SQSTM_RAT
ID SQSTM_RAT Reviewed; 439 AA.
AC O08623; Q8CH59;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Sequestosome-1;
DE AltName: Full=Protein kinase C-zeta-interacting protein;
DE Short=PKC-zeta-interacting protein;
DE AltName: Full=Ubiquitin-binding protein p62;
GN Name=Sqstm1; Synonyms=Zip;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY,
RP OLIGOMERIZATION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH PRKCZ.
RC TISSUE=Brain;
RX PubMed=9177193; DOI=10.1073/pnas.94.12.6191;
RA Puls A., Schmidt S., Grawe F., Stabel S.;
RT "Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-
RT binding protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:6191-6196(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY,
RP OLIGOMERIZATION, AND INTERACTION WITH GABRR1; GABRR2; GABRR3; PRKCZ AND
RP KCNAB2.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=12431995; DOI=10.1074/jbc.m205162200;
RA Croci C., Brandstaetter J.H., Enz R.;
RT "ZIP3, a new splice variant of the PKC-zeta-interacting protein family,
RT binds to GABAC receptors, PKC-zeta, and Kv beta 2.";
RL J. Biol. Chem. 278:6128-6135(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=10366737; DOI=10.1016/s0169-328x(99)00093-5;
RA Nakaso K., Kitayama M., Ishii T., Bannai S., Yanagawa T., Kimura K.,
RA Nakashima K., Ohama E., Yamada K.;
RT "Effects of kainate-mediated excitotoxicity on the expression of rat
RT counterparts of A170 and MSP23 stress proteins in the brain.";
RL Brain Res. Mol. Brain Res. 69:155-163(1999).
RN [5]
RP ALTERNATIVE SPLICING (ISOFORM 2), TISSUE SPECIFICITY, INTERACTION WITH
RP KCNAB1; KCNAB2 AND PRKCZ, OLIGOMERIZATION, DEVELOPMENTAL STAGE, INDUCTION,
RP AND FUNCTION.
RX PubMed=10477520; DOI=10.1126/science.285.5433.1565;
RA Gong J., Xu J., Bezanilla M., van Huizen R., Derin R., Li M.;
RT "Differential stimulation of PKC phosphorylation of potassium channels by
RT ZIP1 and ZIP2.";
RL Science 285:1565-1569(1999).
RN [6]
RP INDUCTION.
RX PubMed=11162503; DOI=10.1006/bbrc.2000.4107;
RA Kuusisto E., Suuronen T., Salminen A.;
RT "Ubiquitin-binding protein p62 expression is induced during apoptosis and
RT proteasomal inhibition in neuronal cells.";
RL Biochem. Biophys. Res. Commun. 280:223-228(2001).
RN [7]
RP INTERACTION WITH NTRK1; TRAF6 AND PRKCZ, AND FUNCTION.
RX PubMed=11244088; DOI=10.1074/jbc.c000869200;
RA Wooten M.W., Seibenhener M.L., Mamidipudi V., Diaz-Meco M.T., Barker P.A.,
RA Moscat J.;
RT "The atypical protein kinase C-interacting protein p62 is a scaffold for
RT NF-kappaB activation by nerve growth factor.";
RL J. Biol. Chem. 276:7709-7712(2001).
RN [8]
RP INTERACTION WITH PRKCZ, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=11500922; DOI=10.1002/jcb.1177;
RA Samuels I.S., Seibenhener M.L., Neidigh K.B.W., Wooten M.W.;
RT "Nerve growth factor stimulates the interaction of ZIP/p62 with atypical
RT protein kinase C and targets endosomal localization: evidence for
RT regulation of nerve growth factor-induced differentiation.";
RL J. Cell. Biochem. 82:452-466(2001).
RN [9]
RP INDUCTION.
RX PubMed=11981755; DOI=10.1053/jhep.2002.32674;
RA Stumptner C., Fuchsbichler A., Heid H., Zatloukal K., Denk H.;
RT "Mallory body -- a disease-associated type of sequestosome.";
RL Hepatology 35:1053-1062(2002).
RN [10]
RP INDUCTION.
