Sequestosome 1

Last updated

SQSTM1
Protein SQSTM1 PDB 1q02.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases SQSTM1 , A170, OSIL, PDB3, ZIP3, p60, p62, p62B, FTDALS3, Sequestosome 1, NADGP, DMRV
External IDs OMIM: 601530; MGI: 107931; HomoloGene: 31202; GeneCards: SQSTM1; OMA:SQSTM1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001142298
NM_001142299
NM_003900

NM_001290769
NM_011018

RefSeq (protein)

NP_001135770
NP_001135771
NP_003891

NP_001277698
NP_035148

Location (UCSC) Chr 5: 179.81 – 179.84 Mb Chr 11: 50.09 – 50.1 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. [5] [6] [7] Also known as the ubiquitin-binding protein p62, [8] it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype. [9]

Contents

Mutations in SQSTM1 are a common cause of Paget's disease of bone. [10]

Interactions

Sequestosome 1 has been shown to interact with:

Role in cancer

The SQSTM1 gene, which is actively transcribed as part of normal cellular function, is sometimes identified in fusion proteins, which can cause cancer when SQSTM1 is abnormally fused to a tyrosine kinase or other pro-proliferation gene. These genes are normally tightly regulated, but when bound to a minimally regulated gene like SQSTM1, they cause abnormal over-expression. [21]

References

  1. 1 2 3 ENSG00000284099 GRCh38: Ensembl release 89: ENSG00000161011, ENSG00000284099 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015837 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. Joung I, Strominger JL, Shin J (July 1996). "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain". Proceedings of the National Academy of Sciences of the United States of America. 93 (12): 5991–5995. Bibcode:1996PNAS...93.5991J. doi: 10.1073/pnas.93.12.5991 . PMC   39176 . PMID   8650207.
  6. Devergne O, Hummel M, Koeppen H, Le Beau MM, Nathanson EC, Kieff E, et al. (February 1996). "A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes". Journal of Virology. 70 (2): 1143–1153. doi:10.1128/JVI.70.2.1143-1153.1996. PMC   189923 . PMID   8551575.
  7. "Entrez Gene: SQSTM1 sequestosome 1".
  8. Online Mendelian Inheritance in Man (OMIM): 601530
  9. Cassidy LD, Narita M (Sep 2015). "GATA get a hold on senescence" (PDF). Science. 349 (6255). New York, N.Y.: 1448–1449. Bibcode:2015Sci...349.1448C. doi:10.1126/science.aad2501. PMID   26404812. S2CID   35805331.
  10. Layfield R, Ciani B, Ralston S, Hocking L, Sheppard P, Searle M, et al. (2004-10-26). "Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone". Biochemical Society Transactions. 32 (Pt 5): 728–730. doi:10.1042/bst0320728. ISSN   0300-5127. PMID   15493999. S2CID   22544044.
  11. Shvets E, Fass E, Scherz-Shouval R, Elazar Z (August 2008). "The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes". Journal of Cell Science. 121 (Pt 16): 2685–2695. doi:10.1242/jcs.026005. PMID   18653543. S2CID   2782335.
  12. Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (May 1998). "Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62". Molecular and Cellular Biology. 18 (5): 3069–3080. doi:10.1128/mcb.18.5.3069. PMC   110686 . PMID   9566925.
  13. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
  14. Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (Jun 1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". The EMBO Journal. 18 (11): 3044–3053. doi:10.1093/emboj/18.11.3044. PMC   1171386 . PMID   10356400.
  15. Sanz L, Diaz-Meco MT, Nakano H, Moscat J (April 2000). "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway". The EMBO Journal. 19 (7): 1576–1586. doi:10.1093/emboj/19.7.1576. PMC   310227 . PMID   10747026.
  16. Wooten MW, Seibenhener ML, Mamidipudi V, Diaz-Meco MT, Barker PA, Moscat J (March 2001). "The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor". Journal of Biological Chemistry. 276 (11): 7709–7712. doi: 10.1074/jbc.C000869200 . PMID   11244088.
  17. 1 2 Geetha T, Wooten MW (February 2003). "Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling". Journal of Biological Chemistry. 278 (7): 4730–4739. doi: 10.1074/jbc.M208468200 . PMID   12471037.
  18. 1 2 Jadhav T, Geetha T, Jiang J, Wooten MW (Jul 2008). "Identification of a consensus site for TRAF6/p62 polyubiquitination". Biochemical and Biophysical Research Communications. 371 (3): 521–524. Bibcode:2008BBRC..371..521J. doi:10.1016/j.bbrc.2008.04.138. PMC   2474794 . PMID   18457658.
  19. Wooten MW, Geetha T, Babu JR, Seibenhener ML, Peng J, Cox N, et al. (March 2008). "Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins". Journal of Biological Chemistry. 283 (11): 6783–6789. doi: 10.1074/jbc.M709496200 . PMID   18174161.
  20. Feng, Lifeng et al. “Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia” Theranostics vol. 7,7 1890-1900. 10 Apr. 2017, doi:10.7150/thno.19135
  21. Badiu DC, Ploscaru IC, Zgura A, Bacinschi X, Smarandache CG, Serban D, et al. (July 2022). "A review of NTRK fusions in cancer". Annals of Medicine and Surgery. 79: 103893. doi:10.1016/j.amsu.2022.103893. ISSN   2049-0801. PMC   9289232 . PMID   35860155.

Further reading