PBRM1

Protein-coding gene in the species Homo sapiens

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)^[1]

Band	3p21.1	Start	52,545,352 bp^[1]
Band	3p21.1	End	52,685,917 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 14 (mouse)^[2]

Band	14\|14 B	Start	30,741,095 bp^[2]
Band	14\|14 B	End	30,843,549 bp^[2]

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

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Protein polybromo-1 (PB1) also known as BRG1-associated factor 180 (BAF180) is a protein that in humans is encoded by the PBRM1 gene.^[5]^[6]^[7]

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.^[8]^[9]

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.^[5]

Clinical significance

PBRM1 is thought to be a tumor suppressor gene in many cancer subtypes largely due to the mutational pattern.^[10] Most notably, mutations and copy number alterations in PBRM1 are highly prevalent in clear cell renal cell carcinoma (ccRCC).^[11]

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).^[12] 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.^[13]^[14] 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.^[15] 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.^[16]^[17]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000163939 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000042323 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b 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.
^ 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.
^ "Entrez Gene: PB1 polybromo 1".
^ 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.
^ "Q86U86 : Protein polybromo-1 (Human)". Universal Protein Resource. UniProt Consortium.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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