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Protein

Sequestosome-1

Gene

Sqstm1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called ALIS (aggresome-like induced structures) and links ALIS to the autophagic machinery. Involved in midbody ring degradation. 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. Adapter that mediates the interaction between TRAF6 and CYLD.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri122 – 167ZZ-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

  • identical protein binding Source: MGI
  • K63-linked polyubiquitin binding Source: UniProtKB
  • protein kinase binding Source: MGI
  • protein kinase C binding Source: UniProtKB
  • SH2 domain binding Source: UniProtKB
  • transcription cofactor activity Source: MGI
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: MGI
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Apoptosis, Autophagy, Differentiation, Immunity

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-205043. NRIF signals cell death from the nucleus.
R-MMU-209543. p75NTR recruits signalling complexes.
R-MMU-209560. NF-kB is activated and signals survival.
R-MMU-446652. Interleukin-1 signaling.
R-MMU-5205685. Pink/Parkin Mediated Mitophagy.

Names & Taxonomyi

Protein namesi
Recommended name:
Sequestosome-1
Alternative name(s):
STONE14
Ubiquitin-binding protein p62
Gene namesi
Name:Sqstm1
Synonyms:A170, STAP
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:107931. Sqstm1.

Subcellular locationi

GO - Cellular componenti

  • aggresome Source: MGI
  • amphisome Source: MGI
  • autolysosome Source: MGI
  • autophagosome Source: UniProtKB
  • cytoplasm Source: MGI
  • cytoplasmic mRNA processing body Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB-KW
  • endoplasmic reticulum Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • inclusion body Source: MGI
  • late endosome Source: UniProtKB-SubCell
  • PML body Source: MGI
  • pre-autophagosomal structure Source: MGI
  • sperm midpiece Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Lysosome, Nucleus

Pathology & Biotechi

Disruption phenotypei

Impaired induced osteoclastogenesis.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi337 – 339DDD → AAA: Greatly decreases interaction with MAP1LC3B. 1 Publication3
Mutagenesisi340W → A: Greatly decreases interaction with MAP1LC3B. 1 Publication1
Mutagenesisi343L → A: Greatly decreases interaction with MAP1LC3B. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000721772 – 442Sequestosome-1Add BLAST441

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei24PhosphoserineCombined sources1
Modified residuei148PhosphotyrosineBy similarity1
Modified residuei176PhosphoserineBy similarity1
Modified residuei178PhosphoserineCombined sources1
Modified residuei207PhosphoserineBy similarity1
Modified residuei249PhosphoserineBy similarity1
Modified residuei266PhosphoserineBy similarity1
Modified residuei269PhosphothreonineCombined sources1
Modified residuei272PhosphothreonineCombined sources1
Modified residuei308PhosphoserineBy similarity1
Modified residuei330PhosphoserineCombined sources1
Modified residuei334PhosphoserineCombined sources1
Modified residuei357PhosphoserineBy similarity1
Modified residuei363PhosphoserineCombined sources1
Modified residuei367PhosphoserineCombined sources1
Modified residuei368PhosphoserineBy similarity1
Modified residuei405Phosphoserine; by ULK1By similarity1

Post-translational modificationi

Phosphorylated. May be phosphorylated by PRKCZ. Phosphorylated in vitro by TTN (By similarity). Phosphorylation at Ser-405 by ULK1 is stimulated by SESN2 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ64337.
PaxDbiQ64337.
PeptideAtlasiQ64337.
PRIDEiQ64337.

PTM databases

iPTMnetiQ64337.
PhosphoSitePlusiQ64337.
SwissPalmiQ64337.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Inductioni

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.7 Publications

Gene expression databases

BgeeiENSMUSG00000015837.
CleanExiMM_SQSTM1.
ExpressionAtlasiQ64337. baseline and differential.
GenevisibleiQ64337. MM.

Interactioni

Subunit structurei

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, TRIM13, 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 probably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with 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. Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By similarity). Interacts with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD. Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other MAP1 LC3 family members, including GABARAP, GABARAPL1 and GABARAPL2; these interactions are necessary for the recruitment MAP1 LC3 family members to inclusion bodies containing polyubiquitinated protein aggregates and for their degradation by autophagy (By similarity). Interacts with FHOD3 (By similarity). Interacts with TRMI5 (By similarity). Interacts with SESN1 (By similarity). Interacts with SESN2 (PubMed:25040165). Interacts with ULK1 (PubMed:25040165).By similarityCurated1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
KEAP1Q141452EBI-645025,EBI-751001From a different organism.
Keap1Q9Z2X86EBI-645025,EBI-647110
MAP1LC3BQ9GZQ86EBI-645025,EBI-373144From a different organism.
Map2k5Q9WVS73EBI-645025,EBI-446144

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201982. 47 interactors.
DIPiDIP-38490N.
IntActiQ64337. 22 interactors.
MINTiMINT-1728610.
STRINGi10090.ENSMUSP00000099835.

