SQSTM_PONAB
ID SQSTM_PONAB Reviewed; 440 AA.
AC Q5RBA5;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Sequestosome-1;
DE AltName: Full=Ubiquitin-binding protein p62;
GN Name=SQSTM1;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. Involved in midbody ring
CC degradation (By similarity). May regulate the activation of NFKB1 by
CC TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role
CC in titin/TTN downstream signaling in muscle cells. May regulate
CC signaling cascades through ubiquitination. Adapter that mediates the
CC interaction between TRAF6 and CYLD (By similarity). May be involved in
CC cell differentiation, apoptosis, immune response and regulation of K(+)
CC channels. Involved in endosome organization by retaining vesicles in
CC the perinuclear cloud: following ubiquitination by RNF26, attracts
CC specific vesicle-associated adapters, forming a molecular bridge that
CC restrains cognate vesicles in the perinuclear region and organizes the
CC endosomal pathway for efficient cargo transport (By similarity).
CC Promotes relocalization of 'Lys-63'-linked ubiquitinated STING1 to
CC autophagosomes (By similarity). Acts as an activator of the NFE2L2/NRF2
CC pathway via interaction with KEAP1: interaction inactivates the
CC BCR(KEAP1) complex, promoting nuclear accumulation of NFE2L2/NRF2 and
CC subsequent expression of cytoprotective genes (By similarity).
CC {ECO:0000250|UniProtKB:O08623, ECO:0000250|UniProtKB:Q13501,
CC ECO:0000250|UniProtKB:Q64337}.
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, NBR1,
CC MAP2K5, TRIM13, TRIM55 and MAPKAPK5. Interacts with the proteasome
CC subunits PSMD4 and PSMC2. Interacts with K63-polyubiquitinated
CC MAPT/TAU. Interacts with IKBKB through PRKCZ and PRKCI. Interacts with
CC NGFR through TRAF6 and bridges that complex to NTRK1. Forms a complex
CC with MAP2K5 and PRKCZ or PRKCI. Component of a ternary complex with
CC PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1
CC probably bridging IKBKB to the TNF-R1 complex composed of TNF-
CC R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with AJUBA, PRKCZ and
CC TRAF6. Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and
CC GABBR3. Interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Interacts
CC with TRAF6 and CYLD. Identified in a complex with TRAF6 and CYLD. Forms
CC an NGF-induced complex with IKBKB, PRKCI and TRAF6. 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 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 TRIM50 (By similarity). Interacts with TRIM16 (By
CC similarity). Interacts with STING1; leading to relocalization of STING1
CC to autophagosomes (By similarity). Interacts (when phosphorylated at
CC Ser-349) with KEAP1; the interaction is direct and inactivates the
CC BCR(KEAP1) complex by sequestering KEAP1 in inclusion bodies, promoting
CC its degradation (By similarity). Interacts with GBP1 (By similarity).
CC Interacts with MOAP1; promoting dissociation of SQSTM1 inclusion bodies
CC that sequester KEAP1 (By similarity). {ECO:0000250|UniProtKB:O08623,
CC ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337}.
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 hepatocellular
CC carcinoma. Colocalizes with TRIM13 in the perinuclear endoplasmic
CC reticulum (By similarity). Co-localizes with TRIM5 in cytoplasmic
CC bodies (By similarity). When nuclear export is blocked by treatment
CC with leptomycin B, accumulates in PML bodies (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q13501}.
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: Ubiquitinated by UBE2J1 and RNF26 at Lys-435: 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-420, 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 -!- PTM: Phosphorylated. May be phosphorylated by PRKCZ (By similarity).
CC Phosphorylated in vitro by TTN. Phosphorylation at Ser-403 by ULK1 is
CC stimulated by SESN2 (By similarity). Phosphorylated at Ser-403 by TBK1,
CC leading to promote relocalization of 'Lys-63'-linked ubiquitinated
CC STING1 to autophagosomes (By similarity). Phosphorylation at Ser-349 by
CC MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1)
CC complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of
CC phase II detoxifying enzymes (By similarity).
