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PBRM1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3G0J, 3HMF, 3IU5, 3IU6, 3K2J, 3LJW, 3MB4, 3TLP, 4Q0N, 4Q0O, 4Y03, 5IID, 5FH7, 5II1, 5II2, 5FH6, 5FH8
Identifiers
Aliases	PBRM1, BAF180, PB1, polybromo 1, SMARCH1, RCC
External IDs	OMIM: 606083; MGI: 1923998; HomoloGene: 10044; GeneCards: PBRM1; OMA:PBRM1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3p21.1 Start 52,545,352 bp End 52,685,917 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14|14 B Start 30,741,095 bp End 30,843,549 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence amniotic fluid sural nerve human penis saphenous vein Achilles tendon mucosa of paranasal sinus thymus epithelium of nasopharynx germinal epithelium Top expressed in Rostral migratory stream Gonadal ridge renal corpuscle medullary collecting duct maxillary prominence atrium saccule mandibular prominence atrioventricular junction primitive streak More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding chromatin binding protein binding DNA translocase activity Cellular component nuclear chromosome nucleus nucleoplasm RSC-type complex Biological process regulation of transcription, DNA-templated transcription, DNA-templated negative regulation of cell population proliferation mitotic cell cycle chromatin remodeling chromatin organization nucleosome disassembly transcription elongation from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 55193 66923 Ensembl ENSG00000163939 ENSMUSG00000042323 UniProt Q86U86 Q8BSQ9 RefSeq (mRNA) NM_018165 NM_018313 NM_181041 NM_181042 NM_001350074 NM_001350075 NM_001350076 NM_001350077 NM_001350078 NM_001350079 NM_001366070 NM_001366071 NM_001366072 NM_001366073 NM_001366074 NM_001366075 NM_001366076 NM_001394867 NM_001394868 NM_001394869 NM_001394870 NM_001394871 NM_001394872 NM_001394873 NM_001394874 NM_001394875 NM_001394877 NM_001394878 NM_001394879 NM_001394880 NM_001394881 NM_001394876 NM_001400470 NM_001400471 NM_001400472 NM_001400473 NM_001400474 NM_001400475 NM_001400479 NM_001400481 NM_001400484 NM_001400487 NM_001400490 NM_001400496 NM_001400500 NM_001400501 NM_001400504 NM_001081251 NM_025847 NM_001359854 NM_001359855 NM_001359856 NM_001359857 NM_001359858 RefSeq (protein) NP_060783 NP_851385 NP_001337003 NP_001337004 NP_001337005 NP_001337006 NP_001337007 NP_001337008 NP_001352999 NP_001353000 NP_001353001 NP_001353002 NP_001353003 NP_001353004 NP_001353005 NP_001074720 NP_001346783 NP_001346784 NP_001346785 NP_001346786 NP_001346787 Location (UCSC) Chr 3: 52.55 – 52.69 Mb Chr 14: 30.74 – 30.84 Mb PubMed search
Wikidata
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Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the PBRM1 gene.

Structure and function

Human PBRM1 is one of three unique components of the SWI/SNF-B (PBAF) chromatin-remodeling complex, which contains at least SMARCA4/BRG1, SMARCB1/SNF5/INI1/BAF47, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, and actin.

Chicken PB1 possesses 5 bromodomains, 2 bromo-adjacent homology (BAH) domains, and 1 truncated high-mobility group (HMG) motif. cPB1 is also homologous to yeast Rsc1, Rsc2, and Rsc4, essential proteins that are required for cell cycle progression through mitosis.

Clinical significance

PBRM1 is thought to be a tumor suppressor gene in many cancer subtypes largely due to the mutational pattern. Most notably, mutations and copy number alterations in PBRM1 are highly prevalent in clear cell renal cell carcinoma (ccRCC).

