セクエストソーム-1

SQSTM1
PDBに登録されている構造
PDB	オルソログ検索: RCSB PDBe PDBj
PDBのIDコード一覧
	1Q02, 2JY7, 2JY8, 2K0B, 2KNV, 4MJS, 4UF8, 4UF9
識別子
記号	SQSTM1, A170, OSIL, PDB3, ZIP3, p60, p62, p62B, FTDALS3, Sequestosome 1, NADGP, DMRV
外部ID	OMIM: 601530 MGI: 107931 HomoloGene: 31202 GeneCards: SQSTM1
遺伝子の位置 (ヒト)
染色体	5番染色体 (ヒト)
終点	179,838,078 bp
遺伝子の位置 (マウス)
染色体	11番染色体 (マウス)
終点	50,101,654 bp
RNA発現パターン
	; ;
	さらなる参照発現データ
遺伝子オントロジー
分子機能	• protein homodimerization activity; • receptor tyrosine kinase binding; • zinc ion binding; • SH2 domain binding; • 金属イオン結合; • protein serine/threonine kinase activity; • K63-linked polyubiquitin modification-dependent protein binding; • 血漿タンパク結合; • identical protein binding; • プロテインキナーゼ結合; • protein kinase C binding; • ubiquitin binding; • 酵素結合; • ubiquitin protein ligase binding; • ionotropic glutamate receptor binding;
細胞の構成要素	• 細胞質; • エンドソーム; • PML body; • late endosome; • Pボディ; • phagophore assembly site; • 核質; • アグリソーム; • オートファゴソーム; • amphisome; • 小胞体; • 封入体; • リソソーム; • sperm midpiece; • エキソソーム; • cytoplasmic vesicle; • 細胞核; • 細胞質基質; • intracellular membrane-bounded organelle; • autolysosome; • ミトコンドリア; • サルコメア; • レビー小体;
生物学的プロセス	• アポトーシス; • タンパク質局在化; • 細胞分化; • positive regulation of protein phosphorylation; • intracellular signal transduction; • ubiquitin-dependent protein catabolic process; • regulation of mitochondrion organization; • protein heterooligomerization; • 免疫系プロセス; • ストレスへの反応; • regulation of Ras protein signal transduction; • negative regulation of apoptotic process; • オートファジー; • endosomal transport; • regulation of protein complex stability; • マイトファジー; • positive regulation of apoptotic process; • regulation of I-kappaB kinase/NF-kappaB signaling; • positive regulation of transcription by RNA polymerase II; • negative regulation of transcription by RNA polymerase II; • タンパク質リン酸化; • mitophagy; • response to mitochondrial depolarisation; • macroautophagy; • endosome organization; • protein localization to perinuclear region of cytoplasm; • response to ischemia; • mitochondrion organization; • aggrephagy; • selective autophagy; • interleukin-1-mediated signaling pathway; • positive regulation of long-term synaptic potentiation; • positive regulation of protein localization to plasma membrane;
	出典:Amigo / QuickGO
オルソログ
	8878
	18412
	ENSG00000161011; ENSG00000284099
	ENSMUSG00000015837
	Q13501
	Q64337
	NM_001142298; NM_001142299; NM_003900
	NM_001290769; NM_011018
	NP_001135770; NP_001135771; NP_003891
	NP_001277698; NP_035148
	ウィキデータ
閲覧/編集ヒト	閲覧/編集マウス

セクエストソーム-1(Sequestosome 1)は、ヒトではSQSTM1遺伝子がコードするタンパク質である^[5]^[6]^[7]。ユビキチン結合タンパク質p62とも呼ばれ^[8]、選択的オートファジーのために標的となる他のタンパク質と結合するオートファゴソームのカーゴタンパク質である。GATA4（英語版）と結合してこれを分解の標的とすると、GATA-4に関連する老化や細胞老化随伴分泌現象（英語版）を阻害することができる^[9]。

モデル生物

SQSTM1遺伝子の機能の研究のためにモデル生物が用いられている。ハイスループットの突然変異誘発により病気の動物モデルを作り出し科学者に頒布するプロジェクトである国際ノックアウトマウスコンソーシアム（英語版）がSqstm1^{tm1a(KOMP)Wtsi}^[10]^[11]と呼ばれるコンディショナルノックアウトマウスの系統を作り出している^[12]^[13]^[14]。

遺伝子欠損の効果を確認するために、規格化された表現型スクリーニングが雄雌の動物に対して行われた^[15]^[16]。22の試験がホモ接合変異マウスに対して行われ、そのうちの1つで重大な異常が観察された。メスは、赤血球分布幅の増加や平均血小板容積の増加等、全血球計算のパラメータが異常値を示した^[15]。

相互作用

セクエストソーム-1は、以下のタンパク質とタンパク質間相互作用する。

出典

[脚注の使い方]

