UniProtKB - Q6R6M4 (U17L2_HUMAN)
Ubiquitin carboxyl-terminal hydrolase 17
USP17L2
Functioni
Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes. Regulates cell proliferation by deubiquitinating and inhibiting RCE1 thereby controlling the small GTPases NRAS and HRAS localization and activation. In parallel, mediates deubiquitination of CDC25A, preventing CDC25A degradation by the proteasome during the G1/S and G2/M phases promoting cell-cycle progression. Also regulates cell proliferation and apoptosis through deubiquitination of SUDS3 a regulator of histone deacetylation. Through activation of the Rho family GTPases RAC1A, CDC42 and RHOA, regulates cell migration. Through the cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains of the cytoplasmic innate immune receptors DDX58 and IFIH1 stimulates the cellular response to viral infection.
9 PublicationsMiscellaneous
Caution
Catalytic activityi
- 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).3 Publications EC:3.4.19.12
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 89 | Nucleophile | 1 | |
Active sitei | 334 | Proton acceptorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- cysteine-type endopeptidase activity Source: GO_Central
- thiol-dependent deubiquitinase Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- CAAX-box protein processing Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- MAPK cascade Source: Reactome
- negative regulation of GTPase activity Source: UniProtKB
- negative regulation of histone deacetylation Source: UniProtKB
- negative regulation of protein processing Source: UniProtKB
- negative regulation of protein targeting to membrane Source: UniProtKB
- positive regulation of GTPase activity Source: UniProtKB
- positive regulation of MDA-5 signaling pathway Source: UniProtKB
- positive regulation of RIG-I signaling pathway Source: UniProtKB
- protein deubiquitination Source: UniProtKB
- protein K48-linked deubiquitination Source: UniProtKB
- protein K63-linked deubiquitination Source: UniProtKB
- regulation of apoptotic process Source: UniProtKB
- regulation of cell migration Source: UniProtKB
- regulation of cell population proliferation Source: UniProtKB
- regulation of defense response to virus by host Source: UniProtKB
- regulation of G2/MI transition of meiotic cell cycle Source: UniProtKB
- regulation of ruffle assembly Source: UniProtKB
- ubiquitin-dependent protein catabolic process Source: InterPro
Keywordsi
Molecular function | Hydrolase, Protease, Thiol protease |
Biological process | Apoptosis, Cell cycle, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q6R6M4 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases R-HSA-9648002, RAS processing |
SABIO-RKi | Q6R6M4 |
SignaLinki | Q6R6M4 |
Protein family/group databases
MEROPSi | C19.023 |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin carboxyl-terminal hydrolase 17 (EC:3.4.19.123 Publications)Short name: USP17 Alternative name(s): Deubiquitinating enzyme 17-like protein 2 Deubiquitinating protein 3 Short name: DUB-3 Ubiquitin carboxyl-terminal hydrolase 17-like protein 2 Ubiquitin thioesterase 17-like protein 2 Ubiquitin-specific-processing protease 17-like protein 2 |
Gene namesi | Name:USP17L2 Synonyms:DUB3, USP17, USP17H, USP17I, USP17J, USP17K, USP17L, USP17M |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:34434, USP17L2 |
MIMi | 610186, gene |
neXtProti | NX_Q6R6M4 |
VEuPathDBi | HostDB:ENSG00000223443 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Nucleus
- Nucleus 1 Publication
Cytosol
- cytosol Source: GO_Central
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Keywords - Cellular componenti
Endoplasmic reticulum, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 89 | C → S: Abolishes both enzymatic activity and effects on cell proliferation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 377630 |
OpenTargetsi | ENSG00000223443 |
PharmGKBi | PA165586023 |
Miscellaneous databases
Pharosi | Q6R6M4, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3739248 |
Genetic variation databases
BioMutai | USP17L2 |
DMDMi | 187663988 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000331644 | 1 – 530 | Ubiquitin carboxyl-terminal hydrolase 17Add BLAST | 530 |
Proteomic databases
PaxDbi | Q6R6M4 |
PeptideAtlasi | Q6R6M4 |
PRIDEi | Q6R6M4 |
PTM databases
iPTMneti | Q6R6M4 |
PhosphoSitePlusi | Q6R6M4 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000223443, Expressed in corpus callosum and 26 other tissues |
Organism-specific databases
HPAi | ENSG00000223443, Tissue enriched (brain) |
Interactioni
Subunit structurei
Interacts with SUDS3; the interaction is direct.
