KDELR2 explained

ER lumen protein retaining receptor 2 is a protein that in humans is encoded by the KDELR2 gene.^{[1] [2] [3]}

Retention of resident soluble proteins in the lumen of the endoplasmic reticulum (ER) is achieved in both yeast and animal cells by their continual retrieval from the cis-Golgi, or a pre-Golgi compartment. Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, lys-asp-glu-leu (KDEL) in animal cells and his-asp-glu-leu (HDEL) in S. cerevisiae. This process is mediated by a receptor that recognizes, and binds the tetrapeptide-containing protein, and returns it to the ER. In yeast, the sorting receptor encoded by a single gene, ERD2, is a seven-transmembrane protein. Unlike yeast, several human homologs of the ERD2 gene, constituting the KDEL receptor gene family, have been described. KDELR2 was the second member of the family to be identified, and it encodes a protein which is 83% identical to the KDELR1 gene product.

Clinical significance

Pathogenic variants in KDELR2 have been linked to Osteogenesis imperfecta.^[4]

See also

• KDELR1
• KDELR3

Further reading

• Pelham HR . The dynamic organisation of the secretory pathway . Cell Structure and Function . 21 . 5 . 413–419 . October 1996 . 9118249 . 10.1247/csf.21.413 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S . Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes . Genome Research . 16 . 1 . 55–65 . January 2006 . 16344560 . 1356129 . 10.1101/gr.4039406 .
• van der Vlies D, Pap EH, Post JA, Celis JE, Wirtz KW . Endoplasmic reticulum resident proteins of normal human dermal fibroblasts are the major targets for oxidative stress induced by hydrogen peroxide . The Biochemical Journal . 366 . Pt 3 . 825–830 . September 2002 . 12071860 . 1222834 . 10.1042/BJ20020618 .
• Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z, Han ZG . Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver . Proceedings of the National Academy of Sciences of the United States of America . 98 . 26 . 15089–15094 . December 2001 . 11752456 . 64988 . 10.1073/pnas.241522398 . free . 2001PNAS...9815089X .

Notes and References

1. Hsu VW, Shah N, Klausner RD . A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1 . Cell . 69 . 4 . 625–635 . May 1992 . 1316805 . 7133352 . 10.1016/0092-8674(92)90226-3 .
2. Lewis MJ, Pelham HR . Sequence of a second human KDEL receptor . Journal of Molecular Biology . 226 . 4 . 913–916 . August 1992 . 1325562 . 10.1016/0022-2836(92)91039-R .
3. Web site: Entrez Gene: KDELR2 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2.
4. Efthymiou S, Herman I, Rahman F, Anwar N, Maroofian R, Yip J, Mitani T, Calame DG, Hunter JV, Sutton VR, Yilmaz Gulec E, Duan R, Fatih JM, Marafi D, Pehlivan D, Jhangiani SN, Gibbs RA, Posey JE, Maqbool S, Lupski JR, Houlden H . Two novel bi-allelic KDELR2 missense variants cause osteogenesis imperfecta with neurodevelopmental features . American Journal of Medical Genetics. Part A . 185 . 7 . 2241–2249 . July 2021 . 33964184 . 8436746 . 10.1002/ajmg.a.62221 .