Reviewed,
UniProtKB/Swiss-Prot Q64337 (SQSTM_MOUSE)
Last modified
November 25, 2008.
Version 69.
History...
Clusters with 100%,
90%,
50% identity |
Documents (2) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Sequestosome-1 Alternative name(s): Ubiquitin-binding protein p62 STONE14 | ||||
| Gene names |
| ||||
| Organism | Mus musculus (Mouse) | ||||
| Taxonomic identifier | 10090 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus |
Protein attributes
| Sequence length | 442 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Adapter protein which binds ubiquitin and 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. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. |
| Subunit structure | Homooligomer or heterooligomer; may form homotypic arrays. Interacts directly with PRKCI and PRKCZ Probable. Interacts with EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MAP2K5, TRIM55 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 problably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 By similarity. |
| Subcellular location | Cytoplasm. Late endosome. Nucleus. Note= Sarcomere. In cardiac muscles localizes to the sarcomeric band. Localizes to late endosomes. May also localize to the nucleus. Accumulates in neurofibrillary tangles and in Lewy bodies of neurons from individuals with Alzheimer and Parkinson disease respectively. Enriched in Rosenthal fibers of pilocytic astrocytoma. In liver cells, accumulates in Mallory bodies associated with alcoholic hepatitis, Wilson disease, indian childhood cirrhosis and in hyaline bodies associated with hepatocellular carcinoma By similarity. |
| Tissue specificity | Widely expressed. |
| Induction | By diethylmaleate, paraquat, menadione, sodium arsenite and cadmium chloride, arsenite and arsenate. By MG132, MG115, lactacystin and proteasome inhibitor I (PSI). By serum starvation, okadaic acid and glucose oxidase. Also up-regulated by RANK-L (at protein level). By etoposide and trichostatin. By the parkinsonian mimetic 6-hydroxydopamine (6-OHDA). By TGF-beta. |
| Domain | The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55 By similarity. The OPR domain mediates homooligomerization and interactions with PRKCZ, PRKCI, MAP2K5 and NBR1 By similarity. The ZZ-type zinc finger mediates the interaction with RIPK1 By similarity. |
| Post-translational modification | Phosphorylated. May be phosphorylated by PRKCZ. Phosphorylated in vitro by TTN By similarity. |
| Miscellaneous | Mice lacking sqstm1 display impaired induced osteoclastogenesis. |
| Sequence similarities | Contains 1 OPR domain. Contains 1 UBA domain. Contains 1 ZZ-type zinc finger. |
Ontologies
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| MAP1LC3B | Q9GZQ8 | 2 | EBI-645025,EBI-373144 | From a different organism. |
| Map2k5 | Q9WVS7 | 2 | EBI-645025,EBI-446144 | |
| Rps27a | P62991 | 1 | EBI-645025,EBI-413074 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q64337-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q64337-2) The sequence of this isoform differs from the canonical sequence as follows: 353-390: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 442 | 442 | Sequestosome-1 | PRO_0000072177 | |||||
Regions | |||||||||
| Domain | 20 – 102 | 83 | OPR | ||||||
| Domain | 391 – 436 | 46 | UBA | ||||||
| Zinc finger | 122 – 167 | 46 | ZZ-type | ||||||
| Region | 1 – 50 | 50 | Interaction with LCK By similarity | ||||||
| Region | 43 – 107 | 65 | Interaction with PRKCZ and dimerization By similarity | ||||||
| Region | 50 – 80 | 31 | Interaction with PAWR By similarity | ||||||
| Region | 122 – 224 | 103 | Interaction with GABRR3 By similarity | ||||||
| Region | 170 – 220 | 51 | LIM protein-binding (LB).**interaction with ajuba and probably limd1 By similarity | ||||||
| Region | 269 – 442 | 174 | Interaction with NTRK1 By similarity | ||||||
| Motif | 228 – 233 | 6 | TRAF6-binding By similarity | ||||||
| Compositional bias | 272 – 296 | 25 | Ser-rich | ||||||
Amino acid modifications | |||||||||
| Modified residue | 24 | 1 | Phosphoserine | ||||||
| Modified residue | 148 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 176 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 207 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 269 | 1 | Phosphothreonine By similarity | ||||||
| Modified residue | 276 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 330 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 334 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 357 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 363 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 367 | 1 | Phosphoserine | ||||||
