Reactome | UniProt:P40818 USP8

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UniProt:P40818 USP8 Show undefined attributes

chain	chain:1-1118
checksum	8B884B7A842F9A9A
comment	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 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).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.SUBUNIT (Microbial infection) Interacts with Zika virus non-structural protein 1.INTERACTION 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 sufficient for RNF41-binding.PTM 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.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).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the peptidase C19 family.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.
crossReference	[DatabaseIdentifier:12148130] PDB:8ADM [DatabaseIdentifier:12815101] ZINC target:P40818 [DatabaseIdentifier:12811761] ZINC - Substances:UBP8_HUMAN [DatabaseIdentifier:12453135] RefSeq:NP_001269978.1 [DatabaseIdentifier:12453136] RefSeq:NP_001122082.1 [DatabaseIdentifier:12453137] RefSeq:NP_005145.3 [DatabaseIdentifier:12284765] Pharos - Targets:P40818 [DatabaseIdentifier:12263547] PRO:P40818 [DatabaseIdentifier:12172747] PDB:2GFO [DatabaseIdentifier:12172748] PDB:2A9U [DatabaseIdentifier:12172745] PDB:8XPN [DatabaseIdentifier:12172743] PDB:2GWF [DatabaseIdentifier:12172744] PDB:8Y9A [DatabaseIdentifier:12160165] PDB:3N3K [DatabaseIdentifier:12163235] PDB:6F09 [DatabaseIdentifier:12172746] PDB:1WHB [DatabaseIdentifier:11512216] ENSEMBL:ENSG00000138592 [DatabaseIdentifier:11627725] ENSEMBL:ENSP00000302239 [DatabaseIdentifier:11627724] ENSEMBL:ENSP00000379721 [DatabaseIdentifier:11627726] ENSEMBL:ENSP00000412682 [DatabaseIdentifier:11750424] ENSEMBL:ENST00000425032 [DatabaseIdentifier:11750423] ENSEMBL:ENST00000396444 [DatabaseIdentifier:11750425] ENSEMBL:ENST00000307179 [DatabaseIdentifier:11780085] Guide to Pharmacology - Targets:3209 [DatabaseIdentifier:11786845] GeneCards:USP8 [DatabaseIdentifier:11802325] GlyGen:P40818 [DatabaseIdentifier:11830500] HMDB Protein:HMDBP10136 [DatabaseIdentifier:11839924] HPA:ENSG00000138592-USP8 [DatabaseIdentifier:11850049] IntEnz:3.4.19.12 [DatabaseIdentifier:12124453] OpenTargets:ENSG00000138592 [DatabaseIdentifier:12135726] Orphanet:USP8
databaseName	UniProt
dbId	66834
description	recommendedName: fullName evidence="19"Ubiquitin carboxyl-terminal hydrolase 8 ecNumber evidence="17"3.4.19.12 alternativeName: Deubiquitinating enzyme 8 alternativeName: Ubiquitin isopeptidase Y shortName: hUBPy alternativeName: Ubiquitin thioesterase 8 alternativeName: Ubiquitin-specific-processing protease 8
displayName	UniProt:P40818 USP8
geneName	USP8 KIAA0055 UBPY
identifier	P40818
isSequenceChanged	false
keyword	3D-structure Alternative splicing Cell cycle Cell membrane Cushing syndrome Cytoplasm Disease variant Endosome Hydrolase Membrane Nucleus Phosphoprotein Protease Proteomics identification Reference proteome SH3-binding Thiol protease Ubl conjugation Ubl conjugation pathway
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	USP8
otherIdentifier	11724333_a_at 11724334_a_at 11724335_s_at 11726705_a_at 16800991 202745_PM_at 202745_at 229501_PM_s_at 229501_s_at 240226_PM_at 240226_at 240751_PM_at 240751_at 2580459 2902230 2902232 2902237 2902238 2902240 2902242 2902244 3593653 3593654 3593655 3593656 3593658 3593659 3593662 3593664 3593665 3593667 3593668 3593669 3593671 3593677 3593678 3593679 3593680 3593681 3593682 3593683 3593685 3593687 3593688 3593689 3593690 3593691 3593692 3593693 3593694 3593695 3593696 3593697 3593698 3593700 3593701 3593702 3593704 3593707 3593709 3593711 39794_at 43467_at 50904_g_at 66444_at 7983663 84430_at 9101 A_14_P124443 A_14_P137196 A_23_P129058 D29956_at GE57157 GE687963 GE841922 GO:0000281 GO:0000910 GO:0002080 GO:0004197 GO:0004843 GO:0005515 GO:0005634 GO:0005737 GO:0005768 GO:0005769 GO:0005829 GO:0005886 GO:0006508 GO:0007032 GO:0007265 GO:0008233 GO:0008234 GO:0010008 GO:0014069 GO:0016020 GO:0016579 GO:0016787 GO:0017124 GO:0030496 GO:0031647 GO:0032880 GO:0043226 GO:0045296 GO:0061578 GO:0070536 GO:0071108 GO:0071549 GO:0090263 GO:0098978 GO:0099576 GO:1905166 GO:1905908 GO:1990090 GO:1990380 HMNXSV003003858 Hs.152818.1.A1_3p_a_at Hs.246180.0.A1_3p_at Hs.291884.0.A1_3p_at ILMN_1715188 ILMN_2094587 PH_hs_0029238 TC15000395.hg g4827053_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-1358714] p-T945-USP8 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-917720] USP8 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000138592] ENSEMBL:ENSG00000138592 USP8 [ReferenceDNASequence:12763497] UCSC:P40818 USP8 [ReferenceDNASequence:11376842] BioGPS Gene:9101 USP8 [ReferenceDNASequence:11403250] COSMIC - genes:USP8 USP8 [ReferenceDNASequence:11412229] CTD Gene:9101 USP8 [ReferenceDNASequence:11440846] dbSNP Gene:9101 USP8 [ReferenceDNASequence:11818485] HGNC:12631 USP8 [ReferenceDNASequence:11914301] KEGG:hsa:9101 USP8 [ReferenceDNASequence:12006631] Monarch:9101 USP8 [ReferenceDNASequence:12090724] NCBI Gene:9101 USP8 [ReferenceDNASequence:12109860] OMIM:603158 USP8
referenceTranscript	[ReferenceRNASequence:12634646] RefSeq:NM_001128610.3 USP8 [ReferenceRNASequence:12634644] RefSeq:NM_001283049.2 USP8 [ReferenceRNASequence:12634645] RefSeq:NM_005154.4 USP8
schemaClass	ReferenceGeneProduct
secondaryIdentifier	UBP8_HUMAN B4DKA8 Q2TB31 Q7Z3U2 Q86VA0 Q8IWI7
sequenceLength	1118
species	[Species:48887] Homo sapiens
stId	uniprot:P40818
url	http://purl.uniprot.org/uniprot/P40818

