InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: USP33

Summary

InnateDB Protein

IDBP-99827.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

USP33

Protein Name

ubiquitin specific peptidase 33

Synonyms

VDU1;

Species

Homo sapiens

Ensembl Protein

ENSP00000350009

InnateDB Gene

IDBG-99821 (USP33)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:12865408, ECO:0000269PubMed:19363159, ECO:0000269PubMed:19424180, ECO:0000269PubMed:23486064}.

Subcellular Localization

Cytoplasm, perinuclear region. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=Associates with centrosomes predominantly in S and G2 phases but less in G1 phase.Isoform 3: Golgi apparatus.

Disease Associations

Tissue Specificity

Widely expressed. {ECO:0000269PubMed:11739384}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 38 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	38 [view]
Protein-Protein	38 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001664	G-protein coupled receptor binding
GO:0004197	cysteine-type endopeptidase activity
GO:0004221	ubiquitin thiolesterase activity
GO:0004843	ubiquitin-specific protease activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0036459	ubiquitinyl hydrolase activity

Biological Process

GO:0006511	ubiquitin-dependent protein catabolic process
GO:0006897	endocytosis
GO:0007411	axon guidance
GO:0008277	regulation of G-protein coupled receptor protein signaling pathway
GO:0016477	cell migration
GO:0016579	protein deubiquitination
GO:0051298	centrosome duplication
GO:0070536	protein K63-linked deubiquitination
GO:0071108	protein K48-linked deubiquitination

Cellular Component

GO:0005737	cytoplasm
GO:0005794	Golgi apparatus
GO:0005813	centrosome
GO:0030891	VCB complex
GO:0048471	perinuclear region of cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR001394 Peptidase C19, ubiquitin carboxyl-terminal hydrolase
IPR001607 Zinc finger, UBP-type
IPR006615 Peptidase C19, ubiquitin-specific peptidase, DUSP domain
IPR028889 Ubiquitin carboxyl-terminal hydrolase-like domain

PFAM

PF00443
PF02148
PF06337

PRINTS

PIRSF

SMART

SM00290
SM00695

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q8TEY7