Alternative titles; symbols
HGNC Approved Gene Symbol: SEC23IP
Cytogenetic location: 10q26.11-q26.12 Genomic coordinates (GRCh38): 10:119,892,730-119,944,657 (from NCBI)
SEC23IP interacts with the SEC23 subunit (see SEC23A, 610511) of the SEC23-SEC24 (see SEC24A, 607183) component of COPII-coated vesicles, which are involved in protein export from endoplasmic reticulum (Mizoguchi et al., 2000).
Using mass spectrometric analysis to identify mouse p125, followed by screening of a human fetal brain cDNA library and 5-prime RACE of a human placenta cDNA library, Tani et al. (1999) cloned SEC23IP, which they designated p125. The deduced 1,000-amino acid protein has a calculated molecular mass of 111.1 kD. It has an N-terminal proline-rich region, followed by a domain containing a GxSxG consensus lipase motif and a C-terminal coiled-coil region. The central and C-terminal regions of p125 share significant similarity with phospholipase A1 (see PLA1A, 607460). Northern blot analysis detected variable expression of a 4.5-kb transcript in all human tissues examined, with highest content in heart, skeletal muscle, and pancreas. Western blot analysis showed colocalization of human p125 with Ergic53 (LMAN1; 601567) and beta-COP (COPB1; 600959) in fractionated rat brain or NRK cells.
Tani et al. (1999) found that mouse brain p125 bound to immobilized Sec23, and they confirmed the interaction between mouse Sec23 and human p125 by yeast 2-hybrid analysis and protein pull-down assays in transfected 293T cells. Mutation analysis revealed that the N-terminal domain of p125 was required for interaction with Sec23. Overexpression of p125 caused dispersion of the Golgi apparatus in Vero green monkey kidney cells and baby hamster kidney cells, suggesting that p125 is involved in the early secretory pathway.
By overexpression in Vero and HEK293 cells, Mizoguchi et al. (2000) found that human p125 colocalized with p115 (USO1; 603344) and GM130 (GOLGA2; 602580), which are involved in vesicle tethering to Golgi membranes. Truncation analysis revealed that the N-terminal proline-rich region of p125 was required for binding to Sec23, and that the proline-rich and phospholipase A1 homology regions were required for localization of p125 in the perinuclear region. Binding of p125 to Sec23 was weaker than binding of Sec24 to Sec23, suggesting that p125 interacts with Sec23 in a transient manner. Overexpression of p125 appeared to stabilize tethering proteins in the perinuclear region.
Hartz (2018) mapped the SEC23IP gene to chromosome 10q26.11-q26.12 based on an alignment of the SEC23IP sequence (GenBank AB09435) with the genomic sequence (GRCh38).
Hartz, P. A. Personal Communication. Baltimore, Md. 1/25/2018.
Mizoguchi, T., Nakajima, K., Hatsuzawa, K., Nagahama, M., Hauri, H.-P., Tagaya, M., Tani, K. Determination of functional regions of p125, a novel mammalian Sec23p-interacting protein. Biochem. Biophys. Res. Commun. 279: 144-149, 2000. [PubMed: 11112430] [Full Text: https://doi.org/10.1006/bbrc.2000.3846]
Tani, K., Mizoguchi, T., Iwamatsu, A., Hatsuzawa, K., Tagaya, M. p125 is a novel mammalian Sec23p-interacting protein with structural similarity to phospholipid-modifying proteins. J. Biol. Chem. 274: 20505-20512, 1999. [PubMed: 10400679] [Full Text: https://doi.org/10.1074/jbc.274.29.20505]