USP8

This gene encodes a protein that belongs to the ubiquitin-specific processing protease family of proteins. The encoded protein is thought to regulate the morphology of the endosome by ubiquitination of proteins on this organelle and is involved in cargo sorting and membrane trafficking at the early endosome stage. This protein is required for the cell to enter the S phase of the cell cycle and also functions as a positive regulator in the Hedgehog signaling pathway in development. Pseudogenes of this gene are present on chromosomes 2 and 6. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

Ubiquitin Specific Peptidase 8

Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controles tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062).

Biological Process cellular response to dexamethasone stimulus Source:Ensembl
Biological Process cellular response to nerve growth factor stimulus Source:Ensembl
Biological Process endosome organization Source:UniProtKB1 Publication
Biological Process mitotic cytokinesis Source:MGI1 Publication
Biological Process negative regulation of lysosomal protein catabolic process Source:FlyBase1 Publication
Biological Process positive regulation of amyloid fibril formation Source:FlyBase1 Publication
Biological Process positive regulation of canonical Wnt signaling pathway Source:FlyBase1 Publication
Biological Process protein deubiquitination Source:UniProtKB1 Publication
Biological Process protein K48-linked deubiquitination Source:UniProtKB1 Publication
Biological Process protein K63-linked deubiquitination Source:UniProtKB1 Publication
Biological Process Ras protein signal transduction Source:GO_Central1 Publication
Biological Process regulation of protein catabolic process at postsynapse, modulating synaptic transmission Source:Ensembl
Biological Process regulation of protein localization Source:UniProtKB1 Publication
Biological Process regulation of protein stability Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:InterPro

Cytoplasm
Nucleus
Endosome membrane
Cell membrane

Pituitary adenoma 4, ACTH-secreting (PITA4):
A form of pituitary adenoma, a neoplasm of the pituitary gland and one of the most common neuroendocrine tumors. Pituitary adenomas are clinically classified as functional and non-functional tumors, and manifest with a variety of features, including local invasion of surrounding structures and excessive hormone secretion. Functional pituitary adenomas are further classified by the type of hormone they secrete. PITA4 results in excessive production of adrenocorticotropic hormone. This leads to hypersecretion of cortisol by the adrenal glands and ACTH-dependent Cushing syndrome. Clinical manifestations of Cushing syndrome include facial and truncal obesity, abdominal striae, muscular weakness, osteoporosis, arterial hypertension, diabetes.

Phosphorylation of Ser-718 is essential for interaction with YWHAE and for cytosol localization. Undergoes dephosphorylation at Ser-718 in the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR-dependent manner.
Ubiquitinated. Inactive form is mostly monoubiquitinated, but polyubiquitination happens too. Ubiquitination is increased in EGF-stimulated cells. Ubiquitination of active form is undetectable, suggesting a possibility that USP8 deubiquitinates itself, thereby regulating its own function (By similarity).