UIMC1 Antibody, Biotin conjugated
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Description
Structure and Function of UIMC1
UIMC1 contains tandem ubiquitin-interacting motifs (UIMs) that bind Lys-63-linked polyubiquitin chains at DNA damage sites, recruiting BRCA1-BARD1 complexes to double-strand breaks (DSBs) . Key features include:
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Molecular Weight: ~80 kDa (calculated), with observed bands between 61–97 kDa due to post-translational modifications .
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Domains: Two UIMs (residues 161–235 and 567–601) critical for ubiquitin binding .
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Pathways: DNA damage repair, BRCA1-A complex assembly, and regulation of homologous recombination .
Biotin Conjugation: Mechanism and Advantages
Biotinylation involves chemically linking biotin to antibodies, enabling detection via streptavidin-enzyme or streptavidin-fluorophore systems. For UIMC1 antibodies, this process enhances sensitivity through signal amplification .
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Applications:
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Benefits:
DNA Damage Response Studies
UIMC1 biotin-conjugated antibodies enable precise tracking of BRCA1-A complex dynamics:
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BRCA1 Recruitment: UIMC1-bound antibodies highlight BRCA1 sequestration at DSBs, promoting non-homologous end joining (NHEJ) over homologous recombination (HR) .
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Ubiquitination Analysis: Detects Lys-63-linked ubiquitin chains on histones H2A/H2AX during damage repair .
Key Experimental Data
| Parameter | Details | Source |
|---|---|---|
| Host Species | Rabbit (polyclonal) | |
| Target Epitope | C-terminal region (AA 567–601) | |
| Cross-Reactivity | Human, mouse | |
| Detection Limit | ≤1 ng of UIMC1 in WB (using streptavidin-HRP) |
Technical Considerations
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Buffer Compatibility: PBS with 0.02% sodium azide; avoid reducing agents to preserve biotin integrity .
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Controls: Use unconjugated UIMC1 antibodies or isotype-matched biotinylated antibodies to validate specificity .
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Biotin Interference: High endogenous biotin (e.g., in egg yolk or serum) may require blocking steps .
Case Study: BRCA1 Mutant Analysis
In BRCA1-Y1853ter mutants, UIMC1 interactions are disrupted, altering BRCA1-A complex localization. Biotin-conjugated UIMC1 antibodies quantified reduced binding affinity (mutant BRCA1 levels: 32.4% of WT) . This highlights their utility in profiling cancer-associated BRCA1 variants.
Product Specs
Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we can ship products within 1-3 business days after receiving your order. Delivery times may vary depending on the purchase method or location. Please contact your local distributor for specific delivery details.
Synonyms
BRCA1-A complex subunit RAP80 antibody; Nuclear zinc finger protein RAP80 antibody; OTTHUMP00000161441 antibody; OTTHUMP00000223372 antibody; OTTHUMP00000223374 antibody; RAP80 antibody; Receptor associated protein 80 antibody; Receptor-associated protein 80 antibody; Retinoid X receptor interacting protein 110 antibody; Retinoid x receptor interacting protein antibody; Retinoid X receptor-interacting protein 110 antibody; RIP110 antibody; Rxrip110 antibody; Ubiquitin interaction motif containing 1 antibody; Ubiquitin interaction motif containing protein 1 antibody; Ubiquitin interaction motif-containing protein 1 antibody; UIMC1 antibody; UIMC1_HUMAN antibody; X2HRIP110 antibody
Target Names
UIMC1
Uniprot No.
Target Background
Function
RAP80 is a ubiquitin-binding protein that specifically recognizes and binds to 'Lys-63'-linked ubiquitin. It plays a critical role in the BRCA1-A complex by specifically binding to 'Lys-63'-linked ubiquitinated histones H2A and H2AX at sites of DNA damage. This interaction facilitates the recruitment of the BRCA1-BARD1 heterodimer to DNA double-strand breaks (DSBs). The BRCA1-A complex also exhibits deubiquitinase activity, specifically removing 'Lys-63'-linked ubiquitin from histones H2A and H2AX. While RAP80 weakly binds monoubiquitin, its affinity for 'Lys-63'-linked ubiquitin is significantly higher. It may interact with monoubiquitinated histones H2A and H2B; however, the relevance of this interaction in vivo remains unclear. Notably, RAP80 does not bind to Lys-48'-linked ubiquitin. It may indirectly act as a transcriptional repressor by inhibiting the interaction between NR6A1 and the corepressor NCOR1.
