DP00238: Breast cancer type 1 susceptibility proteinFASTA viewXML view

General information
DisProt:DP00238
Name:Breast cancer type 1 susceptibility protein
Synonym(s):BRCA1_HUMAN
RING finger protein 53
BRCA1
First appeared in release:Release 2.2 (04/14/2005)
UniProt:P38398
UniGene:Hs.194143
SwissProt: BRCA1_HUMAN
TrEMBL:  
NCBI (GI): 728984
Source organism:Homo sapiens (Human)
Sequence length:1863
Percent disordered:81%
Homologues: 


Native sequence

        10         20         30         40         50         60
         |          |          |          |          |          |
MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ - 60
CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD - 120
EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI - 180
ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ - 240
PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE - 300
KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC - 360
SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD - 420
EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN - 480
LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE - 540
QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI - 600
HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV - 660
RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE - 720
FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ - 780
ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS - 840
RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT - 900
FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG - 960
NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP - 1020
STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL - 1080
NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS - 1140
HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ - 1200
GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL - 1260
LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS - 1320
SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE - 1380
DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE - 1440
DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK - 1500
CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG - 1560
TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT - 1620
DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI - 1680
TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV - 1740
VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL - 1800
GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH - 1860
SHY



Functional narrative    

The BRCA1 tumor suppressor gene is implicated in many cellular pathways including transcription, cell-cycle, checkpoint control, apoptosis and DNA repair. The central disordered region may act as a scaffold for intermolecular interactions crucial for DNA damage reponse.

Region 1: 170-1649 Region 2: 1755-1758 Region 3: 1773-1777 Region 4: 1799-1804 Region 5: 1812-1823

Map of ordered and disordered regions







Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.


Region 1
Type:Disordered
Name: 
Location:170 - 1649
Length:1480
Region sequence:

RIQPQKTSVYIELGSDSSEDTVNKATYCSVGDQELLQITPQGTRDEISLDSAKKAACEFS
ETDVTNTEHHQPSNNDLNTTEKRAAERHPEKYQGSSVSNLHVEPCGTNTHASSLQHENSS
LLLTKDRMNVEKAEFCNKSKQPGLARSQHNRWAGSKETCNDRRTPSTEKKVDLNADPLCE
RKEWNKQKLPCSENPRDTEDVPWITLNSSIQKVNEWFSRSDELLGSDDSHDGESESNAKV
ADVLDVLNEVDEYSGSSEKIDLLASDPHEALICKSERVHSKSVESNIEDKIFGKTYRKKA
SLPNLSHVTENLIIGAFVTEPQIIQERPLTNKLKRKRRPTSGLHPEDFIKKADLAVQKTP
EMINQGTNQTEQNGQVMNITNSGHENKTKGDSIQNEKNPNPIESLEKESAFKTKAEPISS
SISNMELELNIHNSKAPKKNRLRRKSSTRHIHALELVVSRNLSPPNCTELQIDSCSSSEE
IKKKKYNQMPVRHSRNLQLMEGKEPATGAKKSNKPNEQTSKRHDSDTFPELKLTNAPGSF
TKCSNTSELKEFVNPSLPREEKEEKLETVKVSNNAEDPKDLMLSGERVLQTERSVESSSI
SLVPGTDYGTQESISLLEVSTLGKAKTEPNKCVSQCAAFENPKGLIHGCSKDNRNDTEGF
KYPLGHEVNHSRETSIEMEESELDAQYLQNTFKVSKRQSFAPFSNPGNAEEECATFSAHS
GSLKKQSPKVTFECEQKEENQGKNESNIKPVQTVNITAGFPVVGQKDKPVDNAKCSIKGG
SRFCLSSQFRGNETGLITPNKHGLLQNPYRIPPLFPIKSFVKTKCKKNLLEENFEEHSMS
PEREMGNENIPSTVSTISRNNIRENVFKEASSSNINEVGSSTNEVGSSINEIGSSDENIQ
AELGRNRGPKLNAMLRLGVLQPEVYKQSLPGSNCKHPEIKKQEYEEVVQTVNTDFSPYLI
SDNLEQPMGSSHASQVCSETPDDLLDDGEIKEDTSFAENDIKESSAVFSKSVQKGELSRS
PSPFTHTHLAQGYRRGAKKLESSEENLSSEDEELPCFQHLLFGKVNNIPSQSTRHSTVAT
ECLSKNTEENLLSLKNSLNDCSNQVILAKASQEHHLSEETKCSASLFSSQCSELEDLTAN
TNTQDPFLIGSSKQMRHQSESQGVGLSDKELVSDDEERGTGLEENNQEEQSMDSNLGEAA
SGCESETSVSEDCSGLSSQSDILTTQQRDTMQHNLIKLQQEMAELEAVLEQHGSQPSNSY
PSIISDSSALEDLRNPEQSTSEKAVLTSQKSSEYPISQNPEGLSADKFEVSADSSTSKNK
EPGVERSSPSKCPSLDDRWYMHSCSGSLQNRNYPSQEELIKVVDVEEQQLEESGPHDLTE
TSYLPRQDLEGTPYLESGISLFSDDPESDPSEDRAPESARVGNIPSSTSALKVPQLKVAE
SAQSPAAAHTTDTAGYNAMEESVSREKPELTASTERVNKR

