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Protein

Sequestosome-1

Gene

Sqstm1

Organism
Rattus norvegicus (Rat)
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 (By similarity). 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 (By similarity). Involved in midbody ring degradation (By similarity). May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1 (PubMed:11244088, PubMed:11500922). May play a role in titin/TTN downstream signaling in muscle cells (By similarity). May regulate signaling cascades through ubiquitination (By similarity). 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 (By similarity). Involved in endosome organization by retaining vesicles in the perinuclear cloud: following ubiquitination by RNF26, attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport (By similarity).By similarity2 Publications
Isoform 1: More potent than isoform 2 to stimulate PRKCZ-dependent phosphorylation of KCNAB2.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri119 – 164ZZ-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processApoptosis, Autophagy, Differentiation, Immunity
LigandMetal-binding, Zinc

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Sequestosome-1
Alternative name(s):
Protein kinase C-zeta-interacting protein
Short name:
PKC-zeta-interacting protein
Ubiquitin-binding protein p62
Gene namesi
Name:Sqstm1
Synonyms:Zip
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi69287. Sqstm1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7K → A: Loss of interaction with PRKCI. 1 Publication1
Mutagenesisi21 – 22RR → AA: Reduces interaction with PRKCI. 1 Publication2
Mutagenesisi67D → A: No effect on interaction with PRKCI. Abolishes homooligomerization; when associated with A-67. 2 Publications1
Mutagenesisi69D → A: Abolishes homooligomerization; when associated with A-67. 1 Publication1
Mutagenesisi94R → A: Reduces interaction with PRKCI. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000721792 – 439Sequestosome-1Add BLAST438

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei24PhosphoserineBy similarity1
Modified residuei145PhosphotyrosineBy similarity1
Modified residuei173PhosphoserineBy similarity1
Modified residuei175PhosphoserineBy similarity1
Modified residuei204PhosphoserineBy similarity1
Modified residuei246PhosphoserineBy similarity1
Modified residuei263PhosphoserineBy similarity1
Modified residuei266PhosphothreonineCombined sources1
Modified residuei269PhosphoserineBy similarity1
Modified residuei305PhosphoserineBy similarity1
Modified residuei327PhosphoserineBy similarity1
Modified residuei331PhosphoserineBy similarity1
Modified residuei354PhosphoserineCombined sources1
Modified residuei360PhosphoserineBy similarity1
Modified residuei364PhosphoserineBy similarity1
Modified residuei365PhosphoserineBy similarity1
Modified residuei402Phosphoserine; by ULK1By similarity1
Cross-linki434Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Post-translational modificationi

Phosphorylated. Phosphorylated in vitro by TTN (By similarity). May be phosphorylated by PRKCZ. Phosphorylation at Ser-402 by ULK1 is stimulated by SESN2 (By similarity).By similarity1 Publication
Ubiquitinated by RNF26: ubiquitinated SQSTM1 attracts specific vesicle-associated adapters, forming a molecular bridge that restrains cognate vesicles in the perinuclear region and organizes the endosomal pathway for efficient cargo transport. Deubiquitination by USP15 releases target vesicles for fast transport into the cell periphery.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiO08623.
PRIDEiO08623.

PTM databases

iPTMnetiO08623.
PhosphoSitePlusiO08623.

Expressioni

Tissue specificityi

Ubiquitously expressed. In brain, mainly expressed by neurons, especially pyramidal neurons in the cerebral cortex and hippocampus. Also expressed by Purkinje cells and neurons in the dentate nucleus of the cerebellum and neurons of the basal ganglia (at protein level).4 Publications

Developmental stagei

Maximal expression is detected at postnatal day 13 (P13) (at protein level).1 Publication

Inductioni

By the proteasome inhibitors MG132 and lactacystin. By intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC). By okadaic acid and kainate (at protein level). Isoform 1 and isoform 2 relative amounts are changed upon up-regulation of the expression by NGF.5 Publications

Gene expression databases

BgeeiENSRNOG00000003147.
ExpressionAtlasiO08623. baseline and differential.
GenevisibleiO08623. RN.

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, TRIM13, MAP2K5 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. 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. Interacts with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD. Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule (By similarity). 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. Interacts with NGFR through TRAF6 and bridges that complex to NTRK1. Interacts with NBR1 and TRIM55. 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 (By similarity). Interacts with ULK1. Interacts with UBD (By similarity).By similarityCurated

GO - Molecular functioni

Protein-protein interaction databases

BioGridi250206. 24 interactors.
CORUMiO08623.
IntActiO08623. 5 interactors.
STRINGi10116.ENSRNOP00000056021.

Structurei

Secondary structure

1439
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi3 – 11Combined sources9
Beta strandi13 – 15Combined sources3
Beta strandi17 – 29Combined sources13
Beta strandi33 – 35Combined sources3
Helixi41 – 52Combined sources12
Beta strandi61 – 66Combined sources6
Beta strandi72 – 75Combined sources4
Helixi78 – 87Combined sources10
Beta strandi90 – 99Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K6QNMR-B331-346[»]
2KKCNMR-A3-100[»]
2KTRNMR-A/B3-100[»]
ProteinModelPortaliO08623.
SMRiO08623.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08623.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini3 – 100PB1PROSITE-ProRule annotationAdd BLAST98
Domaini388 – 433UBAPROSITE-ProRule annotationAdd BLAST46

