| Identification |
|---|
| HMDB Protein ID
| HMDBP11577 |
| Secondary Accession Numbers
| |
| Name
| Ubiquitin carboxyl-terminal hydrolase 28 |
| Synonyms
|
- Deubiquitinating enzyme 28
- Ubiquitin thiolesterase 28
- 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
|
- Nucleus
- 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
|
|
|
Transmembrane Regions
|
|
| 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
|
| External Links |
|---|
| 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
| - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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