A0A8C0RAP1 · A0A8C0RAP1_CANLF
- ProteinBreast cancer type 1 susceptibility protein homolog
- GeneBRCA1
- StatusUniProtKB unreviewed (TrEMBL)
- Amino acids1878 (go to sequence)
- Protein existencePredicted
- Annotation score5/5
Function
function
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 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 appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. 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. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
Catalytic activity
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBreast cancer type 1 susceptibility protein homolog
- EC number
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Caniformia > Canidae > Canis
Accessions
- Primary accessionA0A8C0RAP1
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex.
Keywords
- Cellular component
PTM/Processing
Keywords
- PTM
Interaction
Subunit
Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1. Interacts with EXD2. Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme.
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 24-65 | RING-type | ||||
Sequence: CPICLELIKEPVSTKCDHIFCKFCMLKLLNQRKGPSQCPLCK | ||||||
Region | 233-254 | Disordered | ||||
Sequence: IEHHQSGNKDLTTTEKHATKKH | ||||||
Compositional bias | 240-254 | Basic and acidic residues | ||||
Sequence: NKDLTTTEKHATKKH | ||||||
Compositional bias | 303-320 | Polar residues | ||||
Sequence: NNSKQPGLARSQQSRWAE | ||||||
Region | 303-329 | Disordered | ||||
Sequence: NNSKQPGLARSQQSRWAESKETCNDRQ | ||||||
Region | 349-368 | Disordered | ||||
Sequence: ELNKQKPPHSDSPRDSQDVP | ||||||
Region | 548-614 | Disordered | ||||
Sequence: NNGPENETEGDYVQKEKNANPTESLEKESAFRTKTEPMSSRISNMELELNSSSSKAPKKNRLRRKSS | ||||||
Compositional bias | 556-581 | Basic and acidic residues | ||||
Sequence: EGDYVQKEKNANPTESLEKESAFRTK | ||||||
Compositional bias | 582-603 | Polar residues | ||||
Sequence: TEPMSSRISNMELELNSSSSKA | ||||||
Region | 730-749 | Disordered | ||||
Sequence: EESRRMTQVSDSTRDPKELV | ||||||
Compositional bias | 1134-1151 | Polar residues | ||||
Sequence: PEQPMGSSRSSQVCSETP | ||||||
Region | 1134-1154 | Disordered | ||||
Sequence: PEQPMGSSRSSQVCSETPDDL | ||||||
Compositional bias | 1183-1201 | Polar residues | ||||
Sequence: QSGEFSRSPSPSDHTRLAQ | ||||||
Region | 1183-1221 | Disordered | ||||
Sequence: QSGEFSRSPSPSDHTRLAQGYQRGTKKLESSEENMSSEE | ||||||
Compositional bias | 1315-1331 | Polar residues | ||||
Sequence: DPFSMFDPTSKQVRHQS | ||||||
Region | 1315-1401 | Disordered | ||||
Sequence: DPFSMFDPTSKQVRHQSENLDVLNDKELVSDDDDEREPGLEEDSPQEEQSVDSDLGEVASGYESETSLSEDCSRLSSQSDILTTQQR | ||||||
Compositional bias | 1341-1364 | Acidic residues | ||||
Sequence: ELVSDDDDEREPGLEEDSPQEEQS | ||||||
Compositional bias | 1374-1401 | Polar residues | ||||
Sequence: SGYESETSLSEDCSRLSSQSDILTTQQR | ||||||
Region | 1419-1504 | Disordered | ||||
Sequence: EAVLEQHESQPSNSSPSLIADSCSPEDLLNPEQNASERVLTSEKSSDSPISQNPESLSTDKFQVFLDSSTSKNGEPGMIRSSPSQS | ||||||
Compositional bias | 1424-1504 | Polar residues | ||||
Sequence: QHESQPSNSSPSLIADSCSPEDLLNPEQNASERVLTSEKSSDSPISQNPESLSTDKFQVFLDSSTSKNGEPGMIRSSPSQS | ||||||
Region | 1570-1590 | Disordered | ||||
Sequence: GISLFSDDPESDPSSHRASEL | ||||||
Domain | 1652-1739 | BRCT | ||||
Sequence: RISMVASGLTPKEFMLVHKFARKHHISLTNLISEETTHVIMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKILDEHDFEV | ||||||
Region | 1743-1764 | Disordered | ||||
Sequence: VVNGRNHQGPKRARESQDRESQ | ||||||
Domain | 1764-1863 | BRCT | ||||
Sequence: QDRKIFRGLEICCYGPFTNMPTDQLEWMVHLCGASVVKEPSLFTLSKGTHPVVVVQPDAWTEDSGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLI |
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,878
- Mass (Da)208,386
- Last updated2022-01-19 v1
- ChecksumC9673F2260889537
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 240-254 | Basic and acidic residues | ||||
Sequence: NKDLTTTEKHATKKH | ||||||
Compositional bias | 303-320 | Polar residues | ||||
Sequence: NNSKQPGLARSQQSRWAE | ||||||
Compositional bias | 556-581 | Basic and acidic residues | ||||
Sequence: EGDYVQKEKNANPTESLEKESAFRTK | ||||||
Compositional bias | 582-603 | Polar residues | ||||
Sequence: TEPMSSRISNMELELNSSSSKA | ||||||
Compositional bias | 1134-1151 | Polar residues | ||||
Sequence: PEQPMGSSRSSQVCSETP | ||||||
Compositional bias | 1183-1201 | Polar residues | ||||
Sequence: QSGEFSRSPSPSDHTRLAQ | ||||||
Compositional bias | 1315-1331 | Polar residues | ||||
Sequence: DPFSMFDPTSKQVRHQS | ||||||
Compositional bias | 1341-1364 | Acidic residues | ||||
Sequence: ELVSDDDDEREPGLEEDSPQEEQS | ||||||
Compositional bias | 1374-1401 | Polar residues | ||||
Sequence: SGYESETSLSEDCSRLSSQSDILTTQQR | ||||||
Compositional bias | 1424-1504 | Polar residues | ||||
Sequence: QHESQPSNSSPSLIADSCSPEDLLNPEQNASERVLTSEKSSDSPISQNPESLSTDKFQVFLDSSTSKNGEPGMIRSSPSQS |