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Q96RU2 (UBP28_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:USP28
Synonyms:KIAA1515
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1077 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 4of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus. Ref.6 Ref.7 Ref.8 Ref.10

Catalytic activity

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).

Subunit structure

Interacts with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC. Ref.6 Ref.7 Ref.8

Subcellular location

Nucleusnucleoplasm Ref.8.

Induction

Down-regulated upon hypoxia. Ref.11

Post-translational modification

Degradaded upon nickel ion level or hypoxia exposure.

Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR. Ref.6

Sequence similarities

Belongs to the peptidase C19 family. USP28 subfamily.

Contains 1 UIM (ubiquitin-interacting motif) repeat.

Contains 1 USP domain.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
Ubl conjugation pathway
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionHydrolase
Protease
Thiol protease
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage checkpoint

Inferred from mutant phenotype Ref.10. Source: UniProtKB

DNA repair

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from direct assay Ref.7. Source: UniProtKB

cellular response to UV

Inferred from direct assay Ref.7. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator

Inferred from direct assay Ref.6. Source: UniProtKB

protein deubiquitination

Inferred from direct assay Ref.6Ref.8Ref.10. Source: UniProtKB

response to ionizing radiation

Inferred from direct assay Ref.6. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentnucleolus

Inferred from direct assay. Source: HPA

nucleoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

nucleus

Inferred from direct assay. Source: HPA

protein complex

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionprotein binding

Inferred from physical interaction Ref.6Ref.8Ref.7. Source: UniProtKB

ubiquitin thiolesterase activity

Inferred from mutant phenotype Ref.6Ref.8. Source: UniProtKB

ubiquitin-specific protease activity

Inferred from direct assay Ref.6Ref.8. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96RU2-1)

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.
Isoform 2 (identifier: Q96RU2-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10771077Ubiquitin carboxyl-terminal hydrolase 28
PRO_0000080657

Regions

Repeat97 – 11620UIM
Domain162 – 650489USP

Sites

Active site1711Nucleophile
Active site6001Proton acceptor By similarity

Amino acid modifications

Modified residue671Phosphoserine Ref.6
Modified residue7141Phosphoserine Ref.6

Natural variations

Alternative sequence769 – 80032Missing in isoform 2.
VSP_015580

Experimental info

Mutagenesis1711C → A: Abolishes deubiquitinase activity. Ref.6 Ref.8
Sequence conflict289 – 30315VQLFY…EGVRE → IVIVMSFLKSLSLCL in BAA96039. Ref.4

Secondary structure

.............. 1077
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 799C758888C67B82

FASTA1,077122,491
        10         20         30         40         50         60 
MTAELQQDDA AGAADGHGSS CQMLLNQLRE ITGIQDPSFL HEALKASNGD ITQAVSLLTD 

        70         80         90        100        110        120 
ERVKEPSQDT VATEPSEVEG SAANKEVLAK VIDLTHDNKD DLQAAIALSL LESPKIQADG 

       130        140        150        160        170        180 
RDLNRMHEAT SAETKRSKRK RCEVWGENPN PNDWRRVDGW PVGLKNVGNT CWFSAVIQSL 

       190        200        210        220        230        240 
FQLPEFRRLV LSYSLPQNVL ENCRSHTEKR NIMFMQELQY LFALMMGSNR KFVDPSAALD 

       250        260        270        280        290        300 
LLKGAFRSSE EQQQDVSEFT HKLLDWLEDA FQLAVNVNSP RNKSENPMVQ LFYGTFLTEG 

       310        320        330        340        350        360 
VREGKPFCNN ETFGQYPLQV NGYRNLDECL EGAMVEGDVE LLPSDHSVKY GQERWFTKLP 

       370        380        390        400        410        420 
PVLTFELSRF EFNQSLGQPE KIHNKLEFPQ IIYMDRYMYR SKELIRNKRE CIRKLKEEIK 

       430        440        450        460        470        480 
ILQQKLERYV KYGSGPARFP LPDMLKYVIE FASTKPASES CPPESDTHMT LPLSSVHCSV 

       490        500        510        520        530        540 
SDQTSKESTS TESSSQDVES TFSSPEDSLP KSKPLTSSRS SMEMPSQPAP RTVTDEEINF 

       550        560        570        580        590        600 
VKTCLQRWRS EIEQDIQDLK TCIASTTQTI EQMYCDPLLR QVPYRLHAVL VHEGQANAGH 

       610        620        630        640        650        660 
YWAYIYNQPR QSWLKYNDIS VTESSWEEVE RDSYGGLRNV SAYCLMYIND KLPYFNAEAA 

