PALB2_HUMAN
ID PALB2_HUMAN Reviewed; 1186 AA.
AC Q86YC2; A6NIE1; Q8N7Y6; Q8ND31; Q9H6W1;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Partner and localizer of BRCA2;
GN Name=PALB2; Synonyms=FANCN;
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=Endometrium;
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., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
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].
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].
RC TISSUE=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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-440 AND 476-1186.
RC TISSUE=Testis;
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 [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH BRCA2.
RX PubMed=16793542; DOI=10.1016/j.molcel.2006.05.022;
RA Xia B., Sheng Q., Nakanishi K., Ohashi A., Wu J., Christ N., Liu X.,
RA Jasin M., Couch F.J., Livingston D.M.;
RT "Control of BRCA2 cellular and clinical functions by a nuclear partner,
RT PALB2.";
RL Mol. Cell 22:719-729(2006).
RN [7]
RP INVOLVEMENT IN SUSCEPTIBILITY TO BREAST CANCER.
RX PubMed=17287723; DOI=10.1038/nature05609;
RA Erkko H., Xia B., Nikkilae J., Schleutker J., Syrjaekoski K., Mannermaa A.,
RA Kallioniemi A., Pylkaes K., Karppinen S.-M., Rapakko K., Miron A.,
RA Sheng Q., Li G., Mattila H., Bell D.W., Haber D.A., Grip M., Reiman M.,
RA Jukkola-Vuorinen A., Mustonen A., Kere J., Aaltonen L.A., Kosma V.-M.,
RA Kataja V., Soini Y., Drapkin R.I., Livingston D.M., Winqvist R.;
RT "A recurrent mutation in PALB2 in Finnish cancer families.";
RL Nature 446:316-319(2007).
RN [8]
RP INVOLVEMENT IN FANCN.
RX PubMed=17200672; DOI=10.1038/ng1942;
RA Xia B., Dorsman J.C., Ameziane N., de Vries Y., Rooimans M.A., Sheng Q.,
RA Pals G., Errami A., Gluckman E., Llera J., Wang W., Livingston D.M.,
RA Joenje H., de Winter J.P.;
RT "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2.";
RL Nat. Genet. 39:159-161(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [11]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH BRCA2.
RX PubMed=19423707; DOI=10.1074/jbc.m109.016717;
RA Sy S.M., Huen M.S., Zhu Y., Chen J.;
RT "PALB2 regulates recombinational repair through chromatin association and
RT oligomerization.";
RL J. Biol. Chem. 284:18302-18310(2009).
RN [12]
RP FUNCTION, IDENTIFICATION IN A BRCA COMPLEX WITH BRCA1 AND BRCA2,
RP INTERACTION WITH BRCA1, AND MUTAGENESIS OF LYS-14; LEU-21; TYR-28; LEU-35
RP AND GLU-42.
RX PubMed=19369211; DOI=10.1073/pnas.0811159106;
RA Sy S.M., Huen M.S., Chen J.;
RT "PALB2 is an integral component of the BRCA complex required for homologous
RT recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-387, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [14]
RP INVOLVEMENT IN PNCA3.
RX PubMed=19264984; DOI=10.1126/science.1171202;
RA Jones S., Hruban R.H., Kamiyama M., Borges M., Zhang X., Parsons D.W.,
RA Lin J.C., Palmisano E., Brune K., Jaffee E.M., Iacobuzio-Donahue C.A.,
RA Maitra A., Parmigiani G., Kern S.E., Velculescu V.E., Kinzler K.W.,
RA Vogelstein B., Eshleman J.R., Goggins M., Klein A.P.;
RT "Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility
RT gene.";
RL Science 324:217-217(2009).
RN [15]
RP INTERACTION WITH MORF4L1.
RX PubMed=20332121; DOI=10.1242/jcs.060178;
RA Hayakawa T., Zhang F., Hayakawa N., Ohtani Y., Shinmyozu K., Nakayama J.,
RA Andreassen P.R.;
RT "MRG15 binds directly to PALB2 and stimulates homology-directed repair of
RT chromosomal breaks.";
RL J. Cell Sci. 123:1124-1130(2010).
RN [16]
RP FUNCTION, AND INTERACTION WITH RAD51.