Structurei

Secondary structure

1442
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni350 – 352Combined sources3
Helixi394 – 405Combined sources12
Helixi411 – 413Combined sources3
Helixi414 – 421Combined sources8
Turni422 – 424Combined sources3
Helixi426 – 432Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RRUNMR-A391-438[»]
2ZJDX-ray1.56B/D334-344[»]
3ADEX-ray2.80B346-359[»]
3B0FX-ray1.40A/B391-438[»]
3WDZX-ray2.60B346-359[»]
ProteinModelPortaliQ64337.
SMRiQ64337.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ64337.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 102PB1PROSITE-ProRule annotationAdd BLAST100
Domaini391 – 436UBAPROSITE-ProRule annotationAdd BLAST46

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 50Interaction with LCKBy similarityAdd BLAST49
Regioni43 – 107Interaction with PRKCZ and dimerizationBy similarityAdd BLAST65
Regioni50 – 80Interaction with PAWRBy similarityAdd BLAST31
Regioni122 – 224Interaction with GABRR3By similarityAdd BLAST103
Regioni170 – 220LIM protein-bindingBy similarityAdd BLAST51
Regioni269 – 442Interaction with NTRK1By similarityAdd BLAST174
Regioni323 – 344MAP1LC3B-bindingBy similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi228 – 233TRAF6-bindingBy similarity6
Motifi338 – 343LIR6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi272 – 296Ser-richAdd BLAST25

Domaini

The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55 (By similarity). Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies (By similarity).By similarity
The PB1 domain mediates homooligomerization and interactions with FHOD3, MAP2K5, NBR1, PRKCI and PRKCZ. Both the PB1 and UBA domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.By similarity
The ZZ-type zinc finger mediates the interaction with RIPK1.By similarity
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.By similarity

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation
Contains 1 ZZ-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri122 – 167ZZ-typePROSITE-ProRule annotationAdd BLAST46

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4582. Eukaryota.
ENOG410XYAV. LUCA.
GeneTreeiENSGT00390000002781.
HOGENOMiHOG000154407.
HOVERGENiHBG052750.
InParanoidiQ64337.
KOiK14381.
OMAiDDELMMG.
OrthoDBiEOG091G08ES.
PhylomeDBiQ64337.
TreeFamiTF328470.

Family and domain databases

CDDicd14320. UBA_SQSTM. 1 hit.
InterProiIPR000270. PB1_dom.
IPR033741. SQSTM_UBA.
IPR015940. UBA.
IPR009060. UBA-like.
IPR000433. Znf_ZZ.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF16577. UBA_5. 1 hit.
PF00569. ZZ. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00165. UBA. 1 hit.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50030. UBA. 1 hit.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q64337-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASFTVKAYL LGKEEATREI RRFSFCFSPE PEAEAQAAAG PGPCERLLSR
60 70 80 90 100
VAVLFPTLRP GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK
110 120 130 140 150
EKKECRREHR PPCAQEAPRN MVHPNVICDG CNGPVVGTRY KCSVCPDYDL
160 170 180 190 200
CSVCEGKGLH REHSKLIFPN PFGHLSDSFS HSRWLRKLKH GHFGWPGWEM
210 220 230 240 250
GPPGNWSPRP PRAGDGRPCP TAESASAPPE DPNVNFLKNV GESVAAALSP
260 270 280 290 300
LGIEVDIDVE HGGKRSRLTP TTPESSSTGT EDKSNTQPSS CSSEVSKPDG
310 320 330 340 350
AGEGPAQSLT EQMKKIALES VGQPEEQMES GNCSGGDDDW THLSSKEVDP
360 370 380 390 400
STGELQSLQM PESEGPSSLD PSQEGPTGLK EAALYPHLPP EADPRLIESL
410 420 430 440
SQMLSMGFSD EGGWLTRLLQ TKNYDIGAAL DTIQYSKHPP PL
Length:442
Mass (Da):48,163
Last modified:November 1, 1996 - v1
Checksum:iED4CCCA7741D35CA
GO
Isoform 2 (identifier: Q64337-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     353-390: Missing.