       670        680        690        700        710        720 
PTESDQMSEV EALSVELKHY IQEDNWRFEQ EVEEWEEEQS CKIPQMESST NSSSQDYSTS 

       730        740        750        760        770        780 
QEPSVASSHG VRCLSSEHAV IVKEQTAQAI ANTARAYEKS GVEAALSEVM LSPAMQGVIL 

       790        800        810        820        830        840 
AIAKARQTFD RDGSEAGLIK AFHEEYSRLY QLAKETPTSH SDPRLQHVLV YFFQNEAPKR 

       850        860        870        880        890        900 
VVERTLLEQF ADKNLSYDER SISIMKVAQA KLKEIGPDDM NMEEYKKWHE DYSLFRKVSV 

       910        920        930        940        950        960 
YLLTGLELYQ KGKYQEALSY LVYAYQSNAA LLMKGPRRGV KESVIALYRR KCLLELNAKA 

       970        980        990       1000       1010       1020 
ASLFETNDDH SVTEGINVMN ELIIPCIHLI INNDISKDDL DAIEVMRNHW CSYLGQDIAE 

      1030       1040       1050       1060       1070 
NLQLCLGEFL PRLLDPSAEI IVLKEPPTIR PNSPYDLCSR FAAVMESIQG VSTVTVK 

« Hide

Isoform 2 [UniParc].

Checksum: 1A10819BCF8CCBC6
Show »

FASTA1,045119,121

References

« Hide 'large scale' references
[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]"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. expand/collapse author list , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"The ubiquitin-specific protease USP28 is required for MYC stability."
Popov N., Wanzel M., Madiredjo M., Zhang D., Beijersbergen R., Bernards R., Moll R., Elledge S.J., Eilers M.
Nat. Cell Biol. 9:765-774(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FBXW7, MUTAGENESIS OF CYS-171.
[9]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS31680.1. [Q96RU2-1]
RefSeqNP_065937.1. NM_020886.2. [Q96RU2-1]
XP_005271696.1. XM_005271639.2. [Q96RU2-2]
UniGeneHs.503891.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2LVANMR-A22-132[»]
ProteinModelPortalQ96RU2.
SMRQ96RU2. Positions 22-132, 161-389, 571-650.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121683. 46 interactions.
IntActQ96RU2. 5 interactions.
MINTMINT-8415329.
STRING9606.ENSP00000003302.

Chemistry

ChEMBLCHEMBL2157853.

Protein family/group databases

MEROPSC19.054.

PTM databases

PhosphoSiteQ96RU2.

Polymorphism databases

DMDM20140700.

Proteomic databases

MaxQBQ96RU2.
PaxDbQ96RU2.
PRIDEQ96RU2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000003302; ENSP00000003302; ENSG00000048028. [Q96RU2-1]
ENST00000260188; ENSP00000260188; ENSG00000048028. [Q96RU2-2]
GeneID57646.
KEGGhsa:57646.
UCSCuc001poh.3. human. [Q96RU2-1]

Organism-specific databases

CTD57646.
GeneCardsGC11M113668.
HGNCHGNC:12625. USP28.
HPAHPA006778.
HPA006779.
MIM610748. gene.
neXtProtNX_Q96RU2.
PharmGKBPA37250.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5077.
HOGENOMHOG000007956.
HOVERGENHBG056030.
InParanoidQ96RU2.
KOK11849.
OMACIASTTQ.
OrthoDBEOG761BSZ.
PhylomeDBQ96RU2.
TreeFamTF329035.

Gene expression databases

ArrayExpressQ96RU2.
BgeeQ96RU2.
CleanExHS_USP28.
GenevestigatorQ96RU2.

Family and domain databases

InterProIPR018200. Pept_C19ubi-hydrolase_C_CS.
IPR001394. Peptidase_C19_UCH.
IPR009060. UBA-like.
IPR003903. Ubiquitin-int_motif.
IPR028889. UCH/PAN2.
[Graphical view]
PfamPF00443. UCH. 1 hit.
[Graphical view]
SMARTSM00726. UIM. 1 hit.
[Graphical view]
SUPFAMSSF46934. SSF46934. 1 hit.
PROSITEPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi57646.
NextBio64378.
PROQ96RU2.
SOURCESearch...

Entry information

Entry nameUBP28_HUMAN
AccessionPrimary (citable) accession number: Q96RU2
Secondary accession number(s): B0YJC0, B0YJC1, Q9P213
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM