BRCA2_FELCA
ID BRCA2_FELCA Reviewed; 3372 AA.
AC Q864S8;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Breast cancer type 2 susceptibility protein homolog;
DE AltName: Full=Fanconi anemia group D1 protein homolog;
GN Name=BRCA2; Synonyms=FANCD1;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=14600353; DOI=10.1292/jvms.65.1123;
RA Oonuma T., Morimatsu M., Ochiai K., Syuto B.;
RT "Properties of the tumor suppressor gene brca2 in the cat.";
RL J. Vet. Med. Sci. 65:1123-1126(2003).
CC -!- FUNCTION: Involved in double-strand break repair and/or homologous
CC recombination. Binds RAD51 and potentiates recombinational DNA repair
CC by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). Acts
CC by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to
CC displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-
CC ssDNA filaments by blocking ATP hydrolysis. Part of a PALB2-scaffolded
CC HR complex containing RAD51C and which is thought to play a role in DNA
CC repair by HR. May participate in S phase checkpoint activation. Binds
CC selectively to ssDNA, and to ssDNA in tailed duplexes and replication
CC fork structures. May play a role in the extension step after strand
CC invasion at replication-dependent DNA double-strand breaks; together
CC with PALB2 is involved in both POLH localization at collapsed
CC replication forks and DNA polymerization activity. In concert with
CC NPM1, regulates centrosome duplication. Interacts with the TREX-2
CC complex (transcription and export complex 2) subunits PCID2 and SEM1,
CC and is required to prevent R-loop-associated DNA damage and thus
CC transcription-associated genomic instability, independently of its
CC known role in homologous recombination (By similarity).
CC {ECO:0000250|UniProtKB:P51587}.
CC -!- SUBUNIT: Monomer and dimer. Interacts with RAD51; regulates RAD51
CC recruitment and function at sites of DNA repair. Interacts with SEM1,
CC WDR16, USP11, DMC1, ROCK2 and NPM1. Interacts with both
CC nonubiquitinated and monoubiquitinated FANCD2; this complex also
CC includes XRCC3 and phosphorylated FANCG. Part of a BRCA complex
CC containing BRCA1, BRCA2 and PALB2. Component of the homologous
CC recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2,
CC DSS1 and RAD51 (By similarity). Within the complex, interacts with
CC ERCC5/XPG and PALB2 (By similarity). Interacts directly with PALB2
CC which may serve as a scaffold for a HR complex containing PALB2, BRCA2,
CC RAD51C, RAD51 and XRCC3. Interacts with BRCA1 only in the presence of
CC PALB2 which serves as the bridging protein. Interacts with POLH; the
CC interaction is direct. Interacts with the TREX-2 complex subunits PCID2
CC and SEM1 (By similarity). Interacts with HSF2BP and BRME1; the
CC interaction with HSF2BP is direct and allows the formation of a ternary
CC complex. The complex BRME1:HSF2BP:BRCA2 interacts with SPATA22, MEIOB
CC and RAD51 (By similarity). {ECO:0000250|UniProtKB:O35923,
CC ECO:0000250|UniProtKB:P51587, ECO:0000250|UniProtKB:P97929}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P51587}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {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-3236 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}.
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DR EMBL; AB107955; BAC75821.2; -; mRNA.
DR RefSeq; NP_001009858.1; NM_001009858.1.
DR SMR; Q864S8; -.
DR IntAct; Q864S8; 1.
DR MINT; Q864S8; -.
DR STRING; 9685.ENSFCAP00000019777; -.
DR GeneID; 493878; -.
DR KEGG; fca:493878; -.
DR CTD; 675; -.
DR eggNOG; KOG4751; Eukaryota.
DR InParanoid; Q864S8; -.
DR OrthoDB; 257485at2759; -.
DR Proteomes; UP000011712; Unplaced.
DR GO; GO:0033593; C:BRCA2-MAGE-D1 complex; ISS:UniProtKB.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0030141; C:secretory granule; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB.
DR GO; GO:0051298; P:centrosome duplication; ISS:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IBA:GO_Central.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd04493; BRCA2DBD_OB1; 1.
DR CDD; cd04495; BRCA2DBD_OB3; 1.
DR Gene3D; 2.40.50.140; -; 3.
DR InterPro; IPR015525; BRCA2.
DR InterPro; IPR015252; BRCA2_hlx.
DR InterPro; IPR036315; BRCA2_hlx_sf.
DR InterPro; IPR015187; BRCA2_OB_1.
DR InterPro; IPR015188; BRCA2_OB_3.
DR InterPro; IPR002093; BRCA2_repeat.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR015205; Tower_dom.
DR PANTHER; PTHR11289; PTHR11289; 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; PF09121; Tower; 1.
DR PIRSF; PIRSF002397; BRCA2; 1.
DR SMART; SM01341; Tower; 1.
DR SUPFAM; SSF50249; SSF50249; 3.
DR SUPFAM; SSF81872; SSF81872; 1.
DR PROSITE; PS50138; BRCA2_REPEAT; 7.