RX PubMed=15158159; DOI=10.1016/j.brainres.2004.03.029;
RA Nakaso K., Yoshimoto Y., Nakano T., Takeshima T., Fukuhara Y., Yasui K.,
RA Araga S., Yanagawa T., Ishii T., Nakashima K.;
RT "Transcriptional activation of p62/A170/ZIP during the formation of the
RT aggregates: possible mechanisms and the role in Lewy body formation in
RT Parkinson's disease.";
RL Brain Res. 1012:42-51(2004).
RN [11]
RP INTERACTION WITH PRKCI, AND MUTAGENESIS OF LYS-7; 21-ARG-ARG-22; ASP-67 AND
RP ARG-94.
RX PubMed=15143057; DOI=10.1074/jbc.m403092200;
RA Hirano Y., Yoshinaga S., Ogura K., Yokochi M., Noda Y., Sumimoto H.,
RA Inagaki F.;
RT "Solution structure of atypical protein kinase C PB1 domain and its mode of
RT interaction with ZIP/p62 and MEK5.";
RL J. Biol. Chem. 279:31883-31890(2004).
RN [12]
RP INTERACTION WITH IKBKB; PRKCI AND TRAF6.
RX PubMed=16079148; DOI=10.1074/jbc.c500237200;
RA Wooten M.W., Geetha T., Seibenhener M.L., Babu J.R., Diaz-Meco M.T.,
RA Moscat J.;
RT "The p62 scaffold regulates nerve growth factor-induced NF-kappaB
RT activation by influencing TRAF6 polyubiquitination.";
RL J. Biol. Chem. 280:35625-35629(2005).
RN [13]
RP INTERACTION WITH NBR1 AND TRIM55, AND SUBCELLULAR LOCATION.
RX PubMed=15802564; DOI=10.1126/science.1110463;
RA Lange S., Xiang F., Yakovenko A., Vihola A., Hackman P., Rostkova E.,
RA Kristensen J., Brandmeier B., Franzen G., Hedberg B., Gunnarsson L.G.,
RA Hughes S.M., Marchand S., Sejersen T., Richard I., Edstroem L., Ehler E.,
RA Udd B., Gautel M.;
RT "The kinase domain of titin controls muscle gene expression and protein
RT turnover.";
RL Science 308:1599-1603(2005).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-266 AND SER-354, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [15]
RP STRUCTURE BY NMR OF 3-100, SUBUNIT, AND MUTAGENESIS OF ASP-67 AND ASP-69.
RX PubMed=19728111; DOI=10.1007/s10858-009-9370-7;
RA Saio T., Yokochi M., Inagaki F.;
RT "The NMR structure of the p62 PB1 domain, a key protein in autophagy and
RT NF-kappaB signaling pathway.";
RL J. Biomol. NMR 45:335-341(2009).
CC -!- FUNCTION: Autophagy receptor required for selective macroautophagy
CC (aggrephagy). Functions as a bridge between polyubiquitinated cargo and
CC autophagosomes. Interacts directly with both the cargo to become
CC degraded and an autophagy modifier of the MAP1 LC3 family. Required
CC both for the formation and autophagic degradation of polyubiquitin-
CC containing bodies, called ALIS (aggresome-like induced structures) and
CC links ALIS to the autophagic machinery (By similarity). Involved in
CC midbody ring degradation (By similarity). May regulate the activation
CC of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1
CC (PubMed:11244088, PubMed:11500922). May play a role in titin/TTN
CC downstream signaling in muscle cells (By similarity). May regulate
CC signaling cascades through ubiquitination (By similarity). Adapter that
CC mediates the interaction between TRAF6 and CYLD (By similarity). May be
CC involved in cell differentiation, apoptosis, immune response and
CC regulation of K(+) channels (By similarity). Involved in endosome
CC organization by retaining vesicles in the perinuclear cloud: following
CC ubiquitination by RNF26, attracts specific vesicle-associated adapters,
CC forming a molecular bridge that restrains cognate vesicles in the
CC perinuclear region and organizes the endosomal pathway for efficient
CC cargo transport (By similarity). Promotes relocalization of 'Lys-63'-
CC linked ubiquitinated STING1 to autophagosomes (By similarity). Acts as
CC an activator of the NFE2L2/NRF2 pathway via interaction with KEAP1:
CC interaction inactivates the BCR(KEAP1) complex, promoting nuclear
CC accumulation of NFE2L2/NRF2 and subsequent expression of cytoprotective
CC genes (By similarity). {ECO:0000250|UniProtKB:Q13501,
CC ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:11244088,
CC ECO:0000269|PubMed:11500922}.
