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SENTRIN-SPECIFIC PROTEASE FAMILY, MEMBER 2; SENP2

SENTRIN-SPECIFIC PROTEASE FAMILY, MEMBER 2; SENP2

Alternative titles; symbolsSUMO-SPECIFIC PROTEASE 2SMT3-SPECIFIC ISOPEPTIDASE 2, MOUSE, HOMOLOG OF; SMT3IP2AXAM2, RAT, HOMOLOG OF; AXAM2KIAA1331HGNC Approved Gen...

Alternative titles; symbols

  • SUMO-SPECIFIC PROTEASE 2
  • SMT3-SPECIFIC ISOPEPTIDASE 2, MOUSE, HOMOLOG OF; SMT3IP2
  • AXAM2, RAT, HOMOLOG OF; AXAM2
  • KIAA1331

HGNC Approved Gene Symbol: SENP2

Cytogenetic location: 3q27.2 Genomic coordinates (GRCh38): 3:185,586,294-185,633,550 (from NCBI)

▼ Description

SUMO1 (UBL1; 601912) is a small ubiquitin-like protein that can be covalently conjugated to other proteins. SENP2 is one of a group of enzymes that process newly synthesized SUMO1 into the conjugatable form and catalyze the deconjugation of SUMO1-containing species.

▼ Cloning and Expression

By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned SENP2, which they designated KIAA1331. The 3-prime untranslated region of the transcript contains several Alu repeats. RT-PCR ELISA detected very high expression in amygdala and moderate to high expression in whole brain and all other tissues and specific brain regions examined.

Zhang et al. (2002) cloned SENP2 by PCR of a fetal brain cDNA library. The deduced 590-amino acid protein contains a unique N-terminal domain and a C-terminal domain of about 200 amino acids that shares significant homology with the catalytic domains of yeast Ulp1 and other SUMO proteases. Indirect immunofluorescence of transfected HeLa cells showed that SENP2 colocalized with lamin B (see 150340) to a ring internal to the RANGAP1 (602362) signal, suggesting that SENP2 localizes to the nucleoplasmic face of the nuclear pore complex.

Nishida et al. (2001) cloned mouse Senp2, which they designated Smt3ip2. The deduced 541 amino acid protein has a calculated molecular mass of 62 kD. Mouse Senp2 is almost identical to human SENP2, although the N terminus of mouse Senp2 is shorter. RT-PCR detected Senp2 expression in mouse brain, heart, and thymus, and in a mouse fibroblast cell line.

▼ Gene Function

Zhang et al. (2002) determined that the N-terminal 63 amino acids of SENP2 contain both a nuclear localization signal and a nuclear pore complex localization signal. SENP2 bound specifically to the C-terminal FG-repeat domain of NUP153 (603948), indicating that NUP153 plays a role in localizing SENP2 to the nuclear pore. Using SUMO-modified RANGAP1 as a test substrate, Zhang et al. (2002) demonstrated that SENP2 could process both SUMO1 and SUMO3 (SMT3H1; 602231) protein conjugates. SUMO1-modified RANGAP1 was more resistant to SENP2 protease activity when it was complexed with UBC9 (601661) and NUP358 (601181).

Hang and Dasso (2002) found that expression of a SENP2 mutant lacking the N-terminal domain resulted in the loss of almost all conjugated forms of epitope-labeled SUMO1. They concluded that SENP2 is more effective in deconjugating nuclear proteins when it is no longer tethered to the nuclear pore.

▼ Mapping

Kazantseva et al. (2006) identified the SENP2 gene within a 350-kb region on chromosome 3q27 centromeric to marker D3S1530.

Tags: 3q27.2