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Protein

Ubiquitin carboxyl-terminal hydrolase 17

Gene

USP17L2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 Publications

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei89 – 891Nucleophile
Active sitei334 – 3341Proton acceptorPROSITE-ProRule annotation

GO - Molecular functioni

  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • CAAX-box protein processing Source: UniProtKB
  • cell cycle checkpoint Source: UniProtKB
  • mitotic cell cycle checkpoint Source: UniProtKB
  • 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 proliferation Source: UniProtKB
  • regulation of defense response to virus by host Source: UniProtKB
  • regulation of ruffle assembly Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis, Cell cycle, Ubl conjugation pathway

Protein family/group databases

MEROPSiC19.023.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:34434. USP17L2.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi89 – 891C → S: Abolishes both enzymatic activity and effects on cell proliferation. 1 Publication

Organism-specific databases

PharmGKBiPA165586023.

Polymorphism and mutation databases

BioMutaiUSP17L2.
DMDMi187663988.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 530530Ubiquitin carboxyl-terminal hydrolase 17PRO_0000331644Add
BLAST

Proteomic databases

PaxDbiQ6R6M4.
PRIDEiQ6R6M4.

PTM databases

iPTMnetiQ6R6M4.
PhosphoSiteiQ6R6M4.

Expressioni

Tissue specificityi

Broadly expressed.1 Publication

Inductioni

Up-regulated by IL4/interleukin-4, IL6/interleukin-6 and chemokines including CXCL8 and CXCL12 (at protein level). Up-regulated during the G1/S transition of the cell cycle.3 Publications

Organism-specific databases

HPAiHPA045642.

Interactioni

Subunit structurei

Interacts with SUDS3; the interaction is direct.1 Publication

Protein-protein interaction databases

BioGridi132019. 10 interactions.
IntActiQ6R6M4. 4 interactions.
STRINGi9606.ENSP00000333329.

Structurei

3D structure databases

ProteinModelPortaliQ6R6M4.
SMRiQ6R6M4. Positions 49-372.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini80 – 375296USPAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni399 – 530132Mediates interaction with SUDS3Add
BLAST

Sequence similaritiesi

Belongs to the peptidase C19 family. USP17 subfamily.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1865. Eukaryota.
ENOG410XQ92. LUCA.
GeneTreeiENSGT00830000128255.
HOGENOMiHOG000144638.
HOVERGENiHBG007129.
InParanoidiQ6R6M4.
KOiK11845.
OrthoDBiEOG091G06D5.
PhylomeDBiQ6R6M4.
TreeFamiTF315281.

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q6R6M4-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:530
Mass (Da):59,619
Last modified:April 29, 2008 - v2
Checksum:iB117BB171376B0E4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661K → E in AAR91701 (PubMed:14699124).Curated
Sequence conflicti214 – 2141S → P in AAR91701 (PubMed:14699124).Curated
Sequence conflicti332 – 3321D → N in AAR91701 (PubMed:14699124).Curated
Sequence conflicti353 – 3531K → E in AAR91701 (PubMed:14699124).Curated
Sequence conflicti357 – 3571C → S in AAR91701 (PubMed:14699124).Curated
Sequence conflicti423 – 4231R → H in AAR91701 (PubMed:14699124).Curated
Sequence conflicti440 – 4401P → L in AAR91701 (PubMed:14699124).Curated
Sequence conflicti462 – 4621N → D in AAR91701 (PubMed:14699124).Curated
Sequence conflicti494 – 4941R → P in AAR91701 (PubMed:14699124).Curated
Sequence conflicti496 – 4961D → H in AAR91701 (PubMed:14699124).Curated
Sequence conflicti500 – 5001V → M in AAR91701 (PubMed:14699124).Curated
Sequence conflicti509 – 5091Q → R in AAR91701 (PubMed:14699124).Curated
Sequence conflicti512 – 5121T → A in AAR91701 (PubMed:14699124).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti438 – 4381K → R.
Corresponds to variant rs12543578 [ dbSNP | Ensembl ].
VAR_059750

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY509884 mRNA. Translation: AAR91701.1.
AC130366 Genomic DNA. No translation available.
CCDSiCCDS43713.1.
RefSeqiNP_958804.2. NM_201402.2.
UniGeneiHs.531448.

Genome annotation databases

EnsembliENST00000333796; ENSP00000333329; ENSG00000223443.
GeneIDi377630.
KEGGihsa:377630.
UCSCiuc003wvc.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY509884 mRNA. Translation: AAR91701.1.
AC130366 Genomic DNA. No translation available.
CCDSiCCDS43713.1.
RefSeqiNP_958804.2. NM_201402.2.
UniGeneiHs.531448.

3D structure databases

ProteinModelPortaliQ6R6M4.
SMRiQ6R6M4. Positions 49-372.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi132019. 10 interactions.
IntActiQ6R6M4. 4 interactions.
STRINGi9606.ENSP00000333329.

Protein family/group databases

MEROPSiC19.023.

PTM databases

iPTMnetiQ6R6M4.
PhosphoSiteiQ6R6M4.

Polymorphism and mutation databases

BioMutaiUSP17L2.
DMDMi187663988.

Proteomic databases

PaxDbiQ6R6M4.
PRIDEiQ6R6M4.

Protocols and materials databases

DNASUi377630.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000333796; ENSP00000333329; ENSG00000223443.
GeneIDi377630.
KEGGihsa:377630.
UCSCiuc003wvc.2. human.

Organism-specific databases

CTDi377630.
GeneCardsiUSP17L2.
H-InvDBHIX0034323.
HGNCiHGNC:34434. USP17L2.
HPAiHPA045642.
MIMi610186. gene.
neXtProtiNX_Q6R6M4.
PharmGKBiPA165586023.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1865. Eukaryota.
ENOG410XQ92. LUCA.
GeneTreeiENSGT00830000128255.
HOGENOMiHOG000144638.
HOVERGENiHBG007129.
InParanoidiQ6R6M4.
KOiK11845.
OrthoDBiEOG091G06D5.
PhylomeDBiQ6R6M4.
TreeFamiTF315281.

Miscellaneous databases

GenomeRNAii377630.
PROiQ6R6M4.
SOURCEiSearch...

Family and domain databases

InterProiIPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
PROSITEiPS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiU17L2_HUMAN
AccessioniPrimary (citable) accession number: Q6R6M4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: April 29, 2008
Last modified: September 7, 2016
This is version 99 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Miscellaneous

Overexpressed in a subset of human breast cancers, overexpression leading to an abnormally high level of CDC25A, which arrests cells through replication stress or premature mitosis, the latter occurring when CDK1 is activated inappropriately.1 Publication

Caution

The RS447 megasatellite DNA is a highly polymorphic conserved tandem repetitive sequence which contains a copy of the USP17 gene. It is present with an interindividual variation in copy number, ranging from 20 to 103, and can be found in the genome both on chromosome 4 and chromosome 8. USP17 is also frequently named DUB3 in the literature. The high similarity between the UPS17-like genes makes impossible to clearly assign data to one of the genes of the family. Oligonucleotides designed in RNAi experiments are for instance not specific of a given UPS17-like gene.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.