Alternative titles; symbols
HGNC Approved Gene Symbol: SYNJ2
Cytogenetic location: 6q25.3 Genomic coordinates (GRCh38): 6:157,981,296-158,099,176 (from NCBI)
Synaptojanin-2 is a ubiquitously expressed inositol polyphosphate 5-phosphatase (Malecz et al., 2000).
By sequencing clones isolated from a size-fractionated brain cDNA library, Nagase et al. (1997) cloned SYNJ2, which they designated KIAA0348. The deduced protein shares 42.4% amino acid identity with rat synaptojanin (SYNJ1; 604297) over 932 amino acids. RT-PCR detected low SYNJ2 expression in kidney, pancreas, thymus, prostate, and ovary.
Seet et al. (1998) cloned several mouse Synj2 isoforms. The longest deduced protein, designated Synj2-alpha, contains 1,216 amino acids and has a calculated molecular mass of 140 kD. Synj2 contains an N-terminal Sac1 (SACM1L; 606869) homology domain, a central inositol 5-prime-phosphatase domain, and a C-terminal proline-rich region. The nucleotide sequence of Synj2-alpha shares 86% identity with the human SYNJ2 clone isolated by Nagase et al. (1997). Synj2 variants arise from the use of 2 possible initiation sites and at least 6 different exons encoding C-terminal domains. Initiation from the alternative start sites results in isoforms that vary in the presence of 84 amino acids in the N-terminal part of the Sac1 homology domain. Database analysis indicated the presence of a third putative initiation site in human SYNJ2, resulting in a protein that lacks most of the Sac1 homology domain. Seet et al. (1998) suggested that variation in the C-terminal proline-rich region, which includes PxxP motifs, may alter interactions between SYNJ2 and SH3 domain-containing proteins.
Nemoto et al. (2001) cloned 2 splice variants of rat Synj2. They designated these variants Synj2b1 and Synj2b2 and referred to the original rat Synj2 cloned by Nemoto et al. (1997) as Synj2a. Synj2a contains a C-terminal PDZ-binding domain, whereas Synj2b1 and Synj2b2 contain multiple potential SH3 domain-binding regions in their C termini. Synj2b2 has a 46-amino acid C-terminal sequence absent in Synj2b1. By RT-PCR of human lung, peripheral leukocytes, placenta, and brain using primers based on the KIAA0348 sequence isolated by Nagase et al. (1997), Nemoto et al. (2001) obtained a human SYNJ2 cDNA encoding a 1,443-amino acid protein. Nemoto et al. (2001) suggested that this human isoform is homologous to rat Synj2b2 and is incomplete at its 5-prime end, lacking the region that encodes the most N-terminal 50 amino acids. By immunofluorescence microscopy, Nemoto et al. (2001) localized the Synj2b isoforms to nerve terminals in rat brain and at spermatid manchette in rat testis.
Nemoto and De Camilli (1999) found that the PDZ domain of rat Omp25 (SYNJ2BP; 609411) interacted with a C-terminal domain of Synj2a. Overexpression of Omp25 resulted in perinuclear clustering of mitochondria in transfected cells, and this effect was mimicked by enforced expression of Synj2a on the mitochondrial outer membrane but not by a Synj2a mutant lacking the inositol 5-phosphatase domain. Nemoto and De Camilli (1999) concluded that OMP25 mediates recruitment of SYNJ2A to mitochondria.
By yeast 2-hybrid analysis and in vitro binding assays, Malecz et al. (2000) showed that a 56-amino acid domain in the C terminus of human SYNJ2 interacted with RAC1 (602048). Expression of constitutively active RAC1 caused the translocation of SYNJ2 from the cytoplasm to the plasma membrane. Both activated RAC1 and a membrane-targeted version of SYNJ2 inhibited endocytosis of EGF receptor (EGFR; 131550) and transferrin receptor (TFRC; 190010), a process that depends on polyphosphoinositides.
Nemoto et al. (2001) found that both amphiphysin (AMPH; 600418) and endophilin (see SH3GL2; 604465) bound rat Synj2b2, but only amphiphysin bound Synj2b1. Nemoto et al. (2001) identified an endophilin-binding site within Synj2b2 that could affinity purify endophilin from rat brain. The SAC1 domain of Synj2 showed phosphoinositide phosphatase activity similar to the Sac1 domain of Synj1.