CC -!- FUNCTION: [Isoform 1]: More potent than isoform 2 to stimulate PRKCZ-
CC dependent phosphorylation of KCNAB2. {ECO:0000269|PubMed:10477520}.
CC -!- SUBUNIT: Homooligomer or heterooligomer; may form homotypic arrays.
CC Interacts directly with PRKCI and PRKCZ (Probable). Interacts with
CC EBI3, LCK, RASA1, PRKCZ, PRKCI, NR2F2, NTRK1, NTRK2, NTRK3, TRIM13,
CC MAP2K5 and MAPKAPK5. Interacts with the proteasome subunits PSMD4 and
CC PSMC2. Interacts with K63-polyubiquitinated MAPT/TAU. Interacts with
CC IKBKB through PRKCZ and PRKCI. Forms a complex with MAP2K5 and PRKCZ or
CC PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-
CC alpha stimulation, interacts with RIPK1 probably bridging IKBKB to the
CC TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a
CC complex with AJUBA, PRKCZ and TRAF6. Interacts with TRAF6 and CYLD.
CC Identified in a complex with TRAF6 and CYLD. Identified in a
CC heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and
CC SQSTM1 both interact with the same ubiquitin molecule (By similarity).
CC Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3.
CC Interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced
CC complex with IKBKB, PRKCI and TRAF6. Interacts with NGFR through TRAF6
CC and bridges that complex to NTRK1. Interacts with NBR1 and TRIM55.
CC Directly interacts with MAP1LC3A and MAP1LC3B, as well as with other
CC MAP1 LC3 family members, including GABARAP, GABARAPL1 and GABARAPL2;
CC these interactions are necessary for the recruitment MAP1 LC3 family
CC members to inclusion bodies containing polyubiquitinated protein
CC aggregates and for their degradation by autophagy (By similarity).
CC Interacts with FHOD3 (By similarity). Interacts with TRMI5 (By
CC similarity). Interacts with SESN1 (By similarity). Interacts with SESN2
CC (By similarity). Interacts with ULK1. Interacts with UBD (By
CC similarity). Interacts with WDR81; the interaction is direct and
CC regulates the interaction of SQSTM1 with ubiquitinated proteins (By
CC similarity). Interacts with WDFY3; this interaction is required to
CC recruit WDFY3 to cytoplasmic bodies and to PML bodies (By similarity).
CC Interacts with TRIM23 (By similarity). Interacts with LRRC25 (By
CC similarity). Interacts with TRIM50 (By similarity). Interacts with
CC TRIM16 (By similarity). Interacts with STING1; leading to
CC relocalization of STING1 to autophagosomes (By similarity). Interacts
CC (when phosphorylated at Ser-348) with KEAP1; the interaction is direct
CC and inactivates the BCR(KEAP1) complex by sequestering KEAP1 in
CC inclusion bodies, promoting its degradation (By similarity). Interacts
CC with GBP1 (By similarity). Interacts with MOAP1; promoting dissociation
CC of SQSTM1 inclusion bodies that sequester KEAP1 (By similarity).
CC {ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337,
CC ECO:0000269|PubMed:10477520, ECO:0000269|PubMed:11244088,
CC ECO:0000269|PubMed:11500922, ECO:0000269|PubMed:12431995,
CC ECO:0000269|PubMed:15143057, ECO:0000269|PubMed:15802564,
CC ECO:0000269|PubMed:16079148, ECO:0000269|PubMed:19728111,
CC ECO:0000269|PubMed:9177193, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q13501}. Late endosome {ECO:0000250}. Nucleus
CC {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Lysosome
CC {ECO:0000250}. Cytoplasmic vesicle, autophagosome {ECO:0000250}.
CC Nucleus, PML body {ECO:0000250|UniProtKB:Q13501}. Cytoplasm, myofibril,
CC sarcomere. Note=In cardiac muscles, localizes to the sarcomeric band.
CC Localizes to late endosomes. May also localize to the nucleus.
