ID BRCA2_MOUSE Reviewed; 3329 AA. AC P97929; F8VPU5; O35922; P97383; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 03-OCT-2012, sequence version 2. DT 02-SEP-2026, entry version 209. DE RecName: Full=Breast cancer type 2 susceptibility protein homolog {ECO:0000305}; DE AltName: Full=Fanconi anemia group D1 protein homolog; GN Name=Brca2 {ECO:0000303|PubMed:9063750, ECO:0000312|MGI:MGI:109337}; GN Synonyms=Fancd1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC STRAIN=129; RX PubMed=9063750; DOI=10.1093/hmg/6.2.291; RA Connor F., Smith A., Wooster R., Stratton M., Dixon A., Campbell E., RA Tait T.M., Freeman T., Ashworth A.; RT "Cloning, chromosomal mapping and expression pattern of the mouse Brca2 RT gene."; RL Hum. Mol. Genet. 6:291-300(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57BL/6J; RX PubMed=9119389; DOI=10.1006/geno.1996.4573; RA Sharan S.K., Bradley A.; RT "Murine Brca2: sequence, map position, and expression pattern."; RL Genomics 40:234-241(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/Sv; RX PubMed=9242436; RA McAllister K.A., Haugen-Strano A., Hagevik S., Brownlee H.A., Collins N.K., RA Futreal P.A., Bennett L.M., Wiseman R.W.; RT "Characterization of the rat and mouse homologues of the BRCA2 breast RT cancer susceptibility gene."; RL Cancer Res. 57:3121-3125(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-200. RX PubMed=8917547; DOI=10.1073/pnas.93.23.13078; RA Rajan J.V., Wang M., Marquis S.T., Chodosh L.A.; RT "Brca2 is coordinately regulated with Brca1 during proliferation and RT differentiation in mammary epithelial cells."; RL Proc. Natl. Acad. Sci. U.S.A. 93:13078-13083(1996). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 569-625. RX PubMed=9196008; DOI=10.1007/s003359900497; RA McAllister K.A., Ramachandran S., Haugen-Strano A., Fiedorek F.T. Jr., RA Wiseman R.W.; RT "Genetic mapping of the Brca2 breast cancer susceptibility gene on mouse RT chromosome 5."; RL Mamm. Genome 8:540-541(1997). RN [7] RP PROTEIN SEQUENCE OF 784-790, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=OF1; TISSUE=Hippocampus; RA Lubec G., Sunyer B., Chen W.-Q.; RL Submitted (JAN-2009) to UniProtKB. RN [8] RP FUNCTION, INTERACTION WITH RAD51, AND DISRUPTION PHENOTYPE. RX PubMed=9126738; DOI=10.1038/386804a0; RA Sharan S.K., Morimatsu M., Albrecht U., Lim D.S., Regel E., Dinh C., RA Sands A., Eichele G., Hasty P., Bradley A.; RT "Embryonic lethality and radiation hypersensitivity mediated by Rad51 in RT mice lacking Brca2."; RL Nature 386:804-810(1997). RN [9] RP INTERACTION WITH HSF2BP. RX PubMed=31242413; DOI=10.1016/j.celrep.2019.05.096; RA Brandsma I., Sato K., van Rossum-Fikkert S.E., van Vliet N., Sleddens E., RA Reuter M., Odijk H., van den Tempel N., Dekkers D.H.W., Bezstarosti K., RA Demmers J.A.A., Maas A., Lebbink J., Wyman C., Essers J., van Gent D.C., RA Baarends W.M., Knipscheer P., Kanaar R., Zelensky A.N.; RT "HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for RT Mouse Spermatogenesis."; RL Cell Rep. 27:3790.e7-3798.e7(2019). RN [10] RP SUBCELLULAR LOCATION, AND INTERACTION WITH HSF2BP AND RAD51. RX PubMed=30760716; DOI=10.1038/s41467-019-08676-2; RA Zhang J., Fujiwara Y., Yamamoto S., Shibuya H.; RT "A meiosis-specific BRCA2 binding protein recruits recombinases to DNA RT double-strand breaks to ensure homologous recombination."; RL Nat. Commun. 