Sequestosome 1 (SQSTM1) Human Recombinant Protein

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: an adapter protein which binds ubiquitin, shuttling proteins to the proteasome. Co-localizes along with the E3 ubiquitin ligase, TRAF6, to aggregates from Alzheimer's disease brains but not in control brain. May regulate the activation of NFKB1 by TNF-alpha, nerve growth factor (NGF) and interleukin-1. May play a role in titin downstream signaling in muscle cells. May regulate signaling cascades through ubiquitination. May be involved in cell differentiation, apoptosis, immune response and regulation of K(+) channels. Forms ternary complexes with PKCZ and Kv-beta2 or PKCZ and GABBR3. Also interacts with KCNAB1, GABRR1, GABRR2 and GABRR3. Interacts with EBI3, LCK, RASA1, PKCZ , PKCI, NR2F2, NTRK1, NTRK2, NTRK3, NBR1, MEK5, 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 MEK5 and PRKCZ or PRKCI. Component of a ternary complex with PAWR and PRKCZ. Upon TNF-alpha stimulation, interacts with RIPK1 problably bridging IKBKB to the TNF-R1 complex composed of TNF-R1/TNFRSF1A, TRADD and RIPK1. Forms a complex with JUB/Ajuba, PRKCZ and TRAF6. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Nuclear receptor co-regulator; Autophagy; Ubiquitin conjugating system

Chromosomal Location of Human Ortholog: 5q35

Cellular Component: nucleoplasm; PML body; lysosome; endoplasmic reticulum; late endosome; cytoplasm; autophagic vacuole; cytoplasmic vesicle; inclusion body; cytosol

Molecular Function: protein serine/threonine kinase activity; identical protein binding; ubiquitin binding; protein binding; protein homodimerization activity; protein kinase C binding; zinc ion binding; SH2 domain binding; receptor tyrosine kinase binding; protein kinase binding

Biological Process: ubiquitin-dependent protein catabolic process; regulation of Ras protein signal transduction; nerve growth factor receptor signaling pathway; immune system process; protein heterooligomerization; macroautophagy; positive regulation of apoptosis; endosome transport; protein amino acid phosphorylation; protein localization; response to stress; autophagy; positive regulation of transcription from RNA polymerase II promoter; positive regulation of protein amino acid phosphorylation; cell differentiation; regulation of I-kappaB kinase/NF-kappaB cascade; positive regulation of macroautophagy; negative regulation of apoptosis

Disease: Frontotemporal Dementia And/or Amyotrophic Lateral Sclerosis 3; Paget Disease Of Bone