Reviewed, UniProtKB/Swiss-Prot Q99728 (BARD1_HUMAN)

Names and origin

Protein names

Recommended name:
    BRCA1-associated RING domain protein 1
      Short name=BARD-1
    EC=6.3.2.-

Gene names

Name:

BARD1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	777 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	The BRCA1-BARD1 heterodimer 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. Ref.6
Pathway	Protein modification; protein ubiquitination.
Subunit structure	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 MERIT40/NBA1.
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.
Post-translational modification	Processed during apoptosis. The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer.
Involvement in disease	Defects in BARD1 are found in primary breast, ovarian and uterine cancers.
Sequence similarities	Contains 3 ANK repeats. Contains 2 BRCT domains. Contains 1 RING-type zinc finger.
Caution	It is uncertain whether Met-1 or Met-26 is the initiator.

Ontologies

Keywords
Biological process	DNA damage DNA repair Ubl conjugation pathway
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	ANK repeat Repeat Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW cell cycle arrest Non-traceable author statement. Source: UniProtKB modification-dependent protein catabolic process Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptosis Inferred from mutant phenotype. Source: UniProtKB negative regulation of mRNA 3'-end processing Non-traceable author statement. Source: UniProtKB negative regulation of protein export from nucleus Inferred from direct assay. Source: UniProtKB positive regulation of apoptosis Inferred from mutant phenotype. Source: UniProtKB positive regulation of protein catabolic process Non-traceable author statement. Source: UniProtKB protein ubiquitination Non-traceable author statement. Source: UniProtKB regulation of phosphorylation Inferred from mutant phenotype. Source: UniProtKB tissue homeostasis Traceable author statement. Source: UniProtKB
Cellular component	BRCA1-A complex Ref.10 Inferred from direct assay. Source: UniProtKB BRCA1-BARD1 complex Inferred from direct assay. Source: UniProtKB cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	RNA binding Inferred from direct assay. Source: MGI kinase binding Non-traceable author statement. Source: UniProtKB protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB protein homodimerization activity Inferred from physical interaction. Source: UniProtKB ubiquitin-protein ligase activity Non-traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRCA1	P38398	5	EBI-473181,EBI-349905
CHD3	Q12873	1	EBI-473181,EBI-523590
CSTF1	Q05048	4	EBI-473181,EBI-1789619
CSTF2	P33240	1	EBI-473181,EBI-711360
GIT1	Q9Y2X7	1	EBI-473181,EBI-466061
KIAA1377	Q9P2H0	1	EBI-473181,EBI-473176
MYST2	O95251	1	EBI-473181,EBI-473199
PCNA	P12004	1	EBI-473181,EBI-358311
POLR1A	O95602	1	EBI-473181,EBI-359472
TCERG1	O14776	1	EBI-473181,EBI-473271
TP53	P04637	1	EBI-473181,EBI-366083
XRCC6	P12956	1	EBI-473181,EBI-353208

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 777

777

BRCA1-associated RING domain protein 1

PRO_0000055819

Regions

Repeat

427 – 459

33

ANK 1

Repeat

460 – 492

33

ANK 2

Repeat

493 – 525

33

ANK 3

Domain

560 – 653

94

BRCT 1

Domain

667 – 777

111

BRCT 2

Zinc finger

50 – 87

38

RING-type

Region

26 – 119

94

Interaction with BRCA1

Compositional bias

400 – 403

4

Poly-Ser

Compositional bias

542 – 545

4

Poly-Leu

Amino acid modifications

Modified residue

148

1

Phosphoserine Ref.9

Modified residue

391

1

Phosphoserine Ref.9

Modified residue

394

1

Phosphothreonine Ref.9

Cross-link

423

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.8

Natural variations

Natural variant

24

1

P → S Common polymorphism in Caucasians; less frequent in Africans. dbSNP rs1048108.

VAR_010354

Natural variant

153

1

K → E Unclassified.

VAR_010355

Natural variant

186

1

S → G: dbSNP rs16852741.

VAR_038371

Natural variant

241

1

S → C: dbSNP rs3738885.

VAR_020109

Natural variant

378

1

R → S: dbSNP rs2229571. Ref.2

VAR_024611

Natural variant

507

1

V → M Unclassified. dbSNP rs2070094.

VAR_010356

Natural variant

557

1

C → S Rare polymorphism in Caucasians. dbSNP rs28997576.

VAR_010357

Natural variant

564

1

Q → H in ovarian cancer.

VAR_010358

Natural variant

645

1

C → R: dbSNP rs34744268.