10:722-722(2019). RN [11] RP INTERACTION WITH BRME1. RX PubMed=32460033; DOI=10.1016/j.celrep.2020.107686; RA Takemoto K., Tani N., Takada-Horisawa Y., Fujimura S., Tanno N., Yamane M., RA Okamura K., Sugimoto M., Araki K., Ishiguro K.I.; RT "Meiosis-Specific C19orf57/4930432K21Rik/BRME1 Modulates Localization of RT RAD51 and DMC1 to DSBs in Mouse Meiotic Recombination."; RL Cell Rep. 31:107686-107686(2020). RN [12] RP INTERACTION WITH HSF2BP AND BRME1. RX PubMed=32845237; DOI=10.7554/elife.56996; RA Felipe-Medina N., Caburet S., Sanchez-Saez F., Condezo Y.B., de Rooij D.G., RA Gomez-H L., Garcia-Valiente R., Todeschini A.L., Duque P., RA Sanchez-Martin M.A., Shalev S.A., Llano E., Veitia R.A., Pendas A.M.; RT "A missense in HSF2BP causing primary ovarian insufficiency affects meiotic RT recombination by its novel interactor C19ORF57/BRME1."; RL Elife 9:0-0(2020). RN [13] RP INTERACTION WITH HSF2BP; BRME1; SPATA22; MEIOB AND RAD51, AND TISSUE RP SPECIFICITY. RX PubMed=32345962; DOI=10.1038/s41467-020-15954-x; RA Zhang J., Gurusaran M., Fujiwara Y., Zhang K., Echbarthi M., Vorontsov E., RA Guo R., Pendlebury D.F., Alam I., Livera G., Emmanuelle M., Wang P.J., RA Nandakumar J., Davies O.R., Shibuya H.; RT "The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs RT the mitotic BRCA2-RAD51 function in cancer cells."; RL Nat. Commun. 11:2055-2055(2020). RN [14] RP X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 2378-3115 IN COMPLEX WITH SEM1, RP AND INTERACTION WITH SEM1. RX PubMed=12228710; DOI=10.1126/science.297.5588.1837; RA Yang H., Jeffrey P.D., Miller J., Kinnucan E., Sun Y., Thoma N.H., RA Zheng N., Chen P.L., Lee W.H., Pavletich N.P.; RT "BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA RT structure."; RL Science 297:1837-1848(2002). CC -!- FUNCTION: Tumor suppressor protein that maintains genome stability CC primarily by repairing damaged DNA through homologous recombination CC (HR) (PubMed:9126738). Facilitates the repair of double-strand breaks CC (DSBs) by binding and mediating the loading of the RAD51 protein onto CC single-stranded DNA (ssDNA), thereby promoting the activity of RAD51, CC which catalyzes DNA strand exchange (By similarity). BRCA2 nucleates CC and stabilizes RAD51 on ssDNA directly and delivers RAD51 to ssDNA- CC double-stranded DNA (dsDNA) junctions by sliding along dsDNA backbone CC (By similarity). RAD51 targeting to ssDNA promotes removal of CC replication protein-A (RPA) from ssDNA and stabilization of RAD51-ssDNA CC filaments by blocking ATP hydrolysis (By similarity). May play a role CC in the extension step after strand invasion at replication-dependent CC DNA double-strand breaks; together with PALB2 is involved in both POLH CC localization at collapsed replication forks and DNA polymerization CC activity (By similarity). Required to prevent R-loop-associated DNA CC damage and thus transcription-associated genomic instability (By CC similarity). Silencing of BRCA2 promotes R-loop accumulation at CC actively transcribed genes in replicating and non-replicating cells, CC suggesting that BRCA2 mediates the control of R-loop associated genomic CC instability, independently of its known role in homologous CC recombination (By similarity). Also promotes RAD51 loading to telomeric CC regions, facilitating telomere replication and capping (By similarity). CC Also required for homologous recombination during meiosis by promoting CC the recruitment of RAD51 and DMC1 recombinases to meiotic DSB sites, CC enabling proper chromosome pairing and crossing over (By similarity). CC Also promotes homologous recombination by inactivating the FIGNL1-FIRRM CC complex to protect RAD51 filament from premature disassembly (By CC similarity). Together with NPM1, may also regulate centrosome CC duplication (By similarity). {ECO:0000250|UniProtKB:P51587, CC ECO:0000269|PubMed:9126738}. CC -!- SUBUNIT: Monomer and dimer (By similarity). Interacts with RAD51; CC regulates RAD51 recruitment and function at sites of DNA repair CC (PubMed:30760716, PubMed:9126738). Interacts with DMC1; regulates DMC1 CC recruitment and function at sites of meiotic double-strand breaks CC (DSBs) (By similarity). Interacts with WDR16, USP11, ROCK2 and NPM1 (By CC similarity). Interacts with SEM1; the interaction masks a nuclear CC export signal in BRCA2 (PubMed:12228710). Interacts with both non- CC ubiquitinated and monoubiquitinated FANCD2; this complex also includes CC XRCC3 and phosphorylated FANCG (By similarity). Part of a BRCA complex CC containing BRCA1, BRCA2 and PALB2 (By similarity). Component of the CC homologous recombination repair (HR) complex composed of ERCC5/XPG, CC BRCA2, PALB2, DSS1 and RAD51 (By similarity). Within the complex, CC interacts with ERCC5/XPG and PALB2 (By similarity). Interacts directly CC with PALB2 which may serve as a scaffold for a HR complex containing CC PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (By similarity). Interacts with CC BRCA1 only in the presence of PALB2 which serves as the bridging CC protein (By similarity). Interacts with POLH; the interaction is direct CC (By similarity). Interacts with the TREX-2 complex subunits PCID2 and CC SEM1 (By similarity). Interacts with HSF2BP and BRME1; the interaction CC with HSF2BP is direct and allows the formation of a ternary complex CC (PubMed:31242413, PubMed:32460033, PubMed:32845237). The complex CC BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB and RAD51 CC (PubMed:30760716, PubMed:32345962). {ECO:0000250|UniProtKB:P51587, CC ECO:0000269|PubMed:12228710, ECO:0000269|PubMed:30760716, CC ECO:0000269|PubMed:31242413, ECO:0000269|PubMed:32345962, CC ECO:0000269|PubMed:32460033, ECO:0000269|PubMed:32845237, CC ECO:0000269|PubMed:9126738}. CC -!- SUBCELLULAR LOCATION: Chromosome {ECO:0000269|PubMed:30760716}. CC Chromosome, telomere {ECO:0000250|UniProtKB:P51587}. Nucleus CC {ECO:0000250|UniProtKB:P51587}. Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000250|UniProtKB:P51587}. CC Note=Colocalizes with ERCC5/XPG to nuclear foci following DNA CC replication stress. {ECO:0000250|UniProtKB:P51587}. CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:9063750). Highest CC expression in cerebellum, testis, ileum, appendix, epididymis, ovary CC and mammary gland (PubMed:32460033, PubMed:9063750). No expression in CC lung (PubMed:9063750). {ECO:0000269|PubMed:32460033, CC ECO:0000269|PubMed:9063750}. CC -!- DEVELOPMENTAL STAGE: In the mammary gland, expression increases CC dramatically during pregnancy. {ECO:0000269|PubMed:9063750}. CC -!- DOMAIN: Interacts with DMC1 and RAD51 through its eight BRCA2 repeats CC and its C-terminal TR2 region. {ECO:0000250|UniProtKB:P51587}. CC -!- PTM: Phosphorylated by ATM upon irradiation-induced DNA damage. CC Phosphorylation by CHEK1 and CHEK2 regulates interaction with RAD51. CC Phosphorylation at Ser-3291 by CDK1 and CDK2 is low in S phase when CC recombination is active, but increases as cells progress towards CC mitosis; this phosphorylation prevents homologous recombination- CC dependent repair during S phase and G2 by inhibiting RAD51 binding. CC {ECO:0000250|UniProtKB:P51587}. CC -!- PTM: Ubiquitinated in the absence of DNA damage; this does not lead to CC proteasomal degradation. In contrast, ubiquitination in response to DNA CC damage leads to proteasomal degradation. CC {ECO:0000250|UniProtKB:P51587}. CC -!- DISRUPTION PHENOTYPE: Embryonic lethality; embryos are normal CC throughout early pre- and post-implantation development, but CC development arrests after day 6.5 of gestation (PubMed:9126738). CC Hypersensitivity to gamma-radiations (PubMed:9126738). CC {ECO:0000269|PubMed:9126738}. 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; U82270; AAB48306.1; -; mRNA. DR EMBL; U65594; AAC23702.1; -; mRNA. DR EMBL; U89652; AAB71377.1; -; mRNA. DR EMBL; AC154885; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; U72947; AAB40720.1; -; mRNA. DR EMBL; U89503; AAC53276.1; -; Genomic_DNA. DR CCDS; CCDS39411.1; -. DR PIR; T30835; T30835. DR PIR; T30904; T30904. DR PIR; T42205; T42205. DR RefSeq; NP_001074470.1; NM_001081001.2. DR RefSeq; NP_033895.2; NM_009765.3. DR RefSeq; XP_036020650.1; XM_036164757.1. DR PDB; 1MIU; X-ray; 3.10 A; A=2378-3115. DR PDB; 1MJE; X-ray; 3.50 A; A=2378-3113. DR SMR; P97929; -. DR BioGRID; 198384; 27. DR ComplexPortal; CPX-972; BRCC ubiquitin ligase complex. DR FunCoup; P97929; 