Reviewed, UniProtKB/Swiss-Prot Q64337 (SQSTM_MOUSE)

Names and origin

Protein names

Recommended name:
    Sequestosome-1
Alternative name(s):
    Ubiquitin-binding protein p62
    STONE14

Gene names

Name:	Sqstm1
Synonyms:	A170, STAP

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

Keywords
Biological process	Apoptosis Differentiation Immune response
Cellular component	Cytoplasm Endosome Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding Zinc
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	apoptosis Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW immune response Inferred from electronic annotation. Source: UniProtKB-KW regulation of I-kappaB kinase/NF-kappaB cascade Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	late endosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	SH2 domain binding Inferred from sequence or structural similarity. Source: UniProtKB protein kinase binding Inferred from sequence or structural similarity. Source: UniProtKB transcription cofactor activity Ref.8 Traceable author statement. Source: MGI ubiquitin binding Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: ED4CCCA7741D35CA	FASTA	442	48,163
	10 20 30 40 50 60 MASFTVKAYL LGKEEATREI RRFSFCFSPE PEAEAQAAAG PGPCERLLSR VAVLFPTLRP 70 80 90 100 110 120 GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK EKKECRREHR PPCAQEAPRN 130 140 150 160 170 180 MVHPNVICDG CNGPVVGTRY KCSVCPDYDL CSVCEGKGLH REHSKLIFPN PFGHLSDSFS 190 200 210 220 230 240 HSRWLRKLKH GHFGWPGWEM GPPGNWSPRP PRAGDGRPCP TAESASAPPE DPNVNFLKNV 250 260 270 280 290 300 GESVAAALSP LGIEVDIDVE HGGKRSRLTP TTPESSSTGT EDKSNTQPSS CSSEVSKPDG 310 320 330 340 350 360 AGEGPAQSLT EQMKKIALES VGQPEEQMES GNCSGGDDDW THLSSKEVDP STGELQSLQM 370 380 390 400 410 420 PESEGPSSLD PSQEGPTGLK EAALYPHLPP EADPRLIESL SQMLSMGFSD EGGWLTRLLQ 430 440 TKNYDIGAAL DTIQYSKHPP PL
	Isoform 2 [UniParc]. Checksum: CF977864ABEA77BA		404	44,192
	10 20 30 40 50 60 MASFTVKAYL LGKEEATREI RRFSFCFSPE PEAEAQAAAG PGPCERLLSR VAVLFPTLRP 70 80 90 100 110 120 GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK EKKECRREHR PPCAQEAPRN 130 140 150 160 170 180 MVHPNVICDG CNGPVVGTRY KCSVCPDYDL CSVCEGKGLH REHSKLIFPN PFGHLSDSFS 190 200 210 220 230 240 HSRWLRKLKH GHFGWPGWEM GPPGNWSPRP PRAGDGRPCP TAESASAPPE DPNVNFLKNV 250 260 270 280 290 300 GESVAAALSP LGIEVDIDVE HGGKRSRLTP TTPESSSTGT EDKSNTQPSS CSSEVSKPDG 310 320 330 340 350 360 AGEGPAQSLT EQMKKIALES VGQPEEQMES GNCSGGDDDW THLSSKEVDP STEADPRLIE 370 380 390 400 SLSQMLSMGF SDEGGWLTRL LQTKNYDIGA ALDTIQYSKH PPPL

References

	« Hide 'large scale' referencesShow '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. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai 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
EMBLGenBankDDBJ	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

Integrated into UniProtKB/Swiss-Prot:	October 11, 2005
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)