUNIT: Part of a BCDX2 complex consisting of RAD51B, RAD51C,
CC RAD51D and XRCC2. Part of a complex consisting of RAD51B, RAD51C,
CC RAD51D, XRCC2 and XRCC3. Interacts with SWSAP1 and ZSWIM7;
CC involved in homologous recombination repair.
CC -!- INTERACTION:
CC Q6NVH7:SWSAP1; NbExp=2; IntAct=EBI-1055693, EBI-5281637;
CC O43543:XRCC2; NbExp=2; IntAct=EBI-1055693, EBI-3918457;
CC -!- SUBCELLULAR LOCATION: Nucleus (Probable).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1; Synonyms=TRAD;
CC IsoId=O75771-1; Sequence=Displayed;
CC Name=2; Synonyms=TRAD-D1, D2;
CC IsoId=O75771-2; Sequence=VSP_005558, VSP_005559;
CC Note=May be produced at very low levels due to a premature stop
CC codon in the mRNA, leading to nonsense-mediated mRNA decay;
CC Name=3; Synonyms=TRAD-D3;
CC IsoId=O75771-3; Sequence=VSP_005560;
CC Name=4; Synonyms=TRAD-D4;
CC IsoId=O75771-4; Sequence=VSP_005561;
CC Name=5; Synonyms=TRAD-D5;
CC IsoId=O75771-5; Sequence=VSP_005562;
CC Name=6; Synonyms=TRAD-D6, D7;
CC IsoId=O75771-6; Sequence=VSP_005563, VSP_005564;
CC Name=7; Synonyms=TRAD-D8;
CC IsoId=O75771-7; Sequence=VSP_005565, VSP_005566;
CC Name=8;
CC IsoId=O75771-8; Sequence=VSP_043658;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in colon, prostate, spleen, testis,
CC ovary, thymus and small intestine. Weakly expressed in leukocytes.
CC -!- DISEASE: Breast-ovarian cancer, familial, 4 (BROVCA4)
CC [MIM:614291]: A condition associated with familial predisposition
CC to cancer of the breast and ovaries. Characteristic features in
CC affected families are an early age of onset of breast cancer
CC (often before age 50), increased chance of bilateral cancers
CC (cancer that develop in both breasts, or both ovaries,
CC independently), frequent occurrence of breast cancer among men,
CC increased incidence of tumors of other specific organs, such as
CC the prostate. Note=Disease susceptibility is associated with
CC variations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the RecA family. RAD51 subfamily.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad51l3/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RAD51L3ID347ch17q12.html";
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DR EMBL; Y15572; CAA75681.1; -; mRNA.
DR EMBL; AF034956; AAC39719.1; -; mRNA.
DR EMBL; AB013341; BAA25914.1; -; mRNA.
DR EMBL; AB016223; BAA31747.1; -; mRNA.
DR EMBL; AB016224; BAA31748.1; -; mRNA.
DR EMBL; AB016225; BAA31749.1; -; mRNA.
DR EMBL; AB018360; BAA33779.1; -; mRNA.
DR EMBL; AB018361; BAA33780.1; -; mRNA.
DR EMBL; AB018362; BAA33781.1; -; mRNA.
DR EMBL; AB018363; BAA33782.1; -; mRNA.
DR EMBL; AB020412; BAA34690.1; -; mRNA.
DR EMBL; AY623116; AAT38112.1; -; Genomic_DNA.
DR EMBL; AK296241; BAG58959.1; -; mRNA.
DR EMBL; AC022916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471147; EAW80181.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80184.1; -; Genomic_DNA.
DR EMBL; CH471147; EAW80196.1; -; Genomic_DNA.
DR EMBL; BC014422; AAH14422.1; -; mRNA.
DR EMBL; AL117459; CAB55937.1; -; mRNA.
DR PIR; T17247; T17247.
DR RefSeq; NP_001136043.1; NM_001142571.1.
DR RefSeq; NP_002869.3; NM_002878.3.
DR RefSeq; NP_598332.1; NM_133629.2.
DR UniGene; Hs.631757; -.
DR PDB; 2KZ3; NMR; -; A=1-83.
DR PDBsum; 2KZ3; -.
DR ProteinModelPortal; O75771; -.
DR SMR; O75771; 1-304.
DR DIP; DIP-24265N; -.
DR IntAct; O75771; 7.
DR MINT; MINT-127795; -.
DR PhosphoSite; O75771; -.
DR PaxDb; O75771; -.
DR PRIDE; O75771; -.
DR DNASU; 5892; -.
DR Ensembl; ENST00000335858; ENSP00000338408; ENSG00000185379.
DR Ensembl; ENST00000345365; ENSP00000338790; ENSG00000185379.
DR Ensembl; ENST00000357906; ENSP00000350581; ENSG00000185379.
DR Ensembl; ENST00000360276; ENSP00000353417; ENSG00000185379.
DR Ensembl; ENST00000394589; ENSP00000378090; ENSG00000185379.
DR Ensembl; ENST00000586044; ENSP00000465584; ENSG00000185379.
DR Ensembl; ENST00000587977; ENSP00000466587; ENSG00000185379.
DR Ensembl; ENST00000588594; ENSP00000465366; ENSG00000185379.
DR Ensembl; ENST00000590016; ENSP00000466399; ENSG00000185379.
DR GeneID; 5892; -.
DR KEGG; hsa:5892; -.
DR UCSC; uc002hir.2; human.
DR CTD; 5892; -.
DR GeneCards; GC17M033427; -.
DR HGNC; HGNC:9823; RAD51D.
DR MIM; 602954; gene.
