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. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). 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.
Subunit:
A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (PubMed:4401210). Identified in a complex with the COP9 signalosome complex (CSN). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct. Forms a complex with SMURF2 and SMAD7. Interacts with TGFBR1. Interacts with SART3; the interaction is direct. May interact with RNF20 and RNF40. Interacts with human papillomavirus type 16 protein E6
Subcellular Location:
Cytoplasm. Nucleus.
Tissue Specificity:
Expressed in skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and ovary, with little or no expression in other tissues.
Post-translational modifications:
Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome.
Ubiquitinated, leading to degradation by the proteasome.
Similarity:
Belongs to the peptidase C19 family.
Contains 1 DUSP domain.
Database links:
Entrez Gene: 395644 Chicken
Entrez Gene: 538284 Cow
Entrez Gene: 100055857 Horse
Entrez Gene: 9958 Human
Entrez Gene: 14479 Mouse
Entrez Gene: 100356438 Rabbit
Entrez Gene: 171329 Rat
Entrez Gene: 100542201 Turkey
Omim: 604731 Human
SwissProt: Q9Y4E8 Human
SwissProt: Q8R5H1 Mouse
Unigene: 434951 Human
Unigene: 244209 Mouse
Unigene: 470032 Mouse
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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