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Q96RU2

- UBP28_HUMAN

UniProt

Q96RU2 - UBP28_HUMAN

Protein

Ubiquitin carboxyl-terminal hydrolase 28

Gene

USP28

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus.4 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).

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei171 – 1711Nucleophile
    Active sitei600 – 6001Proton 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. cell proliferation Source: UniProtKB
    2. cellular response to DNA damage stimulus Source: UniProtKB
    3. cellular response to UV Source: UniProtKB
    4. DNA damage checkpoint Source: UniProtKB
    5. DNA repair Source: UniProtKB-KW
    6. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
    7. protein deubiquitination Source: UniProtKB
    8. response to ionizing radiation Source: UniProtKB
    9. ubiquitin-dependent protein catabolic process Source: InterPro

    Keywords - Molecular functioni

    Hydrolase, Protease, Thiol protease

    Keywords - Biological processi

    DNA damage, DNA repair, Ubl conjugation pathway

    Protein family/group databases

    MEROPSiC19.054.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 28 (EC:3.4.19.12)
    Alternative name(s):
    Deubiquitinating enzyme 28
    Ubiquitin thioesterase 28
    Ubiquitin-specific-processing protease 28
    Gene namesi
    Name:USP28
    Synonyms:KIAA1515
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:12625. USP28.

    Subcellular locationi

    Nucleusnucleoplasm 1 Publication

    GO - Cellular componenti

    1. nucleolus Source: HPA
    2. nucleoplasm Source: UniProtKB
    3. nucleus Source: HPA
    4. protein complex Source: UniProtKB

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi171 – 1711C → A: Abolishes deubiquitinase activity. 2 Publications

    Organism-specific databases

    PharmGKBiPA37250.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10771077Ubiquitin carboxyl-terminal hydrolase 28PRO_0000080657Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei67 – 671Phosphoserine1 Publication
    Modified residuei714 – 7141Phosphoserine1 Publication

    Post-translational modificationi

    Degradaded upon nickel ion level or hypoxia exposure.
    Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ96RU2.
    PaxDbiQ96RU2.
    PRIDEiQ96RU2.

    PTM databases

    PhosphoSiteiQ96RU2.

    Expressioni

    Inductioni

    Down-regulated upon hypoxia.1 Publication

    Gene expression databases

    ArrayExpressiQ96RU2.
    BgeeiQ96RU2.
    CleanExiHS_USP28.
    GenevestigatoriQ96RU2.

    Organism-specific databases

    HPAiHPA006778.
    HPA006779.

    Interactioni

    Subunit structurei

    Interacts with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC.3 Publications

    Protein-protein interaction databases

    BioGridi121683. 46 interactions.
    IntActiQ96RU2. 5 interactions.
    MINTiMINT-8415329.
    STRINGi9606.ENSP00000003302.

    Structurei

    Secondary structure

    1
    1077
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi23 – 3210
    Helixi37 – 4610
    Turni47 – 493
    Helixi51 – 588
    Helixi60 – 634
    Helixi100 – 11112
    Helixi121 – 1233

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2LVANMR-A22-132[»]
    ProteinModelPortaliQ96RU2.
    SMRiQ96RU2. Positions 22-132, 161-389, 571-650.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati97 – 11620UIMAdd
    BLAST
    Domaini162 – 650489USPAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase C19 family. USP28 subfamily.Curated
    Contains 1 USP domain.Curated

    Phylogenomic databases

    eggNOGiCOG5077.
    HOGENOMiHOG000007956.
    HOVERGENiHBG056030.
    InParanoidiQ96RU2.
    KOiK11849.
    OMAiCIASTTQ.
    OrthoDBiEOG761BSZ.
    PhylomeDBiQ96RU2.
    TreeFamiTF329035.