DR MIM; 614291; phenotype.
DR neXtProt; NX_O75771; -.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR PharmGKB; PA34179; -.
DR eggNOG; COG0468; -.
DR HOGENOM; HOG000049134; -.
DR HOVERGEN; HBG057455; -.
DR KO; K10871; -.
DR OMA; CSLSYKA; -.
DR PhylomeDB; O75771; -.
DR GeneWiki; RAD51L3; -.
DR GenomeRNAi; 5892; -.
DR NextBio; 22920; -.
DR PRO; PR:O75771; -.
DR ArrayExpress; O75771; -.
DR Bgee; O75771; -.
DR Genevestigator; O75771; -.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; TAS:ProtInc.
DR GO; GO:0008094; F:DNA-dependent ATPase activity; IEA:InterPro.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0007131; P:reciprocal meiotic recombination; TAS:ProtInc.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR013632; DNA_recomb/repair_Rad51_C.
DR InterPro; IPR016467; DNA_recomb/repair_RecA-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR020588; RecA_ATP-bd.
DR Pfam; PF08423; Rad51; 1.
DR PIRSF; PIRSF005856; Rad51; 1.
DR SMART; SM00382; AAA; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50162; RECA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome;
KW DNA damage; DNA recombination; DNA repair; DNA-binding;
KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome.
FT CHAIN 1 328 DNA repair protein RAD51 homolog 4.
FT /FTId=PRO_0000122942.
FT NP_BIND 107 114 ATP (Potential).
FT REGION 1 83 Preferencially binds ssDNA.
FT COMPBIAS 200 205 Poly-Val.
FT VAR_SEQ 49 88 ALVALRRVLLAQFSAFPVNGADLYEELKTSTAILSTGIGS
FT -> TWRAHSSGNLGGLQLPQVPAGRSWSGVRNALKKAGLGH
FT GGTDGLSLNAFDERGTAVSTSR (in isoform 8).
FT /FTId=VSP_043658.
FT VAR_SEQ 49 49 A -> S (in isoform 2).
FT /FTId=VSP_005558.
FT VAR_SEQ 50 328 Missing (in isoform 2).
FT /FTId=VSP_005559.
FT VAR_SEQ 50 161 Missing (in isoform 3).
FT /FTId=VSP_005560.
FT VAR_SEQ 88 118 SLDKLLDAGLYTGEVTEIVGGPGSGKTQVCL -> RHGGRT
FT QVGTWEDCSCLRSPQGDRGVGSGML (in isoform 6).
FT /FTId=VSP_005563.
FT VAR_SEQ 88 101 SLDKLLDAGLYTGE -> RQKLSGGSRWCMHL (in
FT isoform 5).
FT /FTId=VSP_005562.
FT VAR_SEQ 116 160 Missing (in isoform 4).
FT /FTId=VSP_005561.
FT VAR_SEQ 119 328 Missing (in isoform 6).
FT /FTId=VSP_005564.
FT VAR_SEQ 193 212 VTGSSGTVKVVVVDSVTAVV -> DGIPEHLNHIPHCLHVH
FT LPC (in isoform 7).
FT /FTId=VSP_005565.
FT VAR_SEQ 213 328 Missing (in isoform 7).
FT /FTId=VSP_005566.
FT VARIANT 24 24 R -> S (in dbSNP:rs28363257).
FT /FTId=VAR_020560.
FT VARIANT 165 165 R -> Q (in dbSNP:rs4796033).
FT /FTId=VAR_020561.
FT VARIANT 225 225 A -> T (in dbSNP:rs28363282).
FT /FTId=VAR_020562.
FT VARIANT 232 232 R -> Q (in dbSNP:rs28363283).
FT /FTId=VAR_020563.
FT VARIANT 233 233 E -> G (in dbSNP:rs28363284).
FT /FTId=VAR_020564.
FT CONFLICT 231 231 A -> V (in Ref. 9; CAB55937).
FT HELIX 14 22
FT HELIX 28 31
FT HELIX 36 43
FT HELIX 47 61
SQ SEQUENCE 328 AA; 35049 MW; 6038DA9356DF354A CRC64;
MGVLRVGLCP GLTEEMIQLL RSHRIKTVVD LVSADLEEVA QKCGLSYKAL VALRRVLLAQ
FSAFPVNGAD LYEELKTSTA ILSTGIGSLD KLLDAGLYTG EVTEIVGGPG SGKTQVCLCM
AANVAHGLQQ NVLYVDSNGG LTASRLLQLL QAKTQDEEEQ AEALRRIQVV HAFDIFQMLD
VLQELRGTVA QQVTGSSGTV KVVVVDSVTA VVSPLLGGQQ REGLALMMQL ARELKTLARD
LGMAVVVTNH ITRDRDSGRL KPALGRSWSF VPSTRILLDT IEGAGASGGR RMACLAKSSR
QPTGFQEMVD IGTWGTSEQS ATLQGDQT
//
MIM
602954
*RECORD*
*FIELD* NO
602954
*FIELD* TI
*602954 RAD51, S. CEREVISIAE, HOMOLOG OF, D; RAD51D
;;S. CEREVISIAE RAD51-LIKE 3; RAD51L3;;
read moreTRAD
*FIELD* TX
CLONING
The S. cerevisiae gene RAD51, which encodes a protein related to the
ATP-binding E. coli RecA protein, is critical for DNA repair and meiotic
recombination. Homologs of this gene have been identified in several
species, including mouse and human. Pittman et al. (1998) reported the
identification of a novel member of the RAD51 gene family in both mouse
and human. The mouse cDNA, Rad51d, isolated by screening EST databases
with yeast RAD55 and human RAD51B amino acid sequences, encodes a
predicted 329-amino acid protein with a molecular mass of 35,260 Da.
