4u7i

Structural highlights

Disease

[SPG20_HUMAN] Defects in SPG20 are the cause of spastic paraplegia autosomal recessive type 20 (SPG20) [MIM:275900]; also known as Troyer syndrome (TRS). Spastic paraplegia is a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG20 is characterized by dysarthria, distal amyotrophy, mild developmental delay and short stature.^[1]

Function

[SPG20_HUMAN] May be implicated in endosomal trafficking, or microtubule dynamics, or both.^[2] [IST1_HUMAN] Proposed to be involved in specific functions of the ESCRT machinery. Is required for efficient abscission during cytokinesis, but not for HIV-1 budding. The involvement in the MVB pathway is not established. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells.^{[3] [4]}

References

1. ↑ Patel H, Cross H, Proukakis C, Hershberger R, Bork P, Ciccarelli FD, Patton MA, McKusick VA, Crosby AH. SPG20 is mutated in Troyer syndrome, an hereditary spastic paraplegia. Nat Genet. 2002 Aug;31(4):347-8. Epub 2002 Jul 22. PMID:12134148 doi:10.1038/ng937
2. ↑ Ciccarelli FD, Proukakis C, Patel H, Cross H, Azam S, Patton MA, Bork P, Crosby AH. The identification of a conserved domain in both spartin and spastin, mutated in hereditary spastic paraplegia. Genomics. 2003 Apr;81(4):437-41. PMID:12676568
3. ↑ Bajorek M, Morita E, Skalicky JJ, Morham SG, Babst M, Sundquist WI. Biochemical analyses of human IST1 and its function in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1360-73. doi: 10.1091/mbc.E08-05-0475. Epub 2009, Jan 7. PMID:19129479 doi:http://dx.doi.org/10.1091/mbc.E08-05-0475
4. ↑ Agromayor M, Carlton JG, Phelan JP, Matthews DR, Carlin LM, Ameer-Beg S, Bowers K, Martin-Serrano J. Essential role of hIST1 in cytokinesis. Mol Biol Cell. 2009 Mar;20(5):1374-87. doi: 10.1091/mbc.E08-05-0474. Epub 2009, Jan 7. PMID:19129480 doi:http://dx.doi.org/10.1091/mbc.E08-05-0474