Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP11577
Secondary Accession Numbers
  • 21021
Name Ubiquitin carboxyl-terminal hydrolase 28
Synonyms
  1. Deubiquitinating enzyme 28
  2. Ubiquitin thiolesterase 28
  3. Ubiquitin-specific-processing protease 28
Gene Name USP28
Protein Type Enzyme
Biological Properties
General Function Involved in ubiquitin thiolesterase activity
Specific 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 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus
Pathways Not Available
Reactions Not Available
GO Classification
Function
hydrolase activity, acting on ester bonds
catalytic activity
hydrolase activity
ubiquitin thiolesterase activity
thiolester hydrolase activity
Process
metabolic process
catabolic process
macromolecule catabolic process
cellular macromolecule catabolic process
modification-dependent macromolecule catabolic process
modification-dependent protein catabolic process
ubiquitin-dependent protein catabolic process
Cellular Location
  1. Nucleus
  2. nucleoplasm
Gene Properties
Chromosome Location Chromosome:1
Locus 11q23
SNPs USP28
Gene Sequence
>3234 bp
ATGACTGCGGAGCTGCAGCAGGACGACGCGGCCGGCGCGGCAGACGGCCACGGCTCGAGC
TGCCAAATGCTGTTAAATCAACTGAGAGAAATCACAGGCATTCAGGACCCTTCCTTTCTC
CATGAAGCTCTGAAGGCCAGTAATGGTGACATTACTCAGGCAGTCAGCCTTCTCACTGAT
GAGAGAGTTAAGGAGCCCAGTCAAGACACTGTTGCTACAGAACCATCTGAAGTAGAGGGG
AGTGCTGCCAACAAGGAAGTATTAGCAAAAGTTATAGACCTTACTCATGATAACAAAGAT
GATCTTCAGGCTGCCATTGCTTTGAGTCTACTGGAGTCTCCCAAAATTCAAGCTGATGGA
AGAGATCTTAACAGGATGCATGAAGCAACCTCTGCAGAAACTAAACGCTCAAAGAGAAAA
CGCTGTGAAGTCTGGGGAGAAAACCCCAATCCCAATGACTGGAGGAGAGTTGATGGTTGG
CCAGTTGGGCTGAAAAATGTTGGCAATACATGTTGGTTTAGTGCTGTTATTCAGTCTCTC
TTTCAATTGCCTGAATTTCGAAGACTTGTTCTCAGTTATAGTCTGCCACAAAATGTACTT
GAAAATTGTCGAAGTCATACAGAAAAGAGAAATATCATGTTTATGCAAGAGCTTCAGTAT
TTGTTTGCTCTAATGATGGGATCAAATAGAAAATTTGTAGACCCGTCTGCAGCCCTGGAT
CTATTAAAGGGAGCATTCCGATCATCTGAGGAACAGCAGCAAGATGTGAGTGAATTCACA
CACAAGCTCCTGGATTGGCTAGAGGACGCATTCCAGCTAGCTGTTAATGTTAACAGTCCC
AGGAACAAATCTGAAAATCCAATGGTGCAGCTGTTCTATGGTACTTTCCTGACTGAAGGG
GTTCGTGAAGGAAAACCCTTTTGTAACAATGAGACCTTCGGCCAGTATCCTCTTCAGGTA
AACGGTTATCGCAACTTAGACGAGTGTTTGGAAGGGGCCATGGTGGAGGGTGATGTTGAG
CTTCTTCCCTCCGATCACTCGGTGAAGTATGGACAAGAGCGTTGGTTTACAAAGCTACCT
CCAGTGTTGACCTTTGAACTCTCAAGATTTGAGTTTAATCAGTCCCTTGGGCAGCCAGAG
AAAATTCACAATAAGCTGGAATTTCCTCAGATTATTTATATGGACAGGTACATGTACAGG
AGCAAGGAGCTTATTCGAAATAAGAGAGAGTGTATTCGAAAGTTGAAGGAGGAAATAAAA
ATTCTGCAGCAAAAATTGGAAAGGTATGTGAAATATGGCTCAGGCCCAGCTCGGTTCCCG
CTCCCGGACATGCTGAAATATGTTATTGAATTTGCTAGTACAAAACCTGCCTCAGAAAGC
TGTCCACCTGAAAGTGACACACATATGACATTACCACTTTCTTCAGTGCACTGCTCGGTT
TCTGACCAGACATCCAAGGAAAGTACAAGTACAGAAAGCTCTTCTCAGGATGTTGAAAGT
ACCTTTTCTTCTCCTGAAGATTCTTTACCCAAGTCTAAACCACTGACATCTTCTCGGTCT
TCCATGGAAATGCCTTCACAGCCAGCTCCACGAACAGTCACAGATGAGGAGATAAATTTT
GTTAAGACCTGTCTTCAGAGATGGAGGAGTGAGATTGAACAAGATATACAAGATTTAAAG
ACTTGTATTGCAAGTACTACTCAGACTATTGAACAGATGTACTGCGATCCTCTCCTTCGT
CAGGTGCCTTATCGCTTGCATGCAGTTCTTGTTCATGAAGGACAAGCAAATGCTGGACAC
TATTGGGCCTATATCTATAATCAACCCCGACAGAGCTGGCTCAAGTACAATGACATCTCT
GTTACTGAATCTTCCTGGGAAGAAGTTGAAAGAGATTCCTATGGAGGCCTGAGAAATGTT
AGTGCTTACTGTCTGATGTACATTAATGACAAACTACCCTACTTCAATGCAGAGGCAGCC
CCAACTGAATCAGATCAAATGTCAGAAGTGGAAGCCCTATCTGTGGAACTCAAGCATTAC
ATTCAGGAGGATAACTGGCGGTTTGAGCAGGAAGTAGAGGAGTGGGAAGAAGAGCAGTCT
TGCAAAATCCCTCAAATGGAGTCCTCCACCAACTCCTCATCACAGGACTACTCTACATCA
CAAGAGCCTTCAGTAGCCTCTTCTCATGGGGTTCGCTGCTTGTCGTCTGAGCATGCTGTG
ATTGTAAAGGAGCAAACTGCCCAGGCTATTGCAAACACAGCCCGTGCCTATGAGAAGAGC
GGTGTAGAAGCGGCACTGAGTGAGGTGATGCTGAGCCCTGCCATGCAAGGGGTCATCCTG
GCCATAGCTAAAGCCCGTCAGACCTTTGACCGAGATGGGTCTGAAGCAGGGCTGATTAAG
GCATTCCATGAAGAATACTCCAGGCTCTATCAGCTTGCCAAAGAGACCCCCACCTCTCAC
AGTGATCCTCGACTTCAGCATGTCCTTGTCTACTTTTTCCAAAATGAAGCACCCAAAAGG
GTAGTAGAACGAACCCTTCTGGAACAGTTTGCAGATAAAAATCTTAGCTATGATGAAAGA
TCAATCAGCATTATGAAGGTGGCTCAAGCGAAACTGAAGGAAATTGGTCCAGATGACATG