1000. DR IntAct; P97929; 2. DR MINT; P97929; -. DR STRING; 10090.ENSMUSP00000038576; -. DR GlyGen; P97929; 2 sites. DR iPTMnet; P97929; -. DR PhosphoSitePlus; P97929; -. DR jPOST; P97929; -. DR PaxDb; 10090-ENSMUSP00000038576; -. DR PeptideAtlas; P97929; -. DR ProteomicsDB; 273841; -. DR Antibodypedia; 7788; 358 antibodies from 44 providers. DR DNASU; 12190; -. DR Ensembl; ENSMUST00000044620.11; ENSMUSP00000038576.8; ENSMUSG00000041147.11. DR Ensembl; ENSMUST00000202313.2; ENSMUSP00000144150.2; ENSMUSG00000041147.11. DR GeneID; 12190; -. DR KEGG; mmu:12190; -. DR UCSC; uc009aty.2; mouse. DR AGR; MGI:109337; -. DR CTD; 675; -. DR MGI; MGI:109337; Brca2. DR VEuPathDB; HostDB:ENSMUSG00000041147; -. DR eggNOG; KOG4751; Eukaryota. DR GeneTree; ENSGT00390000003602; -. DR HOGENOM; CLU_000344_0_0_1; -. DR InParanoid; P97929; -. DR OMA; CWYTKLG; -. DR OrthoDB; 21095at2759; -. DR PhylomeDB; P97929; -. DR Reactome; R-MMU-5685939; HDR through MMEJ (alt-NHEJ). DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR). DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates. DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange. DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange. DR BioGRID-ORCS; 12190; 22 hits in 120 CRISPR screens. DR EvolutionaryTrace; P97929; -. DR PRO; PR:P97929; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; P97929; protein. DR Bgee; ENSMUSG00000041147; Expressed in cleaving embryo and 196 other cell types or tissues. DR ExpressionAtlas; P97929; baseline and differential. DR GO; GO:0033593; C:BRCA2-MAGE-D1 complex; ISO:GO_Central. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0005694; C:chromosome; IDA:UniProtKB. DR GO; GO:0000781; C:chromosome, telomeric region; ISO:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:GO_Central. DR GO; GO:1990391; C:DNA repair complex; ISO:GO_Central. DR GO; GO:0000800; C:lateral element; ISO:MGI. DR GO; GO:0000152; C:nuclear ubiquitin ligase complex; ISO:GO_Central. DR GO; GO:0005654; C:nucleoplasm; ISO:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0032991; C:protein-containing complex; ISO:GO_Central. DR GO; GO:0030141; C:secretory granule; ISO:GO_Central. DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; ISO:GO_Central. DR GO; GO:0010484; F:histone H3 acetyltransferase activity; ISO:GO_Central. DR GO; GO:0010485; F:histone H4 acetyltransferase activity; ISO:GO_Central. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0140678; F:molecular function inhibitor activity; ISO:GO_Central. DR GO; GO:0002020; F:protease binding; ISO:GO_Central. DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB. DR GO; GO:0007420; P:brain development; IMP:MGI. DR GO; GO:0008283; P:cell population proliferation; IMP:MGI. DR GO; GO:0071479; P:cellular response to ionizing radiation; ISO:GO_Central. DR GO; GO:0090398; P:cellular senescence; IMP:MGI. DR GO; GO:0051298; P:centrosome duplication; ISO:GO_Central. DR GO; GO:0043009; P:chordate embryonic development; IMP:MGI. DR GO; GO:0051276; P:chromosome organization; IMP:MGI. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:MGI. DR GO; GO:0000730; P:DNA recombinase assembly; ISS:UniProtKB. DR GO; GO:0006310; P:DNA recombination; ISO:GO_Central. DR GO; GO:0006302; P:double-strand break repair; IMP:MGI. DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; ISS:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:MGI. DR GO; GO:0070200; P:establishment of protein localization to telomere; IDA:BHF-UCL. DR GO; GO:0008585; P:female gonad development; IMP:MGI. DR GO; GO:0030097; P:hemopoiesis; IMP:MGI. DR GO; GO:0031619; P:homologous chromosome orientation in meiotic metaphase I; ISO:GO_Central. DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IGI:MGI. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI. DR GO; GO:0007141; P:male meiosis I; IDA:UniProtKB. DR GO; GO:0030879; P:mammary gland development; ISO:GO_Central. DR GO; GO:1990426; P:mitotic recombination-dependent replication fork processing; ISO:GO_Central. DR GO; GO:0035264; P:multicellular organism growth; ISO:GO_Central. DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; ISO:GO_Central. DR GO; GO:0006289; P:nucleotide-excision repair; ISO:GO_Central. DR GO; GO:0001556; P:oocyte maturation; IMP:MGI. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:GO_Central. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:MGI. DR GO; GO:0032465; P:regulation of cytokinesis; IMP:MGI. DR GO; GO:2000001; P:regulation of DNA damage checkpoint; NAS:ComplexPortal. DR GO; GO:0031297; P:replication fork processing; IMP:MGI. DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI. DR GO; GO:0010225; P:response to UV-C; IMP:MGI. DR GO; GO:0010165; P:response to X-ray; IMP:MGI. DR GO; GO:0007283; P:spermatogenesis; IMP:MGI. DR GO; GO:0000722; P:telomere maintenance via recombination; IGI:BHF-UCL. DR CDD; cd04493; BRCA2DBD_OB1; 1. DR CDD; cd04494; BRCA2DBD_OB2; 1. DR CDD; cd04495; BRCA2DBD_OB3; 1. DR FunFam; 2.40.50.140:FF:000205; Breast cancer susceptibility protein 2; 1. DR FunFam; 2.40.50.140:FF:000211; breast cancer type 2 susceptibility protein; 1. DR Gene3D; 6.10.70.10; -; 1. DR Gene3D; 2.40.50.140; Nucleic acid-binding proteins; 3. DR IDEAL; IID50324; -. DR InterPro; IPR015525; BRCA2. DR InterPro; IPR015252; BRCA2_hlx. DR InterPro; IPR036315; BRCA2_hlx_sf. DR InterPro; IPR015187; BRCA2_OB_1. DR InterPro; IPR048262; BRCA2_OB_2_dom. DR InterPro; IPR015188; BRCA2_OB_3. DR InterPro; IPR002093; BRCA2_repeat. DR InterPro; IPR055077; BRCA2_TR2. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR015205; Tower_dom. DR PANTHER; PTHR11289:SF0; BREAST CANCER TYPE 2 SUSCEPTIBILITY PROTEIN; 1. DR PANTHER; PTHR11289; BREAST CANCER TYPE 2 SUSCEPTIBILITY PROTEIN BRCA2; 1. DR Pfam; PF09169; BRCA-2_helical; 1. DR Pfam; PF09103; BRCA-2_OB1; 1. DR Pfam; PF09104; BRCA-2_OB3; 1. DR Pfam; PF00634; BRCA2; 7. DR Pfam; PF22687; BRCA2_TR2; 1. DR Pfam; PF21318; BRCA2DBD_OB2; 1. DR Pfam; PF09121; Tower; 1. DR PIRSF; PIRSF002397; BRCA2; 1. DR SMART; SM01341; Tower; 1. DR SUPFAM; SSF81872; BRCA2 helical domain; 1. DR SUPFAM; SSF81878; BRCA2 tower domain; 1. DR SUPFAM; SSF50249; Nucleic acid-binding proteins; 3. DR PROSITE; PS50138; BRCA2_REPEAT; 6. DR PDBsum; 1MIU; -. DR PDBsum; 1MJE; -. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Chromosome; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; DNA damage; DNA recombination; DNA repair; KW DNA-binding; Meiosis; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Telomere; Tumor suppressor; Ubl conjugation. FT CHAIN 1..3329 FT /note="Breast cancer type 2 susceptibility protein homolog" FT /id="PRO_0000064985" FT REPEAT 981..1015 FT /note="BRCA2 1" FT REPEAT 1192..1226 FT /note="BRCA2 2" FT REPEAT 1394..1428 FT /note="BRCA2 3" FT REPEAT 1491..1525 FT /note="BRCA2 4" FT REPEAT 1623..1657 FT /note="BRCA2 5" FT REPEAT 1924..1958 FT /note="BRCA2 6" FT REPEAT 2004..2038 FT /note="BRCA2 7" FT REGION 1..40 FT /note="Interaction with PALB2" FT /evidence="ECO:0000250|UniProtKB:P51587" FT REGION 37..69 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 207..241 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 628..979 FT /note="Interaction with NPM1" FT /evidence="ECO:0000250|UniProtKB:P51587" FT REGION 628..650 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 934..965 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 982..2035 FT /note="Interaction with RAD51" FT /evidence="ECO:0000269|PubMed:30760716" FT REGION 1296..1340 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2073..2099 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2219..2285 FT /note="Interaction with HSF2BP" FT /evidence="ECO:0000269|PubMed:30760716, FT ECO:0000269|PubMed:32345962" FT REGION 2298..2466 FT /note="Interaction with FANCD2" FT /evidence="ECO:0000250|UniProtKB:P51587" FT REGION 2361..2393 