UniProt Accession

 SQSTM_HUMAN; Q13501; A6NFN7; B2R661; B3KUW5; Q13446; Q9BUV7; Q9BVS6; Q9UEU1 

Genbank Protein ID

 U41806; U46751; AK098077; AK312451; AC008393; BC000951; BC001874; BC003139; BC017222; BC019111; AF060494 

Genbank Nucleotide ID

 AAA93299.1; AAC52070.1; BAG53577.1; BAG35358.1; AAH00951.1; AAH01874.1; AAH03139.1; AAH17222.1; AAH19111.1; AAC64516.1 

Protein Name

 Sequestosome-1 

Protein Synonyms/Alias

 EBI3-associated protein of 60 kDa; EBIAP; p60; Phosphotyrosine-independent ligand for the Lck SH2 domain of 62 kDa; Ubiquitin-binding protein p62 

Gene Name

 SQSTM1 

Gene Synonyms/Alias

 ORCA; OSIL 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
13	VKAYLLGKEDAAREI	ubiquitination	[1, 2, 3, 4, 5]
141	PVVGTRYKCSVCPDY	ubiquitination	[1, 2, 5]
157	LCSVCEGKGLHRGHT	ubiquitination	[1, 2, 3, 5, 6, 7, 8]
165	GLHRGHTKLAFPSPF	ubiquitination	[1, 5]
189	SRWLRKVKHGHFGWP	ubiquitination	[1, 5]
264	IDVEHGGKRSRLTPV	ubiquitination	[1]
281	ESSSTEEKSSSQPSS	ubiquitination	[1, 5]
295	SCCSDPSKPGGNVEG	ubiquitination	[1, 5]
313	SLAEQMRKIALESEG	ubiquitination	[5, 9]
378	QEGPTGLKEAALYPH	ubiquitination	[10]
420	LTRLLQTKNYDIGAA	ubiquitination	[1, 5, 9, 10, 11]
435	LDTIQYSKHPPPL**	acetylation	[12]
435	LDTIQYSKHPPPL**	ubiquitination	[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 13, 14]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572]
 [3] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [4] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [7] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [8] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [9] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [10] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [11] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [12] Monoclonal antibody cocktail as an enrichment tool for acetylome analysis.
 Shaw PG, Chaerkady R, Zhang Z, Davidson NE, Pandey A.
 Anal Chem. 2011 May 15;83(10):3623-6. [PMID: 21466224]
 [13] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [14] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

Functional Description

 Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures). Links ALIS to the autophagic machinery via direct interaction with MAP1 LC3 family members. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin/TTN downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. Adapter that mediates the interaction between TRAF6 and CYLD (By similarity). May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. 

Sequence Annotation

 DOMAIN 20 102 OPR.
 DOMAIN 389 434 UBA.
 ZN_FING 122 167 ZZ-type.
 REGION 1 50 Interaction with LCK.
 REGION 43 107 Interaction with PRKCZ and dimerization
 REGION 50 80 Interaction with PAWR.
 REGION 122 224 Interaction with GABRR3 (By similarity).
 REGION 170 220 LIM protein-binding (LB).
 REGION 269 440 Interaction with NTRK1 (By similarity).
 REGION 321 342 MAP1LC3B-binding.
 MOTIF 228 233 TRAF6-binding.
 MOD_RES 24 24 Phosphoserine (By similarity).
 MOD_RES 148 148 Phosphotyrosine.
 MOD_RES 170 170 Phosphoserine.
 MOD_RES 207 207 Phosphoserine.
 MOD_RES 249 249 Phosphoserine.
 MOD_RES 266 266 Phosphoserine.
 MOD_RES 269 269 Phosphothreonine.
 MOD_RES 272 272 Phosphoserine.
 MOD_RES 328 328 Phosphoserine.
 MOD_RES 332 332 Phosphoserine.
 MOD_RES 355 355 Phosphoserine.
 MOD_RES 361 361 Phosphoserine.
 MOD_RES 365 365 Phosphoserine (By similarity).
 MOD_RES 366 366 Phosphoserine.  

Keyword

 3D-structure; Alternative splicing; Apoptosis; Autophagy; Complete proteome; Cytoplasm; Cytoplasmic vesicle; Differentiation; Direct protein sequencing; Disease mutation; Endoplasmic reticulum; Endosome; Immunity; Lysosome; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 440 AA 

Protein Sequence

Gene Ontology

 GO:0005776; C:autophagic vacuole; IDA:UniProtKB.
 GO:0000932; C:cytoplasmic mRNA processing body; IDA:UniProtKB.
 GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
 GO:0005829; C:cytosol; TAS:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
 GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
 GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0000407; C:pre-autophagosomal structure; IEA:Compara.
 GO:0019901; F:protein kinase binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; NAS:UniProtKB.
 GO:0030971; F:receptor tyrosine kinase binding; TAS:ProtInc.
 GO:0042169; F:SH2 domain binding; IDA:UniProtKB.
 GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0097190; P:apoptotic signaling pathway; TAS:Reactome.
 GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
 GO:0016197; P:endosomal transport; TAS:UniProtKB.
 GO:0035556; P:intracellular signal transduction; TAS:UniProtKB.
 GO:0016236; P:macroautophagy; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0001934; P:positive regulation of protein phosphorylation; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; TAS:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0008104; P:protein localization; TAS:UniProtKB.
 GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB cascade; IMP:UniProtKB.
 GO:0046578; P:regulation of Ras protein signal transduction; NAS:UniProtKB.
 GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc. 

Interpro

 IPR000270; OPR_PB1.
 IPR009060; UBA-like.
 IPR015940; UBA/transl_elong_EF1B_N_euk.
 IPR000433; Znf_ZZ. 

Pfam

 PF00564; PB1
 PF00569; ZZ 

SMART

 SM00666; PB1
 SM00165; UBA
 SM00291; ZnF_ZZ 

PROSITE

 PS50030; UBA
 PS01357; ZF_ZZ_1
 PS50135; ZF_ZZ_2 

PRINTS