Role renal carcinoma

Loss of function mutations in PBRM1 often co-occur with loss of function mutations in the VHL gene in clear cell renal cell carcinoma (ccRCC). The inactivation of PBRM1 in combination with biallelic loss of VHL has been shown to potentiate HIF1α signaling and activate the pro-tumorigenic NF-κB pathway. Genetic loss of PBRM1 is thought to underlie the early initiation of ccRCC due to the sufficiency of conditional deletion of Pbrm1 and Vhl for renal carcinomagenesis in mice. While several studies have identified a favorable outcomes among advanced ccRCC cases with PBRM1 mutations when treated with immune checkpoint inhibitors, there is still debate about the utility of PBRM1 status as a biomarker for response to ICI therapy.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000163939 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000042323 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Xue Y, Canman JC, Lee CS, Nie Z, Yang D, Moreno GT, et al. (November 2000). "The human SWI/SNF-B chromatin-remodeling complex is related to yeast rsc and localizes at kinetochores of mitotic chromosomes". Proceedings of the National Academy of Sciences of the United States of America. 97 (24): 13015–13020. Bibcode:2000PNAS...9713015X. doi:10.1073/pnas.240208597. PMC 27170. PMID 11078522.
6. Yu Y, Zhang C, Zhou G, Wu S, Qu X, Wei H, et al. (August 2001). "Gene expression profiling in human fetal liver and identification of tissue- and developmental-stage-specific genes through compiled expression profiles and efficient cloning of full-length cDNAs". Genome Research. 11 (8): 1392–1403. doi:10.1101/gr.175501. PMC 311073. PMID 11483580.
7. "Entrez Gene: PB1 polybromo 1".
8. Mashtalir N, D'Avino AR, Michel BC, Luo J, Pan J, Otto JE, et al. (November 2018). "Modular Organization and Assembly of SWI/SNF Family Chromatin Remodeling Complexes". Cell. 175 (5): 1272–1288.e20. doi:10.1016/j.cell.2018.09.032. PMC 6791824. PMID 30343899.
9. "Q86U86 : Protein polybromo-1 (Human)". Universal Protein Resource. UniProt Consortium.
10. Shain AH, Pollack JR (2013). "The spectrum of SWI/SNF mutations, ubiquitous in human cancers". PLOS ONE. 8 (1): e55119. Bibcode:2013PLoSO...855119S. doi:10.1371/journal.pone.0055119. PMC 3552954. PMID 23355908.
11. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, et al. (January 2011). "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma". Nature. 469 (7331): 539–542. Bibcode:2011Natur.469..539V. doi:10.1038/nature09639. PMC 3030920. PMID 21248752.
12. Varela I, Tarpey P, Raine K, Huang D, Ong CK, Stephens P, et al. (January 2011). "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma". Nature. 469 (7331): 539–542. Bibcode:2011Natur.469..539V. doi:10.1038/nature09639. PMC 3030920. PMID 21248752.
13. Gao W, Li W, Xiao T, Liu XS, Kaelin WG (January 2017). "Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma". Proceedings of the National Academy of Sciences of the United States of America. 114 (5): 1027–1032. Bibcode:2017PNAS..114.1027G. doi:10.1073/pnas.1619726114. PMC 5293026. PMID 28082722.
14. Yao X, Hong JH, Nargund AM, Ng MS, Heng HL, Li Z, et al. (May 2023). "PBRM1-deficient PBAF complexes target aberrant genomic loci to activate the NF-κB pathway in clear cell renal cell carcinoma". Nature Cell Biology. 25 (5): 765–777. doi:10.1038/s41556-023-01122-y. PMID 37095322. S2CID 258311941.
15. Gu YF, Cohn S, Christie A, McKenzie T, Wolff N, Do QN, et al. (August 2017). "Modeling Renal Cell Carcinoma in Mice: Bap1 and Pbrm1 Inactivation Drive Tumor Grade". Cancer Discovery. 7 (8): 900–917. doi:10.1158/2159-8290.CD-17-0292. PMC 5540776. PMID 28473526.
16. Yang Q, Shen R, Xu H, Shi X, Xu L, Zhang L, et al. (March 2021). "Comprehensive analyses of PBRM1 in multiple cancer types and its association with clinical response to immunotherapy and immune infiltrates". Annals of Translational Medicine. 9 (6): 465. doi:10.21037/atm-21-289. PMC 8039713. PMID 33850862.
17. Carril-Ajuria L, Santos M, Roldán-Romero JM, Rodriguez-Antona C, de Velasco G (December 2019). "Prognostic and Predictive Value of PBRM1 in Clear Cell Renal Cell Carcinoma". Cancers. 12 (1): 16. doi:10.3390/cancers12010016. PMC 7016957. PMID 31861590.

Further reading

• Martens JA, Winston F (April 2003). "Recent advances in understanding chromatin remodeling by Swi/Snf complexes". Current Opinion in Genetics & Development. 13 (2): 136–142. doi:10.1016/S0959-437X(03)00022-4. PMID 12672490.
• Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, et al. (October 2001). "Protein-protein interaction panel using mouse full-length cDNAs". Genome Research. 11 (10): 1758–1765. doi:10.1101/gr.180101. PMC 311163. PMID 11591653.
• Lemon B, Inouye C, King DS, Tjian R (2002). "Selectivity of chromatin-remodelling cofactors for ligand-activated transcription". Nature. 414 (6866): 924–928. doi:10.1038/414924a. PMID 11780067. S2CID 4391100.
• Olave I, Wang W, Xue Y, Kuo A, Crabtree GR (October 2002). "Identification of a polymorphic, neuron-specific chromatin remodeling complex". Genes & Development. 16 (19): 2509–2517. doi:10.1101/gad.992102. PMC 187451. PMID 12368262.
• Horikawa I, Barrett JC (August 2002). "cDNA cloning of the human polybromo-1 gene on chromosome 3p21". DNA Sequence. 13 (4): 211–215. doi:10.1080/1042517021000021590. PMID 12487023. S2CID 23406882.
• Sekine I, Sato M, Sunaga N, Toyooka S, Peyton M, Parsons R, et al. (April 2005). "The 3p21 candidate tumor suppressor gene BAF180 is normally expressed in human lung cancer". Oncogene. 24 (16): 2735–2738. doi:10.1038/sj.onc.1207694. PMID 15735765. S2CID 19875372.
• Yan Z, Cui K, Murray DM, Ling C, Xue Y, Gerstein A, et al. (July 2005). "PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes". Genes & Development. 19 (14): 1662–1667. doi:10.1101/gad.1323805. PMC 1176002. PMID 15985610.
• Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, et al. (August 2005). "Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry". Nature Methods. 2 (8): 591–598. doi:10.1038/nmeth776. PMID 16094384. S2CID 20475874.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–1292. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Chandrasekaran R, Thompson M (April 2007). "Polybromo-1-bromodomains bind histone H3 at specific acetyl-lysine positions". Biochemical and Biophysical Research Communications. 355 (3): 661–666. doi:10.1016/j.bbrc.2007.01.193. PMID 17320048.

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