A0A8C0RAP1 · A0A8C0RAP1_CANLF

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

  • S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.
    EC:2.3.2.27 (UniProtKB | ENZYME | Rhea)

GO annotations

AspectTerm
Cellular ComponentBRCA1-A complex
Cellular ComponentBRCA1-B complex
Cellular ComponentBRCA1-BARD1 complex
Cellular ComponentBRCA1-C complex
Cellular Componentcytoplasm
Cellular ComponentDNA repair complex
Cellular Componentlateral element
Cellular Componentmale germ cell nucleus
Cellular Componentnuclear body
Cellular Componentplasma membrane
Cellular Componentribonucleoprotein complex
Cellular ComponentXY body
Molecular Functiondamaged DNA binding
Molecular FunctionDNA-binding transcription activator activity
Molecular Functionidentical protein binding
Molecular Functionp53 binding
Molecular FunctionRNA binding
Molecular FunctionRNA polymerase binding
Molecular Functiontranscription cis-regulatory region binding
Molecular Functiontranscription coactivator activity
Molecular Functionubiquitin protein ligase binding
Molecular Functionubiquitin-protein transferase activity
Molecular Functionzinc ion binding
Biological Processcellular response to indole-3-methanol
Biological Processcellular response to ionizing radiation
Biological Processcellular response to tumor necrosis factor
Biological Processcentrosome cycle
Biological Processchordate embryonic development
Biological Processchromosome segregation
Biological Processdouble-strand break repair via homologous recombination
Biological Processfatty acid biosynthetic process
Biological Processintrinsic apoptotic signaling pathway in response to DNA damage
Biological Processmitotic G2 DNA damage checkpoint signaling
Biological Processnegative regulation of cell growth
Biological Processnegative regulation of DNA-templated transcription
Biological Processnegative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Biological Processnegative regulation of fatty acid biosynthetic process
Biological Processnegative regulation of gene expression via chromosomal CpG island methylation
Biological Processnegative regulation of intracellular estrogen receptor signaling pathway
Biological Processnegative regulation of reactive oxygen species metabolic process
Biological Processpositive regulation of angiogenesis
Biological Processpositive regulation of DNA repair
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processpositive regulation of vascular endothelial growth factor production
Biological Processpostreplication repair
Biological Processprotein autoubiquitination
Biological Processprotein K6-linked ubiquitination
Biological Processrandom inactivation of X chromosome

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Breast cancer type 1 susceptibility protein homolog
  • EC number

Gene names

    • Name
      BRCA1

Organism names

Accessions

  • Primary accession
    A0A8C0RAP1

Proteomes

Organism-specific databases

Subcellular Location

Chromosome
Cytoplasm
Nucleus
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

PTM/Processing

Keywords

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.

Family & Domains

Features

Showing features for domain, region, compositional bias.

TypeIDPosition(s)Description
Domain24-65RING-type
Region233-254Disordered
Compositional bias240-254Basic and acidic residues
Compositional bias303-320Polar residues
Region303-329Disordered
Region349-368Disordered
Region548-614Disordered
Compositional bias556-581Basic and acidic residues
Compositional bias582-603Polar residues
Region730-749Disordered
Compositional bias1134-1151Polar residues
Region1134-1154Disordered
Compositional bias1183-1201Polar residues
Region1183-1221Disordered
Compositional bias1315-1331Polar residues
Region1315-1401Disordered
Compositional bias1341-1364Acidic residues
Compositional bias1374-1401Polar residues
Region1419-1504Disordered
Compositional bias1424-1504Polar residues
Region1570-1590Disordered
Domain1652-1739BRCT
Region1743-1764Disordered
Domain1764-1863BRCT