VAR_038372

Natural variant

658

1

R → C Rare polymorphism in Caucasians; absent in Africans. dbSNP rs3738888.

VAR_010359

Natural variant

695

1

V → L in breast and ovarian cancer.

VAR_010360

Natural variant

728

1

S → F: dbSNP rs13389423.

VAR_028309

Natural variant

761

1

S → N in uterine cancer.

VAR_010361

Experimental info

Sequence conflict

406

1

R → Q in AAB38316. Ref.1

Secondary structure

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777

Helix Strand Turn

Details...

Helix

35 – 46

12

Beta strand

51 – 53

3

Beta strand

65 – 67

3

Turn

72 – 74

3

Helix

75 – 78

4

Turn

79 – 81

3

Beta strand

84 – 86

3

Helix

99 – 116

18

Helix

431 – 438

8

Helix

441 – 449

9

Helix

464 – 470

7

Helix

474 – 482

9

Helix

492 – 494

3

Helix

497 – 503

7

Helix

507 – 515

9

Helix

530 – 533

4

Helix

537 – 543

7

Beta strand

571 – 576

6

Helix

579 – 591

13

Beta strand

595 – 599

5

Beta strand

606 – 613

8

Helix

618 – 625

8

Beta strand

629 – 632

4

Helix

634 – 642

9

Helix

648 – 650

3

Helix

656 – 665

10

Turn

671 – 674

4

Beta strand

676 – 679

4

Beta strand

684 – 686

3

Helix

688 – 697

10

Beta strand

701 – 705

5

Helix

709 – 711

3

Helix

713 – 715

3

Helix

729 – 731

3

Beta strand

735 – 739

5

Beta strand

750 – 752

3

Beta strand

755 – 759

5

Helix

760 – 769

10

Sequences

	Sequence		Length	Mass (Da)
	Q99728-1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 95E2D904046B5646	FASTA	777	86,648
	10 20 30 40 50 60 MPDNRQPRNR QPRIRSGNEP RSAPAMEPDG RGAWAHSRAA LDRLEKLLRC SRCTNILREP 70 80 90 100 110 120 VCLGGCEHIF CSNCVSDCIG TGCPVCYTPA WIQDLKINRQ LDSMIQLCSK LRNLLHDNEL 130 140 150 160 170 180 SDLKEDKPRK SLFNDAGNKK NSIKMWFSPR SKKVRYVVSK ASVQTQPAIK KDASAQQDSY 190 200 210 220 230 240 EFVSPSPPAD VSERAKKASA RSGKKQKKKT LAEINQKWNL EAEKEDGEFD SKEESKQKLV 250 260 270 280 290 300 SFCSQPSVIS SPQINGEIDL LASGSLTESE CFGSLTEVSL PLAEQIESPD TKSRNEVVTP 310 320 330 340 350 360 EKVCKNYLTS KKSLPLENNG KRGHHNRLSS PISKRCRTSI LSTSGDFVKQ TVPSENIPLP 370 380 390 400 410 420 ECSSPPSCKR KVGGTSGRKN SNMSDEFISL SPGTPPSTLS SSSYRRVMSS PSAMKLLPNM 430 440 450 460 470 480 AVKRNHRGET LLHIASIKGD IPSVEYLLQN GSDPNVKDHA GWTPLHEACN HGHLKVVELL 490 500 510 520 530 540 LQHKALVNTT GYQNDSPLHD AAKNGHVDIV KLLLSYGASR NAVNIFGLRP VDYTDDESMK 550 560 570 580 590 600 SLLLLPEKNE SSSASHCSVM NTGQRRDGPL VLIGSGLSSE QQKMLSELAV ILKAKKYTEF 610 620 630 640 650 660 DSTVTHVVVP GDAVQSTLKC MLGILNGCWI LKFEWVKACL RRKVCEQEEK YEIPEGPRRS 670 680 690 700 710 720 RLNREQLLPK LFDGCYFYLW GTFKHHPKDN LIKLVTAGGG QILSRKPKPD SDVTQTINTV 730 740 750 760 770 AYHARPDSDQ RFCTQYIIYE DLCNYHPERV RQGKVWKAPS SWFIDCVMSF ELLPLDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification of a RING protein that can interact in vivo with the BRCA1 gene product." Wu L.C., Wang Z.W., Tsan J.T., Spillman M.A., Phung A., Xu X.L., Yang M.-C.W., Hwang L.-Y., Bowcock A.M., Baer R. Nat. Genet. 14:430-440(1996) [PubMed: 8944023] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: B-cell.
[2]	"Mutations in the BRCA1-associated RING domain (BARD1) gene in primary breast, ovarian and uterine cancers." Thai T.H., Du F., Tsan J.T., Jin Y., Phung A., Spillman M.A., Massa H.F., Muller C.Y., Ashfaq R., Mathis J.M., Miller D.S., Trask B.J., Baer R., Bowcock A.M. Hum. Mol. Genet. 7:195-202(1998) [PubMed: 9425226] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-378.
[3]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[5]	"Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1." Meza J.E., Brzovic P.S., King M.-C., Klevit R.E. J. Biol. Chem. 274:5659-5665(1999) [PubMed: 10026184] [Abstract] Cited for: DOMAINS.
[6]	"Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50." Kleiman F.E., Manley J.L. Science 285:1576-1579(1999) [PubMed: 10477523] [Abstract] Cited for: POSSIBLE FUNCTION.
[7]	"CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response." Kim H., Huang J., Chen J. Nat. Struct. Mol. Biol. 14:710-715(2007) [PubMed: 17643122] [Abstract] Cited for: IDENTIFICATION IN THE BRCA1-A COMPLEX.
[8]	"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry." Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D. Proteomics 7:868-874(2007) [PubMed: 17370265] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-423, MASS SPECTROMETRY.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148; SER-391 AND THR-394, MASS SPECTROMETRY.
[10]	"NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control." Wang B., Hurov K., Hofmann K., Elledge S.J. Genes Dev. 23:729-739(2009) [PubMed: 19261749] [Abstract] Cited for: IDENTIFICATION IN THE BRCA1-A COMPLEX.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