1 PublicationProtein-protein interaction databases
BioGRIDi | 132019, 27 interactors |
IntActi | Q6R6M4, 4 interactors |
STRINGi | 9606.ENSP00000333329 |
Chemistry databases
BindingDBi | Q6R6M4 |
Miscellaneous databases
RNActi | Q6R6M4, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 80 – 375 | USPAdd BLAST | 296 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 382 – 416 | DisorderedSequence analysisAdd BLAST | 35 | |
Regioni | 399 – 530 | Mediates interaction with SUDS31 PublicationAdd BLAST | 132 | |
Regioni | 490 – 530 | DisorderedSequence analysisAdd BLAST | 41 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 490 – 512 | Polar residuesSequence analysisAdd BLAST | 23 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1865, Eukaryota |
GeneTreei | ENSGT00940000161948 |
HOGENOMi | CLU_008279_10_0_1 |
InParanoidi | Q6R6M4 |
OrthoDBi | 561804at2759 |
PhylomeDBi | Q6R6M4 |
TreeFami | TF315281 |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MEDDSLYLGG EWQFNHFSKL TSSRPDAAFA EIQRTSLPEK SPLSSEARVD
60 70 80 90 100
LCDDLAPVAR QLAPRKKLPL SSRRPAAVGA GLQNMGNTCY ENASLQCLTY
110 120 130 140 150
TPPLANYMLS REHSQTCQRP KCCMLCTMQA HITWALHSPG HVIQPSQALA
160 170 180 190 200
AGFHRGKQED AHEFLMFTVD AMKKACLPGH KQVDHHSKDT TLIHQIFGGC
210 220 230 240 250
WRSQIKCLHC HGISDTFDPY LDIALDIQAA QSVKQALEQL VKPEELNGEN
260 270 280 290 300
AYHCGLCLQR APASKTLTLH TSAKVLILVL KRFSDVTGNK LAKNVQYPEC
310 320 330 340 350
LDMQPYMSQQ NTGPLVYVLY AVLVHAGWSC HDGHYFSYVK AQEGQWYKMD
360 370 380 390 400
DAKVTACSIT SVLSQQAYVL FYIQKSEWER HSESVSRGRE PRALGAEDTD
410 420 430 440 450
RRATQGELKR DHPCLQAPEL DERLVERATQ ESTLDHWKFP QEQNKTKPEF
460 470 480 490 500
NVRKVEGTLP PNVLVIHQSK YKCGMKNHHP EQQSSLLNLS STTRTDQESV
510 520 530
NTGTLASLQG RTRRSKGKNK HSKRALLVCQ
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 66 | K → E in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 214 | S → P in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 332 | D → N in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 353 | K → E in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 357 | C → S in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 423 | R → H in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 440 | P → L in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 462 | N → D in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 494 | R → P in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 496 | D → H in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 500 | V → M in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 509 | Q → R in AAR91701 (PubMed:14699124).Curated | 1 | |
Sequence conflicti | 512 | T → A in AAR91701 (PubMed:14699124).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_059750 | 438 | K → R. Corresponds to variant dbSNP:rs12543578Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY509884 mRNA Translation: AAR91701.1 AC130366 Genomic DNA No translation available. |
CCDSi | CCDS43713.1 |
RefSeqi | NP_958804.2, NM_201402.2 |
Genome annotation databases
Ensembli | ENST00000333796; ENSP00000333329; ENSG00000223443 |
GeneIDi | 377630 |
KEGGi | hsa:377630 |
MANE-Selecti | ENST00000333796.4; ENSP00000333329.3; NM_201402.3; NP_958804.2 |
UCSCi | uc003wvc.2, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY509884 mRNA Translation: AAR91701.1 AC130366 Genomic DNA No translation available. |
CCDSi | CCDS43713.1 |
RefSeqi | NP_958804.2, NM_201402.2 |
3D structure databases
SMRi | Q6R6M4 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 132019, 27 interactors |
IntActi | Q6R6M4, 4 interactors |
STRINGi | 9606.ENSP00000333329 |
Chemistry databases
BindingDBi | Q6R6M4 |
ChEMBLi | CHEMBL3739248 |
Protein family/group databases
MEROPSi | C19.023 |
PTM databases
iPTMneti | Q6R6M4 |
PhosphoSitePlusi | Q6R6M4 |
Genetic variation databases
BioMutai | USP17L2 |
DMDMi | 187663988 |
Proteomic databases
PaxDbi | Q6R6M4 |
PeptideAtlasi | Q6R6M4 |
PRIDEi | Q6R6M4 |
Protocols and materials databases
Antibodypediai | 22144, 122 antibodies from 20 providers |
DNASUi | 377630 |
Genome annotation databases
Ensembli | ENST00000333796; ENSP00000333329; ENSG00000223443 |
GeneIDi | 377630 |
KEGGi | hsa:377630 |
MANE-Selecti | ENST00000333796.4; ENSP00000333329.3; NM_201402.3; NP_958804.2 |
UCSCi | uc003wvc.2, human |
Organism-specific databases
CTDi | 377630 |
DisGeNETi | 377630 |
GeneCardsi | USP17L2 |
HGNCi | HGNC:34434, USP17L2 |
HPAi | ENSG00000223443, Tissue enriched (brain) |
MIMi | 610186, gene |
neXtProti | NX_Q6R6M4 |
OpenTargetsi | ENSG00000223443 |
PharmGKBi | PA165586023 |
VEuPathDBi | HostDB:ENSG00000223443 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1865, Eukaryota |
GeneTreei | ENSGT00940000161948 |
HOGENOMi | CLU_008279_10_0_1 |
InParanoidi | Q6R6M4 |
OrthoDBi | 561804at2759 |
PhylomeDBi | Q6R6M4 |
TreeFami | TF315281 |
Enzyme and pathway databases
PathwayCommonsi | Q6R6M4 |
Reactomei | R-HSA-5689880, Ub-specific processing proteases R-HSA-9648002, RAS processing |
SABIO-RKi | Q6R6M4 |
SignaLinki | Q6R6M4 |
Miscellaneous databases
BioGRID-ORCSi | 377630, 14 hits in 961 CRISPR screens |
GenomeRNAii | 377630 |
Pharosi | Q6R6M4, Tbio |
PROi | PR:Q6R6M4 |
RNActi | Q6R6M4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000223443, Expressed in corpus callosum and 26 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR038765, Papain-like_cys_pep_sf IPR001394, Peptidase_C19_UCH IPR018200, USP_CS IPR028889, USP_dom |
Pfami | View protein in Pfam PF00443, UCH, 1 hit |
SUPFAMi | SSF54001, SSF54001, 1 hit |
PROSITEi | View protein in PROSITE PS00973, USP_2, 1 hit PS50235, USP_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | U17L2_HUMAN | |
Accessioni | Q6R6M4Primary (citable) accession number: Q6R6M4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 29, 2008 |
Last sequence update: | April 29, 2008 | |
Last modified: | February 23, 2022 | |
This is version 131 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Peptidase families
Classification of peptidase families and list of entries - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families