RX PubMed=20871615; DOI=10.1038/nsmb.1915;
RA Buisson R., Dion-Cote A.M., Coulombe Y., Launay H., Cai H., Stasiak A.Z.,
RA Stasiak A., Xia B., Masson J.Y.;
RT "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in
RT stimulating homologous recombination.";
RL Nat. Struct. Mol. Biol. 17:1247-1254(2010).
RN [17]
RP FUNCTION, AND INTERACTION WITH RAD51 AND RAD51AP1.
RX PubMed=20871616; DOI=10.1038/nsmb.1916;
RA Dray E., Etchin J., Wiese C., Saro D., Williams G.J., Hammel M., Yu X.,
RA Galkin V.E., Liu D., Tsai M.S., Sy S.M., Schild D., Egelman E., Chen J.,
RA Sung P.;
RT "Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2.";
RL Nat. Struct. Mol. Biol. 17:1255-1259(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-376, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP ASSOCIATION WITH CHROMATIN, AND ASSOCIATION WITH NUCLEOSOMES.
RX PubMed=22193777; DOI=10.1038/embor.2011.243;
RA Bleuyard J.Y., Buisson R., Masson J.Y., Esashi F.;
RT "ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and
RT facilitates DNA repair.";
RL EMBO Rep. 13:135-141(2012).
RN [21]
RP INVOLVEMENT IN SUSCEPTIBILITY TO BREAST CANCER.
RX PubMed=22241545; DOI=10.1002/humu.22022;
RA Tischkowitz M., Capanu M., Sabbaghian N., Li L., Liang X., Vallee M.P.,
RA Tavtigian S.V., Concannon P., Foulkes W.D., Bernstein L., Bernstein J.L.,
RA Begg C.B.;
RT "Rare germline mutations in PALB2 and breast cancer risk: a population-
RT based study.";
RL Hum. Mutat. 33:674-680(2012).
RN [22]
RP FUNCTION, AND SELF-ASSOCIATION.
RX PubMed=22941656; DOI=10.1093/nar/gks807;
RA Buisson R., Masson J.Y.;
RT "PALB2 self-interaction controls homologous recombination.";
RL Nucleic Acids Res. 40:10312-10323(2012).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-172; SER-190; SER-285;
RP SER-376; SER-387; SER-454; SER-660 AND SER-781, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [24]
RP FUNCTION, INTERACTION WITH BRCA2; RAD51C; RAD51 AND XRCC3, MUTAGENESIS OF
RP THR-1030, AND CHARACTERIZATION OF VARIANTS TRP-939 AND PRO-1143.
RX PubMed=24141787; DOI=10.1038/onc.2013.421;
RA Park J.Y., Singh T.R., Nassar N., Zhang F., Freund M., Hanenberg H.,
RA Meetei A.R., Andreassen P.R.;
RT "Breast cancer-associated missense mutants of the PALB2 WD40 domain, which
RT directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair.";
RL Oncogene 33:4803-4812(2014).
RN [25]
RP FUNCTION, AND INTERACTION WITH POLH.
RX PubMed=24485656; DOI=10.1016/j.celrep.2014.01.009;
RA Buisson R., Niraj J., Pauty J., Maity R., Zhao W., Coulombe Y., Sung P.,
RA Masson J.Y.;
RT "Breast cancer proteins PALB2 and BRCA2 stimulate polymerase eta in
RT recombination-associated DNA synthesis at blocked replication forks.";
RL Cell Rep. 6:553-564(2014).
RN [26]
RP IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH ERCC5 AND BRCA2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026;
RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R.,
RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J.,
RA Sung P., Wiese C., Campisi J., Cooper P.K.;
RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous
RT Recombination and Genome Stability.";
RL Mol. Cell 61:535-546(2016).
RN [27]
RP FUNCTION, SUBUNIT, INTERACTION WITH BRCA1; BRCA2 AND RAD51, SUBCELLULAR
RP LOCATION, VARIANT BC PRO-35, CHARACTERIZATION OF VARIANT BC PRO-35, AND
RP CHARACTERIZATION OF VARIANTS ARG-18; CYS-28 AND HIS-37.
