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Q6R6M4

- U17L2_HUMAN

UniProt

Q6R6M4 - U17L2_HUMAN

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Protein

Ubiquitin carboxyl-terminal hydrolase 17

Gene

USP17L2

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. ubiquitin-specific protease activity Source: UniProtKB
  2. ubiquitin thiolesterase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. CAAX-box protein processing Source: UniProtKB
  3. cell cycle checkpoint Source: UniProtKB
  4. mitotic cell cycle checkpoint Source: UniProtKB
  5. negative regulation of histone deacetylation Source: UniProtKB
  6. negative regulation of protein processing Source: UniProtKB
  7. negative regulation of protein targeting to membrane Source: UniProtKB
  8. negative regulation of Ras GTPase activity Source: UniProtKB
  9. positive regulation of MDA-5 signaling pathway Source: UniProtKB
  10. positive regulation of Rho GTPase activity Source: UniProtKB
  11. positive regulation of RIG-I signaling pathway Source: UniProtKB
  12. protein deubiquitination Source: UniProtKB
  13. protein K48-linked deubiquitination Source: UniProtKB
  14. protein K63-linked deubiquitination Source: UniProtKB
  15. regulation of apoptotic process Source: UniProtKB
  16. regulation of cell migration Source: UniProtKB
  17. regulation of cell proliferation Source: UniProtKB
  18. regulation of defense response to virus by host Source: UniProtKB
  19. regulation of ruffle assembly Source: UniProtKB
  20. 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:3.4.19.12)
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
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:34434. USP17L2.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB
  2. 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.

PTM / Processingi

Molecule processing

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

Proteomic databases

PaxDbiQ6R6M4.
PRIDEiQ6R6M4.

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

Gene expression databases

GenevestigatoriQ6R6M4.

Organism-specific databases

HPAiHPA045642.

Interactioni

Subunit structurei

Interacts with SUDS3; the interaction is direct.1 Publication

Protein-protein interaction databases

BioGridi132019. 7 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

eggNOGiCOG5533.
GeneTreeiENSGT00760000119279.
HOGENOMiHOG000144638.
HOVERGENiHBG007129.
InParanoidiQ6R6M4.
KOiK11845.
OMAiRACDITS.
OrthoDBiEOG73NG35.
PhylomeDBiQ6R6M4.
TreeFamiTF315281.

Family and domain databases

InterProiIPR006861. HABP4_PAIRBP1-bd.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view]
PfamiPF04774. HABP4_PAI-RBP1. 1 hit.
PF00443. 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.1. human.

Polymorphism databases

DMDMi187663988.

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.
CCDSi CCDS43713.1.
RefSeqi NP_958804.2. NM_201402.2.
UniGenei Hs.531448.

3D structure databases

ProteinModelPortali Q6R6M4.
SMRi Q6R6M4. Positions 49-372.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 132019. 7 interactions.
IntActi Q6R6M4. 4 interactions.
STRINGi 9606.ENSP00000333329.

Protein family/group databases

MEROPSi C19.023.

Polymorphism databases

DMDMi 187663988.

Proteomic databases

PaxDbi Q6R6M4.
PRIDEi Q6R6M4.

Protocols and materials databases

DNASUi 377630.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000333796 ; ENSP00000333329 ; ENSG00000223443 .
GeneIDi 377630.
KEGGi hsa:377630.
UCSCi uc003wvc.1. human.

Organism-specific databases

CTDi 377630.
GeneCardsi GC08M011994.
H-InvDB HIX0034323.
HGNCi HGNC:34434. USP17L2.
HPAi HPA045642.
MIMi 610186. gene.
neXtProti NX_Q6R6M4.
PharmGKBi PA165586023.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5533.
GeneTreei ENSGT00760000119279.
HOGENOMi HOG000144638.
HOVERGENi HBG007129.
InParanoidi Q6R6M4.
KOi K11845.
OMAi RACDITS.
OrthoDBi EOG73NG35.
PhylomeDBi Q6R6M4.
TreeFami TF315281.

