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Aliases for USP28 Gene

Aliases for USP28 Gene

  • Ubiquitin Specific Peptidase 28 2 3 5
  • Ubiquitin-Specific-Processing Protease 28 4
  • Ubiquitin Specific Protease 28 2
  • Deubiquitinating Enzyme 28 4
  • Ubiquitin Thioesterase 28 4
  • EC 3.4.19.12 4
  • EC 3.1.2.15 61
  • KIAA1515 4

External Ids for USP28 Gene

Previous GeneCards Identifiers for USP28 Gene

  • GC11M116021
  • GC11M115180
  • GC11M113702
  • GC11M113206
  • GC11M113173
  • GC11M109597
  • GC11M113668

Summaries for USP28 Gene

Entrez Gene Summary for USP28 Gene

  • The protein encoded by this gene is a deubiquitinase involved in the DNA damage pathway and DNA damage-induced apoptosis. Overexpression of this gene is seen in several cancers. [provided by RefSeq, Oct 2016]

GeneCards Summary for USP28 Gene

USP28 (Ubiquitin Specific Peptidase 28) is a Protein Coding gene. Among its related pathways are Deubiquitination and Ubiquitin-Proteasome Dependent Proteolysis. GO annotations related to this gene include cysteine-type endopeptidase activity and thiol-dependent ubiquitin-specific protease activity. An important paralog of this gene is USP25.

UniProtKB/Swiss-Prot for USP28 Gene

  • 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. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306).

No data available for CIViC summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for USP28 Gene

Genomics for USP28 Gene

Regulatory Elements for USP28 Gene

Enhancers for USP28 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH11G113905 1 ENCODE 11.5 -30.9 -30901 1.7 PKNOX1 FOXA2 ARNT FEZF1 ZNF2 FOS TSHZ1 MIER2 ZSCAN16 GLIS1 USP28 ENSG00000270179 HTR3A RNU6-1107P HTR3B
GH11G113872 1.1 ENCODE 10 +0.6 627 4.5 PKNOX1 MLX ARNT ZFP64 SIN3A FEZF1 DMAP1 ZNF2 YY1 ZNF766 RBM7 USP28 LRRC37A13P GC11M113865
GH11G113847 0.9 ENCODE dbSUPER 11.4 +25.9 25932 3.8 ZNF146 CBX3 REST CHD7 ZBTB40 ZNF316 POLR2A SCRT2 POU5F1 KDM1A ATF4P4 USP28 HTR3A LRRC37A13P DRD2 GC11P113860 LOC100421976
GH11G114031 0.5 FANTOM5 10.7 -156.1 -156063 0.1 PKNOX1 FOXA2 HLF FOXA1 NNMT CLDN25 USP28 GC11P114027 GC11P114056
GH11G114774 0.8 dbSUPER 4.4 -903.4 -903449 8.2 CTCF RB1 FEZF1 ZIC2 RAD21 CTBP1 GATA3 ZNF366 SMC3 PRDM10 USP28 GC11M114726 LOC105369505
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around USP28 on UCSC Golden Path with GeneCards custom track

Promoters for USP28 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000045174 170 2001 PKNOX1 MLX ARNT ZFP64 SIN3A DMAP1 ZNF2 YY1 ZNF766 ZNF143

Genomic Location for USP28 Gene

Chromosome:
11
Start:
113,797,874 bp from pter
End:
113,875,570 bp from pter
Size:
77,697 bases
Orientation:
Minus strand

Genomic View for USP28 Gene

Genes around USP28 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP28 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP28 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP28 Gene

Proteins for USP28 Gene

  • Protein details for USP28 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96RU2-UBP28_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 28
    Protein Accession:
    Q96RU2
    Secondary Accessions:
    • B0YJC0
    • B0YJC1
    • Q6NZX9
    • Q9P213

    Protein attributes for USP28 Gene

    Size:
    1077 amino acids
    Molecular mass:
    122491 Da
    Quaternary structure:
    • Interacts with ZNF304 (PubMed:24623306). Interacts with PRKD1 (PubMed:24623306). Interacts with TP53BP1 (PubMed:16901786). Interacts with isoform 1 of FBXW7; following DNA damage, dissociates from FBXW7 leading to degradation of MYC (PubMed:17873522, PubMed:17558397) (PubMed:17873522).