RX PubMed=28319063; DOI=10.1038/onc.2017.46;
RA Foo T.K., Tischkowitz M., Simhadri S., Boshari T., Zayed N., Burke K.A.,
RA Berman S.H., Blecua P., Riaz N., Huo Y., Ding Y.C., Neuhausen S.L.,
RA Weigelt B., Reis-Filho J.S., Foulkes W.D., Xia B.;
RT "Compromised BRCA1-PALB2 interaction is associated with breast cancer
RT risk.";
RL Oncogene 36:4161-4170(2017).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 835-1186 ALONE AND IN COMPLEX WITH
RP A BRCA2 PEPTIDE, AND DOMAIN WD REPEATS.
RX PubMed=19609323; DOI=10.1038/embor.2009.126;
RA Oliver A.W., Swift S., Lord C.J., Ashworth A., Pearl L.H.;
RT "Structural basis for recruitment of BRCA2 by PALB2.";
RL EMBO Rep. 10:990-996(2009).
RN [29]
RP VARIANT [LARGE SCALE ANALYSIS] SER-864.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [30]
RP VARIANTS TYR-46; GLY-219; CYS-334; SER-337; GLN-414; MET-425; THR-491;
RP ARG-515; ARG-559; GLN-672; VAL-712; LEU-728; SER-864; ALA-917; MET-932;
RP TRP-939; VAL-966; GLU-998; THR-1025; ALA-1043; GLY-1075; ALA-1105;
RP HIS-1114; PRO-1143 AND TYR-1170.
RX PubMed=21618343; DOI=10.1002/humu.21478;
RA Hellebrand H., Sutter C., Honisch E., Gross E., Wappenschmidt B., Schem C.,
RA Deissler H., Ditsch N., Gress V., Kiechle M., Bartram C.R.,
RA Schmutzler R.K., Niederacher D., Arnold N., Meindl A.;
RT "Germline mutations in the PALB2 gene are population specific and occur
RT with low frequencies in familial breast cancer.";
RL Hum. Mutat. 32:E2176-E2188(2011).
CC -!- FUNCTION: Plays a critical role in homologous recombination repair
CC (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks
CC (PubMed:16793542, PubMed:19423707, PubMed:19369211, PubMed:22941656,
CC PubMed:24141787, PubMed:28319063). Strongly stimulates the DNA strand-
CC invasion activity of RAD51, stabilizes the nucleoprotein filament
CC against a disruptive BRC3-BRC4 polypeptide and helps RAD51 to overcome
CC the suppressive effect of replication protein A (RPA)
CC (PubMed:20871615). Functionally cooperates with RAD51AP1 in promoting
CC of D-loop formation by RAD51 (PubMed:20871616). Serves as the molecular
CC scaffold in the formation of the BRCA1-PALB2-BRCA2 complex which is
CC essential for homologous recombination (PubMed:19369211). Via its WD
CC repeats is proposed to scaffold a HR complex containing RAD51C and
CC BRCA2 which is thought to play a role in HR-mediated DNA repair
CC (PubMed:24141787). Essential partner of BRCA2 that promotes the
CC localization and stability of BRCA2 (PubMed:16793542). Also enables its
CC recombinational repair and checkpoint functions of BRCA2
CC (PubMed:16793542). May act by promoting stable association of BRCA2
CC with nuclear structures, allowing BRCA2 to escape the effects of
CC proteasome-mediated degradation (PubMed:16793542). Binds DNA with high
CC affinity for D loop, which comprises single-stranded, double-stranded
CC and branched DNA structures (PubMed:20871616). May play a role in the
CC extension step after strand invasion at replication-dependent DNA
CC double-strand breaks; together with BRCA2 is involved in both POLH
CC localization at collapsed replication forks and DNA polymerization
CC activity (PubMed:24485656). {ECO:0000269|PubMed:16793542,
CC ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:19423707,
CC ECO:0000269|PubMed:20871615, ECO:0000269|PubMed:20871616,
CC ECO:0000269|PubMed:22941656, ECO:0000269|PubMed:24141787,
CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:28319063}.
CC -!- SUBUNIT: Homooligomer; dissociated upon DNA damage thus allowing
CC association with BRCA1 (PubMed:19423707, PubMed:28319063).
CC Oligomerization is essential for its focal accumulation at DNA breaks
CC (PubMed:19423707). Part of a BRCA complex containing BRCA1, BRCA2 and
CC PALB2 (PubMed:19369211). Interacts with BRCA1 and this interaction is
CC essential for its function in HRR (PubMed:19369211, PubMed:28319063).
