UniProt functional annotation for Q92905



	UniProt functional annotation for Q92905

UniProt code: Q92905.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2. {ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11337588, ECO:0000269|PubMed:12628923, ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:9535219}.

Cofactor: Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000250};

Subunit: Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1 (PubMed:26456823). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9 isoform 1 (PubMed:26456823). Interacts with COPS9 isoform 2 (PubMed:23776465). The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with ZDHHC16 (PubMed:17123647). Interacts with MINDY3 (PubMed:21499297). Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1 (PubMed:20978819). Interacts with NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation (PubMed:16300740). {ECO:0000269|PubMed:10362352, ECO:0000269|PubMed:10722692, ECO:0000269|PubMed:10766246, ECO:0000269|PubMed:11089976, ECO:0000269|PubMed:11285227, ECO:0000269|PubMed:11709497, ECO:0000269|PubMed:11818334, ECO:0000269|PubMed:12082530, ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14993265, ECO:0000269|PubMed:15126503, ECO:0000269|PubMed:16300740, ECO:0000269|PubMed:17050680, ECO:0000269|PubMed:17123647, ECO:0000269|PubMed:18850735, ECO:0000269|PubMed:19214193, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:21499297, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:23776465, ECO:0000269|PubMed:26456823, ECO:0000269|PubMed:8837781}.

Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:17050680, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399, ECO:0000269|PubMed:9535219}. Nucleus {ECO:0000269|PubMed:17050680, ECO:0000269|PubMed:20978819, ECO:0000269|PubMed:22609399}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:9535219}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000269|PubMed:21102408}. Note=Nuclear localization is diminished in the presence of IFIT3. {ECO:0000269|PubMed:17050680}.

Domain: The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity). {ECO:0000250}.

Miscellaneous: The CSN complex is associated with some 'Lys-63'- specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.

Similarity: Belongs to the peptidase M67A family. CSN5 subfamily. {ECO:0000305}.

Sequence caution: Sequence=AAL82571.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2. {ECO:0000269\|PubMed:11285227, ECO:0000269\|PubMed:11337588, ECO:0000269\|PubMed:12628923, ECO:0000269\|PubMed:12732143, ECO:0000269\|PubMed:19214193, ECO:0000269\|PubMed:20978819, ECO:0000269\|PubMed:22609399, ECO:0000269\|PubMed:9535219}.


Cofactor:		Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240; Evidence={ECO:0000250};
Subunit:		Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1 (PubMed:26456823). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9 isoform 1 (PubMed:26456823). Interacts with COPS9 isoform 2 (PubMed:23776465). The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with ZDHHC16 (PubMed:17123647). Interacts with MINDY3 (PubMed:21499297). Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1 (PubMed:20978819). Interacts with NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation (PubMed:16300740). {ECO:0000269\|PubMed:10362352, ECO:0000269\|PubMed:10722692, ECO:0000269\|PubMed:10766246, ECO:0000269\|PubMed:11089976, ECO:0000269\|PubMed:11285227, ECO:0000269\|PubMed:11709497, ECO:0000269\|PubMed:11818334, ECO:0000269\|PubMed:12082530, ECO:0000269\|PubMed:14500717, ECO:0000269\|PubMed:14993265, ECO:0000269\|PubMed:15126503, ECO:0000269\|PubMed:16300740, ECO:0000269\|PubMed:17050680, ECO:0000269\|PubMed:17123647, ECO:0000269\|PubMed:18850735, ECO:0000269\|PubMed:19214193, ECO:0000269\|PubMed:20978819, ECO:0000269\|PubMed:21499297, ECO:0000269\|PubMed:22609399, ECO:0000269\|PubMed:23776465, ECO:0000269\|PubMed:26456823, ECO:0000269\|PubMed:8837781}.
Subcellular location:		Cytoplasm, cytosol {ECO:0000269\|PubMed:17050680, ECO:0000269\|PubMed:20978819, ECO:0000269\|PubMed:22609399, ECO:0000269\|PubMed:9535219}. Nucleus {ECO:0000269\|PubMed:17050680, ECO:0000269\|PubMed:20978819, ECO:0000269\|PubMed:22609399}. Cytoplasm, perinuclear region {ECO:0000269\|PubMed:9535219}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle {ECO:0000269\|PubMed:21102408}. Note=Nuclear localization is diminished in the presence of IFIT3. {ECO:0000269\|PubMed:17050680}.
Domain:		The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity). {ECO:0000250}.
Miscellaneous:		The CSN complex is associated with some 'Lys-63'- specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.
Similarity:		Belongs to the peptidase M67A family. CSN5 subfamily. {ECO:0000305}.
Sequence caution:		Sequence=AAL82571.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};