6anu

Structural highlights

Disease

[ACTB_HUMAN] Defects in ACTB are a cause of dystonia juvenile-onset (DYTJ) [MIM:607371]. DYTJ is a form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYTJ patients manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss.^[1] Defects in ACTB are the cause of Baraitser-Winter syndrome type 1 (BRWS1) [MIM:243310]. A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss.^[2] [SPTN2_HUMAN] Defects in SPTBN2 are the cause of spinocerebellar ataxia type 5 (SCA5) [MIM:600224]. Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA5 is an autosomal dominant cerebellar ataxia (ADCA). It is a slowly progressive disorder with variable age at onset, ranging between 10 and 50 years.^[3]

Function

[ACTB_HUMAN] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [SPTN2_HUMAN] Probably plays an important role in neuronal membrane skeleton.

See Also

• Actin 3D structures
• Spectrin

References

1. ↑ Procaccio V, Salazar G, Ono S, Styers ML, Gearing M, Davila A, Jimenez R, Juncos J, Gutekunst CA, Meroni G, Fontanella B, Sontag E, Sontag JM, Faundez V, Wainer BH. A mutation of beta -actin that alters depolymerization dynamics is associated with autosomal dominant developmental malformations, deafness, and dystonia. Am J Hum Genet. 2006 Jun;78(6):947-60. Epub 2006 Apr 21. PMID:16685646 doi:S0002-9297(07)63917-2
2. ↑ Riviere JB, van Bon BW, Hoischen A, Kholmanskikh SS, O'Roak BJ, Gilissen C, Gijsen S, Sullivan CT, Christian SL, Abdul-Rahman OA, Atkin JF, Chassaing N, Drouin-Garraud V, Fry AE, Fryns JP, Gripp KW, Kempers M, Kleefstra T, Mancini GM, Nowaczyk MJ, van Ravenswaaij-Arts CM, Roscioli T, Marble M, Rosenfeld JA, Siu VM, de Vries BB, Shendure J, Verloes A, Veltman JA, Brunner HG, Ross ME, Pilz DT, Dobyns WB. De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome. Nat Genet. 2012 Feb 26;44(4):440-4, S1-2. doi: 10.1038/ng.1091. PMID:22366783 doi:10.1038/ng.1091
3. ↑ Ikeda Y, Dick KA, Weatherspoon MR, Gincel D, Armbrust KR, Dalton JC, Stevanin G, Durr A, Zuhlke C, Burk K, Clark HB, Brice A, Rothstein JD, Schut LJ, Day JW, Ranum LP. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet. 2006 Feb;38(2):184-90. Epub 2006 Jan 22. PMID:16429157 doi:10.1038/ng1728
4. ↑ Avery AW, Fealey ME, Wang F, Orlova A, Thompson AR, Thomas DD, Hays TS, Egelman EH. Structural basis for high-affinity actin binding revealed by a beta-III-spectrin SCA5 missense mutation. Nat Commun. 2017 Nov 7;8(1):1350. doi: 10.1038/s41467-017-01367-w. PMID:29116080 doi:http://dx.doi.org/10.1038/s41467-017-01367-w