BRCC3 BRCA1/BRCA2-containing complex subunit 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: BRCC3provided by HGNC
Official Full Name: BRCA1/BRCA2-containing complex subunit 3provided by HGNC
Primary source: HGNC:HGNC:24185
See related: Ensembl:ENSG00000185515 MIM:300617; AllianceGenome:HGNC:24185
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: C6.1A; BRCC36; CXorf53
Summary: This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break sites. The component encoded by this gene can specifically cleave Lys 63-linked polyubiquitin chains, and it regulates the abundance of these polyubiquitin chains in chromatin. The loss of this gene results in abnormal angiogenesis and is associated with syndromic moyamoya, a cerebrovascular angiopathy. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jun 2011]
Expression: Ubiquitous expression in colon (RPKM 4.9), esophagus (RPKM 3.5) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: Xq28

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (155071508..155123077)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (153307916..153359479)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (154299783..154351352)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome.
Title: BRCC3 mediates inflammation and pyroptosis in cerebral ischemia/reperfusion injury by activating the NLRP6 inflammasome.
Identification of BRCC3 and BRCA1 as Regulators of TAZ Stability and Activity.
Title: Identification of BRCC3 and BRCA1 as Regulators of TAZ Stability and Activity.
Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro.
Title: Identification and Verification of the Ability of Cdk5 to Phosphorylate Deubiquitinating Enzyme BRCC3 In Vitro.
ABRO1 stabilizes the deubiquitinase BRCC3 through inhibiting its degradation mediated by the E3 ubiquitin ligase WWP2.
Title: ABRO1 stabilizes the deubiquitinase BRCC3 through inhibiting its degradation mediated by the E3 ubiquitin ligase WWP2.
BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling.
Title: BRCA1-A and BRISC: Multifunctional Molecular Machines for Ubiquitin Signaling.
BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability.
Title: BRCC36 functions noncatalytically to promote antiviral response by maintaining STAT1 protein stability.
Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination.
Title: Vitamin D Receptor Inhibits NLRP3 Activation by Impeding Its BRCC3-Mediated Deubiquitination.
Cell lines and primary mouse cells with inactivation of BRCC3 had a higher sensitivity to doxorubicin.
Title: Functional characterization of BRCC3 mutations in acute myeloid leukemia with t(8;21)(q22;q22.1).
BRCC3 expressed in oligodendrocyte precursor cells in vitro is required for the oligodendrocyte lineage progression toward the mature stage. Lack of BRCC3 function could deteriorate demyelination at the lesion site. An increase in Lys63-linked ubiquitination levels induced by the deregulation of BRCC3 expression promotes the endosomal/lysosomal processing of myelin proteins.
Title: BRCA1/BRCA2-containing complex subunit 3 controls oligodendrocyte differentiation by dynamically regulating lysine 63-linked ubiquitination.
Here we show that in the BRCA1-A complex structure, ABRAXAS integrates the DNA repair protein RAP80 and provides a high-affinity binding site that sequesters the tumor suppressor BRCA1 away from the break site. In the BRISC structure, ABRO1 binds SHMT2alpha, a metabolic enzyme enabling cancer growth in hypoxic environments, which we find prevents BRCC36 from binding and cleaving ubiquitin chains
Title: Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation.

Submit: New GeneRIF Correction See all GeneRIFs (27)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