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2402..2753 FT /note="Interaction with SEM1" FT /evidence="ECO:0000250|UniProtKB:P51587" FT REGION 3188..3253 FT /note="TR2 region" FT /evidence="ECO:0000250|UniProtKB:P51587" FT REGION 3221..3257 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3273..3329 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 2603..2619 FT /note="Nuclear export signal; masked by interaction with FT SEM1" FT /evidence="ECO:0000250|UniProtKB:P51587" FT COMPBIAS 934..953 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 954..965 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1303..1323 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2074..2099 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2377..2393 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3309..3329 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 435 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51587" FT MOD_RES 481 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51587" FT MOD_RES 735 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51587" FT MOD_RES 2048 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51587" FT MOD_RES 3214 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000250|UniProtKB:P51587" FT MOD_RES 3241 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P51587" FT VARIANT 44 FT /note="S -> F (in strain: C57BL/6 and 129/Sv)" FT VARIANT 340 FT /note="T -> P (in strain: 129/Sv)" FT VARIANT 377 FT /note="N -> H (in strain: C57BL/6)" FT VARIANT 407 FT /note="H -> P (in strain: C57BL/6)" FT VARIANT 661 FT /note="I -> V (in strain: C57BL/6)" FT VARIANT 739 FT /note="P -> H (in strain: C57BL/6)" FT VARIANT 1198..1199 FT /note="GF -> RI (in strain: C57BL/6)" FT VARIANT 1257 FT /note="Q -> P (in strain: C57BL/6)" FT VARIANT 1392 FT /note="Q -> R (in strain: C57BL/6)" FT VARIANT 1520..1521 FT /note="FD -> CG (in strain: C57BL/6)" FT VARIANT 1583 FT /note="R -> W (in strain: C57BL/6)" FT VARIANT 1613 FT /note="C -> W (in strain: C57BL/6)" FT VARIANT 1686 FT /note="S -> R (in strain: C57BL/6)" FT VARIANT 1799 FT /note="S -> F (in strain: 129/Sv)" FT VARIANT 1881 FT /note="P -> L (in strain: C57BL/6)" FT VARIANT 1894 FT /note="S -> F (in strain: 129/Sv)" FT VARIANT 2141 FT /note="Q -> K (in strain: C57BL/6)" FT VARIANT 2392 FT /note="S -> R (in strain: C57BL/6)" FT VARIANT 2605 FT /note="K -> Q (in strain: C57BL/6)" FT VARIANT 2648 FT /note="A -> P (in strain: C57BL/6)" FT VARIANT 2717 FT /note="R -> C (in strain: 129/Sv)" FT VARIANT 2729 FT /note="L -> M (in strain: 129/Sv)" FT VARIANT 2814 FT /note="Q -> H (in strain: C57BL/6)" FT VARIANT 2827 FT /note="A -> P (in strain: C57BL/6)" FT VARIANT 2907 FT /note="S -> I (in strain: 129/Sv)" FT VARIANT 2929 FT /note="H -> L (in strain: 129/Sv)" FT VARIANT 3058 FT /note="A -> G (in strain: C57BL/6)" FT VARIANT 3071 FT /note="A -> G (in strain: C57BL/6)" FT VARIANT 3081 FT /note="K -> E (in strain: C57BL/6)" FT VARIANT 3089 FT /note="T -> S (in strain: C57BL/6)" FT VARIANT 3105..3109 FT /note="DSPKW -> SQSQV (in strain: C57BL/6)" FT VARIANT 3220 FT /note="A -> G (in strain: 129/Sv)" FT VARIANT 3238 FT /note="E -> K (in strain: 129/Sv)" FT VARIANT 3243 FT /note="Missing (in strain: C57BL/6)" FT VARIANT 3245 FT /note="R -> K (in strain: 129/Sv)" FT CONFLICT 1038 FT /note="L -> I (in Ref. 1; AAB48306)" FT /evidence="ECO:0000305" FT HELIX 2404..2420 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2430..2435 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2446..2448 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2456..2458 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2462..2464 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2468..2472 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2475..2480 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2486..2489 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2490..2492 