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SQSTM1

This gene encodes a multifunctional protein that binds ubiquitin and regulates activation of the nuclear factor kappa-B (NF-kB) signaling pathway. The protein functions as a scaffolding/adaptor protein in concert with TNF receptor-associated factor 6 to mediate activation of NF-kB in response to upstream signals. Alternatively spliced transcript variants encoding either the same or different isoforms have been identified for this gene. Mutations in this gene result in sporadic and familial Paget disease of bone. [provided by RefSeq, Mar 2009]
SQSTM1
Protein class

Disease related genes, Human disease related genes

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Urothelial cells, Syncytiotrophoblasts)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Cell line enhanced (HDLM-2)

Interaction

Homooligomer or heterooligomer; may form homotypic arrays. Dimerization interferes with ubiquitin binding. Interacts directly with PRKCI and PRKCZ (Probable). Forms ternary complexes with PRKCZ and KCNAB2 or PRKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). 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 JUB/Ajuba, PRKCZ and TRAF6. Interacts with TRAF6 (By similarity). Interacts with CYLD (PubMed:32185393). Identified in a complex with TRAF6 and CYLD (By similarity). Identified in a heterotrimeric complex with ubiquitin and ZFAND5, where ZFAND5 and SQSTM1 both interact with the same ubiquitin molecule. 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. Interacts with FHOD3. Interacts with TRMI5. Interacts with SESN1 (PubMed:23274085). Interacts with SESN2 (PubMed:23274085, PubMed:25040165). Interacts with ULK1 (PubMed:25040165). Interacts with UBD (PubMed:25422469). Interacts with WDR81; the interaction is direct and regulates the interaction of SQSTM1 with ubiquitinated proteins (PubMed:28404643). Interacts with WDFY3; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (PubMed:20168092). Interacts with TRIM23 (PubMed:28871090). Interacts with LRRC25 (PubMed:29288164). Interacts with TRIM50 (PubMed:22792322). Interacts with TRIM16 (PubMed:30143514). Interacts with STING1; leading to relocalization of STING1 to autophagosomes. Interacts (when phosphorylated at Ser-349) with KEAP1; the interaction is direct and inactivates the BCR(KEAP1) complex by sequestering KEAP1 in inclusion bodies, promoting its degradation (PubMed:20495340, PubMed:20452972). Interacts with GBP1 (By similarity). Interacts with MOAP1; promoting dissociation of SQSTM1 inclusion bodies that sequester KEAP1 (PubMed:33393215).

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