ID:UBP8_HUMAN DESCRIPTION: RecName: Full=Ubiquitin carboxyl-terminal hydrolase 8; EC=3.4.19.12; AltName: Full=Deubiquitinating enzyme 8; AltName: Full=Ubiquitin isopeptidase Y; Short=hUBPy; AltName: Full=Ubiquitin thioesterase 8; AltName: Full=Ubiquitin-specific-processing protease 8; FUNCTION: 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. CATALYTIC ACTIVITY: Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C- terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). SUBUNIT: 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. INTERACTION: Q9HD42:CHMP1A; NbExp=2; IntAct=EBI-1050865, EBI-1057156; Q7LBR1:CHMP1B; NbExp=4; IntAct=EBI-1050865, EBI-2118090; SUBCELLULAR LOCATION: Cytoplasm. Nucleus (By similarity). Endosome membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein. INDUCTION: Upon growth stimulation in starved human fibroblasts. Decreases in response to growth arrest induced by cell-cell contact. DOMAIN: The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation. DOMAIN: The rhodanese domain is sufficent for RNF41-binding (By similarity). PTM: Phosphorylation of Ser-718 is essential for interaction with YWHAE and for cytosol localization (By similarity). Undergoes dephosphorylation at Ser-718 in the M phase (By similarity). Tyrosine-phosphorylated in its N-terminal half in an EGFR- dependent manner (By similarity). PTM: 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). SIMILARITY: Belongs to the peptidase C19 family. SIMILARITY: Contains 1 MIT domain. SIMILARITY: Contains 1 rhodanese domain. SEQUENCE CAUTION: Sequence=AAH38801.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=AAH51345.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P40818
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