    Family and domain databases

    InterProiIPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR009060. UBA-like.
    IPR003903. Ubiquitin-int_motif.
    IPR028889. UCH/PAN2.
    [Graphical view]
    PfamiPF00443. UCH. 1 hit.
    [Graphical view]
    SMARTiSM00726. UIM. 1 hit.
    [Graphical view]
    SUPFAMiSSF46934. SSF46934. 1 hit.
    PROSITEiPS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q96RU2-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD     50
    ITQAVSLLTD ERVKEPSQDT VATEPSEVEG SAANKEVLAK VIDLTHDNKD 100
    DLQAAIALSL LESPKIQADG RDLNRMHEAT SAETKRSKRK RCEVWGENPN 150
    PNDWRRVDGW PVGLKNVGNT CWFSAVIQSL FQLPEFRRLV LSYSLPQNVL 200
    ENCRSHTEKR NIMFMQELQY LFALMMGSNR KFVDPSAALD LLKGAFRSSE 250
    EQQQDVSEFT HKLLDWLEDA FQLAVNVNSP RNKSENPMVQ LFYGTFLTEG 300
    VREGKPFCNN ETFGQYPLQV NGYRNLDECL EGAMVEGDVE LLPSDHSVKY 350
    GQERWFTKLP PVLTFELSRF EFNQSLGQPE KIHNKLEFPQ IIYMDRYMYR 400
    SKELIRNKRE CIRKLKEEIK ILQQKLERYV KYGSGPARFP LPDMLKYVIE 450
    FASTKPASES CPPESDTHMT LPLSSVHCSV SDQTSKESTS TESSSQDVES 500
    TFSSPEDSLP KSKPLTSSRS SMEMPSQPAP RTVTDEEINF VKTCLQRWRS 550
    EIEQDIQDLK TCIASTTQTI EQMYCDPLLR QVPYRLHAVL VHEGQANAGH 600
    YWAYIYNQPR QSWLKYNDIS VTESSWEEVE RDSYGGLRNV SAYCLMYIND 650
    KLPYFNAEAA PTESDQMSEV EALSVELKHY IQEDNWRFEQ EVEEWEEEQS 700
    CKIPQMESST NSSSQDYSTS QEPSVASSHG VRCLSSEHAV IVKEQTAQAI 750
    ANTARAYEKS GVEAALSEVM LSPAMQGVIL AIAKARQTFD RDGSEAGLIK 800
    AFHEEYSRLY QLAKETPTSH SDPRLQHVLV YFFQNEAPKR VVERTLLEQF 850
    ADKNLSYDER SISIMKVAQA KLKEIGPDDM NMEEYKKWHE DYSLFRKVSV 900
    YLLTGLELYQ KGKYQEALSY LVYAYQSNAA LLMKGPRRGV KESVIALYRR 950
    KCLLELNAKA ASLFETNDDH SVTEGINVMN ELIIPCIHLI INNDISKDDL 1000
    DAIEVMRNHW CSYLGQDIAE NLQLCLGEFL PRLLDPSAEI IVLKEPPTIR 1050
    PNSPYDLCSR FAAVMESIQG VSTVTVK 1077
    Length:1,077
    Mass (Da):122,491
    Last modified:December 1, 2001 - v1
    Checksum:i799C758888C67B82
    GO
    Isoform 2 (identifier: Q96RU2-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         769-800: Missing.

    Show »
    Length:1,045
    Mass (Da):119,121
    Checksum:i1A10819BCF8CCBC6
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti289 – 30315VQLFY…EGVRE → IVIVMSFLKSLSLCL in BAA96039. 1 PublicationCuratedAdd
    BLAST

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei769 – 80032Missing in isoform 2. 1 PublicationVSP_015580Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF266283 mRNA. Translation: AAK58565.1.
    EF445045 Genomic DNA. Translation: ACA06098.1.
    EF445045 Genomic DNA. Translation: ACA06099.1.
    AP001874 Genomic DNA. No translation available.
    AP003170 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67232.1.
    AB040948 mRNA. Translation: BAA96039.1.
    CCDSiCCDS31680.1. [Q96RU2-1]
    RefSeqiNP_065937.1. NM_020886.2. [Q96RU2-1]
    XP_005271696.1. XM_005271639.2. [Q96RU2-2]
    UniGeneiHs.503891.

    Genome annotation databases

    EnsembliENST00000003302; ENSP00000003302; ENSG00000048028. [Q96RU2-1]
    GeneIDi57646.
    KEGGihsa:57646.
    UCSCiuc001poh.3. human. [Q96RU2-1]

    Polymorphism databases

    DMDMi20140700.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF266283 mRNA. Translation: AAK58565.1 .
    EF445045 Genomic DNA. Translation: ACA06098.1 .
    EF445045 Genomic DNA. Translation: ACA06099.1 .
    AP001874 Genomic DNA. No translation available.
    AP003170 Genomic DNA. No translation available.
    CH471065 Genomic DNA. Translation: EAW67232.1 .
    AB040948 mRNA. Translation: BAA96039.1 .
    CCDSi CCDS31680.1. [Q96RU2-1 ]
    RefSeqi NP_065937.1. NM_020886.2. [Q96RU2-1 ]
    XP_005271696.1. XM_005271639.2. [Q96RU2-2 ]
    UniGenei Hs.503891.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2LVA NMR - A 22-132 [» ]
    ProteinModelPortali Q96RU2.
    SMRi Q96RU2. Positions 22-132, 161-389, 571-650.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121683. 46 interactions.
    IntActi Q96RU2. 5 interactions.
    MINTi MINT-8415329.
    STRINGi 9606.ENSP00000003302.

