Tchem SENP6 Sentrin-specific protease 6

Protein Summary

Description

Protease that deconjugates SUMO1, SUMO2 and SUMO3 from targeted proteins. Processes preferentially poly-SUMO2 and poly-SUMO3 chains, but does not efficiently process SUMO1, SUMO2 and SUMO3 precursors. Deconjugates SUMO1 from RXRA, leading to transcriptional activation. Involved in chromosome alignment and spindle assembly, by regulating the kinetochore CENPH-CENPI-CENPK complex. Desumoylates PML and CENPI, protecting them from degradation by the ubiquitin ligase RNF4, which targets polysumoylated proteins for proteasomal degradation. Desumoylates also RPA1, thus preventing recruitment of RAD51 to the DNA damage foci to initiate DNA repair through homologous recombination. Ubiquitin-like molecules (UBLs), such as SUMO1 (UBL1; MIM 601912), are structurally related to ubiquitin (MIM 191339) and can be ligated to target proteins in a similar manner as ubiquitin. However, covalent attachment of UBLs does not result in degradation of the modified proteins. SUMO1 modification is implicated in the targeting of RANGAP1 (MIM 602362) to the nuclear pore complex, as well as in stabilization of I-kappa-B-alpha (NFKBIA; MIM 164008) from degradation by the 26S proteasome. Like ubiquitin, UBLs are synthesized as precursor proteins, with 1 or more amino acids following the C-terminal glycine-glycine residues of the mature UBL protein. Thus, the tail sequences of the UBL precursors need to be removed by UBL-specific proteases, such as SENP6, prior to their conjugation to target proteins (Kim et al., 2000 [PubMed 10799485]). SENPs also display isopeptidase activity for deconjugation of SUMO-conjugated substrates (Lima and Reverter, 2008 [PubMed 18799455]).[supplied by OMIM, Jun 2009]

Uniprot Accession IDs

• Q9GZR1
• A6NNY9
• O94891
• Q5VUL3
• Q5VUL4
• Q8TBY4
• Q9UJV5

Gene Name

• SENP6

Ensembl ID

• ENST00000370010
• ENSP00000359027
• ENSG00000112701
• ENST00000447266
• ENSP00000402527

Symbol

• KIAA0797
• SSP1
• SUSP1
• SSP1
• SUSP1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
kinase perturbation	0.76
virus perturbation	0.68
tissue sample	0.65
disease perturbation	0.62
histone modification site profile	0.6

Protein Classes

PANTHER Classes

Protein / ... / Cysteine Protease / Sentrin-specific Protease 6

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Sentrin-specific Protease 6

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 236.98   (req: < 5)

Gene RIFs: 18   (req: <= 3)

Antibodies: 393   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 236.98   (req: >= 5)

Gene RIFs: 18   (req: > 3)

Antibodies: 393   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 6

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 27

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0