ANTXR2 explained

Anthrax toxin receptor 2 (also known as capillary morphogenesis gene 2 or CMG2) is a protein that in humans is encoded by the ANTXR2 gene.^{[1] [2] [3]}

Mutations in ANTXR2 are associated with infantile systemic hyalinosis^{[4] [5]} and juvenile systemic hyalinosis, both autosomal recessive disorders.^{[6] [7]} Biallelic missense mutations of ANTXR2 have been described in a case report of atypical infantile systemic hyalinosis with intestinal lymphangiectasia causing protein-losing enteropathy.^{[8] [9]} Deuquet et al. (2009) found that three out of four missense mutations in the von Willebrand domain of ANTXR2 identified from cases of infantile systemic hyalinosis resulted in partial or complete retention of the protein in the endoplasmic reticulum (ER) of transfected HeLa cells and anthrax toxin receptor–deficient Chinese hamster ovary cells, as did a mutation in the transmembrane domain. They speculate that, for certain mutations, assisting the proper folding and surface expression of ANTXR2 by chemical chaperones may allow for rescue of phenotype, as these proteins appeared to be relatively stable in the ER without rapid degradation by endoplasmic-reticulum-associated protein degradation.^[4]

See also

• Anthrax toxin

Further reading

• Toward a complete human genome sequence . Genome Res. . 8 . 11 . 1097–108 . 1999 . 9847074 . 10.1101/gr.8.11.1097. free . Sanger Centre . The . Washington University Genome Sequencing Cente . The .
• 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 .
• Abrami L, Liu S, Cosson P . Anthrax toxin triggers endocytosis of its receptor via a lipid raft-mediated clathrin-dependent process . J. Cell Biol. . 160 . 3 . 321–8 . 2003 . 12551953 . 10.1083/jcb.200211018 . 2172673 . etal.
• Dowling O, Difeo A, Ramirez MC . Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis . Am. J. Hum. Genet. . 73 . 4 . 957–66 . 2003 . 12973667 . 10.1086/378781 . 1180616 . etal.
• Hanks S, Adams S, Douglas J . Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis . Am. J. Hum. Genet. . 73 . 4 . 791–800 . 2003 . 14508707 . 10.1086/378418 . 1180602 . etal.
• 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 .
• Wigelsworth DJ, Krantz BA, Christensen KA . Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen . J. Biol. Chem. . 279 . 22 . 23349–56 . 2004 . 15044490 . 10.1074/jbc.M401292200 . etal. free .
• Lacy DB, Wigelsworth DJ, Scobie HM . Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor . Proc. Natl. Acad. Sci. U.S.A. . 101 . 17 . 6367–72 . 2004 . 15079089 . 10.1073/pnas.0401506101 . 404051 . 2004PNAS..101.6367L . etal. free .
• Colland F, Jacq X, Trouplin V . Functional proteomics mapping of a human signaling pathway . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 . etal.
• Santelli E, Bankston LA, Leppla SH, Liddington RC . Crystal structure of a complex between anthrax toxin and its host cell receptor . Nature . 430 . 7002 . 905–8 . 2004 . 15243628 . 10.1038/nature02763 . 2004Natur.430..905S . 4398499 .
• Lacy DB, Wigelsworth DJ, Melnyk RA . Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation . Proc. Natl. Acad. Sci. U.S.A. . 101 . 36 . 13147–51 . 2004 . 15326297 . 10.1073/pnas.0405405101 . 516539 . 2004PNAS..10113147L . etal. free .
• Abrami L, Lindsay M, Parton RG . Membrane insertion of anthrax protective antigen and cytoplasmic delivery of lethal factor occur at different stages of the endocytic pathway . J. Cell Biol. . 166 . 5 . 645–51 . 2004 . 15337774 . 10.1083/jcb.200312072 . 2172425 . etal.
• 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.
• Lee JY, Tsai YM, Chao SC, Tu YF . Capillary morphogenesis gene-2 mutation in infantile systemic hyalinosis: ultrastructural study and mutation analysis in a Taiwanese infant . Clin. Exp. Dermatol. . 30 . 2 . 176–9 . 2005 . 15725249 . 10.1111/j.1365-2230.2004.01698.x . 45945185 .
• Abrami L, Leppla SH, van der Goot FG . Receptor palmitoylation and ubiquitination regulate anthrax toxin endocytosis . J. Cell Biol. . 172 . 2 . 309–20 . 2006 . 16401723 . 10.1083/jcb.200507067 . 2063559 .
• Gao M, Schulten K . Onset of anthrax toxin pore formation . Biophys. J. . 90 . 9 . 3267–79 . 2007 . 16473908 . 10.1529/biophysj.105.079376 . 1432108 .
• Wei W, Lu Q, Chaudry GJ . The LDL receptor-related protein LRP6 mediates internalization and lethality of anthrax toxin . Cell . 124 . 6 . 1141–54 . 2006 . 16564009 . 10.1016/j.cell.2005.12.045 . etal. free .