Northern blot analysis revealed the presence of multiple transcripts of
the Rad51d gene in all tissues examined. Southern analysis of genomic
DNA from 7 mammalian species demonstrated that the RAD51D gene is
conserved. Pittman et al. (1998) used the mouse nucleotide sequence to
screen a human EST database and identified 2 RAD51D cDNA clones from
human T-lymphocyte and placenta libraries; both cDNAs appeared to be
variants of the mouse gene. The shorter cDNA represented an
alternatively spliced product and excluded sequences corresponding to 2
exons in the mouse gene, one of which encodes the first ATP-binding
motif. The longer cDNA skipped a single exon present in the mouse gene,
resulting in a frameshift and a predicted truncated protein. The authors
stated that if the frameshift is ignored, the full-length putative
289-amino acid protein shares 71% sequence identity with the predicted
mouse protein, and the mouse and human RAD51D genes have 2 conserved
ATP-binding domains similar to other RecA-related genes.
Cartwright et al. (1998) also isolated human and mouse RAD51L3, or
R51H3, cDNAs. They found that the sequence of the predicted 328-amino
acid human protein is 82% identical to that of mouse RAD51L3. Northern
blot analysis revealed that human RAD51L3 is expressed as a 1.7-kb mRNA
in all tissues, with the highest levels in testis.
Kawabata and Saeki (1999) cloned RAD51L3, which they called TRAD, from a
placenta cDNA library based on sequence similarity with the mouse gene.
They obtained the full-length cDNA by PCR of adult and fetal brain cDNA
libraries. The deduced 328-amino acid protein contains both A and B
nucleotide-binding motifs and shares 83% sequence identity with the
mouse protein. Kawabata and Saeki (1999) also identified several
truncated variants, 1 of which lacks the nucleotide-binding sites, that
result from exon skipping. Northern blot analysis revealed a 7.0-bp
transcript in colon and prostate, a 4.8-kb transcript in spleen, colon,
prostate, testis, and ovary, and 1.4-, 1.8-, and 2.5-kb transcripts in
testis, spleen, thymus, prostate, ovary, small intestine, and colon. All
transcripts were expressed at low levels in leukocytes.
GENE FUNCTION
Braybrooke et al. (2000) confirmed the binding and hydrolysis of ATP by
recombinant RAD51L3 in the presence of Mg(2+). Single-stranded DNA was a
more efficient cofactor than double-stranded DNA. They determined that
the binding of DNA to RAD51L3 was sequence- and Mg(2+)-independent.
Using a yeast 2-hybrid assay, Braybrooke et al. (2000) identified a
direct interaction between XRCC2 (600375) and RAD51L3, and they
confirmed the interaction by pull-down assays between recombinant XRCC2
and endogenous RAD51L3 in HeLa cell extracts. Size-exclusion
chromatography followed by Western blot analysis suggested that the 2
proteins exist as a heterodimer of about 70 kD.
Masson et al. (2001) found that antibody directed against RAD51L3
immunoprecipitated a complex from HeLa cell lysates that included XRCC2,
RAD51B (RAD51L1; 602948), and RAD51C (602774), along with endogenous
RAD51L3. Interactions between these proteins were confirmed in pull-down
assays using recombinant proteins expressed in sf9 insect cells. Gel
filtration of the complexes indicated an apparent molecular mass of
about 180 kD, suggesting a 1:1:1:1 stoichiometry of the 4 subunits.
Binding assays, confirmed by electron microscopy, indicated that the
purified complex bound single-stranded or nicked DNA. This binding was
dependent on Mg(2+) but independent of ATP. The DNA-stimulated ATPase
activity of the complex was extremely low. Masson et al. (2001) also
identified a second, heterodimeric protein complex between RAD51C and
XRCC3 (600675). Using coprecipitation and multiple pull-down assays, Liu
et al. (2002) confirmed interaction between the same RAD51 paralogs in
the same 2 distinct protein complexes.
In a yeast 2-hybrid screen of a human brain cDNA library using XRCC2 as
bait, Kurumizaka et al. (2002) found that RAD51L3 interacts directly
with XRCC2. Using a D-loop formation assay, they found that RAD51L3 and
XRCC2, coexpressed and purified from bacterial cultures, catalyze
homologous pairing between a single-stranded oligonucleotide and a
superhelical double-stranded DNA. Significant single- and
double-stranded DNA were bound by the complex in the absence of ATP, but
homologous pairing was dependent on ATP and Mg(2+). By electron
microscopy, they found that RAD51L3 and XRCC2 form a multimeric ring
structure in the absence of DNA, and they form filamentous structures in
the presence of single-stranded DNA.
Tarsounas et al. (2004) reported that RAD51D is involved in telomere
maintenance. Using immunofluorescence labeling, electron microscopy, and
chromatin immunoprecipitation assays, they localized RAD51D to the
telomeres of both meiotic and somatic cells. Telomerase (see
187270)-positive Rad51d -/- Trp53 (191170) -/- primary mouse embryonic
fibroblasts (MEFs) exhibited telomeric DNA repeat shortening compared
with Trp53 -/- or wildtype MEFs. Moreover, elevated levels of
chromosomal aberrations were detected, including telomeric end-to-end
fusions, a signature of telomere dysfunction. Inhibition of RAD51D
synthesis in telomerase-negative immortalized human cells by small
interfering RNA also resulted in telomere erosion and chromosome fusion.