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,878
  • Mass (Da)
    208,386
  • Last updated
    2022-01-19 v1
  • Checksum
    C9673F2260889537
MDLSADRVEEVQNVLNAMQKILECPICLELIKEPVSTKCDHIFCKFCMLKLLNQRKGPSQCPLCKNDITKRSLQESTRFSQLVEELLKIIHAFELDTGLQFADSYNFSKKENNSPEHLKEEVSIIQSMGYRNRAKRLRQSEPENPTLETSLSVQLSNLGIVRSLRTKQQIQPQNKSVYIELGSDSSEDTVNKASSCSVGDDKLEITSQGARAEASLNPAKKAACEFSGDITNIEHHQSGNKDLTTTEKHATKKHPEKYQGISVSNLHVEPCGTNTHASSLQHENSSLLLTKHRMNVEKAEICNNSKQPGLARSQQSRWAESKETCNDRQIPSTEKKVVVNADLLCGRKELNKQKPPHSDSPRDSQDVPWITLNSSIRKVNEWFSRSDEILTSDDSHDRGSELNTEVGGAVEVPNEVGEYSGSSEKIDLMASDPQDAFICESERVHTKPVGGNIEDKIFGKTYRRKASLPKVSHTTEVLTIGACAIEPQTMQTHPFMNKAEHKRRTTSSLHPEDFIKKVELGIVPKTPEKLIEGINQIKRDGHVINITNNGPENETEGDYVQKEKNANPTESLEKESAFRTKTEPMSSRISNMELELNSSSSKAPKKNRLRRKSSARHTCALEFVVNRNLNPPDHSELQIESCSSSEEMKKQHLDQVPVRHNKTLQLMQDKEPAGRAKKSSKPGEQINKRLASHAFPELTLTNVSGFFANYSSSSKPQECINPGLRREEIEESRRMTQVSDSTRDPKELVLSGGRGLQTERSVESTSISLVLDTDYGTQDSISLLEADTLRKAKTVSNQQANLCATIENPKEPIHGCSKDTRNDTEGFVVPLTCKDNHTQETSIEMEESELDTQCLRNMFKVSKRQSFALFSYPRDPEEDCVTVCPRSGAFGKQGPKVTLECGQKEESQGKKESEIRHVQAVHTNAGFSAVSQKAKKPGDFAKCSIKGVSRLCLSSQFKGKETELLIANYHGISQNPYHIPPLSPIRSCVKTLCQENLSEEKFEQHSMSPERAVGNERVIQSTVSTISQNNIRECASKEVGSSSVNEVVSSTNEVGSSVNEVGSSGENIQAELGRNRGPKLNAMLRLGLMQPEVCKQSLSLSNCKHPEMKWQGQSEGAVLSVSADFSPCLISDNPEQPMGSSRSSQVCSETPDDLLNGDKIKGKVSFAESDIKEKSAVFSKSVQSGEFSRSPSPSDHTRLAQGYQRGTKKLESSEENMSSEEEELPCFQHLIFGKVTNMPSQSTSHNAVAAEGLSNKTEENLDSLKNSLSDISNQVPSAKASQEHHLSEEARCSGSLFSSQCSALEDLTVNTNTQDPFSMFDPTSKQVRHQSENLDVLNDKELVSDDDDEREPGLEEDSPQEEQSVDSDLGEVASGYESETSLSEDCSRLSSQSDILTTQQRDTMQDNLIKLQQEMAELEAVLEQHESQPSNSSPSLIADSCSPEDLLNPEQNASERVLTSEKSSDSPISQNPESLSTDKFQVFLDSSTSKNGEPGMIRSSPSQSRLLDTRWYVHSCPRSLQDTNCPSQKELTKVVSMEEQQPTESEARDLMEQSYLSRPDLEGAPYLESGISLFSDDPESDPSSHRASELAHVSSMPTSTSALKLPQFQVEESAKSTAAVHIASTAGYNKSEDSVGIEKPEVISSTRGVNKRISMVASGLTPKEFMLVHKFARKHHISLTNLISEETTHVIMKTDAEFVCERTLKYFLGIAGGKWVVSYFWVTQSIKERKILDEHDFEVRGDVVNGRNHQGPKRARESQDRESQDRKIFRGLEICCYGPFTNMPTDQLEWMVHLCGASVVKEPSLFTLSKGTHPVVVVQPDAWTEDSGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIPRAAADSSQPCV

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias240-254Basic and acidic residues
Compositional bias303-320Polar residues
Compositional bias556-581Basic and acidic residues
Compositional bias582-603Polar residues
Compositional bias1134-1151Polar residues
Compositional bias1183-1201Polar residues
Compositional bias1315-1331Polar residues
Compositional bias1341-1364Acidic residues
Compositional bias1374-1401Polar residues
Compositional bias1424-1504Polar residues

Genome annotation databases

Similar Proteins

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