Human Gene BARD1 (ENST00000260947.9) from GENCODE V44
  Description: Homo sapiens BRCA1 associated RING domain 1 (BARD1), transcript variant 8, non-coding RNA. (from RefSeq NR_104216)
RefSeq Summary (NM_000465): This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013].
Gencode Transcript: ENST00000260947.9
Gencode Gene: ENSG00000138376.11
Transcript (Including UTRs)
   Position: hg38 chr2:214,725,646-214,809,683 Size: 84,038 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg38 chr2:214,728,676-214,809,569 Size: 80,894 Coding Exon Count: 11 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:214,725,646-214,809,683)mRNA (may differ from genome)Protein (777 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCLynxMalacardsMGIneXtProtOMIM
PubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  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";

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: BARD1
Diseases sorted by gene-association score: breast cancer* (341), brca1 hereditary breast and ovarian cancer syndrome* (121), brca2 hereditary breast and ovarian cancer syndrome* (115), breast cancer susceptibility, bard1-related* (100), neuroblastoma, susceptibility (12), hereditary breast ovarian cancer* (8), sporadic breast cancer (6), ovarian cancer, somatic (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.72 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 76.01 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -49.30114-0.432 Picture PostScript Text
3' UTR -663.003030-0.219 Picture PostScript Text

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.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002110 - Ankyrin_rpt
IPR020683 - Ankyrin_rpt-contain_dom
IPR001357 - BRCT_dom
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR017907 - Znf_RING_CS

Pfam Domains:
PF00023 - Ankyrin repeat
PF00533 - BRCA1 C Terminus (BRCT) domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1JM7 - NMR MuPIT 2NTE - X-ray MuPIT 2R1Z - X-ray MuPIT 3C5R - X-ray MuPIT 3FA2 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q99728
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  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.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0016740 transferase activity
GO:0019900 kinase binding
GO:0042803 protein homodimerization activity
GO:0046872 metal ion binding
GO:0046982 protein heterodimerization activity

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

Cellular Component:
GO:0000151 ubiquitin ligase complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0016607 nuclear speck
GO:0031436 BRCA1-BARD1 complex
GO:0036464 cytoplasmic ribonucleoprotein granule
GO:0070531 BRCA1-A complex


-  Descriptions from all associated GenBank mRNAs
  LF205230 - JP 2014500723-A/12733: Polycomb-Associated Non-Coding RNAs.
MA440807 - JP 2018138019-A/12733: Polycomb-Associated Non-Coding RNAs.
LF213837 - JP 2014500723-A/21340: Polycomb-Associated Non-Coding RNAs.
MA449414 - JP 2018138019-A/21340: Polycomb-Associated Non-Coding RNAs.
LF318268 - JP 2014500723-A/125771: Polycomb-Associated Non-Coding RNAs.
MA553845 - JP 2018138019-A/125771: Polycomb-Associated Non-Coding RNAs.
AK310759 - Homo sapiens cDNA, FLJ17801.
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.
JD299355 - Sequence 280379 from Patent EP1572962.
JD236219 - Sequence 217243 from Patent EP1572962.
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.
KX257619 - Homo sapiens BRCA1-associated RING domain 1 lncRNA (BARD1), partial sequence.
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)

-  Other Names for This Gene
  Alternate Gene Symbols: BARD1_HUMAN, ENST00000260947.1, ENST00000260947.2, ENST00000260947.3, ENST00000260947.4, ENST00000260947.5, ENST00000260947.6, ENST00000260947.7, ENST00000260947.8, NR_104216, O43574, Q53SS5, Q99728, uc002veu.1, uc002veu.2, uc002veu.3, uc002veu.4, uc002veu.5
UCSC ID: ENST00000260947.9
RefSeq Accession: NM_000465
Protein: Q99728 (aka BARD1_HUMAN)
CCDS: CCDS2397.1, CCDS74646.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.