CC Colocalizes with TRIM13 on the perinuclear endoplasmic reticulum (By
CC similarity). Commonly found in inclusion bodies containing
CC polyubiquitinated protein aggregates (By similarity). Co-localizes with
CC TRIM5 in cytoplasmic bodies (By similarity). When nuclear export is
CC blocked by treatment with leptomycin B, accumulates in PML bodies (By
CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q13501}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Zip1, B20;
CC IsoId=O08623-1; Sequence=Displayed;
CC Name=2; Synonyms=Zip2, B24;
CC IsoId=O08623-2; Sequence=VSP_015843;
CC Name=3; Synonyms=Zip3;
CC IsoId=O08623-3; Sequence=VSP_015844, VSP_015845;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. In brain, mainly expressed
CC by neurons, especially pyramidal neurons in the cerebral cortex and
CC hippocampus. Also expressed by Purkinje cells and neurons in the
CC dentate nucleus of the cerebellum and neurons of the basal ganglia (at
CC protein level). {ECO:0000269|PubMed:10366737,
CC ECO:0000269|PubMed:10477520, ECO:0000269|PubMed:12431995,
CC ECO:0000269|PubMed:9177193}.
CC -!- DEVELOPMENTAL STAGE: Maximal expression is detected at postnatal day 13
CC (P13) (at protein level). {ECO:0000269|PubMed:10477520}.
CC -!- INDUCTION: By the proteasome inhibitors MG132 and lactacystin. By
CC intoxication with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DCC). By
CC okadaic acid and kainate (at protein level). Isoform 1 and isoform 2
CC relative amounts are changed upon up-regulation of the expression by
CC NGF. {ECO:0000269|PubMed:10366737, ECO:0000269|PubMed:10477520,
CC ECO:0000269|PubMed:11162503, ECO:0000269|PubMed:11981755,
CC ECO:0000269|PubMed:15158159}.
CC -!- DOMAIN: The UBA domain binds specifically 'Lys-63'-linked polyubiquitin
CC chains of polyubiquitinated substrates. Mediates the interaction with
CC TRIM55. Both the UBA and PB1 domains are necessary and sufficient for
CC the localization into the ubiquitin-containing inclusion bodies.
CC {ECO:0000250|UniProtKB:Q13501}.
CC -!- DOMAIN: The PB1 domain mediates homooligomerization and interactions
CC with FHOD3, MAP2K5, NBR1, PRKCI, PRKCZ and WDR81. Both the PB1 and UBA
CC domains are necessary and sufficient for the localization into the
CC ubiquitin-containing inclusion bodies. {ECO:0000250|UniProtKB:Q13501}.
CC -!- DOMAIN: The ZZ-type zinc finger mediates the interaction with RIPK1.
CC {ECO:0000250|UniProtKB:Q13501}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with ATG8 family proteins. {ECO:0000250|UniProtKB:Q13501}.
CC -!- PTM: Phosphorylated (PubMed:9177193). Phosphorylated in vitro by TTN
CC (By similarity). May be phosphorylated by PRKCZ. Phosphorylation at
CC Ser-402 by ULK1 is stimulated by SESN2 (By similarity). Phosphorylated
CC at Ser-402 by TBK1, leading to promote relocalization of 'Lys-63'-
CC linked ubiquitinated STING1 to autophagosomes (By similarity).
CC Phosphorylation at Ser-348 by MTOR promotes interaction with KEAP1 and
CC inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear
CC accumulation and expression of phase II detoxifying enzymes (By
CC similarity). {ECO:0000250|UniProtKB:Q13501,
CC ECO:0000250|UniProtKB:Q64337, ECO:0000269|PubMed:9177193}.
CC -!- PTM: Ubiquitinated by UBE2J1 and RNF26 at Lys-434: ubiquitinated SQSTM1
CC attracts specific vesicle-associated adapters, forming a molecular
CC bridge that restrains cognate vesicles in the perinuclear region and
CC organizes the endosomal pathway for efficient cargo transport.
CC Deubiquitination by USP15 releases target vesicles for fast transport
CC into the cell periphery. Ubiquitinated by the BCR(KEAP1) complex at
CC Lys-419, increasing SQSTM1 sequestering activity and promoting its
CC degradation. Ubiquitinated via 'Lys-29' and 'Lys-33'-linked
CC polyubiquitination leading to xenophagic targeting of bacteria and
CC inhibition of their replication. {ECO:0000250|UniProtKB:Q13501}.
CC -!- MISCELLANEOUS: [Isoform 1]: Major isoform except in central nervous
CC system.
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DR EMBL; Y08355; CAA69642.1; -; mRNA.
