4aw6

Structural highlights

Disease

FACE1_HUMAN Mandibuloacral dysplasia with type B lipodystrophy;Hutchinson-Gilford progeria syndrome;Lethal restrictive dermopathy. Mandibuloacral dysplasia with type B lipodystrophy (MADB) [MIM:608612: A disorder characterized by mandibular and clavicular hypoplasia, acroosteolysis, delayed closure of the cranial suture, joint contractures, and generalized lipodystrophy with loss of subcutaneous fat from the extremities, face, neck and trunk. Note=The disease is caused by mutations affecting the gene represented in this entry.^{[1] [2] [3] [4]} Lethal tight skin contracture syndrome (LTSCS) [MIM:275210: Rare disorder mainly characterized by intrauterine growth retardation, tight and rigid skin with erosions, prominent superficial vasculature and epidermal hyperkeratosis, facial features (small mouth, small pinched nose and micrognathia), sparse/absent eyelashes and eyebrows, mineralization defects of the skull, thin dysplastic clavicles, pulmonary hypoplasia, multiple joint contractures and an early neonatal lethal course. Liveborn children usually die within the first week of life. The overall prevalence of consanguineous cases suggested an autosomal recessive inheritance. Note=The disease is caused by mutations affecting the gene represented in this entry.^[5]

Function

FACE1_HUMAN Proteolytically removes the C-terminal three residues of farnesylated proteins. Acts on lamin A/C.

References

1. ↑ Agarwal AK, Fryns JP, Auchus RJ, Garg A. Zinc metalloproteinase, ZMPSTE24, is mutated in mandibuloacral dysplasia. Hum Mol Genet. 2003 Aug 15;12(16):1995-2001. PMID:12913070
2. ↑ Agarwal AK, Zhou XJ, Hall RK, Nicholls K, Bankier A, Van Esch H, Fryns JP, Garg A. Focal segmental glomerulosclerosis in patients with mandibuloacral dysplasia owing to ZMPSTE24 deficiency. J Investig Med. 2006 May;54(4):208-13. PMID:17152860
3. ↑ Miyoshi Y, Akagi M, Agarwal AK, Namba N, Kato-Nishimura K, Mohri I, Yamagata M, Nakajima S, Mushiake S, Shima M, Auchus RJ, Taniike M, Garg A, Ozono K. Severe mandibuloacral dysplasia caused by novel compound heterozygous ZMPSTE24 mutations in two Japanese siblings. Clin Genet. 2008 Jun;73(6):535-44. doi: 10.1111/j.1399-0004.2008.00992.x. Epub, 2008 Apr 22. PMID:18435794 doi:10.1111/j.1399-0004.2008.00992.x
4. ↑ Ahmad Z, Zackai E, Medne L, Garg A. Early onset mandibuloacral dysplasia due to compound heterozygous mutations in ZMPSTE24. Am J Med Genet A. 2010 Nov;152A(11):2703-10. doi: 10.1002/ajmg.a.33664. PMID:20814950 doi:10.1002/ajmg.a.33664
5. ↑ Navarro CL, De Sandre-Giovannoli A, Bernard R, Boccaccio I, Boyer A, Genevieve D, Hadj-Rabia S, Gaudy-Marqueste C, Smitt HS, Vabres P, Faivre L, Verloes A, Van Essen T, Flori E, Hennekam R, Beemer FA, Laurent N, Le Merrer M, Cau P, Levy N. Lamin A and ZMPSTE24 (FACE-1) defects cause nuclear disorganization and identify restrictive dermopathy as a lethal neonatal laminopathy. Hum Mol Genet. 2004 Oct 15;13(20):2493-503. Epub 2004 Aug 18. PMID:15317753 doi:10.1093/hmg/ddh265
6. ↑ Quigley A, Dong YY, Pike AC, Dong L, Shrestha L, Berridge G, Stansfeld PJ, Sansom MS, Edwards AM, Bountra C, von Delft F, Bullock AN, Burgess-Brown NA, Carpenter EP. The structural basis of ZMPSTE24-dependent laminopathies. Science. 2013 Mar 29;339(6127):1604-7. doi: 10.1126/science.1231513. PMID:23539603 doi:10.1126/science.1231513