Modification type: Fragment
Native
PDB:  
Structural/functional type: Relationship to function unknown
Functional classes: Molecular recognition effectors
Functional subclasses: Protein-protein binding
Detection methods:
  1. Circular dichroism (CD) spectroscopy, far-UV

  2. Nuclear magnetic resonance (NMR)

References:
  1. Mark WY, Liao JC, Lu Y, Ayed A, Laister R, Szymczyna B, Chakrabartty A, Arrowsmith CH. "Characterization of segments from the central region of BRCA1: an intrinsically disordered scaffold for multiple protein-protein and protein-DNA interactions?" J Mol Biol. 2005; 345(2): 275-87. PubMed: 15571721

Comments:
The structure of the 1480 residue central region was investigated by characterizing 21 different fragments.




Region 2
Type:Disordered
Name: 
Location:1755 - 1758
Length:4
Region sequence:

SQDR

Modification type:  
PDB:  
Structural/functional type:  
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (296 K; pH: 6.8; DTT 10 mM; K2HPO4 10 mM; KCl 5 mM; KH2PO4 10 mM)

References:
  1. Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kuhne R, Oschkinat H, Heinemann U. "Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1." Biochemistry. 2004; 43(51): 15983-95. PubMed: 15609993

Comments:
 



Region 3
Type:Disordered
Name: 
Location:1773 - 1777
Length:5
Region sequence:

TNMPT

Modification type:  
PDB:  
Structural/functional type:  
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (296 K; pH: 6.8; DTT 10 mM; K2HPO4 10 mM; KCl 5 mM; KH2PO4 10 mM)

References:
  1. Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kuhne R, Oschkinat H, Heinemann U. "Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1." Biochemistry. 2004; 43(51): 15983-95. PubMed: 15609993

Comments:
 



Region 4
Type:Disordered
Name: 
Location:1799 - 1804
Length:6
Region sequence:

TLGTGV

Modification type:  
PDB:  
Structural/functional type:  
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (296 K; pH: 6.8; DTT 10 mM; K2HPO4 10 mM; KCl 5 mM; KH2PO4 10 mM)

References:
  1. Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kuhne R, Oschkinat H, Heinemann U. "Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1." Biochemistry. 2004; 43(51): 15983-95. PubMed: 15609993

Comments:
 



Region 5
Type:Disordered
Name: 
Location:1812 - 1823
Length:12
Region sequence:

PDAWTEDNGFHA

Modification type:  
PDB:  
Structural/functional type:  
Functional classes:  
Functional subclasses:  
Detection methods:
  1. Nuclear magnetic resonance (NMR) (296 K; pH: 6.8; DTT 10 mM; K2HPO4 10 mM; KCl 5 mM; KH2PO4 10 mM)

References:
  1. Gaiser OJ, Ball LJ, Schmieder P, Leitner D, Strauss H, Wahl M, Kuhne R, Oschkinat H, Heinemann U. "Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1." Biochemistry. 2004; 43(51): 15983-95. PubMed: 15609993

Comments:
 


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