DR EMBL; AF439403; AAO15463.1; -; mRNA.
DR EMBL; BC061575; AAH61575.1; -; mRNA.
DR RefSeq; NP_787037.2; NM_175843.4. [O08623-1]
DR RefSeq; NP_853528.1; NM_181550.1. [O08623-3]
DR RefSeq; XP_006246275.1; XM_006246213.2. [O08623-2]
DR PDB; 2K6Q; NMR; -; B=331-346.
DR PDB; 2KKC; NMR; -; A=3-100.
DR PDB; 2KTR; NMR; -; A/B=3-100.
DR PDBsum; 2K6Q; -.
DR PDBsum; 2KKC; -.
DR PDBsum; 2KTR; -.
DR AlphaFoldDB; O08623; -.
DR BMRB; O08623; -.
DR SMR; O08623; -.
DR BioGRID; 250206; 31.
DR CORUM; O08623; -.
DR IntAct; O08623; 5.
DR MINT; O08623; -.
DR STRING; 10116.ENSRNOP00000056021; -.
DR iPTMnet; O08623; -.
DR PhosphoSitePlus; O08623; -.
DR jPOST; O08623; -.
DR PaxDb; O08623; -.
DR PRIDE; O08623; -.
DR Ensembl; ENSRNOT00000004308; ENSRNOP00000004308; ENSRNOG00000003147. [O08623-2]
DR Ensembl; ENSRNOT00000059255; ENSRNOP00000056021; ENSRNOG00000003147. [O08623-1]
DR GeneID; 113894; -.
DR KEGG; rno:113894; -.
DR UCSC; RGD:69287; rat. [O08623-1]
DR CTD; 8878; -.
DR RGD; 69287; Sqstm1.
DR eggNOG; KOG4582; Eukaryota.
DR GeneTree; ENSGT00390000002781; -.
DR HOGENOM; CLU_038011_1_0_1; -.
DR InParanoid; O08623; -.
DR OMA; IWHPLQW; -.
DR OrthoDB; 1275680at2759; -.
DR PhylomeDB; O08623; -.
DR Reactome; R-RNO-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-RNO-209543; p75NTR recruits signalling complexes.
DR Reactome; R-RNO-209560; NF-kB is activated and signals survival.
DR Reactome; R-RNO-5205685; PINK1-PRKN Mediated Mitophagy.
DR Reactome; R-RNO-9020702; Interleukin-1 signaling.
DR Reactome; R-RNO-9664873; Pexophagy.
DR Reactome; R-RNO-9755511; KEAP1-NFE2L2 pathway.
DR EvolutionaryTrace; O08623; -.
DR PRO; PR:O08623; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003147; Expressed in skeletal muscle tissue and 19 other tissues.
DR ExpressionAtlas; O08623; baseline and differential.
DR Genevisible; O08623; RN.
DR GO; GO:0016235; C:aggresome; ISO:RGD.
DR GO; GO:0044753; C:amphisome; ISO:RGD.
DR GO; GO:0044754; C:autolysosome; ISO:RGD.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0016234; C:inclusion body; ISO:RGD.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0097413; C:Lewy body; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0000407; C:phagophore assembly site; ISO:RGD.
DR GO; GO:0016605; C:PML body; ISO:RGD.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0097225; C:sperm midpiece; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:RGD.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0005080; F:protein kinase C binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0035973; P:aggrephagy; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; ISS:UniProtKB.
DR GO; GO:0070342; P:brown fat cell proliferation; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISO:RGD.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0000423; P:mitophagy; ISO:RGD.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:RGD.
DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD.
DR GO; GO:1905719; P:protein localization to perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0061635; P:regulation of protein complex stability; ISO:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:0098780; P:response to mitochondrial depolarisation; ISO:RGD.
DR GO; GO:0061912; P:selective autophagy; ISS:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd06402; PB1_p62; 1.
DR CDD; cd14320; UBA_SQSTM; 1.
DR Gene3D; 3.30.60.90; -; 1.
DR IDEAL; IID50133; -.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR034866; PB1_p62.
DR InterPro; IPR033741; SQSTM_UBA.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR000433; Znf_ZZ.
DR InterPro; IPR043145; Znf_ZZ_sf.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF16577; UBA_5; 1.
