This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012] See more...

Aliases for USP33 Gene

Aliases for USP33 Gene

  • Ubiquitin Specific Peptidase 33 2 3 5
  • VDU1 2 3 4
  • VHL-Interacting Deubiquitinating Enzyme 1 3 4
  • Ubiquitin-Specific-Processing Protease 33 3 4
  • Ubiquitin Carboxyl-Terminal Hydrolase 33 3 4
  • Deubiquitinating Enzyme 33 3 4
  • Ubiquitin Thioesterase 33 3 4
  • KIAA1097 2 4
  • PVHL-Interacting Deubiquitinating Enzyme 1 3
  • Ubiquitin Specific Protease 33 2
  • Ubiquitin Thiolesterase 33 3
  • EC 3.4.19.12 4
  • EC 3.1.2.15 50
  • USP33 5
  • HVDU1 4

External Ids for USP33 Gene

Previous GeneCards Identifiers for USP33 Gene

  • GC01M077566
  • GC01M077584
  • GC01M077873
  • GC01M078161
  • GC01M076293

Summaries for USP33 Gene

Entrez Gene Summary for USP33 Gene

  • This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

GeneCards Summary for USP33 Gene

USP33 (Ubiquitin Specific Peptidase 33) is a Protein Coding gene. Among its related pathways are Deubiquitination and Ubiquitin-Proteasome Dependent Proteolysis. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and thiol-dependent ubiquitinyl hydrolase activity. An important paralog of this gene is USP20.

UniProtKB/Swiss-Prot Summary for USP33 Gene

  • Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.

Gene Wiki entry for USP33 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for USP33 Gene

Genomics for USP33 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for USP33 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 USP33 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for USP33

Top Transcription factor binding sites by QIAGEN in the USP33 gene promoter:
  • AML1a
  • GR
  • GR-alpha
  • HNF-1
  • HNF-1A
  • NF-E2 p45
  • NF-kappaB
  • NF-kappaB1
  • RelA
  • ZID

Genomic Locations for USP33 Gene

Latest Assembly
chr1:77,695,987-77,759,852
(GRCh38/hg38)
Size:
63,866 bases
Orientation:
Minus strand

Previous Assembly
chr1:78,161,672-78,225,537
(GRCh37/hg19 by Entrez Gene)
Size:
63,866 bases
Orientation:
Minus strand

chr1:78,161,672-78,225,537
(GRCh37/hg19 by Ensembl)
Size:
63,866 bases
Orientation:
Minus strand

Genomic View for USP33 Gene

Genes around USP33 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
USP33 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for USP33 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for USP33 Gene

Proteins for USP33 Gene

  • Protein details for USP33 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q8TEY7-UBP33_HUMAN
    Recommended name:
    Ubiquitin carboxyl-terminal hydrolase 33
    Protein Accession:
    Q8TEY7
    Secondary Accessions:
    • Q8TEY6
    • Q96AV6
    • Q9H9F0
    • Q9UPQ5

    Protein attributes for USP33 Gene

    Size:
    942 amino acids
    Molecular mass:
    106727 Da
    Quaternary structure:
    • Interacts with VHL, leading to its ubiquitination and subsequent degradation. Interacts with ARRB1, ARRB2, ADRB2, DIO2 and ROBO1. Interacts with SELENBP1; in a selenium-dependent manner. Interacts with CCP110.
    SequenceCaution:
    • Sequence=BAA83049.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for USP33 Gene

    Alternative splice isoforms for USP33 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for USP33 Gene

Selected DME Specific Peptides for USP33 Gene

Q8TEY7:
  • QQDAQEFL
  • YSRYGGGP

Post-translational modifications for USP33 Gene

  • Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.
  • Ubiquitination at Lys50, Lys258, and Lys882
  • Modification sites at PhosphoSitePlus

Domains & Families for USP33 Gene

Gene Families for USP33 Gene

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

Protein Domains for USP33 Gene

InterPro:
Blocks:
  • Ubiquitin thiolesterase, family 2
  • Zn-finger in ubiquitin thiolesterase
  • Ubiquitin-specific protease DUSP

