Homo sapiens L. (human) [HSA]

FULL NAME: Breast cancer type 1 susceptibility protein


DESCRIPTION:
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for normal cell cycle progression from G2 to mitosis. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Involved in transcriptional regulation of P21 in response to DNA damage. Required for FANCD2 targeting to sites of DNA damage. May function as a transcriptional regulator. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks.

STRUCTURE SIMILARITY:
Contains 2 BRCT domains.
Contains 1 RING-type zinc finger.


ENZYME REGULATION:
The E3 ubiquitin-protein ligase activity is inhibited by phosphorylation by AURKA. Activity is increased by phosphatase treatment.


POST-TRANSLATIONAL MODIFICATION:
Phosphorylation at Ser-308 by AURKA is required for normal cell cycle progression from G2 to mitosis. Phosphorylated in response to IR, UV, and various stimuli that cause checkpoint activation, probably by ATM or ATR.
Autoubiquitinated, undergoes 'Lys-6'-linked polyubiquitination. 'Lys-6'-linked polyubiquitination does not promote degradation.


RELATED PATHWAY(S):
Fanconi anemia (FA) pathway


RELATED DISEASE(S):
prostate cancer
breast-ovarian cancer familial type 1 (BROVCA1)
breast cancer (BC)


Amino acids sequence

        10         20         30         40         50         60
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ
        70         80         90        100        110        120
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD
       130        140        150        160        170        180
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI
       190        200        210        220        230        240
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ
       250        260        270        280        290        300
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE
       310        320        330        340        350        360
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC
       370        380        390        400        410        420
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD
       430        440        450        460        470        480
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN
       490        500        510        520        530        540
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE
       550        560        570        580        590        600
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI
       610        620        630        640        650        660
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV
       670        680        690        700        710        720
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE
       730        740        750        760        770        780
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ
       790        800        810        820        830        840
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS
       850        860        870        880        890        900
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT
       910        920        930        940        950        960
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG
       970        980        990       1000       1010       1020
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP
      1030       1040       1050       1060       1070       1080
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL
      1090       1100       1110       1120       1130       1140
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS
      1150       1160       1170       1180       1190       1200
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ
      1210       1220       1230       1240       1250       1260
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL
      1270       1280       1290       1300       1310       1320
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS
      1330       1340       1350       1360       1370       1380
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE
      1390       1400       1410       1420       1430       1440
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE
      1450       1460       1470       1480       1490       1500
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK
      1510       1520       1530       1540       1550       1560
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG
      1570       1580       1590       1600       1610       1620
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT
      1630       1640       1650       1660       1670       1680
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI
      1690       1700       1710       1720       1730       1740
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV
      1750       1760       1770       1780       1790       1800
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL
      1810       1820       1830       1840       1850       1860
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH

SHY     

Encoded by BRCA1 gene

FULL NAME: breast cancer 1, early onset


OTHER NAME(S):
BRCAI
BRCC1
BROVCA1
IRIS
PNCA4
PSCP
RNF53


DESCRIPTION:
This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. The encoded protein combines with other tumor suppressors, DNA damage sensors, and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). This gene product associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. This protein thus plays a role in transcription, DNA repair of double-stranded breaks, and recombination. Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. A related pseudogene, which is also located on chromosome 17, has been identified. [provided by RefSeq, May 2009]