Tarsounas et al. (2004) concluded that RAD51D plays a dual cellular role
in both the repair of DNA double-strand breaks and telomere protection
against attrition and fusion.
Adelman et al. (2013) reported that Helq (606769) helicase-deficient
mice exhibit subfertility, germ cell attrition, interstrand crosslink
(ICL) sensitivity, and tumor predisposition, with Helq heterozygous mice
exhibiting a similar, albeit less severe, phenotype than the null,
indicative of haploinsufficiency. Adelman et al. (2013) established that
HELQ interacts directly with the RAD51 paralog complex BCDX2 (RAD51B,
RAD51C, RAD51D, and XRCC2) and functions in parallel to the Fanconi
anemia pathway to promote efficient homologous recombination at damaged
replication forks. Adelman et al. (2013) concluded that their results
revealed a critical role for HELQ in replication-coupled DNA repair,
germ cell maintenance, and tumor suppression in mammals.
MAPPING
By radiation hybrid mapping, Pittman et al. (1998) assigned the RAD51D
gene to chromosome 17q11, in a region showing homology of synteny to
mouse chromosome 11. By interspecific backcross mapping, Pittman et al.
(1998) mapped the mouse Rad51d gene to chromosome 11.
MOLECULAR GENETICS
Loveday et al. (2011) identified nonsense, frameshift, and missense
mutations in the RAD51D gene in 8 unrelated probands from 911
breast-ovarian cancer families. None of the mutations was found among
1,060 controls, although one different frameshift mutation was found.
*FIELD* AV
.0001
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, 1-BP DEL, 363A
In a family with breast-ovarian cancer (614291) in which the proband had
bilateral breast cancer, the first at age 34 and the second at age 52,
Loveday et al. (2011) identified deletion of an adenine at position 363
of the RAD51D gene (363delA). The proband's cancers were both grade 3
invasive ductal carcinoma, and tumor analysis identified loss of the
wildtype allele in one. This mutation was not identified in 1,060
controls.
.0002
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, TRP268TER
In a 3-generation family segregating ovarian cancer and breast cancer
(614291), Loveday et al. (2011) identified a G-to-A transition at
nucleotide 803 of the RAD51D gene, resulting in a trp-to-ter
substitution at codon 268 (W268X). The proband had bilateral serous
adenocarcinoma of the ovaries. The mutation was not identified in 1,060
controls.
.0003
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, ARG186TER
In a 3-generation pedigree segregating ovarian cancer and breast cancer
(614291), Loveday et al. (2011) identified a C-to-T transition at
nucleotide 556 in the RAD51D gene, resulting in an arg-to-ter
substitution at codon 186 (R186X). The proband had ovarian cancer at age
38. Her sister had breast cancer at age 39, a high-grade ductal comedo
carcinoma in situ. An aunt had breast cancer at age 58 that was
characterized as an invasive carcinoma with medullary features. Another
aunt had breast cancer at age 53 that was described as an invasive
ductal carcinoma of no special type, grade 3. There were 4 other
individuals who had died of ovarian cancer ranging in age from 49 to 65
years in whom no molecular testing could be done. This mutation was not
identified in 1,060 controls.
.0004
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, NT480, G-A, +1
In a 3-generation family segregating breast and ovarian cancer (614291),
Loveday et al. (2011) identified a splice site mutation in the RAD51D
gene, 480+1G-A. The proband was a 51-year-old female with invasive
ductal carcinoma of no special type, grade 3. A niece had breast cancer
and an aunt had ovarian cancer.
.0005
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, GLN115HIS
In a 3-generation family segregating breast and ovarian cancer (614291),
Loveday et al. (2011) identified a G-to-C transition at nucleotide 345
of the RAD51D gene, resulting in a gln-to-his substitution at codon 115
(Q115H). This mutation occurs at the final base of exon 4 and disrupts
the splice site and results in skipping of exons 3 and 4. The
45-year-old proband and her 74-year-old aunt had bilateral serous
adenocarcinoma of the ovaries.
.0006
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, ARG253TER
In a family with breast and ovarian cancer (614291) in which 1 sib had
ovarian cancer at the age of 51 and another had breast cancer at the age
of 47, Loveday et al. (2011) identified a C-to-T transition at
nucleotide 757 of the RAD51D gene, resulting in an arg-to-ter codon
substitution at codon 253 (R253X). The ovarian cancer was a
differentiated endometrioid adenocarcinoma.
*FIELD* RF
1. Adelman, C. A.; Lolo, R. L.; Birkbak, N. J.; Murina, O.; Matsuzaki,
K.; Horejsi, Z.; Parmar, K.; Borel, V.; Skehel, J. M.; Stamp, G.;
D'Andrea, A.; Sartori, A. A.; Swanton, C.; Boulton, S. J.: HELQ promotes
RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis. Nature 502:
381-384, 2013.
2. Braybrooke, J. P.; Spink, K. G.; Thacker, J.; Hickson, I. D.:
The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that
forms a complex with XRCC2. J. Biol. Chem. 275: 29100-29106, 2000.
3. Cartwright, R.; Dunn, A. M.; Simpson, P. J.; Tambini, C. E.; Thacker,
J.: Isolation of novel human and mouse genes of the recA/RAD51 recombination-repair
gene family. Nucleic Acids Res. 26: 1653-1659, 1998.
4. Kawabata, M.; Saeki, K.: Multiple alternative transcripts of the
human homologue of the mouse TRAD/R51H3/RAD51D gene, a member of the
rec A/RAD51 gene family. Biochem. Biophys. Res. Commun. 257: 156-162,
1999.