    Three dimensional structures from OCA and Proteopedia for USP28 Gene

    Alternative splice isoforms for USP28 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP28 Gene

Selected DME Specific Peptides for USP28 Gene

Q96RU2:
  • LQYLFAL
  • QQQDVSEFTHKLLDWLEDAFQ
  • LHAVLVH
  • FGQYPLQVNG
  • LPPVLTFELSRFEFNQ

Post-translational modifications for USP28 Gene

  • Degradaded upon nickel ion level or hypoxia exposure.
  • Phosphorylated upon DNA damage at Ser-67 and Ser-714, by ATM or ATR (PubMed:16901786). Phosphorylated by PRKD1 (PubMed:24623306).
  • Ubiquitination at isoforms=2, 3243
  • Modification sites at PhosphoSitePlus

Domains & Families for USP28 Gene

Gene Families for USP28 Gene

Suggested Antigen Peptide Sequences for USP28 Gene

Graphical View of Domain Structure for InterPro Entry

Q96RU2

UniProtKB/Swiss-Prot:

UBP28_HUMAN :
  • Belongs to the peptidase C19 family. USP28 subfamily.
Family:
  • Belongs to the peptidase C19 family. USP28 subfamily.
genes like me logo Genes that share domains with USP28: view

Function for USP28 Gene

Molecular function for USP28 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
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).
UniProtKB/Swiss-Prot 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. Deubiquitinates ZNF304, hence preventing ZNF304 degradation by the proteasome and leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) in a subset of colorectal cancers (CRC) cells (PubMed:24623306).
UniProtKB/Swiss-Prot Induction:
Down-regulated upon hypoxia (PubMed:20046830). Up-regulated by the transcription factor c-Jun/JUN in a KRAS-dependent manner in colorectal cancer (CRC) cells (PubMed:24623306).

Enzyme Numbers (IUBMB) for USP28 Gene

Gene Ontology (GO) - Molecular Function for USP28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA 16901786
GO:0005515 protein binding IPI 16901786
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with USP28: view
genes like me logo Genes that share phenotypes with USP28: view

Animal Model Products

  • Taconic Biosciences Mouse Models for USP28

CRISPR Products

Inhibitory RNA Products

No data available for Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for USP28 Gene

Localization for USP28 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP28 Gene

Nucleus, nucleoplasm.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for USP28 gene
Compartment Confidence
nucleus 5
cytosol 2

Gene Ontology (GO) - Cellular Components for USP28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0016604 nuclear body IDA --
GO:0043234 protein complex IDA 17873522
genes like me logo Genes that share ontologies with USP28: view

Pathways & Interactions for USP28 Gene

genes like me logo Genes that share pathways with USP28: view

Pathways by source for USP28 Gene

SIGNOR curated interactions for USP28 Gene

Activates:

Gene Ontology (GO) - Biological Process for USP28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000077 DNA damage checkpoint IMP 18662541
GO:0006281 DNA repair IEA --
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0006974 cellular response to DNA damage stimulus IEA,IDA 17873522
genes like me logo Genes that share ontologies with USP28: view

Drugs & Compounds for USP28 Gene

(1) Drugs for USP28 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Water Approved Pharma 0
genes like me logo Genes that share compounds with USP28: view

Transcripts for USP28 Gene

Unigene Clusters for USP28 Gene

Ubiquitin specific peptidase 28:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Alternative Splicing Database (ASD) splice patterns (SP) for USP28 Gene

ExUns: 1a · 1b · 1c ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19a ·
SP1: - - - - - -
SP2: - - - - - - - -
SP3: - - - - -
SP4: - -
SP5: - - -
SP6: -
SP7:

ExUns: 19b ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25 ^ 26 ^ 27 ^ 28a · 28b · 28c
SP1:
SP2: -
SP3:
SP4: -
SP5:
SP6:
SP7:

Relevant External Links for USP28 Gene

GeneLoc Exon Structure for
USP28
ECgene alternative splicing isoforms for
USP28

Expression for USP28 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for USP28 Gene

mRNA differential expression in normal tissues according to GTEx for USP28 Gene

This gene is overexpressed in Heart - Left Ventricle (x5.6), Muscle - Skeletal (x5.0), and Heart - Atrial Appendage (x4.1).