CC Interacts with RAD51AP1 and MORF4L1/MRG15 (PubMed:20332121,
CC PubMed:20871616). Component of the homologous recombination repair (HR)
CC complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51
CC (PubMed:26833090). Within the complex, interacts with ERCC5/XPG and
CC BRCA2 (PubMed:26833090). Interacts with BRCA2, RAD51C, RAD51 and XRCC3;
CC the interactions are direct and it may serve as a scaffold for a HR
CC complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3
CC (PubMed:28319063, PubMed:16793542, PubMed:19423707, PubMed:19609323,
CC PubMed:20871615, PubMed:20871616, PubMed:24141787). Interacts with
CC POLH; the interaction is direct (PubMed:24485656).
CC {ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:19369211,
CC ECO:0000269|PubMed:19423707, ECO:0000269|PubMed:19609323,
CC ECO:0000269|PubMed:20332121, ECO:0000269|PubMed:20871615,
CC ECO:0000269|PubMed:20871616, ECO:0000269|PubMed:24141787,
CC ECO:0000269|PubMed:24485656, ECO:0000269|PubMed:26833090,
CC ECO:0000269|PubMed:28319063}.
CC -!- INTERACTION:
CC Q86YC2; P38398: BRCA1; NbExp=27; IntAct=EBI-1222653, EBI-349905;
CC Q86YC2; P51587: BRCA2; NbExp=25; IntAct=EBI-1222653, EBI-79792;
CC Q86YC2; Q14145: KEAP1; NbExp=4; IntAct=EBI-1222653, EBI-751001;
CC Q86YC2; Q9UBU8-2: MORF4L1; NbExp=3; IntAct=EBI-1222653, EBI-10288852;
CC Q86YC2; Q9Y253: POLH; NbExp=7; IntAct=EBI-1222653, EBI-2827270;
CC Q86YC2; Q06609: RAD51; NbExp=8; IntAct=EBI-1222653, EBI-297202;
CC Q86YC2; Q96B01-2: RAD51AP1; NbExp=2; IntAct=EBI-1222653, EBI-1178743;
CC Q86YC2; O43502: RAD51C; NbExp=10; IntAct=EBI-1222653, EBI-2267048;
CC Q86YC2; P51784: USP11; NbExp=2; IntAct=EBI-1222653, EBI-306876;
CC Q86YC2; O43542: XRCC3; NbExp=3; IntAct=EBI-1222653, EBI-2849976;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16793542,
CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:28319063}.
CC Note=Colocalizes with BRCA2 and BRCA1 in nuclear foci.
CC {ECO:0000269|PubMed:16793542, ECO:0000269|PubMed:28319063}.
CC -!- DOMAIN: Interaction with BRCA2 occurs through a hydrophobic pocket at
CC the crossover between WD repeats 4 and 5.
CC {ECO:0000269|PubMed:19609323}.
CC -!- DOMAIN: The coiled coil domain mediates self-association.
CC {ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:22941656}.
CC -!- DOMAIN: The chromatin-association motif (ChAM) mediates association
CC with chromatin, probably through nucleosome core particles,
CC independently from binding to D loop, ssDNA or dsDNA structures.
CC {ECO:0000269|PubMed:19609323, ECO:0000269|PubMed:22193777}.
CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy
CC originating from breast epithelial tissue. Breast neoplasms can be
CC distinguished by their histologic pattern. Invasive ductal carcinoma is
CC by far the most common type. Breast cancer is etiologically and
CC genetically heterogeneous. Important genetic factors have been
CC indicated by familial occurrence and bilateral involvement. Mutations
CC at more than one locus can be involved in different families or even in
CC the same case. {ECO:0000269|PubMed:17287723,
CC ECO:0000269|PubMed:22241545, ECO:0000269|PubMed:28319063}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry. Breast cancer susceptibility is strongly
CC associated with PALB2 truncating mutations. Conversely, rare missense
CC mutations do not strongly influence breast cancer risk
CC (PubMed:22241545). {ECO:0000269|PubMed:22241545}.
CC -!- DISEASE: Fanconi anemia complementation group N (FANCN) [MIM:610832]: A
CC disorder affecting all bone marrow elements and resulting in anemia,
CC leukopenia and thrombopenia. It is associated with cardiac, renal and
CC limb malformations, dermal pigmentary changes, and a predisposition to
CC the development of malignancies. At the cellular level it is associated
CC with hypersensitivity to DNA-damaging agents, chromosomal instability
CC (increased chromosome breakage) and defective DNA repair.
