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] See more...

Aliases for USP28 Gene

Aliases for USP28 Gene

  • Ubiquitin Specific Peptidase 28 2 3 5
  • Ubiquitin-Specific-Processing Protease 28 3 4
  • Ubiquitin Carboxyl-Terminal Hydrolase 28 3 4
  • Deubiquitinating Enzyme 28 3 4
  • Ubiquitin Thioesterase 28 3 4
  • Ubiquitin Carboxyl-Terminal Hydrolase 28 Variant 1 3
  • Ubiquitin Specific Protease 28 2
  • Ubiquitin Thiolesterase 28 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 52
  • 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. Diseases associated with USP28 include Colorectal Cancer. Among its related pathways are Metabolism of proteins and Ubiquitin-Proteasome Dependent Proteolysis. Gene Ontology (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 Summary 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).

Additional gene information for USP28 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP28 Gene

Genomics for USP28 Gene

GeneHancer (GH) Regulatory Elements for USP28 Gene

Promoters and enhancers for USP28 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J113872 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 509.9 +0.8 769 4.8 EP300 NRF1 USF1 POLR2G GTF2E2 PHF8 FOS ZFX ZIC2 POLR2A USP28 lnc-HTR3B-3 LRRC37A13P RF00066-041 lnc-USP28-3
GH11J113905 Enhancer 1.1 Ensembl ENCODE 11.5 -30.9 -30901 1.7 CTCF ZSCAN5C ZNF639 ZNF10 FOXA1 KDM6A ZNF423 TRIM28 ZNF510 ZEB1 USP28 ENSG00000270179 HTR3A RNU6-1107P HTR3B piR-38351-088
GH11J113847 Enhancer 1 Ensembl ENCODE dbSUPER 11.4 +26.4 26407 4.7 USF1 MEF2C POLR2A HDAC2 NANOG MEF2B TCF12 ZNF146 MITF JUND LRRC37A13P ATF4P4 USP28 HTR3A DRD2 RF00026-204 RNU6-1107P LOC100421976 lnc-USP28-3
GH11J113854 Enhancer 1 Ensembl ENCODE dbSUPER 8.7 +16.3 16269 9.8 USF1 TCF7 CREB1 FOXA2 ZBTB17 MAFF MAFK ZFHX2 PRDM6 KDM1A RNU6-1107P RF00026-204 ATF4P4 NNMT HTR3A USP28 LRRC37A13P DRD2 lnc-USP28-3 LOC100421976
GH11J114031 Enhancer 0.6 FANTOM5 Ensembl 10.7 -156.9 -156931 2.2 FOXA2 FOXA1 PKNOX1 EZH2 HLF NNMT CLDN25 USP28 lnc-USP28-2 FJ601666-017
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around USP28 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP28

Top Transcription factor binding sites by QIAGEN in the USP28 gene promoter:
  • c-Myc
  • GATA-1
  • LCR-F1
  • Max1
  • N-Myc
  • Nkx2-5
  • p53
  • S8
  • USF-1
  • USF1

Genomic Locations for USP28 Gene

Genomic Locations for USP28 Gene
chr11:113,797,874-113,875,570
(GRCh38/hg38)
Size:
77,697 bases
Orientation:
Minus strand
chr11:113,668,596-113,746,292
(GRCh37/hg19)
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).

    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

  • Degraded 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 Lys243
  • Modification sites at PhosphoSitePlus

Domains & Families for USP28 Gene

Gene Families for USP28 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for USP28 Gene

Blocks:
  • Ubiquitin interacting motif
  • Ubiquitin thiolesterase, family 2
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for USP28 Gene

GenScript: Design optimal peptide antigens:
  • Ubiquitin carboxyl-terminal hydrolase (B4E3L3_HUMAN)
  • Ubiquitin-specific-processing protease 28 (UBP28_HUMAN)

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 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 CatalyticActivity:
Reaction=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).; EC=3.4.19.12;.
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

