ID:BARD1_HUMAN DESCRIPTION: RecName: Full=BRCA1-associated RING domain protein 1; Short=BARD-1; EC=6.3.2.-; FUNCTION: Probable E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homo- and heterodimer. Heterodimer (RING-type zinc finger) with BRCA1. Heterodimer (via ANK repeats and BRCT domains) with CSTF1/CSTF-50. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, FAM175A/Abraxas, BRCC3/BRCC36, BRE/BRCC45 and BABAM1/NBA1. Interacts with UBXN1. INTERACTION: P38398:BRCA1; NbExp=8; IntAct=EBI-473181, EBI-349905; Q12873:CHD3; NbExp=2; IntAct=EBI-473181, EBI-523590; Q05048:CSTF1; NbExp=4; IntAct=EBI-473181, EBI-1789619; P33240:CSTF2; NbExp=5; IntAct=EBI-473181, EBI-711360; Q9Y2X7:GIT1; NbExp=2; IntAct=EBI-473181, EBI-466061; O95251:KAT7; NbExp=2; IntAct=EBI-473181, EBI-473199; Q9P2H0:KIAA1377; NbExp=2; IntAct=EBI-473181, EBI-473176; O14776:TCERG1; NbExp=2; IntAct=EBI-473181, EBI-473271; SUBCELLULAR LOCATION: Nucleus. Note=During S phase of the cell cycle, colocalizes with BRCA1 into discrete subnuclear foci. Can translocate to the cytoplasm. Localizes at sites of DNA damage at double-strand breaks (DSBs); recruitment to DNA damage sites is mediated by the BRCA1-A complex. PTM: Processed during apoptosis. The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer. SIMILARITY: Contains 4 ANK repeats. SIMILARITY: Contains 2 BRCT domains. SIMILARITY: Contains 1 RING-type zinc finger. CAUTION: It is uncertain whether Met-1 or Met-26 is the initiator. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/BARD1ID756ch2q35.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99728
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000729 DNA double-strand break processing GO:0001894 tissue homeostasis GO:0006260 DNA replication GO:0006281 DNA repair GO:0006303 double-strand break repair via nonhomologous end joining GO:0006974 cellular response to DNA damage stimulus GO:0007050 cell cycle arrest GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination GO:0031441 negative regulation of mRNA 3'-end processing GO:0042325 regulation of phosphorylation GO:0043065 positive regulation of apoptotic process GO:0043066 negative regulation of apoptotic process GO:0045732 positive regulation of protein catabolic process GO:0046826 negative regulation of protein export from nucleus GO:0085020 protein K6-linked ubiquitination
LF213837 - JP 2014500723-A/21340: Polycomb-Associated Non-Coding RNAs. AX794378 - Sequence 1 from Patent WO03051920. JF790280 - Homo sapiens BRCA1 associated RING domain 1 isoform alfa (BARD1) mRNA, complete cds. JF790281 - Homo sapiens BRCA1 associated RING domain 1 isoform beta (BARD1) mRNA, complete cds. U76638 - Human BRCA1-associated RING domain protein (BARD1) mRNA, complete cds. JF790284 - Homo sapiens BRCA1 associated RING domain 1 isoform delta (BARD1) mRNA, complete cds. AK223409 - Homo sapiens mRNA for BRCA1 associated RING domain 1 variant, clone: FCC109A11. BC126426 - Homo sapiens BRCA1 associated RING domain 1, mRNA (cDNA clone MGC:161704 IMAGE:8992142), complete cds. BC126428 - Homo sapiens BRCA1 associated RING domain 1, mRNA (cDNA clone MGC:161706 IMAGE:8992144), complete cds. JF790283 - Homo sapiens BRCA1 associated RING domain 1 isoform phi (BARD1) mRNA, complete cds. AK314260 - Homo sapiens cDNA, FLJ95007, highly similar to Homo sapiens BRCA1 associated RING domain 1 (BARD1), mRNA. JF790286 - Homo sapiens BRCA1 associated RING domain 1 isoform eta (BARD1) mRNA, complete cds. JF790282 - Homo sapiens BRCA1 associated RING domain 1 isoform gamma (BARD1) mRNA, complete cds. KJ905697 - Synthetic construct Homo sapiens clone ccsbBroadEn_15367 BARD1 gene, encodes complete protein. AB590656 - Synthetic construct DNA, clone: pFN21AB5790, Homo sapiens BARD1 gene for BRCA1 associated RING domain 1, without stop codon, in Flexi system. AK301843 - Homo sapiens cDNA FLJ51596 complete cds, highly similar to BRCA1-associated RING domain protein 1. JF790285 - Homo sapiens BRCA1 associated RING domain 1 isoform epsilon (BARD1) mRNA, partial cds. MA449414 - JP 2018138019-A/21340: Polycomb-Associated Non-Coding