Miscellaneous databases

GenomeRNAii 377630.
NextBioi 100679.
PROi Q6R6M4.
SOURCEi Search...

Gene expression databases

Genevestigatori Q6R6M4.

Family and domain databases

InterProi IPR006861. HABP4_PAIRBP1-bd.
IPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR028889. UCH/PAN2.
[Graphical view ]
Pfami PF04774. HABP4_PAI-RBP1. 1 hit.
PF00443. UCH. 1 hit.
[Graphical view ]
PROSITEi PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "DUB-3, a cytokine-inducible deubiquitinating enzyme that blocks proliferation."
    Burrows J.F., McGrattan M.J., Rascle A., Humbert M., Baek K.-H., Johnston J.A.
    J. Biol. Chem. 279:13993-14000(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, INDUCTION BY CYTOKINES, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-89.
  2. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "The DUB/USP17 deubiquitinating enzymes, a multigene family within a tandemly repeated sequence."
    Burrows J.F., McGrattan M.J., Johnston J.A.
    Genomics 85:524-529(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NOMENCLATURE.
  4. "Hyaluronan- and RNA-binding deubiquitinating enzymes of USP17 family members associated with cell viability."
    Shin J.-M., Yoo K.-J., Kim M.-S., Kim D., Baek K.-H.
    BMC Genomics 7:292-292(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NOMENCLATURE, FUNCTION IN APOPTOSIS.
  5. Cited for: FUNCTION IN CELL PROLIFERATION, SUBCELLULAR LOCATION.
  6. "The DUB/USP17 deubiquitinating enzymes: a gene family within a tandemly repeated sequence, is also embedded within the copy number variable beta-defensin cluster."
    Burrows J.F., Scott C.J., Johnston J.A.
    BMC Genomics 11:250-250(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION.
  7. "The deubiquitinating enzyme USP17 is highly expressed in tumor biopsies, is cell cycle regulated, and is required for G1-S progression."
    McFarlane C., Kelvin A.A., de la Vega M., Govender U., Scott C.J., Burrows J.F., Johnston J.A.
    Cancer Res. 70:3329-3339(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  8. "The ubiquitin-specific protease 17 is involved in virus-triggered type I IFN signaling."
    Chen R., Zhang L., Zhong B., Tan B., Liu Y., Shu H.B.
    Cell Res. 20:802-811(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION IN CELLULAR ANTIVIRAL RESPONSE.
  9. "The deubiquitinating enzyme USP17 blocks N-Ras membrane trafficking and activation but leaves K-Ras unaffected."
    de la Vega M., Burrows J.F., McFarlane C., Govender U., Scott C.J., Johnston J.A.
    J. Biol. Chem. 285:12028-12036(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Ubiquitin hydrolase Dub3 promotes oncogenic transformation by stabilizing Cdc25A."
    Pereg Y., Liu B.Y., O'Rourke K.M., Sagolla M., Dey A., Komuves L., French D.M., Dixit V.M.
    Nat. Cell Biol. 12:400-406(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION IN CELL PROLIFERATION.
  11. "Lys-63-specific deubiquitination of SDS3 by USP17 regulates HDAC activity."
    Ramakrishna S., Suresh B., Lee E.J., Lee H.J., Ahn W.S., Baek K.H.
    J. Biol. Chem. 286:10505-10514(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SUDS3, SUBCELLULAR LOCATION.
  12. "The deubiquitinating enzyme USP17 is essential for GTPase subcellular localization and cell motility."
    de la Vega M., Kelvin A.A., Dunican D.J., McFarlane C., Burrows J.F., Jaworski J., Stevenson N.J., Dib K., Rappoport J.Z., Scott C.J., Long A., Johnston J.A.
    Nat. Commun. 2:259-259(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL MIGRATION, INDUCTION BY CHEMOKINE.

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: October 29, 2014
This is version 82 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

External Data

Dasty 3