Nucleic acid sequence

        10         20         30         40         50         60
atggatttat ctgctcttcg cgttgaagaa gtacaaaatg tcattaatgc tatgcagaaa
        70         80         90        100        110        120
atcttagagt gtcccatctg tctggagttg atcaaggaac ctgtctccac aaagtgtgac
       130        140        150        160        170        180
cacatatttt gcaaattttg catgctgaaa cttctcaacc agaagaaagg gccttcacag
       190        200        210        220        230        240
tgtcctttat gtaagaatga tataaccaaa aggagcctac aagaaagtac gagatttagt
       250        260        270        280        290        300
caacttgttg aagagctatt gaaaatcatt tgtgcttttc agcttgacac aggtttggag
       310        320        330        340        350        360
tatgcaaaca gctataattt tgcaaaaaag gaaaataact ctcctgaaca tctaaaagat
       370        380        390        400        410        420
gaagtttcta tcatccaaag tatgggctac agaaaccgtg ccaaaagact tctacagagt
       430        440        450        460        470        480
gaacccgaaa atccttcctt gcaggaaacc agtctcagtg tccaactctc taaccttgga
       490        500        510        520        530        540
actgtgagaa ctctgaggac aaagcagcgg atacaacctc aaaagacgtc tgtctacatt
       550        560        570        580        590        600
gaattgggat ctgattcttc tgaagatacc gttaataagg caacttattg cagtgtggga
       610        620        630        640        650        660
gatcaagaat tgttacaaat cacccctcaa ggaaccaggg atgaaatcag tttggattct
       670        680        690        700        710        720
gcaaaaaagg ctgcttgtga attttctgag acggatgtaa caaatactga acatcatcaa
       730        740        750        760        770        780
cccagtaata atgatttgaa caccactgag aagcgtgcag ctgagaggca tccagaaaag
       790        800        810        820        830        840
tatcagggta gttctgtttc aaacttgcat gtggagccat gtggcacaaa tactcatgcc
       850        860        870        880        890        900
agctcattac agcatgagaa cagcagttta ttactcacta aagacagaat gaatgtagaa
       910        920        930        940        950        960
aaggctgaat tctgtaataa aagcaaacag cctggcttag caaggagcca acataacaga
       970        980        990       1000       1010       1020
tgggctggaa gtaaggaaac atgtaatgat aggcggactc ccagcacaga aaaaaaggta
      1030       1040       1050       1060       1070       1080
gatctgaatg ctgatcccct gtgtgagaga aaagaatgga ataagcagaa actgccatgc
      1090       1100       1110       1120       1130       1140
tcagagaatc ctagagatac tgaagatgtt ccttggataa cactaaatag cagcattcag
      1150       1160       1170       1180       1190       1200
aaagttaatg agtggttttc cagaagtgat gaactgttag gttctgatga ctcacatgat
      1210       1220       1230       1240       1250       1260
ggggagtctg aatcaaatgc caaagtagct gatgtattgg acgttctaaa tgaggtagat
      1270       1280       1290       1300       1310       1320
gaatattctg gttcttcaga gaaaatagac ttactggcca gtgatcctca tgaggcttta
      1330       1340       1350       1360       1370       1380
atatgtaaaa gtgaaagagt tcactccaaa tcagtagaga gtaatattga agacaaaata
      1390       1400       1410       1420       1430       1440
tttgggaaaa cctatcggaa gaaggcaagc ctccccaact taagccatgt aactgaaaat
      1450       1460       1470       1480       1490       1500
ctaattatag gagcatttgt tactgagcca cagataatac aagagcgtcc cctcacaaat
      1510       1520       1530       1540       1550       1560
aaattaaagc gtaaaaggag acctacatca ggccttcatc ctgaggattt tatcaagaaa
      1570       1580       1590       1600       1610       1620
gcagatttgg cagttcaaaa gactcctgaa atgataaatc agggaactaa ccaaacggag
      1630       1640       1650       1660       1670       1680
cagaatggtc aagtgatgaa tattactaat agtggtcatg agaataaaac aaaaggtgat
      1690       1700       1710       1720       1730       1740
tctattcaga atgagaaaaa tcctaaccca atagaatcac tcgaaaaaga atctgctttc
      1750       1760       1770       1780       1790       1800
aaaacgaaag ctgaacctat aagcagcagt ataagcaata tggaactcga attaaatatc
      1810       1820       1830       1840       1850       1860
cacaattcaa aagcacctaa aaagaatagg ctgaggagga agtcttctac caggcatatt