    Chemistry

    ChEMBLi CHEMBL2157853.

    Protein family/group databases

    MEROPSi C19.054.

    PTM databases

    PhosphoSitei Q96RU2.

    Polymorphism databases

    DMDMi 20140700.

    Proteomic databases

    MaxQBi Q96RU2.
    PaxDbi Q96RU2.
    PRIDEi Q96RU2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000003302 ; ENSP00000003302 ; ENSG00000048028 . [Q96RU2-1 ]
    GeneIDi 57646.
    KEGGi hsa:57646.
    UCSCi uc001poh.3. human. [Q96RU2-1 ]

    Organism-specific databases

    CTDi 57646.
    GeneCardsi GC11M113668.
    HGNCi HGNC:12625. USP28.
    HPAi HPA006778.
    HPA006779.
    MIMi 610748. gene.
    neXtProti NX_Q96RU2.
    PharmGKBi PA37250.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5077.
    HOGENOMi HOG000007956.
    HOVERGENi HBG056030.
    InParanoidi Q96RU2.
    KOi K11849.
    OMAi CIASTTQ.
    OrthoDBi EOG761BSZ.
    PhylomeDBi Q96RU2.
    TreeFami TF329035.

    Miscellaneous databases

    GenomeRNAii 57646.
    NextBioi 64378.
    PROi Q96RU2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q96RU2.
    Bgeei Q96RU2.
    CleanExi HS_USP28.
    Genevestigatori Q96RU2.

    Family and domain databases

    InterProi IPR018200. Pept_C19ubi-hydrolase_C_CS.
    IPR001394. Peptidase_C19_UCH.
    IPR009060. UBA-like.
    IPR003903. Ubiquitin-int_motif.
    IPR028889. UCH/PAN2.
    [Graphical view ]
    Pfami PF00443. UCH. 1 hit.
    [Graphical view ]
    SMARTi SM00726. UIM. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46934. SSF46934. 1 hit.
    PROSITEi PS00972. USP_1. 1 hit.
    PS00973. USP_2. 1 hit.
    PS50235. USP_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25."
      Valero R., Bayes M., Francisca Sanchez-Font M., Gonzalez-Angulo O., Gonzalez-Duarte R., Marfany G.
      Genome Biol. 2:RESEARCH0043.1-RESEARCH0043.10(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. NHLBI resequencing and genotyping service (RS&G)
      Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
      Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
      DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 289-1077 (ISOFORM 2).
      Tissue: Brain.
    6. "A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response."
      Zhang D., Zaugg K., Mak T.W., Elledge S.J.
      Cell 126:529-542(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH TP53BP1, PHOSPHORYLATION AT SER-67 AND SER-714, MUTAGENESIS OF CYS-171.
    7. "Fbw7 and Usp28 regulate myc protein stability in response to DNA damage."
      Popov N., Herold S., Llamazares M., Schulein C., Eilers M.
      Cell Cycle 6:2327-2331(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH FBXW7.
    8. Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXW7, MUTAGENESIS OF CYS-171.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    10. "The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint."
      Bassermann F., Frescas D., Guardavaccaro D., Busino L., Peschiaroli A., Pagano M.
      Cell 134:256-267(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Mechanisms of c-myc degradation by nickel compounds and hypoxia."
      Li Q., Kluz T., Sun H., Costa M.
      PLoS ONE 4:E8531-E8531(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: DEGRADATION, INDUCTION.
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "NMR solution structure of the N-terminal domain of human USP28."
      Northeast structural genomics consortium (NESG)
      Submitted (JUL-2012) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 22-132.

    Entry informationi

    Entry nameiUBP28_HUMAN
    AccessioniPrimary (citable) accession number: Q96RU2
    Secondary accession number(s): B0YJC0, B0YJC1, Q9P213
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 27, 2002
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 122 of the entry and version 1 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

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. Peptidase families
      Classification of peptidase families and list of entries
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3