DR Pfam; PF00569; ZZ; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00165; UBA; 1.
DR SMART; SM00291; ZnF_ZZ; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS50030; UBA; 1.
DR PROSITE; PS01357; ZF_ZZ_1; 1.
DR PROSITE; PS50135; ZF_ZZ_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; Autophagy;
KW Cytoplasm; Cytoplasmic vesicle; Differentiation; Endoplasmic reticulum;
KW Endosome; Immunity; Isopeptide bond; Lysosome; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CHAIN 2..439
FT /note="Sequestosome-1"
FT /id="PRO_0000072179"
FT DOMAIN 3..100
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 388..433
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 120..170
FT /note="ZZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT REGION 2..48
FT /note="Interaction with LCK"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 41..105
FT /note="Interaction with PRKCZ and dimerization"
FT /evidence="ECO:0000269|PubMed:10477520,
FT ECO:0000269|PubMed:12431995"
FT REGION 48..78
FT /note="Interaction with PAWR"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 119..221
FT /note="Interaction with GABRR3"
FT /evidence="ECO:0000269|PubMed:12431995"
FT REGION 167..217
FT /note="LIM protein-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 201..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 266..439
FT /note="Interaction with NTRK1"
FT /evidence="ECO:0000269|PubMed:11244088"
FT REGION 320..341
FT /note="MAP1LC3B-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 346..351
FT /note="Interaction with KEAP1"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOTIF 225..230
FT /note="TRAF6-binding"
FT /evidence="ECO:0000250"
FT MOTIF 335..340
FT /note="LIR"
FT COMPBIAS 265..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..371
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 157
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 145
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 204
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 266
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 305
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 348
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 364
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 402
FT /note="Phosphoserine; by ULK1 and TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CROSSLNK 419
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CROSSLNK 434
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT VAR_SEQ 222..248
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_015843"
FT VAR_SEQ 222..234
FT /note="ASAPSEDPNVNFL -> GKAGVCTGFKCHK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12431995"
FT /id="VSP_015844"
FT VAR_SEQ 235..439
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12431995"
FT /id="VSP_015845"
FT MUTAGEN 7
FT /note="K->A: Loss of interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:15143057"
FT MUTAGEN 21..22
FT /note="RR->AA: Reduces interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:15143057"
FT MUTAGEN 67
FT /note="D->A: No effect on interaction with PRKCI. Abolishes
FT homooligomerization; when associated with A-67."
FT /evidence="ECO:0000269|PubMed:15143057,
FT ECO:0000269|PubMed:19728111"
FT MUTAGEN 69
FT /note="D->A: Abolishes homooligomerization; when associated
FT with A-67."
FT /evidence="ECO:0000269|PubMed:19728111"
FT MUTAGEN 94
FT /note="R->A: Reduces interaction with PRKCI."
FT /evidence="ECO:0000269|PubMed:15143057"
FT STRAND 3..11
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 17..29
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:2KKC"
FT HELIX 41..52
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 61..66
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:2KKC"
FT HELIX 78..87
FT /evidence="ECO:0007829|PDB:2KKC"
FT STRAND 90..99
FT /evidence="ECO:0007829|PDB:2KKC"
SQ SEQUENCE 439 AA; 47681 MW; E611F296E2B11464 CRC64;
MASLTVKAYL LGKEEAAREI RRFSFCFSPE PEAEAAAGPG PCERLLSRVA VLFPALRPGG
FQAHYRDEDG DLVAFSSDEE LTMAMSYVKD DIFRIYIKEK KECRREHRPP CAQEARSMVH
PNVICDGCNG PVVGTRYKCS VCPDYDLCSV CEGKGLHREH SKLIFPNPFG HLSDSFSHSR
WLRKLKHGHF GWPGWEMGPP GNWSPRPPRA GDGRPCPTAE SASAPSEDPN VNFLKNVGES
VAAALSPLGI EVDIDVEHGG KRSRLTPTSA ESSSTGTEDK SGTQPSSCSS EVSKPDGAGE
GPAQSLTEQM KKIALESVGQ PEELMESDNC SGGDDDWTHL SSKEVDPSTG ELQSLQMPES
EGPSSLDPSQ EGPTGLKEAA LYPHLPPEAD PRLIESLSQM LSMGFSDEGG WLTRLLQTKN
YDIGAALDTI QYSKHPPPL