5. Kurumizaka, H.; Ikawa, S.; Nakada, M.; Enomoto, R.; Kagawa, W.;
Kinebuchi, T.; Yamazoe, M.; Yokoyama, S.; Shibata, T.: Homologous
pairing and ring and filament structure formation activities of the
human Xrcc2-Rad51D complex. J. Biol. Chem. 277: 14315-14320, 2002.
6. Liu, N.; Schild, D.; Thelen, M. P.; Thompson, L. H.: Involvement
of Rad51C in two distinct protein complexes of Rad51 paralogs in human
cells. Nucleic Acids Res. 30: 1009-1015, 2002.
7. Loveday, C.; Turnbull, C.; Ramsay, E.; Hughes, D.; Ruark, E.; Frankum,
J. R.; Bowden, G.; Kalmyrzaev, B.; Warren-Perry, M.; Snape, K.; Adlard,
J. W.; Barwell, J.; and 31 others Germline mutations in RAD51D
confer susceptibility to ovarian cancer. Nature Genet. 43: 879-882,
2011.
8. Masson, J.-Y.; Tarsounas, M. C.; Stasiak, A. Z.; Stasiak, A.; Shah,
R.; McIlwraith, M. J.; Benson, F. E.; West, S. C.: Identification
and purification of two distinct complexes containing the five RAD51
paralogs. Genes Dev. 15: 3296-3307, 2001.
9. Pittman, D. L.; Weinberg, L. R.; Schimenti, J. C.: Identification,
characterization, and genetic mapping of Rad51d, a new mouse and human
RAD51/RecA-related gene. Genomics 49: 103-111, 1998.
10. Tarsounas, M.; Munoz, P.; Claas, A.; Smiraldo, P. G.; Pittman,
D. L.; Blasco, M. A.; West, S. C.: Telomere maintenance requires
the RAD51D recombination/repair protein. Cell 117: 337-347, 2004.
*FIELD* CN
Ada Hamosh - updated: 12/04/2013
Ada Hamosh - updated: 10/7/2011
Stylianos E. Antonarakis - updated: 6/9/2004
Patricia A. Hartz - updated: 8/21/2002
Rebekah S. Rasooly - updated: 9/30/1998
*FIELD* CD
Sheryl A. Jankowski: 8/10/1998
*FIELD* ED
alopez: 12/04/2013
alopez: 10/17/2011
terry: 10/7/2011
mgross: 6/9/2004
mgross: 8/21/2002
alopez: 9/30/1998
carol: 8/10/1998
*RECORD*
*FIELD* NO
602954
*FIELD* TI
*602954 RAD51, S. CEREVISIAE, HOMOLOG OF, D; RAD51D
;;S. CEREVISIAE RAD51-LIKE 3; RAD51L3;;
read moreTRAD
*FIELD* TX
CLONING
The S. cerevisiae gene RAD51, which encodes a protein related to the
ATP-binding E. coli RecA protein, is critical for DNA repair and meiotic
recombination. Homologs of this gene have been identified in several
species, including mouse and human. Pittman et al. (1998) reported the
identification of a novel member of the RAD51 gene family in both mouse
and human. The mouse cDNA, Rad51d, isolated by screening EST databases
with yeast RAD55 and human RAD51B amino acid sequences, encodes a
predicted 329-amino acid protein with a molecular mass of 35,260 Da.
Northern blot analysis revealed the presence of multiple transcripts of
the Rad51d gene in all tissues examined. Southern analysis of genomic
DNA from 7 mammalian species demonstrated that the RAD51D gene is
conserved. Pittman et al. (1998) used the mouse nucleotide sequence to
screen a human EST database and identified 2 RAD51D cDNA clones from
human T-lymphocyte and placenta libraries; both cDNAs appeared to be
variants of the mouse gene. The shorter cDNA represented an
alternatively spliced product and excluded sequences corresponding to 2
exons in the mouse gene, one of which encodes the first ATP-binding
motif. The longer cDNA skipped a single exon present in the mouse gene,
resulting in a frameshift and a predicted truncated protein. The authors
stated that if the frameshift is ignored, the full-length putative
289-amino acid protein shares 71% sequence identity with the predicted
mouse protein, and the mouse and human RAD51D genes have 2 conserved
ATP-binding domains similar to other RecA-related genes.
Cartwright et al. (1998) also isolated human and mouse RAD51L3, or
R51H3, cDNAs. They found that the sequence of the predicted 328-amino
acid human protein is 82% identical to that of mouse RAD51L3. Northern
blot analysis revealed that human RAD51L3 is expressed as a 1.7-kb mRNA
in all tissues, with the highest levels in testis.
Kawabata and Saeki (1999) cloned RAD51L3, which they called TRAD, from a
placenta cDNA library based on sequence similarity with the mouse gene.
They obtained the full-length cDNA by PCR of adult and fetal brain cDNA
libraries. The deduced 328-amino acid protein contains both A and B
nucleotide-binding motifs and shares 83% sequence identity with the
mouse protein. Kawabata and Saeki (1999) also identified several
truncated variants, 1 of which lacks the nucleotide-binding sites, that
result from exon skipping. Northern blot analysis revealed a 7.0-bp
transcript in colon and prostate, a 4.8-kb transcript in spleen, colon,
prostate, testis, and ovary, and 1.4-, 1.8-, and 2.5-kb transcripts in
testis, spleen, thymus, prostate, ovary, small intestine, and colon. All
transcripts were expressed at low levels in leukocytes.