Show »
Length:404
Mass (Da):44,192
Checksum:iCF977864ABEA77BA
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015842353 – 390Missing in isoform 2. 2 PublicationsAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24629.1. [Q64337-1]
CCDS70176.1. [Q64337-2]
PIRiJC4978.
RefSeqiNP_001277698.1. NM_001290769.1. [Q64337-2]
NP_035148.1. NM_011018.3. [Q64337-1]
UniGeneiMm.40828.

Genome annotation databases

EnsembliENSMUST00000015981; ENSMUSP00000015981; ENSMUSG00000015837. [Q64337-2]
ENSMUST00000102774; ENSMUSP00000099835; ENSMUSG00000015837. [Q64337-1]
GeneIDi18412.
KEGGimmu:18412.
UCSCiuc007irw.2. mouse. [Q64337-1]
uc007irx.2. mouse. [Q64337-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS24629.1. [Q64337-1]
CCDS70176.1. [Q64337-2]
PIRiJC4978.
RefSeqiNP_001277698.1. NM_001290769.1. [Q64337-2]
NP_035148.1. NM_011018.3. [Q64337-1]
UniGeneiMm.40828.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RRUNMR-A391-438[»]
2ZJDX-ray1.56B/D334-344[»]
3ADEX-ray2.80B346-359[»]
3B0FX-ray1.40A/B391-438[»]
3WDZX-ray2.60B346-359[»]
ProteinModelPortaliQ64337.
SMRiQ64337.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201982. 47 interactors.
DIPiDIP-38490N.
IntActiQ64337. 22 interactors.
MINTiMINT-1728610.
STRINGi10090.ENSMUSP00000099835.

PTM databases

iPTMnetiQ64337.
PhosphoSitePlusiQ64337.
SwissPalmiQ64337.

Proteomic databases

EPDiQ64337.
PaxDbiQ64337.
PeptideAtlasiQ64337.
PRIDEiQ64337.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015981; ENSMUSP00000015981; ENSMUSG00000015837. [Q64337-2]
ENSMUST00000102774; ENSMUSP00000099835; ENSMUSG00000015837. [Q64337-1]
GeneIDi18412.
KEGGimmu:18412.
UCSCiuc007irw.2. mouse. [Q64337-1]
uc007irx.2. mouse. [Q64337-2]

Organism-specific databases

CTDi8878.
MGIiMGI:107931. Sqstm1.

Phylogenomic databases

eggNOGiKOG4582. Eukaryota.
ENOG410XYAV. LUCA.
GeneTreeiENSGT00390000002781.
HOGENOMiHOG000154407.
HOVERGENiHBG052750.
InParanoidiQ64337.
KOiK14381.
OMAiDDELMMG.
OrthoDBiEOG091G08ES.
PhylomeDBiQ64337.
TreeFamiTF328470.

Enzyme and pathway databases

ReactomeiR-MMU-205043. NRIF signals cell death from the nucleus.
R-MMU-209543. p75NTR recruits signalling complexes.
R-MMU-209560. NF-kB is activated and signals survival.
R-MMU-446652. Interleukin-1 signaling.
R-MMU-5205685. Pink/Parkin Mediated Mitophagy.

Miscellaneous databases

ChiTaRSiSqstm1. mouse.
EvolutionaryTraceiQ64337.
PROiQ64337.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000015837.
CleanExiMM_SQSTM1.
ExpressionAtlasiQ64337. baseline and differential.
GenevisibleiQ64337. MM.

Family and domain databases

CDDicd14320. UBA_SQSTM. 1 hit.
InterProiIPR000270. PB1_dom.
IPR033741. SQSTM_UBA.
IPR015940. UBA.
IPR009060. UBA-like.
IPR000433. Znf_ZZ.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF16577. UBA_5. 1 hit.
PF00569. ZZ. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00165. UBA. 1 hit.
SM00291. ZnF_ZZ. 1 hit.
[Graphical view]
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS50030. UBA. 1 hit.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSQSTM_MOUSE
AccessioniPrimary (citable) accession number: Q64337
Secondary accession number(s): Q99JM8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: November 1, 1996
Last modified: November 30, 2016
This is version 150 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.