Suggested Antigen Peptide Sequences for USP33 Gene

GenScript: Design optimal peptide antigens:
  • VHL-interacting deubiquitinating enzyme 1 (UBP33_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q8TEY7

UniProtKB/Swiss-Prot:

UBP33_HUMAN :
  • The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue.
  • Belongs to the peptidase C19 family. USP20/USP33 subfamily.
Domain:
  • The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue.
Family:
  • Belongs to the peptidase C19 family. USP20/USP33 subfamily.
genes like me logo Genes that share domains with USP33: view

Function for USP33 Gene

Molecular function for USP33 Gene

UniProtKB/Swiss-Prot Function:
Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
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;.

Enzyme Numbers (IUBMB) for USP33 Gene

Phenotypes From GWAS Catalog for USP33 Gene

Gene Ontology (GO) - Molecular Function for USP33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001664 G protein-coupled receptor binding IPI 19424180
GO:0004197 cysteine-type endopeptidase activity IMP 19363159
GO:0004843 thiol-dependent ubiquitin-specific protease activity TAS 11739384
GO:0005515 protein binding IPI 11739384
GO:0008233 peptidase activity IEA --
genes like me logo Genes that share ontologies with USP33: view
genes like me logo Genes that share phenotypes with USP33: view

Animal Models for USP33 Gene

MGI Knock Outs for USP33:
  • Usp33 Usp33<tm1a(EUCOMM)Wtsi>

Animal Models for research

  • Taconic Biosciences Mouse Models for USP33

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for USP33

Clone products for research

  • Addgene plasmids for USP33

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for USP33 Gene

Localization for USP33 Gene

Subcellular locations from UniProtKB/Swiss-Prot for USP33 Gene

Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Associates with centrosomes predominantly in S and G2 phases but less in G1 phase (PubMed:23486064). {ECO:0000269 PubMed:23486064}.
[Isoform 3]: Golgi apparatus.

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 USP33 gene
Compartment Confidence
cytoskeleton 5
golgi apparatus 5
nucleus 4
cytosol 4
extracellular 2
endosome 2
lysosome 2
plasma membrane 1
mitochondrion 1
endoplasmic reticulum 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for USP33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IBA,TAS 11739384
GO:0005794 Golgi apparatus IEA,IDA --
GO:0005813 centrosome IDA 23486064
GO:0005815 microtubule organizing center IEA --
genes like me logo Genes that share ontologies with USP33: view

Pathways & Interactions for USP33 Gene

PathCards logo

SuperPathways for USP33 Gene

genes like me logo Genes that share pathways with USP33: view

Pathways by source for USP33 Gene

1 Qiagen pathway for USP33 Gene
  • Ubiquitin-Proteasome Dependent Proteolysis

Gene Ontology (GO) - Biological Process for USP33 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006511 ubiquitin-dependent protein catabolic process TAS 11739384
GO:0006897 endocytosis IEA --
GO:0007411 axon guidance ISS --
GO:0008277 regulation of G protein-coupled receptor signaling pathway IMP 19363159
genes like me logo Genes that share ontologies with USP33: view

No data available for SIGNOR curated interactions for USP33 Gene

Drugs & Compounds for USP33 Gene

(1) Drugs for USP33 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 USP33: view

Transcripts for USP33 Gene

mRNA/cDNA for USP33 Gene

13 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
18 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 USP33

Clone products for research

  • Addgene plasmids for USP33

Alternative Splicing Database (ASD) splice patterns (SP) for USP33 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4 ^ 5 ^ 6 ^ 7a · 7b · 7c ^ 8a · 8b ^ 9 ^ 10 ^ 11 ^ 12a · 12b · 12c ^ 13 ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19 ^
SP1: - -
SP2: - - -
SP3:
SP4:
SP5: - - -
SP6:
SP7:
SP8:
SP9:

ExUns: 20
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for USP33 Gene

GeneLoc Exon Structure for
USP33

Expression for USP33 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for USP33 Gene

Protein differential expression in normal tissues from HIPED for USP33 Gene

This gene is overexpressed in Placenta (67.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for USP33 Gene



Protein tissue co-expression partners for USP33 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for USP33

SOURCE GeneReport for Unigene cluster for USP33 Gene:

Hs.480597

mRNA Expression by UniProt/SwissProt for USP33 Gene:

Q8TEY7-UBP33_HUMAN
Tissue specificity: Widely expressed.