CC {ECO:0000250|UniProtKB:Q13501, ECO:0000250|UniProtKB:Q64337}.
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DR EMBL; CR858746; CAH90955.1; -; mRNA.
DR RefSeq; NP_001125548.1; NM_001132076.1.
DR AlphaFoldDB; Q5RBA5; -.
DR BMRB; Q5RBA5; -.
DR SMR; Q5RBA5; -.
DR GeneID; 100172461; -.
DR CTD; 8878; -.
DR eggNOG; KOG4582; Eukaryota.
DR InParanoid; Q5RBA5; -.
DR OrthoDB; 1275680at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005776; C:autophagosome; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0000932; C:P-body; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0030017; C:sarcomere; IEA:UniProtKB-SubCell.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; ISS:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
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:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:1905719; P:protein localization to perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0061912; P:selective autophagy; ISS:UniProtKB.
DR CDD; cd06402; PB1_p62; 1.
DR CDD; cd14320; UBA_SQSTM; 1.
DR Gene3D; 3.30.60.90; -; 1.
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 2: Evidence at transcript level;
KW Acetylation; Apoptosis; Autophagy; Cytoplasm; Cytoplasmic vesicle;
KW Differentiation; Endoplasmic reticulum; Endosome; Immunity;
KW Isopeptide bond; Lysosome; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CHAIN 2..440
FT /note="Sequestosome-1"
FT /id="PRO_0000072178"
FT DOMAIN 3..102
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 389..434
FT /note="UBA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT ZN_FING 123..173
FT /note="ZZ-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT REGION 2..50
FT /note="Interaction with LCK"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 43..107
FT /note="Interaction with PRKCZ and dimerization"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 50..80
FT /note="Interaction with PAWR"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 122..224
FT /note="Interaction with GABRR3"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 170..220
FT /note="LIM protein-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 197..235
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 264..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..440
FT /note="Interaction with NTRK1"
FT /evidence="ECO:0000250|UniProtKB:O08623"
FT REGION 321..342
FT /note="MAP1LC3B-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT REGION 347..352
FT /note="Interaction with KEAP1"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOTIF 228..233
FT /note="TRAF6-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOTIF 336..341
FT /note="LIR"
FT COMPBIAS 269..306
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 314..328
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..372
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 131
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
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 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
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 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
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 BINDING 163
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 148
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 170
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 176
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 207
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 269
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 272
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 365
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64337"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT MOD_RES 403
FT /note="Phosphoserine; by ULK1 and TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CROSSLNK 420
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13501"
SQ SEQUENCE 440 AA; 47613 MW; 2A9733AC1C9D819D CRC64;
MASLTVKAYL LGKEDAAREI RRFSFCCSPE PEAEAEAAAG PGPCERLLSR VAALFPALRP
GGFQAHYRDE DGDLVAFSSD EELTMAMSYV KDDIFRIYIK EKKECRRDHR PPCAQEAPRN
MVHPNVICDG CNGPVVGTRY KCSVCPDYDL CSVCEGKGLH RGHTKLAFPS PFGHLSEGFS
HSRWLRKVKH GHFGWSGWEM GPPGNWSPRP PRAGEARPGP TAESASGPSE DPSVNLLKNV
GESVAAALSP LGIEVDIDVE HGGKRSRLTP VSPESSSTEE KSSSQPSSCC SDPSKPGGNV
EGATQSLAEQ MRKIALESEG RPEEQMESDN CSGGDDDWTH LSSKEVDPST GELQSLQMPE
SEGPSSLDPS QEGPTGLKEA ALYPHLPPEA DPRLIESLSQ MLSMGFSDEG GRLTRLLQTK
NYDIGAALDT IQYSKHPPPL