Phenotypes From GWAS Catalog for USP28 Gene

Gene Ontology (GO) - Molecular Function for USP28 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity IBA 21873635
GO:0004843 thiol-dependent ubiquitin-specific protease activity IDA,IBA 16901786
GO:0005515 protein binding IEA,IPI 16901786
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase 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

Clone Products

  • Addgene plasmids for USP28

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
cytoskeleton 2
cytosol 2
plasma membrane 1
extracellular 1
mitochondrion 1
endoplasmic reticulum 1
endosome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear bodies (3)
  • Nucleoplasm (3)
See all subcellular structures

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:0032991 protein-containing complex IDA 17873522
genes like me logo Genes that share ontologies with USP28: view

Pathways & Interactions for USP28 Gene

PathCards logo

SuperPathways for USP28 Gene

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

Pathways by source for USP28 Gene

1 Qiagen pathway for USP28 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis

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 IDA,IEA 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

mRNA/cDNA for USP28 Gene

22 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
15 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for USP28

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

Expression for USP28 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and 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, MaxQB, and MOPED for USP28 Gene



Protein tissue co-expression partners for USP28 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for 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

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 31 30
  • 98.67 (n)
OneToOne
dog
(Canis familiaris)
Mammalia USP28 31 30
  • 90.72 (n)
OneToOne
cow
(Bos Taurus)
Mammalia USP28 31 30
  • 90.71 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Usp28 30
  • 87.79 (n)
mouse
(Mus musculus)
Mammalia Usp28 17 31 30
  • 87.02 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia USP28 31
  • 68 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia USP28 31
  • 47 (a)
OneToOne
chicken
(Gallus gallus)
Aves USP28 31 30
  • 69.09 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia USP28 31
  • 58 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia usp28 30
  • 63.75 (n)
Str.12044 30
zebrafish
(Danio rerio)
Actinopterygii usp28 31 30
  • 61.73 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea K02C4.3 31
  • 17 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP2 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 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)
Aminode:
Evolutionary constrained regions (ECRs) for USP28: view image

Paralogs for USP28 Gene

(1) SIMAP similar genes for USP28 Gene using alignment to 14 proteins:

  • UBP28_HUMAN
  • B4E3L3_HUMAN
  • F5GZ74_HUMAN
  • F5H2G4_HUMAN
  • F5H6Q3_HUMAN
  • G3V1N5_HUMAN
  • H0YFA0_HUMAN
  • H0YFD7_HUMAN
  • H0YFT9_HUMAN
  • H0YFX3_HUMAN
  • H0YG96_HUMAN
  • H0YH19_HUMAN
  • L8EA89_HUMAN
  • Q6NZX9_HUMAN
genes like me logo Genes that share paralogs with USP28: view

Variants for USP28 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP28 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
786926 Benign: not provided 113,801,625(-) T/A SYNONYMOUS_VARIANT
rs193920846 Uncertain Significance: Malignant tumor of prostate 113,834,299(-) G/A MISSENSE_VARIANT,FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for USP28 Gene

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)

Additional Variant Information for USP28 Gene

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

SNP Genotyping and Copy Number Assay Products

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

Disorders for USP28 Gene

MalaCards: The human disease database

(1) MalaCards diseases for USP28 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
colorectal cancer
  • crc
- elite association - COSMIC cancer census association via MalaCards
Search USP28 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for USP28

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

No data available for 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 biology 2001) 2 3 4 23 54
  2. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. (PMID: 24623306) Serra RW … Green MR (eLife 2014) 3 4 54
  3. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. (PMID: 18662541) Bassermann F … Pagano M (Cell 2008) 3 4 54
  4. The ubiquitin-specific protease USP28 is required for MYC stability. (PMID: 17558397) Popov N … Eilers M (Nature cell biology 2007) 3 4 54
  5. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. (PMID: 17873522) Popov N … Eilers M (Cell cycle (Georgetown, Tex.) 2007) 3 4 54

Products for USP28 Gene

Sources for USP28 Gene