AATATGGAAGAGTACAAGAAGTGGCATGAAGATTATAGTTTGTTCCGAAAAGTGTCTGTG
TATCTCCTAACAGGCCTAGAACTCTATCAAAAAGGAAAGTACCAAGAGGCACTTTCCTAC
CTGGTATATGCCTACCAGAGCAATGCTGCCCTGCTGATGAAGGGGCCCCGCCGGGGGGTC
AAAGAATCCGTGATTGCTTTATACCGAAGAAAATGCCTTCTGGAGCTGAATGCCAAAGCA
GCTTCTCTTTTTGAAACAAATGATGATCACTCCGTAACTGAGGGCATTAATGTGATGAAT
GAACTGATCATCCCCTGCATTCACCTTATCATTAATAATGACATTTCCAAGGATGATCTG
GATGCCATTGAGGTCATGAGAAACCATTGGTGCTCTTACCTTGGGCAAGATATTGCAGAA
AATCTGCAGCTGTGCCTAGGGGAGTTTCTACCCAGACTTCTAGATCCTTCTGCAGAAATC
ATCGTCTTGAAAGAGCCTCCAACTATTCGACCCAATTCTCCCTATGACCTATGTAGCCGA
TTTGCAGCTGTCATGGAGTCAATTCAGGGAGTTTCAACTGTGACAGTGAAATAA
Protein Properties
Number of Residues 1077
Molecular Weight 122490.0
Theoretical pI 4.84
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence
>Ubiquitin carboxyl-terminal hydrolase 28
MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLTD
ERVKEPSQDTVATEPSEVEGSAANKEVLAKVIDLTHDNKDDLQAAIALSLLESPKIQADG
RDLNRMHEATSAETKRSKRKRCEVWGENPNPNDWRRVDGWPVGLKNVGNTCWFSAVIQSL
FQLPEFRRLVLSYSLPQNVLENCRSHTEKRNIMFMQELQYLFALMMGSNRKFVDPSAALD
LLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEG
VREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLP
PVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIK
ILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSV
SDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINF
VKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGH
YWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINDKLPYFNAEAA
PTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSTNSSSQDYSTS
QEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEVMLSPAMQGVIL
AIAKARQTFDRDGSEAGLIKAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKR
VVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKKWHEDYSLFRKVSV
YLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKA
ASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAE
NLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVK
GenBank ID Protein 16507200
UniProtKB/Swiss-Prot ID Q96RU2
UniProtKB/Swiss-Prot Entry Name UBP28_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_020886.2
GeneCard ID USP28
GenAtlas ID USP28
HGNC ID HGNC:12625
References
General References
  1. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ: ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science. 2007 May 25;316(5828):1160-6. [PubMed:17525332 ]
  2. Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y: Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature. 2006 Mar 23;440(7083):497-500. [PubMed:16554811 ]
  3. Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O: 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. DNA Res. 2000 Apr 28;7(2):143-50. [PubMed:10819331 ]
  4. Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A, Pagano M: The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell. 2008 Jul 25;134(2):256-67. doi: 10.1016/j.cell.2008.05.043. [PubMed:18662541 ]
  5. Popov N, Herold S, Llamazares M, Schulein C, Eilers M: Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. Cell Cycle. 2007 Oct 1;6(19):2327-31. Epub 2007 Jul 26. [PubMed:17873522 ]
  6. Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R, Bernards R, Moll R, Elledge SJ, Eilers M: The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007 Jul;9(7):765-74. Epub 2007 Jun 10. [PubMed:17558397 ]
  7. Valero R, Bayes M, Francisca Sanchez-Font M, Gonzalez-Angulo O, Gonzalez-Duarte R, Marfany G: Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25. Genome Biol. 2001;2(10):RESEARCH0043. Epub 2001 Sep 13. [PubMed:11597335 ]
  8. Zhang D, Zaugg K, Mak TW, Elledge SJ: A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response. Cell. 2006 Aug 11;126(3):529-42. [PubMed:16901786 ]
  9. Li Q, Kluz T, Sun H, Costa M: Mechanisms of c-myc degradation by nickel compounds and hypoxia. PLoS One. 2009 Dec 31;4(12):e8531. doi: 10.1371/journal.pone.0008531. [PubMed:20046830 ]