This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. The encoded protein is also able to release NEDD8, a ubiquitin-like protein, from NEDD8-conjugated proteins. This gene has been referred to a... See more...

Aliases for USP21 Gene

Aliases for USP21 Gene

  • Ubiquitin Specific Peptidase 21 2 3 5
  • Ubiquitin Carboxyl-Terminal Hydrolase 21 3 4
  • Ubiquitin Specific Protease 21 2 3
  • Deubiquitinating Enzyme 21 3 4
  • Ubiquitin Thioesterase 21 3 4
  • USP16 2 3
  • USP23 3 4
  • Ubiquitin-Specific Processing Protease 21 3
  • Ubiquitin-Specific-Processing Protease 21 4
  • Ubiquitin-Specific Protease 16 3
  • Ubiquitin Thiolesterase 21 3
  • NEDD8-Specific Protease 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 50
  • USP21 5

External Ids for USP21 Gene

Previous HGNC Symbols for USP21 Gene

  • USP23

Previous GeneCards Identifiers for USP21 Gene

  • GC01P158840
  • GC01P156861
  • GC01P157907
  • GC01P158346
  • GC01P157942
  • GC01P159395
  • GC01P161129
  • GC01P132486

Summaries for USP21 Gene

Entrez Gene Summary for USP21 Gene

  • This gene encodes a member of the C19 peptidase family, also known as family 2 of ubiquitin carboxy-terminal hydrolases. The encoded protein cleaves ubiquitin from ubiquitinated proteins for recycling in intracellular protein degradation. The encoded protein is also able to release NEDD8, a ubiquitin-like protein, from NEDD8-conjugated proteins. This gene has been referred to as USP16 and USP23 but is now known as USP21. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

GeneCards Summary for USP21 Gene

USP21 (Ubiquitin Specific Peptidase 21) is a Protein Coding gene. Among its related pathways are Signaling by GPCR and TNF signaling. Gene Ontology (GO) annotations related to this gene include transcription coactivator activity and cysteine-type peptidase activity. An important paralog of this gene is USP2.

UniProtKB/Swiss-Prot Summary for USP21 Gene

  • Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation. Regulates gene expression via histone H2A deubiquitination (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (PubMed:10799498). Deubiquitinates BAZ2A/TIP5 leading to its stabilization (PubMed:26100909).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP21 Gene

Genomics for USP21 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for USP21 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around USP21 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP21

Top Transcription factor binding sites by QIAGEN in the USP21 gene promoter:
  • ATF-2
  • c-Jun
  • CREB
  • deltaCREB
  • GATA-1
  • HNF-4alpha1
  • HNF-4alpha2
  • p53

Genomic Locations for USP21 Gene

Latest Assembly
chr1:161,159,450-161,165,752
(GRCh38/hg38)
Size:
6,303 bases
Orientation:
Plus strand

Previous Assembly
chr1:161,129,290-161,135,513
(GRCh37/hg19 by Entrez Gene)
Size:
6,224 bases
Orientation:
Plus strand

chr1:161,129,240-161,135,513
(GRCh37/hg19 by Ensembl)
Size:
6,274 bases
Orientation:
Plus strand

Genomic View for USP21 Gene

Genes around USP21 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP21 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP21 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP21 Gene

Proteins for USP21 Gene

  • Protein details for USP21 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UK80-UBP21_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 21
    Protein Accession:
    Q9UK80
    Secondary Accessions:
    • Q59H60
    • Q5BKT5
    • Q5VTW9
    • Q5VTX0
    • Q9BTV1
    • Q9HBS2
    • Q9NYN4

    Protein attributes for USP21 Gene

    Size:
    565 amino acids
    Molecular mass:
    62656 Da
    Quaternary structure:
    • Interacts with BEND3 and BAZ2A/TIP5.
    SequenceCaution:
    • Sequence=AAF61308.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAG17222.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=BAD92136.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for USP21 Gene

    Alternative splice isoforms for USP21 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP21 Gene