CC {ECO:0000269|PubMed:17200672}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Pancreatic cancer 3 (PNCA3) [MIM:613348]: A malignant neoplasm
CC of the pancreas. Tumors can arise from both the exocrine and endocrine
CC portions of the pancreas, but 95% of them develop from the exocrine
CC portion, including the ductal epithelium, acinar cells, connective
CC tissue, and lymphatic tissue. {ECO:0000269|PubMed:19264984}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15140.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL834425; CAD39086.1; -; mRNA.
DR EMBL; CR749637; CAH18431.1; -; mRNA.
DR EMBL; AC008870; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471145; EAW55813.1; -; Genomic_DNA.
DR EMBL; BC044254; AAH44254.1; -; mRNA.
DR EMBL; AK025469; BAB15140.1; ALT_INIT; mRNA.
DR EMBL; AK097533; BAC05090.1; -; mRNA.
DR CCDS; CCDS32406.1; -.
DR RefSeq; NP_078951.2; NM_024675.3.
DR PDB; 2W18; X-ray; 1.90 A; A=835-1186.
DR PDB; 3EU7; X-ray; 2.20 A; A=835-1186.
DR PDBsum; 2W18; -.
DR PDBsum; 3EU7; -.
DR AlphaFoldDB; Q86YC2; -.
DR SMR; Q86YC2; -.
DR BioGRID; 122843; 78.
DR ComplexPortal; CPX-845; BRCA1-PALB2-BRCA2 homologous recombination DNA repair complex.
DR DIP; DIP-38427N; -.
DR ELM; Q86YC2; -.
DR IntAct; Q86YC2; 39.
DR MINT; Q86YC2; -.
DR STRING; 9606.ENSP00000261584; -.
DR GlyGen; Q86YC2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q86YC2; -.
DR PhosphoSitePlus; Q86YC2; -.
DR BioMuta; PALB2; -.
DR DMDM; 74727919; -.
DR CPTAC; CPTAC-3284; -.
DR EPD; Q86YC2; -.
DR jPOST; Q86YC2; -.
DR MassIVE; Q86YC2; -.
DR MaxQB; Q86YC2; -.
DR PaxDb; Q86YC2; -.
DR PeptideAtlas; Q86YC2; -.
DR PRIDE; Q86YC2; -.
DR ProteomicsDB; 70395; -.
DR Antibodypedia; 26008; 255 antibodies from 35 providers.
DR CPTC; Q86YC2; 1 antibody.
DR DNASU; 79728; -.
DR Ensembl; ENST00000261584.9; ENSP00000261584.4; ENSG00000083093.10.
DR GeneID; 79728; -.
DR KEGG; hsa:79728; -.
DR MANE-Select; ENST00000261584.9; ENSP00000261584.4; NM_024675.4; NP_078951.2.
DR UCSC; uc002dlx.2; human.
DR CTD; 79728; -.
DR DisGeNET; 79728; -.
DR GeneCards; PALB2; -.
DR GeneReviews; PALB2; -.
DR HGNC; HGNC:26144; PALB2.
DR HPA; ENSG00000083093; Low tissue specificity.
DR MalaCards; PALB2; -.
DR MIM; 114480; phenotype.
DR MIM; 610355; gene.
DR MIM; 610832; phenotype.
DR MIM; 613348; phenotype.
DR neXtProt; NX_Q86YC2; -.
DR OpenTargets; ENSG00000083093; -.
DR Orphanet; 1333; Familial pancreatic carcinoma.
DR Orphanet; 84; Fanconi anemia.
DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome.
DR Orphanet; 227535; Hereditary breast cancer.
DR PharmGKB; PA162398608; -.
DR VEuPathDB; HostDB:ENSG00000083093; -.
DR eggNOG; ENOG502QRAP; Eukaryota.
DR GeneTree; ENSGT00390000014423; -.
DR HOGENOM; CLU_008217_0_0_1; -.
DR InParanoid; Q86YC2; -.
DR OMA; GHCQKED; -.
DR OrthoDB; 710645at2759; -.
DR PhylomeDB; Q86YC2; -.
DR TreeFam; TF351544; -.
DR PathwayCommons; Q86YC2; -.