PE 2: Evidence at transcript level;
KW Cytoplasm; Cytoskeleton; DNA damage; DNA recombination; DNA repair;
KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Tumor suppressor; Ubl conjugation.
FT CHAIN 1..3372
FT /note="Breast cancer type 2 susceptibility protein homolog"
FT /id="PRO_0000227014"
FT REPEAT 994..1028
FT /note="BRCA2 1"
FT REPEAT 1208..1242
FT /note="BRCA2 2"
FT REPEAT 1417..1451
FT /note="BRCA2 3"
FT REPEAT 1518..1552
FT /note="BRCA2 4"
FT REPEAT 1663..1697
FT /note="BRCA2 5"
FT REPEAT 1925..1959
FT /note="BRCA2 6"
FT REPEAT 1995..2029
FT /note="BRCA2 7"
FT REGION 1..40
FT /note="Interaction with PALB2"
FT /evidence="ECO:0000250"
FT REGION 234..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 630..992
FT /note="Interaction with NPM1"
FT /evidence="ECO:0000250"
FT REGION 704..783
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 995..2026
FT /note="Interaction with RAD51"
FT /evidence="ECO:0000250|UniProtKB:P97929"
FT REGION 1867..1891
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2034..2062
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2213..2279
FT /note="Interaction with HSF2BP"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT REGION 2359..2395
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2425..2776
FT /note="Interaction with SEM1"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT REGION 3181..3203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3308..3372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 2626..2642
FT /note="Nuclear export signal; masked by interaction with
FT SEM1"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT COMPBIAS 234..251
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 704..724
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 744..760
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2359..2384
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3308..3325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 1924
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 1990
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 2039
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 3236
FT /note="Phosphoserine; by CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 3264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51587"
FT MOD_RES 3331
FT /note="Phosphothreonine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P51587"
SQ SEQUENCE 3372 AA; 377345 MW; 37F23DA23CA94665 CRC64;
MPIGCKERPT FFEIFRTRCN KADLGPISLN WFEELCLEAP PYNSEPTEES GYKISYEPNL
FKTPQRKPCH QLASTPIIFK EQGLIPPIYQ QSPLKELGKD ITNSKHRSCC TMKSKMDQTN
DVTSPPLNSC LSESPLLRST HVTPQREKSV VCGSLFHTPK LTKGQTPKRI SESLGAEVDP
DMSWSSSLAT PPTLSSTVLI VRDEEASAAV FPNDTTAIFK SYFCNHDESL KKNDRFIPSG
PDSENKSQRE AKSQGLGKMV GNSCDKVNSC KDPFGNSTLN VLEDGVRERV ADVSEEDSFP
LCVPKCKTRN LQKIKTSKTR KNIFNETTDE CKEAKKQMKE NKHSFVSEME ANASDPLDSN
VTNQKPFGNG SDKISKEVVL SSASESCHLT LSGLNGTHME KLPLLCISSC DQNNSEKDLI
TTEKECTNFI ILEDSLPQIS GVPKCTEKIL NEEIVVNKID EGQCLESHED SILAVKQAVF
ETSLIASPLQ GIRKSIFRIR ESPEETFSAV FSNNITDPNF KEEHEASESV LEKHSICSQK
EDSLSTSSLD NGSWPATIKH TSVALKNSGL ISTLKKKTKK FIYVVNDETS YQGLKTQKDQ
