PALB2

Partner and localizer of BRCA2
PyMOL rendered image based on 3EU7​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2W18​, 3EU7​
Identifiers
Symbols	PALB2 ; FANCN; PNCA3
External IDs	OMIM: 610355 MGI: 3040695 HomoloGene: 11652 GeneCards: PALB2 Gene
Gene ontology Molecular function • DNA binding • protein binding Cellular component • nucleoplasm Biological process • double-strand break repair via homologous recombination • somitogenesis • inner cell mass cell proliferation • DNA repair • mesoderm development • organ morphogenesis • post-anal tail morphogenesis • negative regulation of apoptotic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	79728	233826
Ensembl	ENSG00000083093	ENSMUSG00000044702
UniProt	Q86YC2	Q3U0P1
RefSeq (mRNA)	NM_024675	NM_001081238
RefSeq (protein)	NP_078951	NP_001074707
Location (UCSC)	Chr 16: 23.6 – 23.64 Mb	Chr 7: 122.11 – 122.13 Mb
PubMed search

Partner and localizer of BRCA2, also known as PALB2 or FANCN, is a protein which in humans is encoded by the PALB2 gene.^[1][2][3]

Function

Characterized domaines of PALB2

This gene encodes a protein that functions in genome maintenance (double strand break repair). This protein binds to and colocalizes with the breast cancer 2 early onset protein (BRCA2) in nuclear foci and likely permits the stable intranuclear localization and accumulation of BRCA2.^[1] PALB2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion, a vital step of homologous recombination.^[4] PALB2 can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.^[4]

Clinical significance

Variants in the PALB2 gene are associated with an increased risk of developing breast cancer ^[5] of magnitude similar to that associated with BRCA2 mutations ^[6] and PALB2-deficient cells are sensitive to PARP inhibitors.^[4]

PALB2 was recently identified as a susceptibility gene for familial pancreatic cancer by scientists at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins. This has paved for the way for developing a new gene test for families where pancreatic cancer occurs in multiple family members.^[7] Tests for PALB2 have been developed by Ambry Genetics ^[8] and Myriad Genetics^[9] that are now available. The PALB2 Interest Group (PALB2.org) is an international consortium of scientists and clinicians who coordinate research into this gene.

Biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia.^[3]

See also

• Fanconi anemia
• BRCA2
• DNA repair
• Tumor suppressor gene
• PALB2 Interest Group

References

1. "Entrez Gene: PALB2 partner and localizer of BRCA2".
2. Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (June 2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2". Mol. Cell 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542.
3. Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP (February 2007). "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2". Nat. Genet. 39 (2): 159–61. doi:10.1038/ng1942. PMID 17200672.
4. Buisson R, Dion-Côté AM, Coulombe Y, Launay H, Cai H, Stasiak AZ, Stasiak A, Xia B, Masson JY (2010). "Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination.". Nature Structural & Molecular Biology 17 (10): 1247–54. doi:10.1038/nsmb.1915. PMID 20871615.
5. Chen P, Liang J, Wang Z, Zhou X, Chen L, Li M, Xie D, Hu Z, Shen H, Wang H (September 2008). "Association of common PALB2 polymorphisms with breast cancer risk: a case-control study". Clin. Cancer Res. 14 (18): 5931–7. doi:10.1158/1078-0432.CCR-08-0429. PMID 18794107.
6. Antoniou A, et al. (August 7, 2014). "Breast-Cancer Risk in Families with Mutations in PALB2". N Engl J Med 2014 371: 497–506. doi:10.1056/NEJMoa1400382.
7. Jones S, Hruban RH, Kamiyama M, Borges M, Zhang X, Parsons DW, Lin JC, Palmisano E, Brune K, Jaffee EM, Iacobuzio-Donahue CA, Maitra A, Parmigiani G, Kern SE, Velculescu VE, Kinzler KW, Vogelstein B, Eshleman JR, Goggins M, Klein AP (2009). "Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene.". Science 324 (5924): 217. doi:10.1126/science.1171202. PMC 2684332. PMID 19264984.
8. "Ambry Genetics".
9. "Myriad Genetics".

Further reading

• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins.". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Xia B, Sheng Q, Nakanishi K, Ohashi A, Wu J, Christ N, Liu X, Jasin M, Couch FJ, Livingston DM (2006). "Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2.". Mol. Cell 22 (6): 719–29. doi:10.1016/j.molcel.2006.05.022. PMID 16793542.
• Rahman N, Seal S, Thompson D, Kelly P, Renwick A, Elliott A, Reid S, Spanova K, Barfoot R, Chagtai T, Jayatilake H, McGuffog L, Hanks S, Evans DG, Eccles D, Easton DF, Stratton MR (2007). "PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.". Nat. Genet. 39 (2): 165–7. doi:10.1038/ng1959. PMC 2871593. PMID 17200668.
• Reid S, Schindler D, Hanenberg H, Barker K, Hanks S, Kalb R, Neveling K, Kelly P, Seal S, Freund M, Wurm M, Batish SD, Lach FP, Yetgin S, Neitzel H, Ariffin H, Tischkowitz M, Mathew CG, Auerbach AD, Rahman N (2007). "Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.". Nat. Genet. 39 (2): 162–4. doi:10.1038/ng1947. PMID 17200671.
• Xia B, Dorsman JC, Ameziane N, de Vries Y, Rooimans MA, Sheng Q, Pals G, Errami A, Gluckman E, Llera J, Wang W, Livingston DM, Joenje H, de Winter JP (2007). "Fanconi anemia is associated with a defect in the BRCA2 partner PALB2.". Nat. Genet. 39 (2): 159–61. doi:10.1038/ng1942. PMID 17200672.
• Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Kataja V, Soini Y, Drapkin RI, Livingston DM, Winqvist R (2007). "A recurrent mutation in PALB2 in Finnish cancer families.". Nature 446 (7133): 316–9. doi:10.1038/nature05609. PMID 17287723.
• Tischkowitz M, Xia B, Sabbaghian N, Reis-Filho JS, Hamel N, Li G, van Beers EH, Li L, Khalil T, Quenneville LA, Omeroglu A, Poll A, Lepage P, Wong N, Nederlof PM, Ashworth A, Tonin PN, Narod SA, Livingston DM, Foulkes WD (2007). "Analysis of PALB2/FANCN-associated breast cancer families.". Proc. Natl. Acad. Sci. U.S.A. 104 (16): 6788–93. doi:10.1073/pnas.0701724104. PMC 1871863. PMID 17420451.
• Oliver AW, Swift S, Lord CJ, Ashworth A, Pearl LH (2009). "Structural basis for recruitment of BRCA2 by PALB2.". EMBO Reports 10 (9): 990–6. doi:10.1038/embor.2009.126. PMC 2750052. PMID 19609323.