ERGIC2 explained

Endoplasmic reticulum-Golgi intermediate compartment protein 2 (ERGIC2) ^[1] is a gene located on human chromosome 12p11. It encodes a protein of 377 amino acid residues. ERGIC2 protein is also known as PTX1, CDA14 or Erv41.

Function

The biological function of ERGIC2 protein is unknown, although it was initially identified as a candidate tumor suppressor of prostate cancer,^[2] and has been shown to induce cell growth arrest and senescence, to suppress colony formation in soft agar, and to decrease invasive potential of human prostate cancer cell line (PC-3 cells).^[3] It is now believed to be a chaperon molecule involved in protein trafficking between the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and Golgi.

Structure and interactions

The protein contains two hydrophobic transmembrane domains that help anchoring the molecule on the ER membrane, such that its large luminal domain orients inside the ER lumen and both the N- and C-termini are facing the cytosol. ERGIC2 forms a complex with two other proteins, ERGIC3 and ERGIC32, resulting in a shuttle for protein trafficking between ER and Golgi.^[4] It has been shown to interact with a number of proteins, such as beta-amyloid,^[5] protein elongation factor 1alpha,^[6] and otoferlin.^[7] Therefore, it may play an important role in cellular functions besides of being a component of a protein trafficking shuttle.More recently, a variant transcript of ERGIC2 has been reported.^[8] It has a deletion of four bases at the junction of exons 8 and 9, resulting a frame-shift mutation after codon #189. The variant transcript encodes a truncated protein of 215 residues, which loses 45% of the luminal domain and the transmembrane domain near the C-terminus. This effectively abrogates its function as a protein transporter. A similar variant is also reported in armadillo. So this is not a random mutation. The function of this truncated protein is unknown.

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Kwok SC, Liu X, Mangel P, Daskal I . PTX1(ERGIC2)-VP22 fusion protein upregulates interferon-beta in prostate cancer cell line PC-3 . DNA Cell Biol. . 25 . 9 . 523–9 . 2006 . 16989575 . 10.1089/dna.2006.25.523 .

Notes and References

1. Web site: Entrez Gene: ERGIC2 ERGIC and golgi 2.
2. Kwok SC, Liu X, Daskal I . Molecular cloning, expression, localization, and gene organization of PTX1, a human nuclear protein that is downregulated in prostate cancer . DNA Cell Biol. . 20 . 6 . 349–57 . 2001 . 11445006 . 10.1089/10445490152122460 .
3. Liu X, Daskal I, Kwok SC . Effects of PTX1 expression on growth and tumorigenicity of the prostate cancer cell line PC-3 . DNA Cell Biol. . 22 . 7 . 469–74 . 2003 . 12932305 . 10.1089/104454903322247343 .
4. Breuza L, Halbeisen R, Jenö P . Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46 . J. Biol. Chem. . 279 . 45 . 47242–53 . 2004 . 15308636 . 10.1074/jbc.M406644200 . etal. free .
5. Nelson TJ, Alkon DL . Protection against beta-amyloid-induced apoptosis by peptides interacting with beta-amyloid. . J Biol Chem . 282 . 43 . 31238–49 . 2007 . 17761669 . 10.1074/jbc.M705558200. free .
6. Yang YF, Chou MY, Fan CY, Chen SF, Lyu PC, Liu CC, Tseng TL . The possible interaction of CDA14 and protein elongation factor 1alpha. . Biochim Biophys Acta . 1784 . 2 . 312–8 . 2008 . 17980171 . 10.1016/j.bbapap.2007.10.006.
7. Zak M, Breß A, Brandt N, Franz C, Ruth P, Pfister M, Knipper M, Blin N . Ergic2, a brain specific interacting partner of otoferlin. . Cell Physiol Biochem . 29 . 5–6 . 941–8 . 2012 . 22613993 . 10.1159/000188338. free .
8. Kwok SC, Kumar S, Dai G . Characterization of a variant ERGIC2 transcript . DNA Cell Biol. . 33 . 2 . 73–78 . 2014 . 24303950 . 10.1089/dna.2013.2225 .