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-1358714] p-T945-USP8 [cytosol] [EntityWithAccessionedSequence:R-HSA-917720] USP8 [cytosol]
(referenceSequence)	[ModifiedResidue:1358715] O-phospho-L-threonine at 945
(interactor)	[UndirectedInteraction:11138905] UniProt:P31946 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11146213] UniProt:O89100 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11151765] UniProt:Q96CF2 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11201705] UniProt:Q9HD42 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11202781] UniProt:P31947 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11210709] UniProt:Q99814 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11243345] UniProt:P61981 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11264753] UniProt:P62258 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11286743] UniProt:Q16665 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11288025] UniProt:P63104 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11292597] UniProt:O75791 <-> UniProt:P40818 (IntAct) [UndirectedInteraction:11294575] UniProt:P40818 <-> UniProt:P27348 (IntAct) [UndirectedInteraction:11294577] UniProt:P40818 <-> UniProt:Q04917 (IntAct) [UndirectedInteraction:11294579] UniProt:P40818 <-> UniProt:Q7LBR1 (IntAct) [UndirectedInteraction:11294581] UniProt:P40818 <-> IntAct:EBI-4399559 (IntAct) [UndirectedInteraction:11294583] UniProt:P40818 <-> UniProt:Q14596 (IntAct) [UndirectedInteraction:11294585] UniProt:P40818 <-> UniProt:Q01151 (IntAct) [UndirectedInteraction:11294587] UniProt:P40818 <-> UniProt:Q9Y6H6 (IntAct) [UndirectedInteraction:11294589] UniProt:P40818 <-> UniProt:P09619 (IntAct)