      1870       1880       1890       1900       1910       1920
catgcgcttg aactagtagt cagtagaaat ctaagcccac ctaattgtac tgaattgcaa
      1930       1940       1950       1960       1970       1980
attgatagtt gttctagcag tgaagagata aagaaaaaaa agtacaacca aatgccagtc
      1990       2000       2010       2020       2030       2040
aggcacagca gaaacctaca actcatggaa ggtaaagaac ctgcaactgg agccaagaag
      2050       2060       2070       2080       2090       2100
agtaacaagc caaatgaaca gacaagtaaa agacatgaca gcgatacttt cccagagctg
      2110       2120       2130       2140       2150       2160
aagttaacaa atgcacctgg ttcttttact aagtgttcaa ataccagtga acttaaagaa
      2170       2180       2190       2200       2210       2220
tttgtcaatc ctagccttcc aagagaagaa aaagaagaga aactagaaac agttaaagtg
      2230       2240       2250       2260       2270       2280
tctaataatg ctgaagaccc caaagatctc atgttaagtg gagaaagggt tttgcaaact
      2290       2300       2310       2320       2330       2340
gaaagatctg tagagagtag cagtatttca ttggtacctg gtactgatta tggcactcag
      2350       2360       2370       2380       2390       2400
gaaagtatct cgttactgga agttagcact ctagggaagg caaaaacaga accaaataaa
      2410       2420       2430       2440       2450       2460
tgtgtgagtc agtgtgcagc atttgaaaac cccaagggac taattcatgg ttgttccaaa
      2470       2480       2490       2500       2510       2520
gataatagaa atgacacaga aggctttaag tatccattgg gacatgaagt taaccacagt
      2530       2540       2550       2560       2570       2580
cgggaaacaa gcatagaaat ggaagaaagt gaacttgatg ctcagtattt gcagaataca
      2590       2600       2610       2620       2630       2640
ttcaaggttt caaagcgcca gtcatttgct ccgttttcaa atccaggaaa tgcagaagag
      2650       2660       2670       2680       2690       2700
gaatgtgcaa cattctctgc ccactctggg tccttaaaga aacaaagtcc aaaagtcact
      2710       2720       2730       2740       2750       2760
tttgaatgtg aacaaaagga agaaaatcaa ggaaagaatg agtctaatat caagcctgta
      2770       2780       2790       2800       2810       2820
cagacagtta atatcactgc aggctttcct gtggttggtc agaaagataa gccagttgat
      2830       2840       2850       2860       2870       2880
aatgccaaat gtagtatcaa aggaggctct aggttttgtc tatcatctca gttcagaggc
      2890       2900       2910       2920       2930       2940
aacgaaactg gactcattac tccaaataaa catggacttt tacaaaaccc atatcgtata
      2950       2960       2970       2980       2990       3000
ccaccacttt ttcccatcaa gtcatttgtt aaaactaaat gtaagaaaaa tctgctagag
      3010       3020       3030       3040       3050       3060
gaaaactttg aggaacattc aatgtcacct gaaagagaaa tgggaaatga gaacattcca
      3070       3080       3090       3100       3110       3120
agtacagtga gcacaattag ccgtaataac attagagaaa atgtttttaa agaagccagc
      3130       3140       3150       3160       3170       3180
tcaagcaata ttaatgaagt aggttccagt actaatgaag tgggctccag tattaatgaa
      3190       3200       3210       3220       3230       3240
ataggttcca gtgatgaaaa cattcaagca gaactaggta gaaacagagg gccaaaattg
      3250       3260       3270       3280       3290       3300
aatgctatgc ttagattagg ggttttgcaa cctgaggtct ataaacaaag tcttcctgga
      3310       3320       3330       3340       3350       3360
agtaattgta agcatcctga aataaaaaag caagaatatg aagaagtagt tcagactgtt
      3370       3380       3390       3400       3410       3420
aatacagatt tctctccata tctgatttca gataacttag aacagcctat gggaagtagt
      3430       3440       3450       3460       3470       3480
catgcatctc aggtttgttc tgagacacct gatgacctgt tagatgatgg tgaaataaag
      3490       3500       3510       3520       3530       3540
gaagatacta gttttgctga aaatgacatt aaggaaagtt ctgctgtttt tagcaaaagc
      3550       3560       3570       3580       3590       3600
gtccagaaag gagagcttag caggagtcct agccctttca cccatacaca tttggctcag
      3610       3620       3630       3640       3650       3660
ggttaccgaa gaggggccaa gaaattagag tcctcagaag agaacttatc tagtgaggat
      3670       3680       3690       3700       3710       3720
gaagagcttc cctgcttcca acacttgtta tttggtaaag taaacaatat accttctcag
      3730       3740       3750       3760       3770       3780