U76638 mRNA. Translation: AAB38316.1.
AF038042 , AF038034, AF038035, AF038036, AF038037, AF038038, AF038039, AF038040, AF038041 Genomic DNA. Translation: AAB99978.1.
AC016708 Genomic DNA. Translation: AAX93130.1.
BC126426 mRNA. Translation: AAI26427.1.

IPI

IPI00017746.

RefSeq

NP_000456.2.

UniGene

Hs.591642

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JM7	NMR	-	B	26-140	[»]
2NTE	X-ray	1.90	A/B	568-777	[»]
2R1Z	X-ray	2.10	A/B	569-777	[»]
3C5R	X-ray	2.00	A/B	425-555	[»]
3FA2	X-ray	2.20	A/B	566-777	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24200N.

IntAct

Q99728. 25 interactions.

STRING

Q99728.

PTM databases

PhosphoSite

Q99728.

Proteomic databases

PeptideAtlas

Q99728.

PRIDE

Q99728.

Genome annotation databases

Ensembl

ENST00000260947; ENSP00000260947; ENSG00000138376; Homo sapiens. [Genome view]
ENST00000421162; ENSP00000392245; ENSG00000138376; Homo sapiens. [Genome view]
ENST00000432456; ENSP00000405020; ENSG00000138376; Homo sapiens. [Genome view]
ENST00000449967; ENSP00000406752; ENSG00000138376; Homo sapiens. [Genome view]
ENST00000455743; ENSP00000412186; ENSG00000138376; Homo sapiens. [Genome view]

GeneID

580.

KEGG

hsa:580.

NMPDR

fig|9606.3.peg.19278.

UCSC

uc002veu.2. human.

Organism-specific databases

CTD

580.

GeneCards

GC02M215301.

H-InvDB

HIX0030010.

HGNC

HGNC:952. BARD1.

MIM

601593. gene.

PharmGKB

PA25256.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q99728.

HOVERGEN

Q99728.

OMA

VCYTPAW.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.

Gene expression databases

ArrayExpress

Q99728.

Bgee

Q99728.

CleanEx

HS_BARD1.

Genevestigator

Q99728.

GermOnline

ENSG00000138376. Homo sapiens.

Family and domain databases

InterPro

IPR002110. ANK.
IPR001357. BRCT.
IPR001841. Znf_RING.
IPR017907. Znf_RING_CS.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 1 hit.

Pfam

PF00023. Ank. 3 hits.
PF00533. BRCT. 2 hits.
[Graphical view]

SMART

SM00248. ANK. 3 hits.
SM00292. BRCT. 2 hits.
SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 3 hits.
PS50172. BRCT. 2 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

2367.

SOURCE

Search...

Entry information

Entry name

BARD1_HUMAN

Accession

Primary (citable) accession number: Q99728
Secondary accession number(s): O43574, Q53SS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	October 17, 2006
Last modified:	November 3, 2009
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.