Rhomboid-related protein 2 explained

Rhomboid-related protein 2 is a protein that in humans is encoded by the RHBDL2 gene.^[1]

Function

The protein encoded by this gene is a member of the rhomboid protease family of integral membrane proteins. This family contains proteins that are related to Drosophila rhomboid-1. Members of this family are found in both prokaryotes and eukaryotes and are thought to function as intramembrane serine proteases.

RHBDL2 functions as a sheddase and is localized to the plasma membrane.^[2] Known substrates of RHBDL2 include thrombomodulin and epidermal growth factor; profiling of the substrate repertoire of RHBDL2 has identified a number of additional type I membrane proteins substrates, including BCAM, SPINT1, and CLCP1.^[3]

Further reading

• Adrain C, Strisovsky K, Zettl M, Hu L, Lemberg MK, Freeman M . Mammalian EGF receptor activation by the rhomboid protease RHBDL2 . EMBO Reports . 12 . 5 . 421–7 . May 2011 . 21494248 . 3090019 . 10.1038/embor.2011.50 .
• Pascall JC, Brown KD . Intramembrane cleavage of ephrinB3 by the human rhomboid family protease, RHBDL2 . Biochemical and Biophysical Research Communications . 317 . 1 . 244–52 . April 2004 . 15047175 . 10.1016/j.bbrc.2004.03.039 .
• Cheng TL, Wu YT, Lin HY, Hsu FC, Liu SK, Chang BI, Chen WS, Lai CH, Shi GY, Wu HL . 6 . Functions of rhomboid family protease RHBDL2 and thrombomodulin in wound healing . The Journal of Investigative Dermatology . 131 . 12 . 2486–94 . December 2011 . 21833011 . 10.1038/jid.2011.230 . free .
• Xu J, Zheng SL, Isaacs SD, Wiley KE, Wiklund F, Sun J, Kader AK, Li G, Purcell LD, Kim ST, Hsu FC, Stattin P, Hugosson J, Adolfsson J, Walsh PC, Trent JM, Duggan D, Carpten J, Grönberg H, Isaacs WB . 6 . Inherited genetic variant predisposes to aggressive but not indolent prostate cancer . Proceedings of the National Academy of Sciences of the United States of America . 107 . 5 . 2136–40 . February 2010 . 20080650 . 2836698 . 10.1073/pnas.0914061107 . 2010PNAS..107.2136X . free .
• Urban S, Freeman M . Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain . Molecular Cell . 11 . 6 . 1425–34 . June 2003 . 12820957 . 10.1016/s1097-2765(03)00181-3 . free .
• Urban S, Lee JR, Freeman M . Drosophila rhomboid-1 defines a family of putative intramembrane serine proteases . Cell . 107 . 2 . 173–82 . October 2001 . 11672525 . 10.1016/s0092-8674(01)00525-6 . 9026083 . free .
• Lei X, Li YM . The processing of human rhomboid intramembrane serine protease RHBDL2 is required for its proteolytic activity . Journal of Molecular Biology . 394 . 5 . 815–25 . December 2009 . 19850051 . 10.1016/j.jmb.2009.10.025 .

Notes and References

1. Web site: Entrez Gene: Rhomboid, veinlet-like 2 (Drosophila) .
2. Lichtenthaler SF, Lemberg MK, Fluhrer R . Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments . The EMBO Journal . 37 . 15 . August 2018 . 29976761 . 10.15252/embj.201899456 . 6068445 .
3. Johnson N, Březinová J, Stephens E, Burbridge E, Freeman M, Adrain C, Strisovsky K . Quantitative proteomics screen identifies a substrate repertoire of rhomboid protease RHBDL2 in human cells and implicates it in epithelial homeostasis . Scientific Reports . 7 . 1 . 7283 . August 2017 . 28779096 . 10.1038/s41598-017-07556-3 . 5544772 . 2017NatSR...7.7283J .