GENE FUNCTION
Braybrooke et al. (2000) confirmed the binding and hydrolysis of ATP by
recombinant RAD51L3 in the presence of Mg(2+). Single-stranded DNA was a
more efficient cofactor than double-stranded DNA. They determined that
the binding of DNA to RAD51L3 was sequence- and Mg(2+)-independent.
Using a yeast 2-hybrid assay, Braybrooke et al. (2000) identified a
direct interaction between XRCC2 (600375) and RAD51L3, and they
confirmed the interaction by pull-down assays between recombinant XRCC2
and endogenous RAD51L3 in HeLa cell extracts. Size-exclusion
chromatography followed by Western blot analysis suggested that the 2
proteins exist as a heterodimer of about 70 kD.
Masson et al. (2001) found that antibody directed against RAD51L3
immunoprecipitated a complex from HeLa cell lysates that included XRCC2,
RAD51B (RAD51L1; 602948), and RAD51C (602774), along with endogenous
RAD51L3. Interactions between these proteins were confirmed in pull-down
assays using recombinant proteins expressed in sf9 insect cells. Gel
filtration of the complexes indicated an apparent molecular mass of
about 180 kD, suggesting a 1:1:1:1 stoichiometry of the 4 subunits.
Binding assays, confirmed by electron microscopy, indicated that the
purified complex bound single-stranded or nicked DNA. This binding was
dependent on Mg(2+) but independent of ATP. The DNA-stimulated ATPase
activity of the complex was extremely low. Masson et al. (2001) also
identified a second, heterodimeric protein complex between RAD51C and
XRCC3 (600675). Using coprecipitation and multiple pull-down assays, Liu
et al. (2002) confirmed interaction between the same RAD51 paralogs in
the same 2 distinct protein complexes.
In a yeast 2-hybrid screen of a human brain cDNA library using XRCC2 as
bait, Kurumizaka et al. (2002) found that RAD51L3 interacts directly
with XRCC2. Using a D-loop formation assay, they found that RAD51L3 and
XRCC2, coexpressed and purified from bacterial cultures, catalyze
homologous pairing between a single-stranded oligonucleotide and a
superhelical double-stranded DNA. Significant single- and
double-stranded DNA were bound by the complex in the absence of ATP, but
homologous pairing was dependent on ATP and Mg(2+). By electron
microscopy, they found that RAD51L3 and XRCC2 form a multimeric ring
structure in the absence of DNA, and they form filamentous structures in
the presence of single-stranded DNA.
Tarsounas et al. (2004) reported that RAD51D is involved in telomere
maintenance. Using immunofluorescence labeling, electron microscopy, and
chromatin immunoprecipitation assays, they localized RAD51D to the
telomeres of both meiotic and somatic cells. Telomerase (see
187270)-positive Rad51d -/- Trp53 (191170) -/- primary mouse embryonic
fibroblasts (MEFs) exhibited telomeric DNA repeat shortening compared
with Trp53 -/- or wildtype MEFs. Moreover, elevated levels of
chromosomal aberrations were detected, including telomeric end-to-end
fusions, a signature of telomere dysfunction. Inhibition of RAD51D
synthesis in telomerase-negative immortalized human cells by small
interfering RNA also resulted in telomere erosion and chromosome fusion.
Tarsounas et al. (2004) concluded that RAD51D plays a dual cellular role
in both the repair of DNA double-strand breaks and telomere protection
against attrition and fusion.
Adelman et al. (2013) reported that Helq (606769) helicase-deficient
mice exhibit subfertility, germ cell attrition, interstrand crosslink
(ICL) sensitivity, and tumor predisposition, with Helq heterozygous mice
exhibiting a similar, albeit less severe, phenotype than the null,
indicative of haploinsufficiency. Adelman et al. (2013) established that
HELQ interacts directly with the RAD51 paralog complex BCDX2 (RAD51B,
RAD51C, RAD51D, and XRCC2) and functions in parallel to the Fanconi
anemia pathway to promote efficient homologous recombination at damaged
replication forks. Adelman et al. (2013) concluded that their results
revealed a critical role for HELQ in replication-coupled DNA repair,
germ cell maintenance, and tumor suppression in mammals.
MAPPING
By radiation hybrid mapping, Pittman et al. (1998) assigned the RAD51D
gene to chromosome 17q11, in a region showing homology of synteny to
mouse chromosome 11. By interspecific backcross mapping, Pittman et al.
(1998) mapped the mouse Rad51d gene to chromosome 11.
MOLECULAR GENETICS
Loveday et al. (2011) identified nonsense, frameshift, and missense
mutations in the RAD51D gene in 8 unrelated probands from 911
breast-ovarian cancer families. None of the mutations was found among
1,060 controls, although one different frameshift mutation was found.
*FIELD* AV
.0001
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, 1-BP DEL, 363A
In a family with breast-ovarian cancer (614291) in which the proband had
bilateral breast cancer, the first at age 34 and the second at age 52,
Loveday et al. (2011) identified deletion of an adenine at position 363
of the RAD51D gene (363delA). The proband's cancers were both grade 3
invasive ductal carcinoma, and tumor analysis identified loss of the
wildtype allele in one. This mutation was not identified in 1,060
controls.
.0002
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, TRP268TER
In a 3-generation family segregating ovarian cancer and breast cancer
(614291), Loveday et al. (2011) identified a G-to-A transition at
nucleotide 803 of the RAD51D gene, resulting in a trp-to-ter
substitution at codon 268 (W268X). The proband had bilateral serous
adenocarcinoma of the ovaries. The mutation was not identified in 1,060
controls.