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; Q86YC2; -.
DR SIGNOR; Q86YC2; -.
DR BioGRID-ORCS; 79728; 209 hits in 1085 CRISPR screens.
DR ChiTaRS; PALB2; human.
DR EvolutionaryTrace; Q86YC2; -.
DR GeneWiki; PALB2; -.
DR GenomeRNAi; 79728; -.
DR Pharos; Q86YC2; Tbio.
DR PRO; PR:Q86YC2; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q86YC2; protein.
DR Bgee; ENSG00000083093; Expressed in secondary oocyte and 146 other tissues.
DR ExpressionAtlas; Q86YC2; baseline and differential.
DR Genevisible; Q86YC2; HS.
DR GO; GO:1990391; C:DNA repair complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IC:ComplexPortal.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:Ensembl.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl.
DR GO; GO:0007498; P:mesoderm development; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR Gene3D; 2.130.10.10; -; 1.
DR IDEAL; IID00249; -.
DR InterPro; IPR042417; PALB2.
DR InterPro; IPR031920; PALB2_WD40.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR14662; PTHR14662; 1.
DR Pfam; PF16756; PALB2_WD40; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Disease variant; DNA damage; DNA recombination;
KW DNA repair; DNA-binding; Fanconi anemia; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Tumor suppressor; WD repeat.
FT CHAIN 1..1186
FT /note="Partner and localizer of BRCA2"
FT /id="PRO_0000252391"
FT REPEAT 854..915
FT /note="WD 1"
FT REPEAT 917..961
FT /note="WD 2"
FT REPEAT 962..1009
FT /note="WD 3"
FT REPEAT 1010..1052
FT /note="WD 4"
FT REPEAT 1058..1109
FT /note="WD 5"
FT REPEAT 1115..1153
FT /note="WD 6"
FT REPEAT 1155..1186
FT /note="WD 7"
FT REGION 1..579
FT /note="DNA-binding (with the preference D loop > dsDNA >
FT ssDNA)"
FT REGION 1..319
FT /note="Interaction with BRCA1"
FT /evidence="ECO:0000269|PubMed:19369211"
FT REGION 1..200
FT /note="Interaction with RAD51"
FT REGION 1..160
FT /note="Required for its oligomerization and is important
FT for its focal concentration at DNA damage sites"
FT REGION 52..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..157
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 252..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 395..446
FT /note="ChAM (Chromatin-association motif); required for
FT chromatin association, mediates nucleosome association"
FT REGION 440..525
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 679..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..798
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 775..1186
FT /note="Required for interaction with POLH and POLH DNA
FT synthesis stimulation"
FT /evidence="ECO:0000269|PubMed:24485656"
FT REGION 853..1186
FT /note="Interaction with RAD51, BRCA2 and POLH"
FT /evidence="ECO:0000269|PubMed:24485656"
FT COILED 9..41
FT /evidence="ECO:0000255"
FT COMPBIAS 123..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..495
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 684..698
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 781
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 18
FT /note="K -> R (decreases double-stranded DNA break-
FT initiated homologous recombination; dbSNP:rs138789658)"
FT /evidence="ECO:0000269|PubMed:28319063"
FT /id="VAR_079842"
FT VARIANT 28
FT /note="Y -> C (abrogates the interaction with BRCA1;
FT decreases double-stranded DNA break-initiated homologous
FT recombination; reduces PALB2 and RAD51 localization to
FT ionizing radiation-induced foci; may weaken
FT homooligomerization; dbSNP:rs515726129)"
FT /evidence="ECO:0000269|PubMed:28319063"
FT /id="VAR_079843"
FT VARIANT 35
FT /note="L -> P (in BC; abrogates the interaction with BRCA1;
FT abrogates double-stranded DNA break-initiated homologous
FT recombination; abrogates PALB2 and RAD51 localization to
FT ionizing radiation-induced foci; may weaken
FT homooligomerization; dbSNP:rs141047069)"
FT /evidence="ECO:0000269|PubMed:28319063"
FT /id="VAR_079844"
FT VARIANT 37
FT /note="R -> H (decreases double-stranded DNA break-
FT initiated homologous recombination; dbSNP:rs202194596)"
FT /evidence="ECO:0000269|PubMed:28319063"
FT /id="VAR_079845"
FT VARIANT 46