By Northern and Western blot analyses, Spaenij-Dekking et al. (2003) showed that SYNJ2 expression was increased in hairy cell leukemia (HCL) samples compared with other B cells. They also found that an epitope of SYNJ2 was an autoantigen for HCL-specific T cells.
Chuang et al. (2004) found that small interfering RNA-mediated depletion of RAC1 or SYNJ2 in 2 human glioblastoma cell lines inhibited migration of the cells through 3-dimensional gel and rat brain slices, and it inhibited cell migration on glioma-derived extracellular matrix. Depletion of RAC1 or SYNJ2 inhibited formation of lamellipodia and invadopodia, specialized membrane structures involved in extracellular matrix degradation. Chuang et al. (2004) concluded that SYNJ2 and RAC1 contribute to cell invasion and migration by regulating the formation of invadopodia and lamellipodia.
By radiation hybrid analysis, Nagase et al. (1997) mapped the SYNJ2 gene to chromosome 6. By FISH, Seet et al. (1998) mapped the mouse Synj2 gene to chromosome 17A2-A3.1.
Chuang, Y., Tran, N. L., Rusk, N., Nakada, M., Berens, M. E., Symons, M. Role of synaptojanin 2 in glioma cell migration and invasion. Cancer Res. 64: 8271-8275, 2004. [PubMed: 15548694] [Full Text: https://doi.org/10.1158/0008-5472.CAN-04-2097]
Malecz, N., McCabe, P. C., Spaargaren, C., Qiu, R.-G., Chuang, Y., Symons, M. Synaptojanin 2, a novel Rac1 effector that regulates clathrin-mediated endocytosis. Curr. Biol. 10: 1383-1386, 2000. [PubMed: 11084340] [Full Text: https://doi.org/10.1016/s0960-9822(00)00778-8]
Nagase, T., Ishikawa, K., Nakajima, D., Ohira, M., Seki, N., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. DNA Res. 4: 141-150, 1997. [PubMed: 9205841] [Full Text: https://doi.org/10.1093/dnares/4.2.141]
Nemoto, Y., Arribas, M., Haffner, C., DeCamilli, P. Synaptojanin 2, a novel synaptojanin isoform with a distinct targeting domain and expression pattern. J. Biol. Chem. 272: 30817-30821, 1997. [PubMed: 9388224] [Full Text: https://doi.org/10.1074/jbc.272.49.30817]
Nemoto, Y., De Camilli, P. Recruitment of an alternatively spliced form of synaptojanin 2 to mitochondria by the interaction with the PDZ domain of a mitochondrial outer membrane protein. EMBO J. 18: 2991-3006, 1999. [PubMed: 10357812] [Full Text: https://doi.org/10.1093/emboj/18.11.2991]
Nemoto, Y., Wenk, M. R., Watanabe, M., Daniell, L., Murakami, T., Ringstad, N., Yamada, H., Takei, K., De Camilli, P. Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals. J. Biol. Chem. 276: 41133-41142, 2001. [PubMed: 11498538] [Full Text: https://doi.org/10.1074/jbc.M106404200]
Seet, L.-F., Cho, S., Hessel, A., Dumont, D. J. Molecular cloning of multiple isoforms of synaptojanin 2 and assignment of the gene to mouse chromosome 17A2-3.1. Biochem. Biophys. Res. Commun. 247: 116-122, 1998. [PubMed: 9636665] [Full Text: https://doi.org/10.1006/bbrc.1998.8564]
Spaenij-Dekking, E. H. A., Van Delft, J., Van der Meijden, E., Hiemstra, H. S., Falkenburg, J. H. F., Koning, F., Drijfhout, J. W., Kluin-Nelemans, J. C. Synaptojanin 2 is recognized by HLA class II-restricted hairy cell leukemia-specific T cells. Leukemia 17: 2467-2473, 2003. [PubMed: 14562116] [Full Text: https://doi.org/10.1038/sj.leu.2403174]