.0003
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, ARG186TER
In a 3-generation pedigree segregating ovarian cancer and breast cancer
(614291), Loveday et al. (2011) identified a C-to-T transition at
nucleotide 556 in the RAD51D gene, resulting in an arg-to-ter
substitution at codon 186 (R186X). The proband had ovarian cancer at age
38. Her sister had breast cancer at age 39, a high-grade ductal comedo
carcinoma in situ. An aunt had breast cancer at age 58 that was
characterized as an invasive carcinoma with medullary features. Another
aunt had breast cancer at age 53 that was described as an invasive
ductal carcinoma of no special type, grade 3. There were 4 other
individuals who had died of ovarian cancer ranging in age from 49 to 65
years in whom no molecular testing could be done. This mutation was not
identified in 1,060 controls.
.0004
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, NT480, G-A, +1
In a 3-generation family segregating breast and ovarian cancer (614291),
Loveday et al. (2011) identified a splice site mutation in the RAD51D
gene, 480+1G-A. The proband was a 51-year-old female with invasive
ductal carcinoma of no special type, grade 3. A niece had breast cancer
and an aunt had ovarian cancer.
.0005
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, GLN115HIS
In a 3-generation family segregating breast and ovarian cancer (614291),
Loveday et al. (2011) identified a G-to-C transition at nucleotide 345
of the RAD51D gene, resulting in a gln-to-his substitution at codon 115
(Q115H). This mutation occurs at the final base of exon 4 and disrupts
the splice site and results in skipping of exons 3 and 4. The
45-year-old proband and her 74-year-old aunt had bilateral serous
adenocarcinoma of the ovaries.
.0006
BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4
RAD51D, ARG253TER
In a family with breast and ovarian cancer (614291) in which 1 sib had
ovarian cancer at the age of 51 and another had breast cancer at the age
of 47, Loveday et al. (2011) identified a C-to-T transition at
nucleotide 757 of the RAD51D gene, resulting in an arg-to-ter codon
substitution at codon 253 (R253X). The ovarian cancer was a
differentiated endometrioid adenocarcinoma.
*FIELD* RF
1. Adelman, C. A.; Lolo, R. L.; Birkbak, N. J.; Murina, O.; Matsuzaki,
K.; Horejsi, Z.; Parmar, K.; Borel, V.; Skehel, J. M.; Stamp, G.;
D'Andrea, A.; Sartori, A. A.; Swanton, C.; Boulton, S. J.: HELQ promotes
RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis. Nature 502:
381-384, 2013.
2. Braybrooke, J. P.; Spink, K. G.; Thacker, J.; Hickson, I. D.:
The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that
forms a complex with XRCC2. J. Biol. Chem. 275: 29100-29106, 2000.
3. Cartwright, R.; Dunn, A. M.; Simpson, P. J.; Tambini, C. E.; Thacker,
J.: Isolation of novel human and mouse genes of the recA/RAD51 recombination-repair
gene family. Nucleic Acids Res. 26: 1653-1659, 1998.
4. Kawabata, M.; Saeki, K.: Multiple alternative transcripts of the
human homologue of the mouse TRAD/R51H3/RAD51D gene, a member of the
rec A/RAD51 gene family. Biochem. Biophys. Res. Commun. 257: 156-162,
1999.
5. Kurumizaka, H.; Ikawa, S.; Nakada, M.; Enomoto, R.; Kagawa, W.;
Kinebuchi, T.; Yamazoe, M.; Yokoyama, S.; Shibata, T.: Homologous
pairing and ring and filament structure formation activities of the
human Xrcc2-Rad51D complex. J. Biol. Chem. 277: 14315-14320, 2002.
6. Liu, N.; Schild, D.; Thelen, M. P.; Thompson, L. H.: Involvement
of Rad51C in two distinct protein complexes of Rad51 paralogs in human
cells. Nucleic Acids Res. 30: 1009-1015, 2002.
7. Loveday, C.; Turnbull, C.; Ramsay, E.; Hughes, D.; Ruark, E.; Frankum,
J. R.; Bowden, G.; Kalmyrzaev, B.; Warren-Perry, M.; Snape, K.; Adlard,
J. W.; Barwell, J.; and 31 others Germline mutations in RAD51D
confer susceptibility to ovarian cancer. Nature Genet. 43: 879-882,
2011.
8. Masson, J.-Y.; Tarsounas, M. C.; Stasiak, A. Z.; Stasiak, A.; Shah,
R.; McIlwraith, M. J.; Benson, F. E.; West, S. C.: Identification
and purification of two distinct complexes containing the five RAD51
paralogs. Genes Dev. 15: 3296-3307, 2001.
9. Pittman, D. L.; Weinberg, L. R.; Schimenti, J. C.: Identification,
characterization, and genetic mapping of Rad51d, a new mouse and human
RAD51/RecA-related gene. Genomics 49: 103-111, 1998.
10. Tarsounas, M.; Munoz, P.; Claas, A.; Smiraldo, P. G.; Pittman,
D. L.; Blasco, M. A.; West, S. C.: Telomere maintenance requires
the RAD51D recombination/repair protein. Cell 117: 337-347, 2004.
*FIELD* CN
Ada Hamosh - updated: 12/04/2013
Ada Hamosh - updated: 10/7/2011
Stylianos E. Antonarakis - updated: 6/9/2004
Patricia A. Hartz - updated: 8/21/2002
Rebekah S. Rasooly - updated: 9/30/1998
*FIELD* CD
Sheryl A. Jankowski: 8/10/1998
*FIELD* ED
alopez: 12/04/2013
alopez: 10/17/2011
terry: 10/7/2011
mgross: 6/9/2004
mgross: 8/21/2002
alopez: 9/30/1998
carol: 8/10/1998
MIM
614291
*RECORD*
*FIELD* NO
614291
*FIELD* TI
#614291 BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4; BROVCA4
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moresusceptibility to familial breast-ovarian cancer-4 (BROVCA4) results
from heterozygous germline mutation in the RAD51D gene (602954) on
chromosome 17q11.
