Alternative titles; symbols
HGNC Approved Gene Symbol: STRN3
Cytogenetic location: 14q12 Genomic coordinates (GRCh38): 14:30,893,804-31,026,379 (from NCBI)
By expression screening a HepG2 cDNA library with serum from a patient with bladder cancer and metastatic adenocarcinoma of the lung, Muro et al. (1995) cloned STRN3, which they called SG2NA. The 3-prime end of the transcript contains 3 putative polyadenylation signals and 5 ATTTA destabilization motifs. The deduced 713-amino acid SG2NA protein has a calculated molecular mass of 77.7 kD. It has 2 mixed charge clusters and a negative charge cluster in the N-terminal half and 6 WD-40 repeats in the C-terminal half. It also has several PEST-like protein degradation motifs. Immunofluorescence microscopy of HepG2 cells revealed nuclear localization, with highest expression during late S and G2 phases of the cell cycle. Western blot analysis of HeLa cells and SDS-PAGE of in vitro translated protein detected several SG2NA protein bands between about 60 and 110 kD.
By PCR of a human brain cDNA library, followed by screening a human caudate nucleus cDNA library, Castets et al. (2000) cloned SG2NA. The deduced 713-amino acid protein has a structure identical to that of striatin (STRN; 614765) and zinedin (STRN4; 614767), including a putative N-terminal caveolin (see CAV1, 601047)-binding domain, followed by a coiled-coil region, a putative calmodulin (see 114180)-binding domain, and 8 WD-repeats spread over the C-terminal half. Sequencing of partial cDNA clones also revealed a splice variant, which they called SG2NA-beta. This variant retains exons 8 and 9, which SG2NA lacks, and encodes a deduced 797-amino acid protein. Northern blot analysis of mouse tissues detected high expression of Sg2na in brain, cerebellum, and skeletal muscle, with much weaker expression in all other tissues examined. Western blot analysis detected mouse Sg2na protein with apparent molecular masses of 112, 102, and 94 kD in brain and cerebellum. The 94-kD protein was also detected in heart, skeletal muscle, kidney, lung, liver, and spleen. Immunohistochemical analysis of rat brain sections revealed that striatin and Sg2na were expressed in dendrites, but not axons, and were generally found in different types of neurons. In rat brain homogenates, about half of all striatin, Sg2na, and zinedin were membrane-bound and released by detergents.
Castets et al. (2000) determined that the STRN3 gene contains 18 coding exons. Exons 8 and 9 are subject to alternative splicing.
Using FISH, Castets et al. (2000) mapped the STRN3 gene to chromosome 14q13-q21.
Moreno et al. (2000) used a relatively nonspecific antibody against regulatory B-prime subunits of PP2A to immunoprecipitate related proteins from NIH3T3 mouse fibroblasts. Mass spectrometric analysis of proteins separated by 2-dimensional gel revealed the presence of striatin and Sg2na at apparent molecular masses of 110 and 93 kD, respectively, in addition to catalytic (see PPP2CA, 176915) and structural (see PPP2R1A, 605983) subunits, and several unidentified proteins. Antibodies directed against striatin and Sg2na immunoprecipitated catalytic and structural PP2A subunits in reciprocal experiments. No B-type regulatory subunits, such as B56 (PPP2R5D; 601646), were detected in the immunoprecipitates. Striatin and Sg2na complexes showed phosphatase activity that was largely inhibited by okadaic acid and was independent of calcium. Deletion of the C terminus of the PP2A catalytic subunit did not affect the association of striatin or Sg2na in PP2A complexes, suggesting that they may be atypical B-type regulatory subunits. Both striatin and Sg2na also bound immobilized calmodulin in a calcium-dependent manner.
Castets et al. (2000) found that cytosolic rat brain striatin, zinedin, and all 3 isoforms of Sg2na bound immobilized calmodulin in the presence of calcium and were eluted with EDTA.
Using human cancer cells, Madsen et al. (2015) showed that STRIP1 (617918), STRIP2 (617919), and STRN3 were part of a striatin-interacting phosphatase and kinase (STRIPAK) complex that regulated the cytoskeleton. In tumors, this STRIPAK complex was required for metastasis.
In a study of 1,751 knockout alleles created by the International Mouse Phenotyping Consortium (IMPC), Dickinson et al. (2016) found that knockout of the mouse homolog of human STRN3 is homozygous-lethal (defined as absence of homozygous mice after screening of at least 28 pups before weaning). Strn3 homozygous knockout embryos had subtle but consistent cardiac septal defects at E15.5 and showed severe edema and sporadic hemorrhaging.
Castets, F., Rakitina, T., Gaillard, S., Moqrich, A., Mattei, M.-G., Monneron, A. Zinedin, SG2NA, and striatin are calmodulin-binding, WD repeat proteins principally expressed in the brain. J. Biol. Chem. 275: 19970-19977, 2000. [PubMed: 10748158] [Full Text: https://doi.org/10.1074/jbc.M909782199]
Dickinson, M. E., Flenniken, A. M., Ji, X., Teboul, L., Wong, M. D., White, J. K., Meehan, T. F., Weninger, W. J., Westerberg, H., Adissu, H., Baker, C. N., Bower, L., and 73 others. High-throughput discovery of novel developmental phenotypes. Nature 537: 508-514, 2016. Note: Erratum: Nature 551: 398 only, 2017. [PubMed: 27626380] [Full Text: https://doi.org/10.1038/nature19356]
Madsen, C. D., Hooper, S., Tozluoglu, M., Bruckbauer, A., Fletcher, G., Erler, J. T., Bates, P. A., Thompson, B., Sahai, E. STRIPAK components determine mode of cancer cell migration and metastasis. Nature Cell Biol. 17: 68-80, 2015. [PubMed: 25531779] [Full Text: https://doi.org/10.1038/ncb3083]
Moreno, C. S., Park, S., Nelson, K., Ashby, D., Hubalek, F., Lane, W. S., Pallas, D. C. WD40 repeat proteins striatin and S/G2 nuclear autoantigen are members of a novel family of calmodulin-binding proteins that associate with protein phosphatase 2A. J. Biol. Chem. 275: 5257-5263, 2000. [PubMed: 10681496] [Full Text: https://doi.org/10.1074/jbc.275.8.5257]
Muro, Y., Chan, E. K. L., Landberg, G., Tan, E. M. A cell-cycle nuclear autoantigen containing WD-40 motifs expressed mainly in S and G2 phase cells. Biochem. Biophys. Res. Commun. 207: 1029-1037, 1995. [PubMed: 7864889] [Full Text: https://doi.org/10.1006/bbrc.1995.1288]