Evidence on tissue expression from TISSUES for USP33 Gene

  • Nervous system(4.9)
  • Liver(4.3)
  • Eye(4.3)
  • Thyroid gland(2.3)
  • Kidney(2.3)
  • Intestine(2)
  • Skin(2)
genes like me logo Genes that share expression patterns with USP33: view

Primer products for research

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 USP33 Gene

Orthologs for USP33 Gene

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

Orthologs for USP33 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia USP33 29 30
  • 99.65 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia USP33 29 30
  • 94.4 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia USP33 29 30
  • 94.11 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Usp33 29
  • 88.73 (n)
Mouse
(Mus musculus)
Mammalia Usp33 29 16 30
  • 87.13 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia USP33 30
  • 85 (a)
OneToOne
Chicken
(Gallus gallus)
Aves USP33 29 30
  • 78.99 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia USP33 30
  • 79 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia usp33 29
  • 73.59 (n)
Zebrafish
(Danio rerio)
Actinopterygii usp33 29 30
  • 67.23 (n)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG8494 30
  • 31 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea usp-33 30
  • 21 (a)
OneToMany
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes UBP10 30
  • 16 (a)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea -- 30
  • 42 (a)
OneToMany
Species where no ortholog for USP33 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)
  • 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)
  • Oppossum (Monodelphis domestica)
  • 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 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)

Evolution for USP33 Gene

ENSEMBL:
Gene Tree for USP33 (if available)
TreeFam:
Gene Tree for USP33 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for USP33: view image
Alliance of Genome Resources:
Additional Orthologs for USP33

Paralogs for USP33 Gene

(13) SIMAP similar genes for USP33 Gene using alignment to 6 proteins:

  • UBP33_HUMAN
  • E9PLK7_HUMAN
  • E9PP47_HUMAN
  • E9PQP0_HUMAN
  • H0YCV3_HUMAN
  • H0YD08_HUMAN
genes like me logo Genes that share paralogs with USP33: view

Variants for USP33 Gene

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for USP33 Gene

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

Structural Variations from Database of Genomic Variants (DGV) for USP33 Gene

Variant ID Type Subtype PubMed ID
esv3586528 CNV loss 21293372
nsv470719 CNV gain 18288195
nsv508326 CNV deletion 20534489
nsv546591 CNV gain 21841781
nsv830303 CNV loss 17160897

Variation tolerance for USP33 Gene

Residual Variation Intolerance Score: 10.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.96; 36.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for USP33 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
USP33
Leiden Open Variation Database (LOVD)
USP33

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for USP33 Gene

Disorders for USP33 Gene

Additional Disease Information for USP33

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform

No disorders were found for USP33 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for USP33 Gene

Publications for USP33 Gene

  1. Human selenium binding protein-1 (hSP56) interacts with VDU1 in a selenium-dependent manner. (PMID: 19118533) Jeong JY … Sytkowski AJ (Biochemical and biophysical research communications 2009) 3 4 22
  2. Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein. (PMID: 11739384) Li Z … Wu G (The Journal of biological chemistry 2002) 3 4 22
  3. USP33 regulates centrosome biogenesis via deubiquitination of the centriolar protein CP110. (PMID: 23486064) Li J … Dynlacht BD (Nature 2013) 3 4
  4. Meta-analyses of genes modulating intracellular T3 bio-availability reveal a possible role for the DIO3 gene in osteoarthritis susceptibility. (PMID: 20724312) Meulenbelt I … Slagboom PE (Annals of the rheumatic diseases 2011) 3 40
  5. Isoform-specific localization of the deubiquitinase USP33 to the Golgi apparatus. (PMID: 21801292) Thorne C … Clague MJ (Traffic (Copenhagen, Denmark) 2011) 3 4

Products for USP33 Gene

Sources for USP33 Gene