Sequestosome 1

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype.

Model organisms

Sqstm1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology	Abnormal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Salmonella infection	Normal
Citrobacter infection	Normal
All tests and analysis from

Model organisms have been used in the study of SQSTM1 function. A conditional knockout mouse line, called Sqstm1^{tm1a(KOMP)Wtsi} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on homozygous mutant mice and one significant abnormality was observed: females had abnormal complete blood count parameters, including an increased red blood cell distribution width and increased mean platelet volume.

Interactions

Sequestosome 1 has been shown to interact with:

• MAP1LC3A,
• PRKCI,
• RAD23A,
• RIPK1,
• TRAF6
• TrkA, and
• TrkB.