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 48Interaction with LCKBy similarityAdd BLAST47
Regioni41 – 105Interaction with PRKCZ and dimerizationAdd BLAST65
Regioni48 – 78Interaction with PAWRBy similarityAdd BLAST31
Regioni119 – 221Interaction with GABRR31 PublicationAdd BLAST103
Regioni167 – 217LIM protein-bindingBy similarityAdd BLAST51
Regioni266 – 439Interaction with NTRK11 PublicationAdd BLAST174
Regioni320 – 341MAP1LC3B-bindingBy similarityAdd BLAST22

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi225 – 230TRAF6-bindingBy similarity6
Motifi335 – 340LIR6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi269 – 293Ser-richAdd BLAST25

Domaini

The UBA domain binds specifically 'Lys-63'-linked polyubiquitin chains of polyubiquitinated substrates. Mediates the interaction with TRIM55. Both the UBA and PB1 domains are necessary and sufficient for the localization into the ubiquitin-containing inclusion bodies.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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri119 – 164ZZ-typePROSITE-ProRule annotationAdd BLAST46

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4582. Eukaryota.
ENOG410XYAV. LUCA.
GeneTreeiENSGT00390000002781.
HOGENOMiHOG000154407.
HOVERGENiHBG052750.
InParanoidiO08623.
KOiK14381.
OMAiSVCPNYD.
OrthoDBiEOG091G08ES.
PhylomeDBiO08623.

Family and domain databases

CDDicd06402. PB1_p62. 1 hit.
cd14320. UBA_SQSTM. 1 hit.
InterProiView protein in InterPro
IPR000270. PB1_dom.
IPR034866. PB1_p62.
IPR033741. SQSTM_UBA.
IPR015940. UBA.
IPR009060. UBA-like.
IPR000433. Znf_ZZ.
PfamiView protein in Pfam
PF00564. PB1. 1 hit.
PF16577. UBA_5. 1 hit.
PF00569. ZZ. 1 hit.
SMARTiView protein in SMART
SM00666. PB1. 1 hit.
SM00165. UBA. 1 hit.
SM00291. ZnF_ZZ. 1 hit.
SUPFAMiSSF46934. SSF46934. 1 hit.
PROSITEiView protein in PROSITE
PS51745. PB1. 1 hit.
PS50030. UBA. 1 hit.
PS01357. ZF_ZZ_1. 1 hit.
PS50135. ZF_ZZ_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O08623-1) [UniParc]FASTAAdd to basket
Also known as: Zip1, B20

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
MASLTVKAYL LGKEEAAREI RRFSFCFSPE PEAEAAAGPG PCERLLSRVA
60 70 80 90 100
VLFPALRPGG FQAHYRDEDG DLVAFSSDEE LTMAMSYVKD DIFRIYIKEK
110 120 130 140 150
KECRREHRPP CAQEARSMVH PNVICDGCNG PVVGTRYKCS VCPDYDLCSV
160 170 180 190 200
CEGKGLHREH SKLIFPNPFG HLSDSFSHSR WLRKLKHGHF GWPGWEMGPP
210 220 230 240 250
GNWSPRPPRA GDGRPCPTAE SASAPSEDPN VNFLKNVGES VAAALSPLGI
260 270 280 290 300
EVDIDVEHGG KRSRLTPTSA ESSSTGTEDK SGTQPSSCSS EVSKPDGAGE
310 320 330 340 350
GPAQSLTEQM KKIALESVGQ PEELMESDNC SGGDDDWTHL SSKEVDPSTG
360 370 380 390 400
ELQSLQMPES EGPSSLDPSQ EGPTGLKEAA LYPHLPPEAD PRLIESLSQM
410 420 430
LSMGFSDEGG WLTRLLQTKN YDIGAALDTI QYSKHPPPL
Note: Major isoform except in central nervous system.
Length:439
Mass (Da):47,681
Last modified:July 1, 1997 - v1
Checksum:iE611F296E2B11464
GO
Isoform 2 (identifier: O08623-2) [UniParc]FASTAAdd to basket
Also known as: Zip2, B24

The sequence of this isoform differs from the canonical sequence as follows:
     222-248: Missing.

Show »
Length:412
Mass (Da):45,001
Checksum:i0AF172634A51767A
GO
Isoform 3 (identifier: O08623-3) [UniParc]FASTAAdd to basket
Also known as: Zip3

The sequence of this isoform differs from the canonical sequence as follows:
     222-234: ASAPSEDPNVNFL → GKAGVCTGFKCHK
     235-439: Missing.

Show »
Length:234
Mass (Da):26,067
Checksum:iB0D9DCF8BD017FBA
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015843222 – 248Missing in isoform 2. CuratedAdd BLAST27
Alternative sequenceiVSP_015844222 – 234ASAPS…NVNFL → GKAGVCTGFKCHK in isoform 3. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_015845235 – 439Missing in isoform 3. 1 PublicationAdd BLAST205

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08355 mRNA. Translation: CAA69642.1.
AF439403 mRNA. Translation: AAO15463.1.
BC061575 mRNA. Translation: AAH61575.1.
RefSeqiNP_787037.2. NM_175843.4. [O08623-1]
NP_853528.1. NM_181550.1. [O08623-3]
XP_006246275.1. XM_006246213.2. [O08623-2]
UniGeneiRn.107103.

Genome annotation databases

EnsembliENSRNOT00000059255; ENSRNOP00000056021; ENSRNOG00000003147. [O08623-1]
GeneIDi113894.
KEGGirno:113894.
UCSCiRGD:69287. rat. [O08623-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSQSTM_RAT
AccessioniPrimary (citable) accession number: O08623
Secondary accession number(s): Q8CH59
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: July 1, 1997
Last modified: September 27, 2017
This is version 148 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references