InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: USP15

Summary

InnateDB Protein

IDBP-44315.7

Last Modified

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

Gene Symbol

USP15

Protein Name

ubiquitin specific peptidase 15

Synonyms

UNPH-2; UNPH4;

Species

Homo sapiens

Ensembl Protein

ENSP00000258123

InnateDB Gene

IDBG-44309 (USP15)

Protein Structure

UniProt Annotation

Function

Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates as well as 'Lys-48'-linked polyubiquitin chains, protecting them against proteasomal degradation. Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP. Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway. {ECO:0000269PubMed:16005295, ECO:0000269PubMed:17318178, ECO:0000269PubMed:19553310, ECO:0000269PubMed:19576224, ECO:0000269PubMed:19826004, ECO:0000269PubMed:21947082, ECO:0000269PubMed:22344298}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:21947082}. Nucleus {ECO:0000269PubMed:21947082}.

Disease Associations

Tissue Specificity

Expressed in skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and ovary, with little or no expression in other tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 137 experimentally validated interaction(s) in this database.

Experimentally validated
Total	137 [view]
Protein-Protein	136 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004197	cysteine-type endopeptidase activity
GO:0004221	ubiquitin thiolesterase activity
GO:0004843	ubiquitin-specific protease activity
GO:0005160	transforming growth factor beta receptor binding
GO:0036459	ubiquitinyl hydrolase activity
GO:0042802	identical protein binding
GO:0046332	SMAD binding

Biological Process

GO:0006511	ubiquitin-dependent protein catabolic process
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0008152	metabolic process
GO:0016579	protein deubiquitination
GO:0030509	BMP signaling pathway
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0035520	monoubiquitinated protein deubiquitination
GO:0060389	pathway-restricted SMAD protein phosphorylation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR001394 Peptidase C19, ubiquitin carboxyl-terminal hydrolase
IPR006615 Peptidase C19, ubiquitin-specific peptidase, DUSP domain
IPR013792 RNA 3\'-terminal phosphate cyclase/enolpyruvate transferase, alpha/beta
IPR028889 Ubiquitin carboxyl-terminal hydrolase-like domain
IPR029071 Ubiquitin-related domain

PFAM

PF00443
PF06337

PRINTS

PIRSF

SMART

SM00695

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9Y4E8