QSGLMNYSAQ FEANVLEGPL TFANADSGLL HSSVKKTCLQ NDSKEPILSL TNSFGTLLRK
VSNKGSSSPN NKIISQDLDY KEAKIKKEKL QSFISTETNC LSSLQEKHCE DDTKSQRVAD
RKEEILPAVS QPSVPYSEVE DSGIHFQTLK SFSSDPDKSS QLTPHPRDPP SNPVGLSRGR
ESYEVSETLK CKNHEAGFEL TKTMENSQEI HVLNEHAKKA KLLSTEKYVT EASPSMKVPF
NQNAHLTIIQ KDQKETTLIS KITMNPNSEE LFPDGDNFVF KITKERNVPV LGSIKELQDS
DLCCVKEPVL ENSTMVVYTD MDDKQAAKVS ITKGFDSSNI DDLTEKDRNS IKQQLRMTLD
QDSKSDITLD SDMKSNGNND YMDNWARLSD PILNHNFGNG FRTASNKEIK LSEHNIKKSK
MLFKDIEERY PTNLACIEIV NTPLESQEKL SKPHILDPQS INTVSGCVQS SAYVSDSENR
HTTPPTLSLK RDFDSNHNLT PSQKAEITEL STILEESGSQ FEFTQFRKPS HLKQKNPCEM
PEKHLTISNT TPEEQKDGHL RLTINALSIS QGDSSKKFEG IIGGKQKLAC LSKTSCNKSA
SGHLTGKNEV EFRGFYSARG TKLNVCSEAL QKAKKLFSDL ENISEETSVE VDRSFSSSKC
NGSVSMFKKE NCNNEKKLNE KNNKYRLILQ NNIEMTTGIF VAEDTEGYKR NIENKANKYT
DASRNVYNFR EADGSDSSKN DTVYIHKEEN GLPYIDQHDI DLKLSSQFIK EGNTQIKEGL
SDLTCLEVVK AEETLHVNTS NKEHLTANTM GRITKDFDIF DVSFQTASGK NIRVSRASLN
KVTNLLDQKC TEEELNNFAD SLNSELLSGI DINKADISHH GEMEILKKRQ MKESDLTGTE
NKSLTLQQRP EYEIKKIKEP TILGFHTASG KRIEIAKESL DKVKNLFDEQ EQDKSEMTNF
SHRGTKMSKG REECEGGLRL ACKTIEITPA SKEEEMQKPL EKNLVSNEIV VVPRLLSDNL
YKQTENLKIP NRASLKVKVH ENTGKETAKK PTTCTNQSTY SATENSALSF YTGHGRKISV
SQSSILEVKK WLRGGELDDQ PEKTVYNISE YLPKSKVDNS GIEPVVRNVG ERENTSVSEI
MFTVREADTD PQSVNEDICV QRLVTNFSCK KENTAIKVTV SDSNNFDSTQ KLNSDSNDAV
PVYTTASSER VLVAHETKVA EGFTENCSMA IKQTTKSKPG KIVAGYRKAP DDSEDTICPN
SLDGAECSSP SHKDFAETQS EQTPQLNQSI SGFKKRSEIP PHQINLKTSD ICKLSTGKRL
QSISYTNACG IFSTASGKCV QVSDAALQKA RQVFSKVEDS AKQPFSKVSF KHNEDHSDKF
TREENTMIHT PQNLLSSAFS GFSTASGKQV PVSESALCKV KGILEEFDVM RTECGPQRSP
TSRQDVSKMP PPSCVENKTP KHSVNSKLEK AYNKEFKLSS NSKIENGSSE NHSVQVSPYP
SQFKQDKQLI QGNKASLVEN IHLLEKEQAL PKNIKWKLET EAFPNLPLKT DTAIHSTDSK
DPENYFETET VEIAKAFMED GELTDADLLS HARHFLPTCQ HSEETLVSNS RRGKRRGVLV
SVGEPPIKRN LLNEFDRIIK NQEKSLKASK STPDGIIKDR SLFMHHISLE PVTCGPFSTT
KKRQEIQNPN FTAPGQKFLS KSHFYEHLAL EKSSSNVSIS GQPFCTVPAT RSEKRGHSIT
PSKPVKVFVP PFKTKSRFLQ DEQHISKNTH VEENKQKPNN IDEHSSGDSK NNINNSEIHQ
LNKNNSSQAA TMVFTKCEKE PLDLIASLQN ARDIQDMRIR EKRKQHIFPQ PGSLFLAKTS
TVPRISLRVA VEGRVPSACS HKQLYMYGVS KHCVKINSKN AESFQFHTQD YFGKEVQWAK
EGIQLADGGW LIPSNDGKAG KEEFYRALCD TPGVDPNLIS RIWVYNHYRW IIWKLAAMEF
AFPKEFANRC LSPERVLLQL KYRYDMEIDR SKRSAIKKIM ERDDTAAKTL VLCISETISS
STDLSETSGS KTSGVGTKNV GIVELTDGWY AIKAQLDPPL LALVKKGRLT VGHKIIIHGA
ELAGSPDACT PLEAPESLIL KISANSTRPA CWYAKLGFFP DPRPFPLPLS SLFSDGGNVG
CVDVVIQRTY PIQWMEKTPS GLCIFRNERE EEREATKYAE AQQKKLEVLF NKIQAEFEKH
DENITKRCVP LRALTRQQVC ALQDGAELYE AVKNAPDPAS LEAYFSEEQI RALNNHRQML
NDKKQAQIQL EFRKAMESAE QGEQMLPRDV TTVWKMRIIS YGKKEKDSVT LSIWRPSSDL
YSLLTEGKRY RIYHLATSQS KSKSERAHIQ LTATKKTQYQ QLPASDELLF QVYQPREPLY
FNKLLDPDFQ PPCSEVDLIG FVVSVVKKIG FAPLVYLSDE CHNLLAIKVW TDLNEDIVKP
HTLIAASNLQ WRPESKSGIP TLFAGDFSRF SASPKEGHFQ ETFHKMKNTI ENVETFCNDA
ENKLVHILNA NSPKVSTPMK DYASEPHTIQ TVLGLGNKLS MSSPNSEMNY QSPLSLCKPK
AKSVPTPGSA QMTSKSCYKG ERELDDPKTC KKRKALDFLS RLPLPPPVSP ICTFVSPAAQ
KAFQPPRSCG TKYETPIKKR ELNSPQMTPL KFNDTSLVES DSIADEELAL INTQALLSGL
AGEDQLMSLN DSPRTAPTSS KDYVRPKSYP TAPGIRDCEN PQASTEGGEP DVQDTDTVKR
SSMRLQRRQQ QT