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2495..2497 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2503..2505 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 2509..2511 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2512..2514 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 2518..2527 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2538..2554 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2560..2562 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2564..2569 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2570..2580 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2581..2586 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2592..2597 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2606..2608 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2640..2643 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2648..2653 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 2655..2662 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2671..2674 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2675..2677 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2679..2681 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2696..2699 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 2701..2703 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2704..2707 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2713..2715 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2726..2728 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2731..2733 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2736..2746 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2747..2749 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2751..2754 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 2756..2758 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2760..2763 FT /evidence="ECO:0007829|PDB:1MJE" FT HELIX 2767..2778 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2779..2781 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2782..2791 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2813..2817 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2822..2830 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2833..2835 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2836..2840 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2848..2850 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2851..2853 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2855..2871 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2873..2876 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2877..2881 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2889..2900 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2904..2910 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2913..2918 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2924..2930 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2938..2940 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2945..2957 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2961..2964 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2965..2967 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 2977..2980 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2981..2983 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 2986..2989 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 2990..3001 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3004..3006 FT /evidence="ECO:0007829|PDB:1MJE" FT STRAND 3009..3013 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3015..3017 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3019..3026 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3037..3044 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3050..3052 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3056..3058 FT /evidence="ECO:0007829|PDB:1MIU" FT STRAND 3063..3067 FT /evidence="ECO:0007829|PDB:1MIU" FT TURN 3071..3073 