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000161011、ENSG00000284099 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000015837 - Ensembl, May 2017
^ Human PubMed Reference:
^ Mouse PubMed Reference:
^ “Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain”. Proc Natl Acad Sci U S A 93 (12): 5991-5. (July 1996). doi:10.1073/pnas.93.12.5991. PMC 39176. PMID 8650207.
^ “A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes”. J Virol 70 (2): 1143-53. (February 1996). PMC 189923. PMID 8551575.
^ “Entrez Gene: SQSTM1 sequestosome 1”. 2019年5月8日閲覧。
^ Online 'Mendelian Inheritance in Man' (OMIM) 601530
^ “GATA get a hold on senescence”. Science 349 (6255): 1448-9. (2015). doi:10.1126/science.aad2501. PMID 26404812.
^ “Allele details | International Mouse Phenotyping Consortium”. www.mousephenotype.org. 2019年5月8日閲覧。
^ “Mouse Genome Informatics”. 2019年5月8日閲覧。
^ “A conditional knockout resource for the genome-wide study of mouse gene function”. Nature 474 (7351): 337-342. (2011). doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ “Mouse library set to be knockout”. Nature 474 (7351): 262-3. (2011). doi:10.1038/474262a. PMID 21677718.
^ “A Mouse for All Reasons”. Cell 128 (1): 9-13. (2007). doi:10.1016/j.cell.2006.12.018. PMID 17218247.
^ ^a ^b Gerdin, Ak (2010). “The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice” (英語). Acta Ophthalmologica 88 (s246): 0–0. doi:10.1111/j.1755-3768.2010.4142.x. ISSN 1755-3768.
^ “The mouse genetics toolkit: revealing function and mechanism.”. Genome Biol 12 (6): 224. (2011). doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
^ “The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes”. J. Cell Sci. 121 (Pt 16): 2685-95. (August 2008). doi:10.1242/jcs.026005. PMID 18653543.
^ “Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62”. Mol. Cell. Biol. 18 (5): 3069-80. (May 1998). doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.
^ “Towards a proteome-scale map of the human protein-protein interaction network”. Nature 437 (7062): 1173-8. (October 2005). doi:10.1038/nature04209. PMID 16189514.
^ “The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation”. EMBO J. 18 (11): 3044-53. (1999). doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400.
^ “The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway”. EMBO J. 19 (7): 1576-86. (April 2000). doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026.
^ “The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor”. J. Biol. Chem. 276 (11): 7709-12. (March 2001). doi:10.1074/jbc.C000869200. PMID 11244088.
^ ^a ^b “Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling”. J. Biol. Chem. 278 (7): 4730-9. (February 2003). doi:10.1074/jbc.M208468200. PMID 12471037.
^ ^a ^b “Identification of a consensus site for TRAF6/p62 polyubiquitination”. Biochem. Biophys. Res. Commun. 371 (3): 521-4. (2008). doi:10.1016/j.bbrc.2008.04.138. PMC 2474794. PMID 18457658.
^ “Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins”. J. Biol. Chem. 283 (11): 6783-9. (March 2008). doi:10.1074/jbc.M709496200. PMID 18174161.
^ 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

関連文献

“Structure and functional properties of the ubiquitin binding protein p62”. FEBS Lett. 512 (1-3): 19-24. (2002). doi:10.1016/S0014-5793(02)02286-X. PMID 11852044.
“Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone”. Biochem. Soc. Trans. 32 (Pt 5): 728-30. (2005). doi:10.1042/BST0320728. PMID 15493999.
“Genetics of Paget's disease of bone”. Joint Bone Spine 73 (3): 243-8. (2006). doi:10.1016/j.jbspin.2005.05.009. PMID 16574459.
“Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region”. Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12338-42. (1996). doi:10.1073/pnas.92.26.12338. PMC 40352. PMID 8618896.
“Interactions involving the human RNA polymerase II transcription/nucleotide excision repair complex TFIIH, the nucleotide excision repair protein XPG, and Cockayne syndrome group B (CSB) protein”. Biochemistry 35 (7): 2157-67. (1996). doi:10.1021/bi9524124. PMID 8652557.
“p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins”. J. Biol. Chem. 271 (34): 20235-7. (1996). doi:10.1074/jbc.271.34.20235. PMID 8702753.
“A p56(lck) ligand serves as a coactivator of an orphan nuclear hormone receptor”. J. Biol. Chem. 271 (44): 27197-200. (1996). doi:10.1074/jbc.271.44.27197. PMID 8910285.
“The receptor-like protein-tyrosine phosphatase DEP-1 is constitutively associated with a 64-kDa protein serine/threonine kinase”. J. Biol. Chem. 272 (18): 12158-63. (1997). doi:10.1074/jbc.272.18.12158. PMID 9115287.
“Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62”. Mol. Cell. Biol. 18 (5): 3069-80. (1998). doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.
“Genomic structure and promoter analysis of the p62 gene encoding a non-proteasomal multiubiquitin chain binding protein”. FEBS Lett. 435 (2-3): 138-42. (1998). doi:10.1016/S0014-5793(98)01021-7. PMID 9762895.
“The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation”. EMBO J. 18 (11): 3044-53. (1999). doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400.
“Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent”. Am. J. Pathol. 154 (6): 1701-10. (1999). doi:10.1016/S0002-9440(10)65426-0. PMC 1866621. PMID 10362795.
“p62 functions as a p38 MAP kinase regulator”. Biochem. Biophys. Res. Commun. 269 (2): 521-5. (2000). doi:10.1006/bbrc.2000.2333. PMID 10708586.
“The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway”. EMBO J. 19 (7): 1576-86. (2000). doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026.
“The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor”. J. Biol. Chem. 276 (11): 7709-12. (2001). doi:10.1074/jbc.C000869200. PMID 11244088.
“Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies”. NeuroReport 12 (10): 2085-90. (2001). doi:10.1097/00001756-200107200-00009. PMID 11447312.
“Paget disease of bone: mapping of two loci at 5q35-qter and 5q31”. Am. J. Hum. Genet. 69 (3): 528-43. (2001). doi:10.1086/322975. PMC 1235483. PMID 11473345.
“p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition”. FEBS Lett. 510 (1-2): 57-61. (2002). doi:10.1016/S0014-5793(01)03224-0. PMID 11755531.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000161011、ENSG00000284099 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000015837 - Ensembl, May 2017