| Modified residue | 368 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 353 – 390 | 38 | Missing in isoform 2. | VSP_015842 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Murine peritoneal macrophages induce a novel 60-kDa protein with structural similarity to a tyrosine kinase p56lck-associated protein in reponse to oxidative stress." Ishii T., Yanagawa T., Kawane T., Yuki K., Seita J., Yoshida H., Bannai S. Biochem. Biophys. Res. Commun. 226:456-460(1996) [PubMed: 8806656] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION. Strain: ddY. Tissue: Macrophage. |
| [2] | "Murine cDNA similar to EBI3-associated protein p60 mRNA." Morris J.C., Long A., Finnerty H., Fitz L., Towler P., Turner K., Wood C.R. Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: BALB/c. |
| [3] | "The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: C57BL/6J. Tissue: Skin. |
| [4] | The mouse genome sequencing consortium Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Strain: FVB/N. Tissue: Mammary gland. |
| [6] | "Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages." Ishii T., Yanagawa T., Yuki K., Kawane T., Yoshida H., Bannai S. Biochem. Biophys. Res. Commun. 232:33-37(1997) [PubMed: 9125146] [Abstract] Cited for: INDUCTION. |
| [7] | "Phosphorylation of A170 stress protein by casein kinase II-like activity in macrophages." Yanagawa T., Yuki K., Yoshida H., Bannai S., Ishii T. Biochem. Biophys. Res. Commun. 241:157-163(1997) [PubMed: 9405250] [Abstract] Cited for: PHOSPHORYLATION. |
| [8] | "Cloning, expression profile, and genomic organization of the mouse STAP/A170 gene." Okazaki M., Ito S., Kawakita K., Takeshita S., Kawai S., Makishima F., Oda H., Kakinuma A. Genomics 60:87-95(1999) [PubMed: 10458914] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION. |
| [9] | "Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells." Kuusisto E., Suuronen T., Salminen A. Biochem. Biophys. Res. Commun. 280:223-228(2001) [PubMed: 11162503] [Abstract] Cited for: INDUCTION. |
| [10] | "Activation of Nrf2 and accumulation of ubiquitinated A170 by arsenic in osteoblasts." Aono J., Yanagawa T., Itoh K., Li B., Yoshida H., Kumagai Y., Yamamoto M., Ishii T. Biochem. Biophys. Res. Commun. 305:271-277(2003) [PubMed: 12745069] [Abstract] Cited for: INDUCTION. |
| [11] | "The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis." Duran A., Serrano M., Leitges M., Flores J.M., Picard S., Brown J.P., Moscat J., Diaz-Meco M.T. Dev. Cell 6:303-309(2004) [PubMed: 14960283] [Abstract] Cited for: FUNCTION, INDUCTION, INTERACTION WITH TRAF6. |
| [12] | "Phosphoproteomic analysis of the developing mouse brain." Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P. Mol. Cell. Proteomics 3:1093-1101(2004) [PubMed: 15345747] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-367, MASS SPECTROMETRY. Tissue: Brain. |
| [13] | "Microarray expression profiling identifies early signaling transcripts associated with 6-OHDA-induced dopaminergic cell death." Holtz W.A., Turetzky J.M., O'Malley K.L. Antioxid. Redox Signal. 7:639-648(2005) [PubMed: 15890008] [Abstract] Cited for: INDUCTION. |
| [14] | "Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, MASS SPECTROMETRY. Tissue: Liver. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U40930 mRNA. Translation: AAB17127.1. U57413 mRNA. Translation: AAB02908.1. AK028898 mRNA. Translation: BAC26183.1. AL627187 Genomic DNA. Translation: CAI25117.1. AL627187 Genomic DNA. Translation: CAI25118.1. BC006019 mRNA. Translation: AAH06019.1. | |
| PIR | JC4978. |
| RefSeq | NP_035148.1. |
| UniGene | Mm.458013 |
3D structure databases | |
| SMR | Q64337. Positions 389-438. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q64337. |
PTM databases | |
| PhosphoSite | Q64337. |
Genome annotation databases | |
| Ensembl | ENSMUSG00000015837. Mus musculus. [Contig view] |
| GeneID | 18412. |
| KEGG | mmu:18412. |
Organism-specific databases | |
| MGI | MGI:107931. Sqstm1. |
Phylogenomic databases | |
| HOGENOM | Q64337. |
| HOVERGEN | Q64337. |
Gene expression databases | |
| CleanEx | MM_SQSTM1. |
| GermOnline | ENSMUSG00000015837. Mus musculus. |
Family and domain databases | |
| InterPro | IPR000270. OPR_PB1. IPR015940. UBA/transl_elong_EF1B_N_euk. IPR000433. Znf_ZZ. [Graphical view] |
| Pfam | PF00564. PB1. 1 hit. PF00569. ZZ. 1 hit. [Graphical view] |
| SMART | SM00666. PB1. 1 hit. SM00165. UBA. 1 hit. SM00291. ZnF_ZZ. 1 hit. [Graphical view] |
| PROSITE | PS50030. UBA. 1 hit. PS01357. ZF_ZZ_1. 1 hit. PS50135. ZF_ZZ_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 294036. |
| SOURCE | Search... |
Entry information
| Entry name | SQSTM_MOUSE | ||||||||
| Accession | Primary (citable) accession number: Q64337 Secondary accession number(s): Q99JM8 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| MGD cross-references Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


