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Protein

BRISC and BRCA1-A complex member 2

Gene

BABAM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX (PubMed:17525341, PubMed:19261746, PubMed:19261749, PubMed:19261748). In the BRCA1-A complex, it acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer (PubMed:21282113, PubMed:19261748). Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:19214193, PubMed:24075985, PubMed:25283148, PubMed:26195665). Within the BRISC complex, acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity (PubMed:21282113). The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). The BRISC complex plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins. May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway. May regulate TNF-alpha signaling through its interactions with TNFRSF1A; however these effects may be indirect (PubMed:15465831).1 Publication5 Publications

GO - Molecular functioni

  • peroxisome targeting sequence binding Source: UniProtKB
  • polyubiquitin modification-dependent protein binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle Source: UniProtKB-KW
  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • covalent chromatin modification Source: UniProtKB-KW
  • double-strand break repair Source: UniProtKB
  • double-strand break repair via nonhomologous end joining Source: Reactome
  • G2 DNA damage checkpoint Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • protein K63-linked deubiquitination Source: UniProtKB
  • response to ionizing radiation Source: UniProtKB
  • signal transduction Source: ProtInc

Keywordsi

Molecular functionChromatin regulator
Biological processApoptosis, Cell cycle, Cell division, DNA damage, DNA repair, Mitosis, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-5689901. Metalloprotease DUBs.
R-HSA-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
R-HSA-5693571. Nonhomologous End-Joining (NHEJ).
R-HSA-5693607. Processing of DNA double-strand break ends.
R-HSA-69473. G2/M DNA damage checkpoint.

Names & Taxonomyi

Protein namesi
Recommended name:
BRISC and BRCA1-A complex member 2Imported
Alternative name(s):
BRCA1-A complex subunit BRE
BRCA1/BRCA2-containing complex subunit 451 Publication
Brain and reproductive organ-expressed protein1 Publication
Gene namesi
Name:BABAM2Imported
Synonyms:BRCC45, BRE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000158019.20.
HGNCiHGNC:1106. BABAM2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi9577.
OpenTargetsiENSG00000158019.
PharmGKBiPA25419.

Polymorphism and mutation databases

BioMutaiBRE.
DMDMi229462810.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002241891 – 383BRISC and BRCA1-A complex member 2Add BLAST383

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9NXR7.
PaxDbiQ9NXR7.
PeptideAtlasiQ9NXR7.
PRIDEiQ9NXR7.

PTM databases

iPTMnetiQ9NXR7.
PhosphoSitePlusiQ9NXR7.

Expressioni

Tissue specificityi

Expressed in all cell lines examined. Highly expressed in placenta.1 Publication

Inductioni

Down-regulated by DNA-damaging agents in fibroblasts, by retinoic acid in brain glioma U-251MG and promyelocytic HL-60 cell lines, and by bacterial lipopolysaccharides (LPS) in peripheral blood mononuclear cells (PBMC).2 Publications

Gene expression databases

BgeeiENSG00000158019.
CleanExiHS_BRE.
ExpressionAtlasiQ9NXR7. baseline and differential.
GenevisibleiQ9NXR7. HS.

Organism-specific databases

HPAiHPA017926.

Interactioni

Subunit structurei

Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:21282113, PubMed:24075985). Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1, BRCC3/BRCC36 and BABAM1/NBA1. Binds polyubiquitin. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19214193, PubMed:21282113, PubMed:24075985, PubMed:25283148). Identified in a complex with SHMT2 and the other subunits of the BRISC complex (PubMed:24075985). Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BRCC3/BRCC36 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. May interact with FAS and TNFRSF1A (PubMed:15465831).1 Publication8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BABAM1Q9NWV83EBI-949389,EBI-745725

GO - Molecular functioni

  • polyubiquitin modification-dependent protein binding Source: UniProtKB
  • tumor necrosis factor receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114946. 61 interactors.
CORUMiQ9NXR7.
IntActiQ9NXR7. 24 interactors.
MINTiMINT-2867020.
STRINGi9606.ENSP00000343412.

Chemistry databases

BindingDBiQ9NXR7.

Structurei

3D structure databases

ProteinModelPortaliQ9NXR7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 147UEV-like 1Add BLAST118
Regioni275 – 364UEV-like 2Add BLAST90

Domaini

Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin.1 Publication

Sequence similaritiesi

Belongs to the BABAM2 family.Sequence analysis

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IFRG. Eukaryota.
ENOG410Y1T7. LUCA.
GeneTreeiENSGT00390000004208.
HOVERGENiHBG071492.
InParanoidiQ9NXR7.
KOiK12173.
OMAiFSNIPVY.
OrthoDBiEOG091G0TW1.
PhylomeDBiQ9NXR7.
TreeFamiTF328507.