FT /note="H -> Y"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066361"
FT VARIANT 219
FT /note="D -> G (in dbSNP:rs45594034)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066362"
FT VARIANT 309
FT /note="I -> V (in dbSNP:rs3809683)"
FT /id="VAR_032959"
FT VARIANT 334
FT /note="Y -> C (in dbSNP:rs200620434)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066363"
FT VARIANT 337
FT /note="L -> S (in dbSNP:rs45494092)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066364"
FT VARIANT 414
FT /note="R -> Q (in dbSNP:rs749461008)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066365"
FT VARIANT 425
FT /note="V -> M (in dbSNP:rs576081828)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066366"
FT VARIANT 491
FT /note="A -> T (in dbSNP:rs577969558)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066367"
FT VARIANT 515
FT /note="K -> R (in dbSNP:rs515726072)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066368"
FT VARIANT 559
FT /note="Q -> R (in dbSNP:rs152451)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066369"
FT VARIANT 672
FT /note="E -> Q (in dbSNP:rs45532440)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066370"
FT VARIANT 712
FT /note="A -> V (in dbSNP:rs141458731)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066371"
FT VARIANT 728
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066372"
FT VARIANT 864
FT /note="P -> S (in dbSNP:rs45568339)"
FT /evidence="ECO:0000269|PubMed:18987736,
FT ECO:0000269|PubMed:21618343"
FT /id="VAR_054150"
FT VARIANT 917
FT /note="V -> A (in dbSNP:rs763645981)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066373"
FT VARIANT 932
FT /note="V -> M (in dbSNP:rs45624036)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066374"
FT VARIANT 939
FT /note="L -> W (may be associated with breast cancer
FT susceptibility; reduces interaction with BRCA2, RAD51 and
FT XRCC3; decreases double-stranded DNA break-initiated
FT homologous recombination; increases sensitivity to IR;
FT dbSNP:rs45478192)"
FT /evidence="ECO:0000269|PubMed:21618343,
FT ECO:0000269|PubMed:24141787"
FT /id="VAR_066375"
FT VARIANT 966
FT /note="I -> V (in dbSNP:rs786204248)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066376"
FT VARIANT 998
FT /note="G -> E (may be associated with breast cancer
FT susceptibility; dbSNP:rs45551636)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066377"
FT VARIANT 1025
FT /note="A -> T (in dbSNP:rs746872839)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066378"
FT VARIANT 1043
FT /note="G -> A (may be associated with breast cancer
FT susceptibility; reduces interaction with BRCA2, RAD51C,
FT RAD51 and XRCC3; decreases double-stranded DNA break-
FT initiated homologous recombination; increases sensitivity
FT to IR; dbSNP:rs377713277)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066379"
FT VARIANT 1075
FT /note="S -> G"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066380"
FT VARIANT 1105
FT /note="V -> A"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066381"
FT VARIANT 1114
FT /note="Q -> H (in dbSNP:rs1567206753)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066382"
FT VARIANT 1143
FT /note="L -> P (may be associated with breast cancer
FT susceptibility; dbSNP:rs62625284)"
FT /evidence="ECO:0000269|PubMed:21618343,
FT ECO:0000269|PubMed:24141787"
FT /id="VAR_066383"
FT VARIANT 1170
FT /note="H -> Y (in dbSNP:rs200283306)"
FT /evidence="ECO:0000269|PubMed:21618343"
FT /id="VAR_066384"
FT MUTAGEN 14
FT /note="K->A: Loss of interaction with BRCA1 but no effect
FT on interaction with BRCA2."
FT /evidence="ECO:0000269|PubMed:19369211"
FT MUTAGEN 21
FT /note="L->A: Loss of interaction with BRCA1 but no effect
FT on interaction with BRCA2."
FT /evidence="ECO:0000269|PubMed:19369211"
FT MUTAGEN 28
FT /note="Y->A: Loss of interaction with BRCA1 but no effect
FT on interaction with BRCA2."
FT /evidence="ECO:0000269|PubMed:19369211"
FT MUTAGEN 35
FT /note="L->A: Loss of interaction with BRCA1 but no effect
FT on interaction with BRCA2."
FT /evidence="ECO:0000269|PubMed:19369211"
FT MUTAGEN 42
FT /note="E->A: Loss of interaction with BRCA1 but no effect
FT on interaction with BRCA2."
