SQSTM1 / p62 Mouse Monoclonal Antibody [10-E10]

Function

Sequestosome 1 (SQSTM1, p62) is a ubiquitin binding protein involved in cell signaling, oxidative stress and autophagy. It was first identified as a protein that binds to the SH2 domain of p56Lck and independently found to interact with PKCζ. SQSTM1 was subsequently found to interact with ubiquitin, providing a scaffold for several signaling proteins and triggering degradation of proteins through the proteasome or lysosome. Interaction between SQSTM1 and TRAF6 leads to the K63-linked polyubiquitination of TRAF6 and subsequent activation of the NF-κB pathway. It may play a role in titin/TTN downstream signaling in muscle cells and regulate signaling cascades through ubiquitination. P62 may be involved in cell differentiation, apoptosis, immune response and regulation of K+ channels.

Background References

1. "The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway." Sanz L., Diaz-Meco M.T., Nakano H., Moscat J. EMBO J. 19:1576-1586(2000)

2. "Sequestosome 1/p62 is a polyubiquitin chain binding protein involved in ubiquitin proteasome degradation." Seibenhener M.L., Babu J.R., Geetha T., Wong H.C., Krishna N.R., Wooten M.W. Mol. Cell. Biol. 24:8055-8068(2004)

3. "Identification of SQSTM1 mutations in familial Paget\'s disease in Australian pedigrees." Good D.A., Busfield F., Fletcher B.H., Lovelock P.K., Duffy D.L., Kesting J.B., Andersen J., Shaw J.T.E.Bone 35:277-282(2004)

Tissue Specificity

Ubiquitously expressed.

Post-translational Modification

Phosphorylated. May be phosphorylated by PRKCZ (By similarity). Phosphorylated in vitro by TTN. Phosphorylation at Ser-403 by ULK1 is stimulated by SESN2. Phosphorylated at Ser-403 by TBK1, leading to promote relocalization of 'Lys-63'-linked ubiquitinated STING1 to autophagosomes. Phosphorylation at Ser-349 by MTOR promotes interaction with KEAP1 and inactivation of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (By similarity).; 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. Ubiquitinated by the BCR(KEAP1) complex at Lys-420, increasing SQSTM1 sequestering activity and promoting its degradation. Ubiquitinated via 'Lys-29' and 'Lys-33'-linked polyubiquitination leading to xenophagic targeting of bacteria and inhibition of their replication.

Subcellular Location

Cytoplasm, Nucleus

UNIPROT

SwissProt: Q13501 Human

SwissProt: Q64337 Mouse

SwissProt: O08623 Rat

Synonyms