Gene References Into Functions
- The formation of RAP80-BRCA1 complex foci is regulated by USP13. USP13 interacts with and deubiquitinates RAP80, influencing its role in the DNA damage response. PMID: 28569838
- RAP80 deficiency reduces the protein levels of p32 and p32-dependent mitochondrial translating proteins, such as Rieske and COX1. PMID: 28842250
- Low RAP80 mRNA expression correlates with sporadic high-grade serous ovarian carcinoma. PMID: 27443420
- RAP80 serves as a critical gatekeeper in preventing epithelial-mesenchymal transition-induced metastasis and malignant phenotypes of cancer while preserving DNA integrity. PMID: 26748910
- Data suggest that the RAP80 SIM (SUMO interacting motif) binds SUMO-2; both specificity and affinity are enhanced through phosphorylation of the canonical CK2 (casein kinase 2) site within the SIM. PMID: 26719330
- Impaired TIP60-mediated H4K16 acetylation contributes to the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia pathway-deficient cells. PMID: 26446986
- TRAIP/RNF206 is essential for the recruitment of RAP80 to sites of DNA damage. PMID: 26781088
- FANCG plays a new role in homologous recombination repair of interstrand crosslinks through K63Ub-mediated interaction with the Rap80-BRCA1 complex. PMID: 25132264
- Patients with low RAP80 expression received gemcitabine/cisplatin, while those with intermediate/high RAP80 expression and low/intermediate BRCA1 expression received docetaxel/cisplatin. PMID: 25164908
- Data indicate that a single point deletion (DeltaE81) in RAP80 disrupts multivalent interactions with polyubiquitin. PMID: 24627472
- RAP80 links ubiquitin- and SUMO-dependent DSB recognition, demonstrating that RNF4-synthesized hybrid SUMO-ubiquitin chains are recognized by RAP80 to promote BRCA1 recruitment and DNA repair. PMID: 23211528
- Post-translational phosphorylation of RAP80 by the Cdk1-cyclin B(1) complex is crucial for RAP80's functional sensitivity to IR and G(2)/M checkpoint control. PMID: 23264621
- Loss of RAP80 abolishes the recruitment of the BRCA1-A complex to DNA lesions in response to DNA damage. PMID: 22792303
- The APC/C(Cdc20) or APC/C(Cdh1) complexes regulate RAP80 stability during mitosis to the G(1) phase, and these events are critical for a novel function of RAP80 in mitotic progression. PMID: 22426463
- RNF168, its paralog RNF169, RAD18, and the BRCA1-interacting RAP80 protein accumulate at DNA double-strand break sites through the use of bipartite modules composed of ubiquitin binding domains. PMID: 22742833
- A model is proposed where SUMO and Ub modification are coordinated to recruit Rap80 and BRCA1 to DNA damage sites. PMID: 22689573
- MDC1 is required for the recruitment of RAP80 to DNA double-strand breaks. PMID: 21857162
- The interaction between MDC1 and RAP80 necessitates the tandem BRCT domain of MDC1 and the ubiquitin-interacting motifs of RAP80. PMID: 21622030
- A model is proposed where the BRCA1-RAP80 complex restricts nuclease accessibility to DSBs, preventing excessive end resection and potentially detrimental homology-directed DSB repair mechanisms that can compromise genome integrity. PMID: 21335604
- RAP80/BRCA1 complexes suppress excessive double-strand break end processing, HR-type double-strand break repair, and overt chromosomal instability. PMID: 21406551
- RAP80 is a novel nuclear protein that interacts with the retinoid-related testis-associated receptor. PMID: 12080054
- Abraxas and RAP80 are essential for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID: 17525340
- Data support a model where ubiquitin chains at DNA damage sites serve as a targeting mechanism for specific BRCA1 complexes; RAP80 may represent a new class of DNA repair proteins that utilize tandem UIM domains for recruitment to DSBs. PMID: 17525341
- RAP80, a BRCA1-interacting protein in humans, has been identified. PMID: 17525342
- RAP80/UIMC1, a protein highly expressed in the testis, has been identified as a new cancer-associated antigen. PMID: 17562356
- The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and participates in the DNA damage repair response. PMID: 17621610
- RAP80 interacts with the SUMO-conjugating enzyme UBC9 and is a novel target for sumoylation. PMID: 17698038
- The human Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. PMID: 18077395
- Mutational analysis in 168 multiple-case breast/ovarian cancer families, negative for mutations in BRCA1 or BRCA2, suggests that RAP80 does not play a significant role as a high-penetrance breast cancer susceptibility gene. PMID: 18270812
- Truncating mutations of the RAP80 gene do not appear to be a cause of familial breast cancer. A novel RAP80 haplotype or rare missense mutations (p.Ala342Thr, p.Met353Thr, and p.Tyr575Asp) may be associated with a modest increased risk of breast cancer. PMID: 18306035
- UV irradiation induces translocation of RAP80 to DNA damage foci that colocalize with gamma-H2AX. PMID: 18519686
- Depletion of RAP80 or RNF8 impairs the translocation of BRCA1 to DNA damage sites, leading to defective cell cycle checkpoint control and DSB repair. PMID: 18550271
- It is unlikely that moderate to highly penetrant alleles of either RAP80 or Abraxas confer a significantly high relative risk of breast cancer. PMID: 18695986
- MERIT40 represents a novel factor that links BRCA1-Rap80 complex integrity, DSB recognition, and ubiquitin chain hydrolytic activities to the DNA damage response. PMID: 19261746
- Critical constitutional mutations in RAP80 abrogate DNA damage responses (DDR) function and may contribute to genetic predisposition to cancer. PMID: 19305427
- Findings demonstrate how the sequence between the Rap80 ubiquitin interacting motifs positions the domains for efficient avid polyubiquitin binding across a single K63 linkage, defining selectivity. PMID: 19328070
- RAP80 was a significant factor for survival in patients treated according to BRCA1 levels. PMID: 19415121
- Data reveal that RAP80 can function in an autoregulatory loop consisting of RAP80, HDM2, and the p53 master regulatory network, suggesting a crucial role for this loop in genome stability and oncogenesis. PMID: 19433585
- Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) PMID: 19448621
- Observational study and meta-analysis of gene-disease association. (HuGE Navigator) PMID: 19064572
- Observational study of gene-disease association. (HuGE Navigator) PMID: 18270812
Database Links
Protein Families
RAP80 family
Subcellular Location
Nucleus. Note=Localizes at sites of DNA damage at double-strand breaks (DSBs).
Tissue Specificity
Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis.
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