For a discussion of genetic heterogeneity of breast-ovarian cancer
susceptibility, see BROVCA1 (604370).
For general discussions of breast cancer and ovarian cancer, see 114480
and 167000, respectively.
CLINICAL FEATURES
Loveday et al. (2011) identified 8 families with breast-ovarian cancer
associated with mutation in the RAD51D gene. Pathology information was
available for 4 ovarian cancers from RAD51D mutation carriers; 3 of the
cancers were serous adenocarcinoma and 1 was an endometrioid cancer. Of
8 breast cancers for which pathologic information was available, 7 were
ductal in origin and 1 was a carcinoma with medullary features. Receptor
status was available from 5 breast cancers, of which 3 were
estrogen-receptor (see 133430)-positive and 2 negative.
MOLECULAR GENETICS
Loveday et al. (2011) investigated the role of RAD51D in cancer
susceptibility and identified 8 inactivating RAD51D mutations in
unrelated individuals from 911 breast-ovarian cancer families compared
with 1 inactivating mutation identified in 1,060 controls (P = 0.01).
The association was found principally with ovarian cancer, with 3
mutations identified in the 59 pedigrees with 3 or more individuals with
ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for
RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P
= 4.8 x 10(-6)). By contrast, Loveday et al. (2011) estimated the
relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50).
Loveday et al. (2011) concluded that RAD51D mutation testing may have
clinical utility in individuals with ovarian cancer and their families.
They also demonstrated that cells deficient in RAD51D are sensitive to
treatment with a PARP (173870) inhibitor, suggesting a possible
therapeutic approach for cancers arising in RAD51D mutation carriers.
Loveday et al. (2011) identified nonsense, frameshift, and missense
mutations in RAD51D patients with a family history of breast and
predominantly ovarian cancer (e.g., 602954.0001).
*FIELD* RF
1. Loveday, C.; Turnbull, C.; Ramsay, E.; Hughes, D.; Ruark, E.; Frankum,
J. R.; Bowden, G.; Kalmyrzaev, B.; Warren-Perry, M.; Snape, K.; Adlard,
J. W.; Barwell, J.; and 31 others Germline mutations in RAD51D
confer susceptibility to ovarian cancer. Nature Genet. 43: 879-882,
2011.
*FIELD* CD
Ada Hamosh: 10/13/2011
*FIELD* ED
alopez: 10/17/2011
*RECORD*
*FIELD* NO
614291
*FIELD* TI
#614291 BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 4; BROVCA4
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moresusceptibility to familial breast-ovarian cancer-4 (BROVCA4) results
from heterozygous germline mutation in the RAD51D gene (602954) on
chromosome 17q11.
For a discussion of genetic heterogeneity of breast-ovarian cancer
susceptibility, see BROVCA1 (604370).
For general discussions of breast cancer and ovarian cancer, see 114480
and 167000, respectively.
CLINICAL FEATURES
Loveday et al. (2011) identified 8 families with breast-ovarian cancer
associated with mutation in the RAD51D gene. Pathology information was
available for 4 ovarian cancers from RAD51D mutation carriers; 3 of the
cancers were serous adenocarcinoma and 1 was an endometrioid cancer. Of
8 breast cancers for which pathologic information was available, 7 were
ductal in origin and 1 was a carcinoma with medullary features. Receptor
status was available from 5 breast cancers, of which 3 were
estrogen-receptor (see 133430)-positive and 2 negative.
MOLECULAR GENETICS
Loveday et al. (2011) investigated the role of RAD51D in cancer
susceptibility and identified 8 inactivating RAD51D mutations in
unrelated individuals from 911 breast-ovarian cancer families compared
with 1 inactivating mutation identified in 1,060 controls (P = 0.01).
The association was found principally with ovarian cancer, with 3
mutations identified in the 59 pedigrees with 3 or more individuals with
ovarian cancer (P = 0.0005). The relative risk of ovarian cancer for
RAD51D mutation carriers was estimated to be 6.30 (95% CI 2.86-13.85, P
= 4.8 x 10(-6)). By contrast, Loveday et al. (2011) estimated the
relative risk of breast cancer to be 1.32 (95% CI 0.59-2.96, P = 0.50).
Loveday et al. (2011) concluded that RAD51D mutation testing may have
clinical utility in individuals with ovarian cancer and their families.
They also demonstrated that cells deficient in RAD51D are sensitive to
treatment with a PARP (173870) inhibitor, suggesting a possible
therapeutic approach for cancers arising in RAD51D mutation carriers.
Loveday et al. (2011) identified nonsense, frameshift, and missense
mutations in RAD51D patients with a family history of breast and
predominantly ovarian cancer (e.g., 602954.0001).
*FIELD* RF
1. Loveday, C.; Turnbull, C.; Ramsay, E.; Hughes, D.; Ruark, E.; Frankum,
J. R.; Bowden, G.; Kalmyrzaev, B.; Warren-Perry, M.; Snape, K.; Adlard,
J. W.; Barwell, J.; and 31 others Germline mutations in RAD51D
confer susceptibility to ovarian cancer. Nature Genet. 43: 879-882,
2011.
*FIELD* CD
Ada Hamosh: 10/13/2011
*FIELD* ED
alopez: 10/17/2011