Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q6R6M4

- U17L2_HUMAN

UniProt

Q6R6M4 - U17L2_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 81 (01 Oct 2014)
      Sequence version 2 (29 Apr 2008)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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. protein binding Source: UniProtKB
    2. ubiquitin-specific protease activity Source: UniProtKB
    3. 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

    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

    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.
    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

    MEDDSLYLGG EWQFNHFSKL TSSRPDAAFA EIQRTSLPEK SPLSSEARVD    50
    LCDDLAPVAR QLAPRKKLPL SSRRPAAVGA GLQNMGNTCY ENASLQCLTY 100
    TPPLANYMLS REHSQTCQRP KCCMLCTMQA HITWALHSPG HVIQPSQALA 150
    AGFHRGKQED AHEFLMFTVD AMKKACLPGH KQVDHHSKDT TLIHQIFGGC 200
    WRSQIKCLHC HGISDTFDPY LDIALDIQAA QSVKQALEQL VKPEELNGEN 250
    AYHCGLCLQR APASKTLTLH TSAKVLILVL KRFSDVTGNK LAKNVQYPEC 300
    LDMQPYMSQQ NTGPLVYVLY AVLVHAGWSC HDGHYFSYVK AQEGQWYKMD 350
    DAKVTACSIT SVLSQQAYVL FYIQKSEWER HSESVSRGRE PRALGAEDTD 400
    RRATQGELKR DHPCLQAPEL DERLVERATQ ESTLDHWKFP QEQNKTKPEF 450
    NVRKVEGTLP PNVLVIHQSK YKCGMKNHHP EQQSSLLNLS STTRTDQESV 500
    NTGTLASLQG RTRRSKGKNK HSKRALLVCQ 530
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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.
    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

    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 1, 2014
    This is version 81 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