FT /evidence="ECO:0000269|PubMed:19369211"
FT MUTAGEN 1030
FT /note="T->I: Unstable and promotes protein degradation;
FT reduces interaction with RAD51C and RAD51."
FT /evidence="ECO:0000269|PubMed:24141787"
FT STRAND 855..861
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 869..877
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 884..913
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 919..922
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 932..936
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 938..947
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 958..972
FT /evidence="ECO:0007829|PDB:2W18"
FT TURN 973..975
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 976..984
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 988..994
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1000..1006
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1013..1020
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1025..1030
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1033..1039
FT /evidence="ECO:0007829|PDB:2W18"
FT TURN 1040..1042
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1045..1050
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1053..1055
FT /evidence="ECO:0007829|PDB:3EU7"
FT STRAND 1059..1066
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1069..1075
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1090..1096
FT /evidence="ECO:0007829|PDB:2W18"
FT TURN 1097..1100
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1101..1108
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1118..1124
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1127..1132
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1137..1141
FT /evidence="ECO:0007829|PDB:2W18"
FT TURN 1142..1144
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1146..1151
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1161..1164
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1166..1174
FT /evidence="ECO:0007829|PDB:2W18"
FT STRAND 1180..1185
FT /evidence="ECO:0007829|PDB:2W18"
SQ SEQUENCE 1186 AA; 131295 MW; 215EC32291315FA2 CRC64;
MDEPPGKPLS CEEKEKLKEK LAFLKREYSK TLARLQRAQR AEKIKHSIKK TVEEQDCLSQ
QDLSPQLKHS EPKNKICVYD KLHIKTHLDE ETGEKTSITL DVGPESFNPG DGPGGLPIQR
TDDTQEHFPH RVSDPSGEQK QKLPSRRKKQ QKRTFISQER DCVFGTDSLR LSGKRLKEQE
EISSKNPARS PVTEIRTHLL SLKSELPDSP EPVTEINEDS VLIPPTAQPE KGVDTFLRRP
NFTRATTVPL QTLSDSGSSQ HLEHIPPKGS SELTTHDLKN IRFTSPVSLE AQGKKMTVST
DNLLVNKAIS KSGQLPTSSN LEANISCSLN ELTYNNLPAN ENQNLKEQNQ TEKSLKSPSD
TLDGRNENLQ ESEILSQPKS LSLEATSPLS AEKHSCTVPE GLLFPAEYYV RTTRSMSNCQ
RKVAVEAVIQ SHLDVKKKGF KNKNKDASKN LNLSNEETDQ SEIRMSGTCT GQPSSRTSQK
LLSLTKVSSP AGPTEDNDLS RKAVAQAPGR RYTGKRKSAC TPASDHCEPL LPTSSLSIVN
RSKEEVTSHK YQHEKLFIQV KGKKSRHQKE DSLSWSNSAY LSLDDDAFTA PFHRDGMLSL
KQLLSFLSIT DFQLPDEDFG PLKLEKVKSC SEKPVEPFES KMFGERHLKE GSCIFPEELS
PKRMDTEMED LEEDLIVLPG KSHPKRPNSQ SQHTKTGLSS SILLYTPLNT VAPDDNDRPT
TDMCSPAFPI LGTTPAFGPQ GSYEKASTEV AGRTCCTPQL AHLKDSVCLA SDTKQFDSSG
SPAKPHTTLQ VSGRQGQPTC DCDSVPPGTP PPIESFTFKE NQLCRNTCQE LHKHSVEQTE
TAELPASDSI NPGNLQLVSE LKNPSGSCSV DVSAMFWERA GCKEPCIITA CEDVVSLWKA
LDAWQWEKLY TWHFAEVPVL QIVPVPDVYN LVCVALGNLE IREIRALFCS SDDESEKQVL
LKSGNIKAVL GLTKRRLVSS SGTLSDQQVE VMTFAEDGGG KENQFLMPPE ETILTFAEVQ
GMQEALLGTT IMNNIVIWNL KTGQLLKKMH IDDSYQASVC HKAYSEMGLL FIVLSHPCAK
ESESLRSPVF QLIVINPKTT LSVGVMLYCL PPGQAGRFLE GDVKDHCAAA ILTSGTIAIW
DLLLGQCTAL LPPVSDQHWS FVKWSGTDSH LLAGQKDGNI FVYHYS