Protein differential expression in normal tissues from HIPED for USP28 Gene

This gene is overexpressed in Bone (35.2) and Fetal heart (14.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for USP28 Gene



Protein tissue co-expression partners for USP28 Gene

NURSA nuclear receptor signaling pathways regulating expression of USP28 Gene:

USP28

SOURCE GeneReport for Unigene cluster for USP28 Gene:

Hs.503891

Evidence on tissue expression from TISSUES for USP28 Gene

  • Nervous system(4.3)
  • Liver(4.2)
  • Eye(4)
  • Muscle(2.2)
genes like me logo Genes that share expression patterns with USP28: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP28 Gene

Orthologs for USP28 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for USP28 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia USP28 34 35
  • 98.67 (n)
dog
(Canis familiaris)
Mammalia USP28 34 35
  • 90.72 (n)
cow
(Bos Taurus)
Mammalia USP28 34 35
  • 90.71 (n)
rat
(Rattus norvegicus)
Mammalia Usp28 34
  • 87.79 (n)
mouse
(Mus musculus)
Mammalia Usp28 34 16 35
  • 87.02 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia USP28 35
  • 68 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia USP28 35
  • 47 (a)
OneToOne
chicken
(Gallus gallus)
Aves USP28 34 35
  • 69.09 (n)
lizard
(Anolis carolinensis)
Reptilia USP28 35
  • 58 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia usp28 34
  • 63.75 (n)
Str.12044 34
zebrafish
(Danio rerio)
Actinopterygii usp28 34 35
  • 61.73 (n)
worm
(Caenorhabditis elegans)
Secernentea K02C4.3 35
  • 17 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP2 37
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 37 (a)
OneToMany
Species where no ortholog for USP28 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for USP28 Gene

ENSEMBL:
Gene Tree for USP28 (if available)
TreeFam:
Gene Tree for USP28 (if available)

Paralogs for USP28 Gene

Paralogs for USP28 Gene

genes like me logo Genes that share paralogs with USP28: view

Variants for USP28 Gene

Sequence variations from dbSNP and Humsavar for USP28 Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type
rs193920846 Uncertain significance 113,834,299(-) TTGTT(C/T)TCAGT reference, missense, utr-variant-5-prime
rs1000009709 -- 113,871,101(+) ATTGG(C/G)AGTGT intron-variant
rs1000023270 -- 113,840,844(+) GTGGA(C/T)AATTC intron-variant
rs1000044947 -- 113,822,790(+) TCACA(A/G)TACAT intron-variant
rs1000070362 -- 113,797,991(+) CAGAA(G/T)CCTTT utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for USP28 Gene

Variant ID Type Subtype PubMed ID
esv2761711 CNV gain 21179565
esv3627781 CNV loss 21293372
nsv497 CNV insertion 18451855
nsv832273 CNV loss 17160897

Variation tolerance for USP28 Gene

Residual Variation Intolerance Score: 3.28% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.89; 35.30% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for USP28 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP28

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for USP28 Gene

Disorders for USP28 Gene

Relevant External Links for USP28

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
USP28

No disorders were found for USP28 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for USP28 Gene

Publications for USP28 Gene

  1. Characterization of alternatively spliced products and tissue- specific isoforms of USP28 and USP25. (PMID: 11597335) Valero R. … Marfany G. (Genome Biol. 2001) 2 3 4 22 64
  2. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. (PMID: 24623306) Serra R.W. … Green M.R. (Elife 2014) 3 4 64
  3. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. (PMID: 18662541) Bassermann F. … Pagano M. (Cell 2008) 3 4 64
  4. The ubiquitin-specific protease USP28 is required for MYC stability. (PMID: 17558397) Popov N. … Eilers M. (Nat. Cell Biol. 2007) 3 4 64
  5. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. (PMID: 17873522) Popov N. … Eilers M. (Cell Cycle 2007) 3 4 64

Products for USP28 Gene

  • Addgene plasmids for USP28

Sources for USP28 Gene

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