Aliases for USP8 Gene
-
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]
GeneCards Summary for USP8 Gene
USP8 (Ubiquitin Specific Peptidase 8) is a Protein Coding gene. Diseases associated with USP8 include Pituitary Adenoma 4, Acth-Secreting and Conn's Syndrome. Among its related pathways are Signaling by ERBB2 and Deubiquitination. Gene Ontology (GO) annotations related to this gene include SH3 domain binding and cysteine-type deubiquitinase activity. An important paralog of this gene is USP32.
UniProtKB/Swiss-Prot Summary for USP8 Gene
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 controls 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). ( UBP8_HUMAN,P40818 )
Protein details for USP8 Gene (UniProtKB/Swiss-Prot)
- Protein Symbol:
- P40818-UBP8_HUMAN
- Recommended name:
- Ubiquitin carboxyl-terminal hydrolase 8
Protein attributes for USP8 Gene
- Size:
- 1118 amino acids
- Molecular mass:
- 127523 Da
- Quaternary structure:
-
- Forms a ternary complex with RNF128 and OTUB1.
Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1.
Interacts with STAM2 (via SH3 domain).
Interacts with DNAJB3, EGFR, EPS15, RASGRF1, RNF41, YWHAE, YWHAG and YWHAZ (By similarity).
Interacts with NBR1, RASGRF1, RNF41 and IST1.
Associates with the ESCRT-0 complex and with microtubules (By similarity).
Interacts with BIRC6/bruce and KIF23/MKLP1. - (Microbial infection) Interacts with Zika virus non-structural protein 1.
Post-translational modifications for USP8 Gene
-
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.
( P40818-UBP8_HUMAN ) -
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).
( P40818-UBP8_HUMAN ) - Modification sites at PhosphoSitePlus ( P40818 )
- Modification sites at neXtProt ( NX_P40818 )
- Glycosylation from GlyGen (P40818) 2 sites, 1 O-linked glycan (2 sites)
UniProtKB/Swiss-Prot:
UBP8_HUMAN :- The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.
- Belongs to the peptidase C19 family.
- Domain:
-
- The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.
- The rhodanese domain is sufficient for RNF41-binding.
- Family:
-
- Belongs to the peptidase C19 family.
Pathways by source for USP8 Gene
2 PubChem pathways for USP8 Gene
14 Reactome pathways for USP8 Gene
See All 14 »- Deubiquitination
- Downregulation of ERBB2 signaling
- Downregulation of ERBB2:ERBB3 signaling
- Metabolism of proteins
- Negative regulation of MET activity
- Forms a ternary complex with RNF128 and OTUB1.
Inga kommentarer:
Skicka en kommentar