Mouse anti-Human, mouse UBQLN2 Monoclonal Antibody | anti-UBQLN2 antibody

UBQLN2 Antibody

Cat. Num. AAA415251

• Gene Names: UBQLN2; DSK2; ALS15; CHAP1; N4BP4; PLIC2; HRIHFB2157
• Reactivity: Human, mouse
• Applications: Immunofluorescence, Western Blot
• Purity: Affinity purified
• Synonyms: UBQLN2; Monoclonal Antibody; UBQLN2 Antibody; anti-UBQLN2 antibody

• Host: Mouse
• Reactivity: Human, mouse
• Clonality: Monoclonal
• Isotype: IgG1
• Purity/Purification: Affinity purified
• Form/Format: Liquid
• Concentration: 100ug/100ul (varies by lot)
• Sequence Length: 624

• Applicable Applications for anti-UBQLN2 antibody: Immunofluorescence (IF), Western Blot (WB)
• Application Notes: Try at dilutions of ~1:1,000 for immunofluorescence. For western blots try at 1:1,000-2,000.
• Immunogen: Ubiquilin 2, also known as PLIC2 and Chap1, is a member of the ubiquilin protein family, which regulate the degradation of cellular proteins through proteasome or autophage-like pathways (1, 2, 3). Humans have four ubiquilin genes, each encoding a separate protein referred to as Ubiquilin 1, 2, 3 and 4. All ubiquilins contain an N-terminal ubiquitin-like (UBL) domain and a C-terminal ubiquitin-associated (UBA) domain, while the central part of the molecules are highly variable. The UBL domains bind subunits of the proteasome, and the UBA domains binds to polyubiquitin chains that are typically conjugated onto proteins marked for proteosomal degradation (1). Ubiquilin 2 has a unique region close to the C terminus containing 12 PXX tandem collagen like repeats, where P is proline and X is most cases valine, glycine, isoleucine or threonine. Teepu Siddique and his collaborators have identified mutations in the ubiquilin 2 gene leading to protein point mutations which were important contributors to several forms of amyotrophic lateral sclerosis (ALS) and Frontotemporal lobar degeneration (FTLD). Interestingly, these mutations involved alterations in proline residues in the PXX repeat region (P497H, P497S, P506T, P509S and P525S, ref. 4). Recently, the Lee and Trojanowski group investigated C9orf72 hexanucleotide expansion and ubiquilin 2 pathology in patients with ALS and FTLD by genetic analysis and immunohistochemistry and found distinct ubiquilin 2 pathology in ALS and FTLD-TDP with C9orf72 expansion (5). C9orf72 hexonucleotide expansion is the most commmon cause to date of familial ALS and FTLD (6, 7). Ubiquilin 2 protein is of different molecular size in mouse and human, 638 and 624 amino acids respectively. As a result the mouse protein, endogenously expressed in rodent 3T3 cells, runs on SDS-PAGE and western blots slightly slower than the human protein. Our antibody MCA-6H9 was raised against human ubiquilin 2 expressed in and purified from E. coli. The HGNC name for this protein is UBQLN2.
• Storage Buffer: PBS, pH 7.4 with 0.02% sodium azide.
• Preparation and Storage: Store at -20 degree C/1 year

Western Blot (WB)

References

1. Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio R E, Kedersha N L, Gill G, Howley PM. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Molec. Cell 6: 409-419 (2000).2. N'Diaye EN, Kajihara KK, Hsieh I, Morisaki H, Debnath J, Brown EJ. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep. 10:173-9 (2009).3. Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, Ugolino J, Fang S, Cuervo AM, Nixon RA, Monteiro MJ. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum Mol Genet. Aug 15;19 (16): 3219-32. Epub Jun 7 (2010).4. Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, AjroudK, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature Aug 21;477(7363):211-5 （2011).5. Brettschneider J, Van Deerlin VM, Robinson JL, Kwong L, Lee EB, Ali YO, Safren N, Monteiro MJ, Toledo JB, Elman L, McCluskey L, Irwin DJ, Grossman M, Molina-Porcel L, Lee VM, Trojanowski JQ. Pattern of ubiquilin pathology in ALS and FTLD indicates presence of c9orf72 hexanucleotide expansion. Acta Neuropathol. Jun;123 (6):825-39 （2012).6. Renton AE, Majounie E, Waite AA, et al. Hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron. Oct 20;72(2):257-68 (2011).7. DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, Nicholson AM, Finch NA, Flynn H, Adamson J, Kouri N, Wojtas A, Sengdy P, Hsiung GY, Karydas A, Seeley WW, Josephs KA, Coppola G, Geschwind DH, Wszolek ZK, Feldman H, Knopman DS, Petersen RC, Miller BL, Dickson DW, Boylan KB, Graff-Radford NR, Rademakers R. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron.Oct 20;72(2):245-56 (2011).

NCBI and Uniprot Product Information

• NCBI GI #: 16753207
• NCBI GeneID: 29978
• NCBI Accession #: NP_038472.2
• NCBI GenBank Nucleotide #: NM_013444.3
• UniProt Accession #: Q9UHD9; O94798; Q5D027; Q9H3W6; Q9HAZ4
• Molecular Weight: 65,696 Da
• NCBI Official Full Name: ubiquilin-2
• NCBI Official Synonym Full Names: ubiquilin 2
• NCBI Official Symbol: UBQLN2
• NCBI Official Synonym Symbols: DSK2; ALS15; CHAP1; N4BP4; PLIC2; HRIHFB2157
• NCBI Protein Information: ubiquilin-2; Nedd4 binding protein 4; ubiquitin-like product Chap1/Dsk2; protein linking IAP with cytoskeleton 2
• UniProt Protein Name: Ubiquilin-2
• Protein Family: Ubiquilin
• UniProt Gene Name: UBQLN2
• UniProt Synonym Gene Names: N4BP4; PLIC2; PLIC-2; hPLIC-2
• UniProt Entry Name: UBQL2_HUMAN

NCBI Description

This gene encodes an ubiquitin-like protein (ubiquilin) that shares high degree of similarity with related products in yeast, rat and frog. Ubiquilins contain a N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases; and thus, are thought to functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. This ubiquilin has also been shown to bind the ATPase domain of the Hsp70-like Stch protein. [provided by RefSeq, Oct 2009]

Uniprot Description

Function: Increases the half-life of proteins destined to be degraded by the proteasome; may modulate proteasome-mediated protein degradation. Ref.2

Subunit structure: Binds UBE3A and BTRC. Interacts with the 19S proteasome subunit. Ref.1 Ref.2

Subcellular location: Cytoplasm. Nucleus. Note: Where it colocalizes with the proteasome. Associated with fibers in mitotic cells. Ref.2 Ref.7

Induction: Highly expressed in mitotic cells from metaphase to telophase. Expression in non-mitotic cells is very low.

Involvement in disease: Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia (ALS15) [MIM:300857]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. Patients with ALS15 may develop frontotemporal dementia.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13 Ref.14

Sequence similarities: Contains 1 UBA domain.Contains 1 ubiquitin-like domain.