Selected DME Specific Peptides for USP21 Gene

Q9UK80:
  • QQDAQEFL
  • EEELESEN
  • DLFVGQLKS
  • YLEREDS
  • NLGNTCF

Post-translational modifications for USP21 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for USP21 Gene

Gene Families for USP21 Gene

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

Protein Domains for USP21 Gene

InterPro:
Blocks:
  • Ubiquitin thiolesterase, family 2

Suggested Antigen Peptide Sequences for USP21 Gene

GenScript: Design optimal peptide antigens:
  • Ubiquitin-specific-processing protease 21 (UBP21_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9UK80

UniProtKB/Swiss-Prot:

UBP21_HUMAN :
  • Belongs to the peptidase C19 family. USP21 subfamily.
Family:
  • Belongs to the peptidase C19 family. USP21 subfamily.
genes like me logo Genes that share domains with USP21: view

Function for USP21 Gene

Molecular function for USP21 Gene

UniProtKB/Swiss-Prot Function:
Deubiquitinates histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A releaves the repression of di- and trimethylation of histone H3 at 'Lys-4', resulting in regulation of transcriptional initiation. Regulates gene expression via histone H2A deubiquitination (By similarity). Also capable of removing NEDD8 from NEDD8 conjugates but has no effect on Sentrin-1 conjugates (PubMed:10799498). Deubiquitinates BAZ2A/TIP5 leading to its stabilization (PubMed:26100909).
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;.
GENATLAS Biochemistry:
ubiquitin specific protease 21,acting as an efficient deubiquitinating enzyme,deubiquitin enzyme family

Enzyme Numbers (IUBMB) for USP21 Gene

Phenotypes From GWAS Catalog for USP21 Gene

Gene Ontology (GO) - Molecular Function for USP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003713 transcription coactivator activity ISS --
GO:0004843 thiol-dependent ubiquitin-specific protease activity ISS --
GO:0005515 protein binding IPI 19615732
GO:0008233 peptidase activity IEA --
GO:0008234 cysteine-type peptidase activity ISS --
genes like me logo Genes that share ontologies with USP21: view
genes like me logo Genes that share phenotypes with USP21: view

Animal Models for USP21 Gene

MGI Knock Outs for USP21:
  • Usp21 Usp21<tm1a(EUCOMM)Wtsi>

Animal Models for research

  • Taconic Biosciences Mouse Models for USP21

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP21

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for USP21 Gene

Localization for USP21 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP21 Gene

Cytoplasm. Nucleus.

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 USP21 gene
Compartment Confidence
nucleus 5
cytosol 5
plasma membrane 4
extracellular 1
cytoskeleton 1
mitochondrion 1
peroxisome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Plasma membrane (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for USP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IBA 21873635
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IDA --
genes like me logo Genes that share ontologies with USP21: view

Pathways & Interactions for USP21 Gene

genes like me logo Genes that share pathways with USP21: view

Pathways by source for USP21 Gene

1 KEGG pathway for USP21 Gene
1 Qiagen pathway for USP21 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis

Gene Ontology (GO) - Biological Process for USP21 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006325 chromatin organization IEA --
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IEA --
GO:0016578 histone deubiquitination ISS --
GO:0016579 protein deubiquitination TAS --
genes like me logo Genes that share ontologies with USP21: view

No data available for SIGNOR curated interactions for USP21 Gene

Drugs & Compounds for USP21 Gene

(1) Drugs for USP21 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 USP21: view

Transcripts for USP21 Gene

mRNA/cDNA for USP21 Gene

4 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
10 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP21

Alternative Splicing Database (ASD) splice patterns (SP) for USP21 Gene

ExUns: 1a · 1b · 1c · 1d ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c · 4d ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^
SP1: - - - -
SP2: - - - - -
SP3: - - - - -
SP4: - - - -
SP5: -
SP6: - -
SP7: -
SP8: - -
SP9: -
SP10: -
SP11: - -

ExUns: 15a · 15b ^ 16a · 16b
SP1:
SP2: -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for USP21 Gene

