BARD1

Protein identityUniProt · HPA

UniProt accession

Q99728

Gene

BARD1

Ensembl

ENSG00000138376

Chromosome

2

Canonical length

777 aa

Protein class

Cancer-related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nuclear speckles,Cytoplasmic bodies

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

777 residues, UniProt reviewed canonical sequence.

>Q99728|BARD1
     1  MPDNRQPRNR QPRIRSGNEP RSAPAMEPDG RGAWAHSRAA LDRLEKLLRC SRCTNILREP
    61  VCLGGCEHIF CSNCVSDCIG TGCPVCYTPA WIQDLKINRQ LDSMIQLCSK LRNLLHDNEL
   121  SDLKEDKPRK SLFNDAGNKK NSIKMWFSPR SKKVRYVVSK ASVQTQPAIK KDASAQQDSY
   181  EFVSPSPPAD VSERAKKASA RSGKKQKKKT LAEINQKWNL EAEKEDGEFD SKEESKQKLV
   241  SFCSQPSVIS SPQINGEIDL LASGSLTESE CFGSLTEVSL PLAEQIESPD TKSRNEVVTP
   301  EKVCKNYLTS KKSLPLENNG KRGHHNRLSS PISKRCRTSI LSTSGDFVKQ TVPSENIPLP
   361  ECSSPPSCKR KVGGTSGRKN SNMSDEFISL SPGTPPSTLS SSSYRRVMSS PSAMKLLPNM
   421  AVKRNHRGET LLHIASIKGD IPSVEYLLQN GSDPNVKDHA GWTPLHEACN HGHLKVVELL
   481  LQHKALVNTT GYQNDSPLHD AAKNGHVDIV KLLLSYGASR NAVNIFGLRP VDYTDDESMK
   541  SLLLLPEKNE SSSASHCSVM NTGQRRDGPL VLIGSGLSSE QQKMLSELAV ILKAKKYTEF
   601  DSTVTHVVVP GDAVQSTLKC MLGILNGCWI LKFEWVKACL RRKVCEQEEK YEIPEGPRRS
   661  RLNREQLLPK LFDGCYFYLW GTFKHHPKDN LIKLVTAGGG QILSRKPKPD SDVTQTINTV
   721  AYHARPDSDQ RFCTQYIIYE DLCNYHPERV RQGKVWKAPS SWFIDCVMSF ELLPLDS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against BARD1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

11 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about BARD1.

Disease | GeneticClinVar

637 pathogenic / likely-pathogenic of 4,588 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial cancer of breast
• Hereditary cancer-predisposing syndrome
• BARD1-related cancer predisposition
• Hereditary breast ovarian cancer syndrome
• Gastric cancer

ReferencesPubMed · IEDB

Publications for BARD1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.36

gnomAD pLI

0

gnomAD missense Z

-0.55

DepMap mean gene effect

-0.7

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to ionizing radiation
• chromatin remodeling
• DNA damage response
• DNA repair
• DNA strand resection involved in replication fork processing
• homologous recombination
• mitotic G2/M transition checkpoint
• negative regulation of apoptotic process
• negative regulation of cell cycle
• negative regulation of protein export from nucleus
• positive regulation of apoptotic process
• positive regulation of protein catabolic process
• protein K6-linked ubiquitination
• protein ubiquitination
• regulation of cell cycle
• regulation of DNA damage checkpoint
• regulation of DNA repair
• regulation of phosphorylation
• regulation of transcription by RNA polymerase II
• tissue homeostasis
• negative regulation of mRNA 3'-end processing

Molecular functions

• histone H2AK127 ubiquitin ligase activity
• histone H2AK129 ubiquitin ligase activity
• kinase binding
• protein heterodimerization activity
• protein homodimerization activity
• RNA binding
• ubiquitin-modified histone reader activity
• ubiquitin-protein transferase activity
• zinc ion binding

Cellular components

• BRCA1-A complex
• BRCA1-B complex
• BRCA1-BARD1 complex
• BRCA1-C complex
• cytoplasm
• cytoplasmic ribonucleoprotein granule
• nuclear speck
• nuclear ubiquitin ligase complex
• nucleoplasm
• nucleus
• ubiquitin ligase complex

Protein domainsUniProt · Pfam · InterPro

• BRCT domain
• Zinc finger, RING-type
• Ankyrin repeat
• Zinc finger, RING/FYVE/PHD-type
• Zinc finger, RING-type, conserved site
• BRCT domain superfamily
• Ankyrin repeat-containing domain superfamily
• BRCA1 C Terminus (BRCT) domain
• Ankyrin repeats (3 copies)
• BARD1, Zinc finger, RING-type
• zf-RING of BARD1-type protein

KeywordsUniProt

• ANK repeat
• DNA damage
• DNA repair
• Isopeptide bond
• Metal-binding
• Nucleus
• Phosphoprotein
• Repeat
• Transferase
• Ubl conjugation
• Ubl conjugation pathway
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of BARD1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• UBXN1
• BRCA1
• CHD3
• CSTF1
• CSTF2
• GIT1
• KAT7
• TCERG1
• TP53