Notes and References

1. Bell SE, Mavila A, Salazar R, Bayless KJ, Kanagala S, Maxwell SA, Davis GE . Differential gene expression during capillary morphogenesis in 3D collagen matrices: regulated expression of genes involved in basement membrane matrix assembly, cell cycle progression, cellular differentiation and G-protein signaling . J Cell Sci . 114 . Pt 15 . 2755–73 . Oct 2001 . 10.1242/jcs.114.15.2755 . 11683410 .
2. Scobie HM, Rainey GJ, Bradley KA, Young JA . Human capillary morphogenesis protein 2 functions as an anthrax toxin receptor . Proc Natl Acad Sci U S A . 100 . 9 . 5170–4 . Apr 2003 . 12700348 . 154317 . 10.1073/pnas.0431098100 . 2003PNAS..100.5170S . free .
3. Web site: Entrez Gene: ANTXR2 anthrax toxin receptor 2.
4. Deuquet J, Abrami L, Difeo A, Ramirez MC, Martignetti JA, Gisou van der Goot F. Systemic Hyalinosis Mutations in the CMG2 Ectodomain Leading to Loss of Function Through Retention in the Endoplasmic Reticulum. Human Mutation. 30. 4. 583–589. 2009. 10.1002/humu.20872. 19191226. free.
5. Web site: HYALINE FIBROMATOSIS SYNDROME; HFS. Online Mendelian Inheritance in Man.
   1. 228600
   . 30 January 2024. Kniffin. Cassandra L.. McKusick. Victor A.. 14 January 2013. Originally published 3 June 1986.
6. Dowling O, Difeo A, Ramirez MC, Tukel T, Narla G, Bonafe L, Kayserili H, Yuksel-Apak M, Paller AS, Norton K, Teebi AS, Grum-Tokars V, Martin GS, Davis GE, Glucksman MJ, Martignetti JA. Mutations in Capillary Morphogenesis Gene-2 Result in the Allelic Disorders Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis. The American Journal of Human Genetics. 73. 4. 10.1086/378781. 2003. 957–966. 12973667. 1180616. free.
7. El-Kamah GY, Fong K, El-Ruby M, Afifi HH, Clements SE, Lai-Cheong JE, Amr K, El-Darouti M, McGrath JA. Spectrum of mutations in the ANTXR2 (CMG2) gene in infantile systemic hyalinosis and juvenile hyaline fibromatosis. British Journal of Dermatology. 163. 1. 2010. 213–215. 10.1111/j.1365-2133.2010.09769.x. 20331448. 232096 .
8. Alreheili K, AlMehaidib A, Alsaleem K, Banemi M, Aldekhail W, Al-Mayouf SM. Intestinal lymphangiectasia in a patient with infantile systemic hyalinosis syndrome: a rare cause of protein-losing enteropathy. Annals of Saudi Medicine. 32. 2. 206–208. 2012. 10.5144/0256-4947.2012.206. free. 22366835. 6086646.
9. Ozen A, Lenardo MJ. Protein-Losing Enteropathy. The New England Journal of Medicine. 389. 2023. 733–748. 8. 10.1056/NEJMra2301594. 37611123. 261099908 .