ECD16978 (e-PCR)
- UniSTS:297992

ECD09788 (e-PCR)
- UniSTS:290829

ECD23674 (e-PCR)
- UniSTS:304658

ECD19304 (e-PCR)
- UniSTS:300311

ECD08012 (e-PCR)
- UniSTS:289060

STS-X64643 (e-PCR)
- UniSTS:35369

ECD20615 (e-PCR)
- UniSTS:301614

ECD22941 (e-PCR)
- UniSTS:303926

ECD09059 (e-PCR)
- UniSTS:290105

ECD01065 (e-PCR)
- UniSTS:282172

ECD14725 (e-PCR)
- UniSTS:295745

ECD09588 (e-PCR)
- UniSTS:290629

ECD20126 (e-PCR)
- UniSTS:301130

ECD18081 (e-PCR)
- UniSTS:299092

ECD07563 (e-PCR)
- UniSTS:288614

ECD04214 (e-PCR)
- UniSTS:285292

ECD05774 (e-PCR)
- UniSTS:286836

ECD23789 (e-PCR)
- UniSTS:304773

ECD21738 (e-PCR)
- UniSTS:302731

RH79163 (e-PCR)
- UniSTS:87186

ECD11213 (e-PCR)
- UniSTS:292249

ECD14814 (e-PCR)
- UniSTS:295834

ECD09419 (e-PCR)
- UniSTS:290462

ECD16104 (e-PCR)
- UniSTS:297119

ECD13023 (e-PCR)
- UniSTS:294054

ECD15347 (e-PCR)
- UniSTS:296364

ECD19968 (e-PCR)
- UniSTS:300972

ECD15348 (e-PCR)
- UniSTS:296365

ECD16890 (e-PCR)
- UniSTS:297904

ECD11247 (e-PCR)
- UniSTS:292283

ECD13301 (e-PCR)
- UniSTS:294331

ECD12533 (e-PCR)
- UniSTS:293566

ECD02005 (e-PCR)
- UniSTS:283106

ECD13341 (e-PCR)
- UniSTS:294371

ECD22603 (e-PCR)
- UniSTS:303589

ECD00985 (e-PCR)
- UniSTS:282094

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables K63-linked deubiquitinase activity	IDA Inferred from Direct Assay more info	PubMed
enables K63-linked deubiquitinase activity	TAS Traceable Author Statement more info
enables cysteine-type deubiquitinase activity	IEA Inferred from Electronic Annotation more info
enables enzyme regulator activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metal-dependent deubiquitinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metallopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metallopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables polyubiquitin modification-dependent protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables polyubiquitin modification-dependent protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA repair-dependent chromatin remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ionizing radiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic G2 DNA damage checkpoint signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitotic G2/M transition checkpoint	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NLRP3 inflammasome complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of NLRP3 inflammasome complex assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein K63-linked deubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein K63-linked deubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in regulation of DNA damage checkpoint	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of DNA repair	NAS Non-traceable Author Statement more info	PubMed
acts_upstream_of_or_within response to X-ray	IDA Inferred from Direct Assay more info	PubMed
involved_in response to ionizing radiation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of BRCA1-A complex	IBA Inferred from Biological aspect of Ancestor more info
part_of BRCA1-A complex	IDA Inferred from Direct Assay more info	PubMed
part_of BRCA1-A complex	NAS Non-traceable Author Statement more info	PubMed
part_of BRISC complex	IBA Inferred from Biological aspect of Ancestor more info
part_of BRISC complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
part_of nuclear ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
located_in spindle pole	IEA Inferred from Electronic Annotation more info
part_of ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: lys-63-specific deubiquitinase BRCC36

Names: BRCA1-A complex subunit BRCC36; BRCA1/BRCA2-containing complex subunit 36; BRISC complex subunit BRCC36

NP_001018065.1

EC 3.1.2.15

NP_001229569.1

EC 3.1.2.15

NP_077308.1

EC 3.1.2.15

XP_005274808.1

EC 3.1.2.15

XP_054183838.1

EC 3.1.2.15

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047184.1 RefSeqGene

Range

5089..56658

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001018055.3 → NP_001018065.1 lys-63-specific deubiquitinase BRCC36 isoform 2

See identical proteins and their annotated locations for NP_001018065.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

BC002999, BP304352, BX293995, X64643

Consensus CDS

CCDS56612.1

Related

ENSP00000328641.7, ENST00000330045.12

Conserved Domains (1) summary

cd08068
Location:13 → 267

MPN_BRCC36; Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex
NM_001242640.2 → NP_001229569.1 lys-63-specific deubiquitinase BRCC36 isoform 3

See identical proteins and their annotated locations for NP_001229569.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, and lacks an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AK299194, BC002999, BP304352, BX293995

Consensus CDS

CCDS56610.1

UniProtKB/Swiss-Prot

P46736

Related

ENSP00000344103.4, ENST00000340647.8

Conserved Domains (1) summary

cd08068
Location:13 → 268

MPN_BRCC36; Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex
NM_024332.4 → NP_077308.1 lys-63-specific deubiquitinase BRCC36 isoform 1

See identical proteins and their annotated locations for NP_077308.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC002999, BP304352, BX293995

Consensus CDS

CCDS56611.1

UniProtKB/Swiss-Prot

A6QRF8, A6QRF9, A8MUX5, A8MWH0, A9Z1Y0, A9Z1Y5, B1B062, B4DQN7, P46736, Q16107, Q53YX5, Q9BTZ6

Related

ENSP00000358474.1, ENST00000369462.5

Conserved Domains (1) summary

cd08068
Location:13 → 292

MPN_BRCC36; Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000023.11 Reference GRCh38.p14 Primary Assembly

Range

155071508..155123077

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005274751.5 → XP_005274808.1 lys-63-specific deubiquitinase BRCC36 isoform X1

See identical proteins and their annotated locations for XP_005274808.1

Conserved Domains (1) summary

cd08068
Location:13 → 293

MPN_BRCC36; Mov34/MPN/PAD-1 family: BRCC36, a subunit of BRCA1-A complex