[3] Human PubMed Reference:

[4] Mouse PubMed Reference:

[pmid8650207-5] “Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain”. Proc Natl Acad Sci U S A 93 (12): 5991-5. (July 1996). doi:10.1073/pnas.93.12.5991. PMC 39176. PMID 8650207.

[pmid8551575-6] “A novel interleukin-12 p40-related protein induced by latent Epstein-Barr virus infection in B lymphocytes”. J Virol 70 (2): 1143-53. (February 1996). PMC 189923. PMID 8551575.

[7] “Entrez Gene: SQSTM1 sequestosome 1”. 2019年5月8日閲覧。

[8] Online 'Mendelian Inheritance in Man' (OMIM) 601530

[pmid26404812-9] “GATA get a hold on senescence”. Science 349 (6255): 1448-9. (2015). doi:10.1126/science.aad2501. PMID 26404812.

[10] “Allele details | International Mouse Phenotyping Consortium”. www.mousephenotype.org. 2019年5月8日閲覧。

[mgi_allele_ref-11] “Mouse Genome Informatics”. 2019年5月8日閲覧。

[pmid21677750-12] “A conditional knockout resource for the genome-wide study of mouse gene function”. Nature 474 (7351): 337-342. (2011). doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-13] “Mouse library set to be knockout”. Nature 474 (7351): 262-3. (2011). doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-14] “A Mouse for All Reasons”. Cell 128 (1): 9-13. (2007). doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[:0-15] Gerdin, Ak (2010). “The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice” (英語). Acta Ophthalmologica 88 (s246): 0–0. doi:10.1111/j.1755-3768.2010.4142.x. ISSN 1755-3768.

[pmid21722353-16] “The mouse genetics toolkit: revealing function and mechanism.”. Genome Biol 12 (6): 224. (2011). doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

[pmid18653543-17] “The N-terminus and Phe52 residue of LC3 recruit p62/SQSTM1 into autophagosomes”. J. Cell Sci. 121 (Pt 16): 2685-95. (August 2008). doi:10.1242/jcs.026005. PMID 18653543.

[pmid9566925-18] “Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62”. Mol. Cell. Biol. 18 (5): 3069-80. (May 1998). doi:10.1128/mcb.18.5.3069. PMC 110686. PMID 9566925.

[pmid16189514-19] “Towards a proteome-scale map of the human protein-protein interaction network”. Nature 437 (7062): 1173-8. (October 2005). doi:10.1038/nature04209. PMID 16189514.

[pmid10356400-20] “The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation”. EMBO J. 18 (11): 3044-53. (1999). doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400.

[pmid10747026-21] “The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway”. EMBO J. 19 (7): 1576-86. (April 2000). doi:10.1093/emboj/19.7.1576. PMC 310227. PMID 10747026.

[pmid11244088-22] “The atypical protein kinase C-interacting protein p62 is a scaffold for NF-kappaB activation by nerve growth factor”. J. Biol. Chem. 276 (11): 7709-12. (March 2001). doi:10.1074/jbc.C000869200. PMID 11244088.

[pmid12471037-23] “Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling”. J. Biol. Chem. 278 (7): 4730-9. (February 2003). doi:10.1074/jbc.M208468200. PMID 12471037.

[pmid18457658-24] “Identification of a consensus site for TRAF6/p62 polyubiquitination”. Biochem. Biophys. Res. Commun. 371 (3): 521-4. (2008). doi:10.1016/j.bbrc.2008.04.138. PMC 2474794. PMID 18457658.

[pmid18174161-25] “Essential role of sequestosome 1/p62 in regulating accumulation of Lys63-ubiquitinated proteins”. J. Biol. Chem. 283 (11): 6783-9. (March 2008). doi:10.1074/jbc.M709496200. PMID 18174161.

[26] 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

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