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 3074..3080 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 3082..3085 FT /evidence="ECO:0007829|PDB:1MIU" FT HELIX 3090..3102 FT /evidence="ECO:0007829|PDB:1MIU" SQ SEQUENCE 3329 AA; 370664 MW; 50A32E8BADE2CF7E CRC64; MPVEYKRRPT FWEIFKARCS TADLGPISLN WFEELSSEAP PYNSEPPEES EYKPHGYEPQ LFKTPQRNPP YHQFASTPIM FKERSQTLPL DQSPFRELGK VVASSKHKTH SKKKTKVDPV VDVASPPLKS CLSESPLTLR CTQAVLQREK PVVSGSLFYT PKLKEGQTPK PISESLGVEV DPDMSWTSSL ATPPTLSSTV LIARDEEARS SVTPADSPAT LKSCFSNHNE SPQKNDRSVP SVIDSENKNQ QEAFSQGLGK MLGDSSGKRN SFKDCLRKPI PNILEDGETA VDTSEEDSFS LCFPKRRTRN LQKMRMGKTR KKIFSETRTD ELSEEARRQT DDKNSFVFEM ELRESDPLDP GVTSQKPFYS QNEEICNEAV QCSDSRWSQS NLSGLNETQT GKITLPHISS HSQNISEDFI DMKKEGTGSI TSEKSLPHIS SLPEPEKMFS EETVVDKEHE GQHFESLEDS IAGKQMVSRT SQAACLSPSI RKSIFKMREP LDETLGTVFS DSMTNSTFTE EHEASACGLG ILTACSQRED SICPSSVDTG SWPTTLTDTS ATVKNAGLIS TLKNKKRKFI YSVSDDASLQ GKKLQTHRQL ELTNLSAQLE ASAFEVPLTF TNVNSGIPDS SDKKRCLPND PEEPSLTNSF GTATSKEISY IHALISQDLN DKEAIVIEEK PQPYTAREAD FLLCLPERTC ENDQKSPKVS NGKEKVLVSA CLPSAVQLSS ISFESQENPL GDHNGTSTLK LTPSSKLPLS KADMVSREKM CKMPEKLQCE SCKVNIELSK NILEVNEICI LSENSKTPGL LPPGENIIEV ASSMKSQFNQ NAKIVIQKDQ KGSPFISEVA VNMNSEELFP DSGNNFAFQV TNKCNKPDLG SSVELQEEDL SHTQGPSLKN SPMAVDEDVD DAHAAQVLIT KDSDSLAVVH DYTEKSRNNI EQHQKGTEDK DFKSNSSLNM KSDGNSDCSD KWSEFLDPVL NHNFGGSFRT ASNKEIKLSE HNVKKSKMFF KDIEEQYPTR LACIDIVNTL PLANQKKLSE PHIFDLKSVT TVSTQSHNQS SVSHEDTDTA PQMLSSKQDF HSNNLTTSQK AEITELSTIL EESGSQFEFT QFRKPSHIAQ NTSEVPGNQM VVLSTASKEW KDTDLHLPVD PSVGQTDHSK QFEGSAGVKQ SFPHLLEDTC NKNTSCFLPN INEMEFGGFC SALGTKLSVS NEALRKAMKL FSDIENSEEP SAKVGPRGFS SSAHHDSVAS VFKIKKQNTE KSFDEKSSKC QVTLQNNIEM TTCIFVGRNP EKYIKNTKHE DSYTSSQRNN LENSDGSMSS TSGPVYIHKG DSDLPADQGS KCPESCTQYA REENTQIKEN ISDLTCLEIM KAEETCMKSS DKKQLPSDKM EQNIKEFNIS FQTASGKNTR VSKESLNKSV NIFNRETDEL TVISDSLNSK ILHGINKDKM HTSCHKKAIS IKKVFEDHFP IVTVSQLPAQ QHPEYEIEST KEPTLLSFHT ASGKKVKIMQ ESLDKVKNLF DETQYVRKTA SFSQGSKPLK DSKKELTLAY EKIEVTASKC EEMQNFVSKE TEMLPQQNYH MYRQTENLKT SNGTSSKVQE NIENNVEKNP RICCICQSSY PVTEDSALAY YTEDSRKTCV RESSLSKGRK WLREQGDKLG TRNTIKIECV KEHTEDFAGN ASYEHSLVII RTEIDTNHVS ENQVSTLLSD PNVCHSYLSQ SSFCHCDDMH NDSGYFLKNK IDSDVPPDMK NAEGNTISPR VSATKERNLH PQTINEYCVQ KLETNTSPHA NKDVAIDPSL LDSRNCKVGS LVFITAHSQE TERTKEIVTD NCYKIVEQNR QSKPDTCQTS CHKVLDDSKD FICPSSSGDV CINSRKDSFC PHNEQILQHN QSMSGLKKAA TPPVGLETWD TSKSIREPPQ AAHPSRTYGI FSTASGKAIQ VSDASLEKAR QVFSEMDGDA KQLSSMVSLE GNEKPHHSVK RENSVVHSTQ GVLSLPKPLP GNVNSSVFSG FSTAGGKLVT VSESALHKVK GMLEEFDLIR TEHTLQHSPI PEDVSKILPQ PCAEIRTPEY PVNSKLQKTY NDKSSLPSNY KESGSSGNTQ SIEVSLQLSQ MERNQDTQLV LGTKVSHSKA NLLGKEQTLP QNIKVKTDEM KTFSDVPVKT NVGEYYSKES ENYFETEAVE SAKAFMEDDE LTDSEQTHAK CSLFTCPQNE TLFNSRTRKR GGVTVDAVGQ PPIKRSLLNE FDRIIESKGK SLTPSKSTPD GTVKDRSLFT HHMSLEPVTC GPFCSSKERQ GAQRPHLTSP AQELLSKGHP WRHSALEKSP SSPIVSILPA HDVSATRTER TRHSGKSTKV FVPPFKMKSQ FHGDEHFNSK NVNLEGKNQK STDGDREDGN DSHVRQFNKD LMSSLQSARD LQDMRIKNKE RRHLRLQPGS LYLTKSSTLP RISLQAAVGD RAPSACSPKQ LYIYGVSKEC INVNSKNAEY FQFDIQDHFG KEDLCAGKGF QLADGGWLIP SNDGKAGKEE FYRALCDTPG VDPKLISSIW VANHYRWIVW KLAAMEFAFP KEFANRCLNP ERVLLQLKYR YDVEIDNSRR SALKKILERD DTAAKTLVLC ISDIISPSTK VSETSGGKTS GEDANKVDTI ELTDGWYAVR AQLDPPLMAL VKSGKLTVGQ KIITQGAELV GSPDACAPLE APDSLRLKIS ANSTRPARWH SRLGFFRDPR PFPLPLSSLF SDGGNVGCVD IIVQRVYPLQ WVEKTVSGLY IFRSEREEEK EALRFAEAQQ KKLEALFTKV HTEFKDHEED TTQRCVLSRT LTRQQVHALQ DGAELYAAVQ YASDPDHLEA CFSEEQLRAL NNYRQMLNDK KQARIQSEFR KALESAEKEE GLSRDVTTVW KLRVTSYKKK EKSALLSIWR PSSDLSSLLT EGKRYRIYHL AVSKSKSKFE RPSIQLTATK RTQYQQLPVS SETLLQVYQP RESLHFSRLS DPAFQPPCSE VDVVGVVVSV VKPIGLAPLV YLSDECLNLL VVKFGIDLNE DIKPRVLIAA SNLQCQPEST SGVPTLFAGH FSIFSASPKE AYFQEKVNNL KHAIENIDTF YKEAEKKLIH VLEGDSPKWS TPNKDPTREP HAASTCCASD LLGSGGQFLR ISPTGQQSYQ SPLSHCTLKG KSMPLAHSAQ MAAKSWSGEN EIDDPKTCRK RRALDFLSRL PLPSPVSPIC TFVSPAAQKA FQPPRSCGTK YATPIKKEPS SPRRRTPFQK TSGVSLPDCD SVADEELALL STQALTPDSV GGNEQAFPGD STRNPQPAQR PDQQVGPRSR KESLRDCRGD SSEKLAVES //