GeneLoc Exon Structure for
USP21

Expression for USP21 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for USP21 Gene

Protein differential expression in normal tissues from HIPED for USP21 Gene

This gene is overexpressed in Fetal Brain (60.7) and Tlymphocyte (8.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for USP21 Gene



Protein tissue co-expression partners for USP21 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for USP21

SOURCE GeneReport for Unigene cluster for USP21 Gene:

Hs.8015

mRNA Expression by UniProt/SwissProt for USP21 Gene:

Q9UK80-UBP21_HUMAN
Tissue specificity: Highly expressed in heart, pancreas and skeletal muscle. Also expressed in brain, placenta, liver and kidney, and at very low level in lung.

Evidence on tissue expression from TISSUES for USP21 Gene

  • Nervous system(4.8)
  • Kidney(4.4)
  • Lung(4.2)
genes like me logo Genes that share expression patterns with USP21: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for USP21 Gene

Orthologs for USP21 Gene

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

Orthologs for USP21 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia USP21 29 30
  • 99.35 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia USP21 29 30
  • 93.75 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Usp21 29 16 30
  • 92.27 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Usp21 29
  • 92.15 (n)
Dog
(Canis familiaris)
Mammalia USP21 29 30
  • 92.09 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia USP21 30
  • 79 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia USP21 30
  • 61 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia usp21 29
  • 60.13 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC563546 29
  • 57.38 (n)
USP21 30
  • 51 (a)
OneToOne
Dr.18585 29
Fruit Fly
(Drosophila melanogaster)
Insecta CG14619 30
  • 19 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP11 32
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 32 (a)
OneToMany
Species where no ortholog for USP21 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Chicken (Gallus gallus)
  • 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)
  • 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)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for USP21 Gene

ENSEMBL:
Gene Tree for USP21 (if available)
TreeFam:
Gene Tree for USP21 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for USP21: view image
Alliance of Genome Resources:
Additional Orthologs for USP21

Paralogs for USP21 Gene

(3) SIMAP similar genes for USP21 Gene using alignment to 4 proteins:

  • UBP21_HUMAN
  • L8E8G0_HUMAN
  • V9GY36_HUMAN
  • V9GYJ6_HUMAN

Pseudogenes.org Pseudogenes for USP21 Gene

genes like me logo Genes that share paralogs with USP21: view

Variants for USP21 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP21 Gene

SNP ID Clinical significance and condition Chr 01 pos Variation AA Info Type
rs1127525 -- p.Pro336Thr
rs17356051 -- p.Gly321Asp
rs34779722 -- p.Pro91Ser

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for USP21 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Variation tolerance for USP21 Gene

Residual Variation Intolerance Score: 22.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.65; 56.90% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for USP21 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP21
Leiden Open Variation Database (LOVD)
USP21

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for USP21 Gene

Disorders for USP21 Gene

Additional Disease Information for USP21

No disorders were found for USP21 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for USP21 Gene

Publications for USP21 Gene

  1. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins. (PMID: 10799498) Gong L … Yeh ET (The Journal of biological chemistry 2000) 2 3 4 22
  2. Sequencing, tissue distribution and chromosomal assignment of a novel ubiquitin-specific protease USP23. (PMID: 10786635) Smith TS … Southan C (Biochimica et biophysica acta 2000) 3 4 22
  3. BEND3 represses rDNA transcription by stabilizing a NoRC component via USP21 deubiquitinase. (PMID: 26100909) Khan A … Prasanth SG (Proceedings of the National Academy of Sciences of the United States of America 2015) 3 4
  4. A global survey of CRM1-dependent nuclear export sequences in the human deubiquitinase family. (PMID: 21888622) García-Santisteban I … Rodríguez JA (The Biochemical journal 2012) 3 4
  5. Polyubiquitin binding and cross-reactivity in the USP domain deubiquitinase USP21. (PMID: 21399617) Ye Y … Komander D (EMBO reports 2011) 3 4

Products for USP21 Gene

Sources for USP21 Gene