RNAs. LF205230 - JP 2014500723-A/12733: Polycomb-Associated Non-Coding RNAs. LF318268 - JP 2014500723-A/125771: Polycomb-Associated Non-Coding RNAs. AK310759 - Homo sapiens cDNA, FLJ17801. JD299355 - Sequence 280379 from Patent EP1572962. JD236219 - Sequence 217243 from Patent EP1572962. KX257619 - Homo sapiens BRCA1-associated RING domain 1 lncRNA (BARD1), partial sequence. MA440807 - JP 2018138019-A/12733: Polycomb-Associated Non-Coding RNAs. MA553845 - JP 2018138019-A/125771: Polycomb-Associated Non-Coding RNAs. JF790287 - Homo sapiens BRCA1 associated RING domain 1 isoform pi (BARD1) mRNA, partial cds. JD537772 - Sequence 518796 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_bard1Pathway - BRCA1-dependent Ub-ligase activity
Reactome (by CSHL, EBI, and GO)
Protein Q99728 (Reactome details) participates in the following event(s):
R-HSA-5659781 BRCA1 forms a heterodimer with BARD1 R-HSA-5689649 BAP1 binds BRCA1:BARD1 R-HSA-5683385 Formation of BRCA1-A complex at DNA DSBs R-HSA-5684108 BRCA1 binds phosphorylated RBBP8 R-HSA-5684071 RNF4 ubiquitinates MDC1 R-HSA-5686410 BLM mediates dissolution of double Holliday junction R-HSA-5686657 ERCC1:XPF cleaves flaps generated by SSA R-HSA-5686685 RIF1 and PAX1IP bind TP53BP1 at DNA DSBs R-HSA-5693589 D-loop dissociation and strand annealing R-HSA-5693551 Phosphorylation of BRCA1-A complex at multiple sites by ATM R-HSA-5691411 BRCA1-A complex deubiquitinates K63polyUb-histone H2A R-HSA-5683735 CHEK2 is recruited to DNA DSBs R-HSA-5683801 CHEK2 phosphorylates BRCA1 R-HSA-69891 Phosphorylation and activation of CHEK2 by ATM R-HSA-5684052 PIAS4 SUMOylates MDC1 R-HSA-5693608 Initial resection of double-strand break ends R-HSA-5693542 Association of RPA complexes with ssDNA at resected DNA DSBs R-HSA-5685994 Long-range resection of DNA DSBs by EXO1 or DNA2 R-HSA-5685341 BCDX2 complex stabilizes RAD51 filament R-HSA-5693561 RAD51 binds BRCA2 at resected DNA DSBs R-HSA-5685985 EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment R-HSA-5684875 Binding of ATR:ATRIP to RPA at resected DNA DSBs R-HSA-5693620 D-loop formation mediated by PALB2, BRCA2 and RAD51 R-HSA-5685838 CX3 complex binds D-loop structures R-HSA-5685011 ATR activation at DNA DSBs R-HSA-5684887 Activation of CHEK1 at resected DNA DSBs R-HSA-5684882 CHEK1 is recruited to resected DNA DSBs R-HSA-5693580 Association of RAD52 with the RPA complex at resected DNA DSBs R-HSA-5685156 ATR phosphorylates RPA2 R-HSA-5693593 D-loop extension by DNA polymerases R-HSA-5693584 Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2) R-HSA-5686440 MUS81:EME1,EME2 cleaves D-loop R-HSA-5693564 Association of RAD51 with RAD52:DNA double-strand break ends R-HSA-6799332 ATR phosphorylates TP53 R-HSA-5686642 RAD52 promotes single strand annealing at resected DNA DSBs R-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-5689603 UCH proteinases R-HSA-5693606 DNA Double Strand Break Response R-HSA-5688426 Deubiquitination R-HSA-5693607 Processing of DNA double-strand break ends R-HSA-5693568 Resolution of D-loop Structures through Holliday Junction Intermediates R-HSA-5685938 HDR through Single Strand Annealing (SSA) R-HSA-5693571 Nonhomologous End-Joining (NHEJ) R-HSA-5693554 Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA) R-HSA-5693532 DNA Double-Strand Break Repair R-HSA-597592 Post-translational protein modification R-HSA-5693567 HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA) R-HSA-5693537 Resolution of D-Loop Structures R-HSA-5689901 Metalloprotease DUBs R-HSA-73894 DNA Repair R-HSA-392499 Metabolism of proteins R-HSA-69473 G2/M DNA damage checkpoint R-HSA-5693616 Presynaptic phase of homologous DNA pairing and strand exchange R-HSA-5693538 Homology Directed Repair R-HSA-5685942 HDR through Homologous Recombination (HRR) R-HSA-69481 G2/M Checkpoints R-HSA-5693579 Homologous DNA Pairing and Strand Exchange R-HSA-69620 Cell Cycle Checkpoints R-HSA-1640170 Cell Cycle R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation R-HSA-5633007 Regulation of TP53 Activity R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