tctactaggc atagcaccgt tgctaccgag tgtctgtcta agaacacaga ggagaattta
      3790       3800       3810       3820       3830       3840
ttatcattga agaatagctt aaatgactgc agtaaccagg taatattggc aaaggcatct
      3850       3860       3870       3880       3890       3900
caggaacatc accttagtga ggaaacaaaa tgttctgcta gcttgttttc ttcacagtgc
      3910       3920       3930       3940       3950       3960
agtgaattgg aagacttgac tgcaaataca aacacccagg atcctttctt gattggttct
      3970       3980       3990       4000       4010       4020
tccaaacaaa tgaggcatca gtctgaaagc cagggagttg gtctgagtga caaggaattg
      4030       4040       4050       4060       4070       4080
gtttcagatg atgaagaaag aggaacgggc ttggaagaaa ataatcaaga agagcaaagc
      4090       4100       4110       4120       4130       4140
atggattcaa acttaggtga agcagcatct gggtgtgaga gtgaaacaag cgtctctgaa
      4150       4160       4170       4180       4190       4200
gactgctcag ggctatcctc tcagagtgac attttaacca ctcagcagag ggataccatg
      4210       4220       4230       4240       4250       4260
caacataacc tgataaagct ccagcaggaa atggctgaac tagaagctgt gttagaacag
      4270       4280       4290       4300       4310       4320
catgggagcc agccttctaa cagctaccct tccatcataa gtgactcttc tgcccttgag
      4330       4340       4350       4360       4370       4380
gacctgcgaa atccagaaca aagcacatca gaaaaagcag tattaacttc acagaaaagt
      4390       4400       4410       4420       4430       4440
agtgaatacc ctataagcca gaatccagaa ggcctttctg ctgacaagtt tgaggtgtct
      4450       4460       4470       4480       4490       4500
gcagatagtt ctaccagtaa aaataaagaa ccaggagtgg aaaggtcatc cccttctaaa
      4510       4520       4530       4540       4550       4560
tgcccatcat tagatgatag gtggtacatg cacagttgct ctgggagtct tcagaataga
      4570       4580       4590       4600       4610       4620
aactacccat ctcaagagga gctcattaag gttgttgatg tggaggagca acagctggaa
      4630       4640       4650       4660       4670       4680
gagtctgggc cacacgattt gacggaaaca tcttacttgc caaggcaaga tctagaggga
      4690       4700       4710       4720       4730       4740
accccttacc tggaatctgg aatcagcctc ttctctgatg accctgaatc tgatccttct
      4750       4760       4770       4780       4790       4800
gaagacagag ccccagagtc agctcgtgtt ggcaacatac catcttcaac ctctgcattg
      4810       4820       4830       4840       4850       4860
aaagttcccc aattgaaagt tgcagaatct gcccagagtc cagctgctgc tcatactact
      4870       4880       4890       4900       4910       4920
gatactgctg ggtataatgc aatggaagaa agtgtgagca gggagaagcc agaattgaca
      4930       4940       4950       4960       4970       4980
gcttcaacag aaagggtcaa caaaagaatg tccatggtgg tgtctggcct gaccccagaa
      4990       5000       5010       5020       5030       5040
gaatttatgc tcgtgtacaa gtttgccaga aaacaccaca tcactttaac taatctaatt
      5050       5060       5070       5080       5090       5100
actgaagaga ctactcatgt tgttatgaaa acagatgctg agtttgtgtg tgaacggaca
      5110       5120       5130       5140       5150       5160
ctgaaatatt ttctaggaat tgcgggagga aaatgggtag ttagctattt ctgggtgacc
      5170       5180       5190       5200       5210       5220
cagtctatta aagaaagaaa aatgctgaat gagcatgatt ttgaagtcag aggagatgtg
      5230       5240       5250       5260       5270       5280
gtcaatggaa gaaaccacca aggtccaaag cgagcaagag aatcccagga cagaaagatc
      5290       5300       5310       5320       5330       5340
ttcagggggc tagaaatctg ttgctatggg cccttcacca acatgcccac agatcaactg
      5350       5360       5370       5380       5390       5400
gaatggatgg tacagctgtg tggtgcttct gtggtgaagg agctttcatc attcaccctt
      5410       5420       5430       5440       5450       5460
ggcacaggtg tccacccaat tgtggttgtg cagccagatg cctggacaga ggacaatggc
      5470       5480       5490       5500       5510       5520
ttccatgcaa ttgggcagat gtgtgaggca cctgtggtga cccgagagtg ggtgttggac
      5530       5540       5550       5560       5570       5580
agtgtagcac tctaccagtg ccaggagctg gacacctacc tgatacccca gatcccccac
      5590
agccactact ga    

Last modification date: Oct. 2, 2011