Family and domain databases

Gene3Di3.10.110.10. 2 hits.
InterProiView protein in InterPro
IPR010358. BRE.
IPR016135. UBQ-conjugating_enzyme/RWD.
PANTHERiPTHR15189. PTHR15189. 1 hit.
PfamiView protein in Pfam
PF06113. BRE. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms may exist.Curated
Isoform 21 Publication (identifier: Q9NXR7-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPEVALNRI SPMLSPFISS VVRNGKVGLD ATNCLRITDL KSGCTSLTPG
60 70 80 90 100
PNCDRFKLHI PYAGETLKWD IIFNAQYPEL PPDFIFGEDA EFLPDPSALQ
110 120 130 140 150
NLASWNPSNP ECLLLVVKEL VQQYHQFQCS RLRESSRLMF EYQTLLEEPQ
160 170 180 190 200
YGENMEIYAG KKNNWTGEFS ARFLLKLPVD FSNIPTYLLK DVNEDPGEDV
210 220 230 240 250
ALLSVSFEDT EATQVYPKLY LSPRIEHALG GSSALHIPAF PGGGCLIDYV
260 270 280 290 300
PQVCHLLTNK VQYVIQGYHK RREYIAAFLS HFGTGVVEYD AEGFTKLTLL
310 320 330 340 350
LMWKDFCFLV HIDLPLFFPR DQPTLTFQSV YHFTNSGQLY SQAQKNYPYS
360 370 380
PRWDGNEMAK RAKAYFKTFV PQFQEAAFAN GKL
Length:383
Mass (Da):43,552
Last modified:May 5, 2009 - v2
Checksum:iD830226E2B8F2C4B
GO
Isoform 1Curated (identifier: Q9NXR7-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     364-383: AYFKTFVPQFQEAAFANGKL → GCQGSRDACSPWEQVLAFAVAKTGCKLLQPQRNWPSSRGPPWRASEGERTAQ

Show »
Length:415
Mass (Da):46,974
Checksum:i0501C5447AAFB3BA
GO
Isoform 31 Publication (identifier: Q9NXR7-3) [UniParc]FASTAAdd to basket
Also known as: Alpha a'

The sequence of this isoform differs from the canonical sequence as follows:
     363-383: KAYFKTFVPQFQEAAFANGKL → NSRRQHLPMESSRKHQS

Show »
Length:379
Mass (Da):43,224
Checksum:i2A8816CC439FDFB5
GO
Isoform 4 (identifier: Q9NXR7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     364-383: AYFKTFVPQFQEAAFANGKL → RESNRDGEESSSA

Show »
Length:376
Mass (Da):42,697
Checksum:i56488D883F2A27AE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti192V → L in BAF83775 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_051957363 – 383KAYFK…ANGKL → NSRRQHLPMESSRKHQS in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_051956364 – 383AYFKT…ANGKL → GCQGSRDACSPWEQVLAFAV AKTGCKLLQPQRNWPSSRGP PWRASEGERTAQ in isoform 1. 1 PublicationAdd BLAST20
Alternative sequenceiVSP_037261364 – 383AYFKT…ANGKL → RESNRDGEESSSA in isoform 4. 1 PublicationAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L38616 mRNA. Translation: AAA64231.1.
AF420605 mRNA. Translation: AAL17818.1.
AY438031 mRNA. Translation: AAR30499.1.
AF015767 mRNA. Translation: AAB69387.1.
AF420602 mRNA. Translation: AAL17814.1.
AF420603 mRNA. Translation: AAL17816.1.
AK000097 mRNA. Translation: BAA90943.1.
AK291086 mRNA. Translation: BAF83775.1.
AC021171 Genomic DNA. Translation: AAY24156.1.
AC093690 Genomic DNA. No translation available.
AC096552 Genomic DNA. Translation: AAX88935.1.
CH471053 Genomic DNA. Translation: EAX00545.1.
CH471053 Genomic DNA. Translation: EAX00546.1.
CH471053 Genomic DNA. Translation: EAX00547.1.
CH471053 Genomic DNA. Translation: EAX00548.1.
BC001251 mRNA. Translation: AAH01251.1.
CCDSiCCDS1763.1. [Q9NXR7-2]
CCDS1764.1. [Q9NXR7-1]
CCDS1765.1. [Q9NXR7-4]
PIRiJC2472.
RefSeqiNP_001248769.1. NM_001261840.1. [Q9NXR7-3]
NP_001316041.1. NM_001329112.1. [Q9NXR7-2]
NP_001316042.1. NM_001329113.1. [Q9NXR7-1]
NP_004890.2. NM_004899.4. [Q9NXR7-1]
NP_954661.1. NM_199191.2. [Q9NXR7-2]
NP_954662.1. NM_199192.2. [Q9NXR7-4]
NP_954663.1. NM_199193.2. [Q9NXR7-4]
NP_954664.1. NM_199194.2. [Q9NXR7-2]
UniGeneiHs.258314.

Genome annotation databases

EnsembliENST00000342045; ENSP00000339371; ENSG00000158019. [Q9NXR7-2]
ENST00000344773; ENSP00000343412; ENSG00000158019. [Q9NXR7-1]
ENST00000361704; ENSP00000354699; ENSG00000158019. [Q9NXR7-4]
ENST00000379624; ENSP00000368945; ENSG00000158019. [Q9NXR7-2]
ENST00000379632; ENSP00000368953; ENSG00000158019. [Q9NXR7-4]
GeneIDi9577.
KEGGihsa:9577.
UCSCiuc002rlq.4. human. [Q9NXR7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiBABA2_HUMAN
AccessioniPrimary (citable) accession number: Q9NXR7
Secondary accession number(s): A8K4X1
, D6W562, D6W563, Q13880, Q4ZFX8, Q53SD0, Q969X9, Q96P06
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2006
Last sequence update: May 5, 2009
Last modified: October 25, 2017
This is version 134 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families