5j4o

Structural highlights

Disease

[SPTA1_HUMAN] Defects in SPTA1 are the cause of elliptocytosis type 2 (EL2) [MIM:130600]. EL2 is a Rhesus-unlinked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]} Defects in SPTA1 are a cause of hereditary pyropoikilocytosis (HPP) [MIM:266140]. HPP is an autosomal recessive disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.^[13] Defects in SPTA1 are the cause of spherocytosis type 3 (SPH3) [MIM:270970]; also known as hereditary spherocytosis type 3 (HS3). Spherocytosis is a hematologic disorder leading to chronic hemolytic anemia and characterized by numerous abnormally shaped erythrocytes which are generally spheroidal. SPH3 is characterized by severe hemolytic anemia. Inheritance is autosomal recessive.

Function

[SPTA1_HUMAN] Spectrin is the major constituent of the cytoskeletal network underlying the erythrocyte plasma membrane. It associates with band 4.1 and actin to form the cytoskeletal superstructure of the erythrocyte plasma membrane.

References

1. ↑ Sahr KE, Tobe T, Scarpa A, Laughinghouse K, Marchesi SL, Agre P, Linnenbach AJ, Marchesi VT, Forget BG. Sequence and exon-intron organization of the DNA encoding the alpha I domain of human spectrin. Application to the study of mutations causing hereditary elliptocytosis. J Clin Invest. 1989 Oct;84(4):1243-52. PMID:2794061 doi:http://dx.doi.org/10.1172/JCI114291
2. ↑ Parquet N, Devaux I, Boulanger L, Galand C, Boivin P, Lecomte MC, Dhermy D, Garbarz M. Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis: further support for a triple-stranded folding unit model of the spectrin heterodimer contact site. Blood. 1994 Jul 1;84(1):303-8. PMID:8018926
3. ↑ Coetzer TL, Sahr K, Prchal J, Blacklock H, Peterson L, Koler R, Doyle J, Manaster J, Palek J. Four different mutations in codon 28 of alpha spectrin are associated with structurally and functionally abnormal spectrin alpha I/74 in hereditary elliptocytosis. J Clin Invest. 1991 Sep;88(3):743-9. PMID:1679439 doi:http://dx.doi.org/10.1172/JCI115371
4. ↑ Floyd PB, Gallagher PG, Valentino LA, Davis M, Marchesi SL, Forget BG. Heterogeneity of the molecular basis of hereditary pyropoikilocytosis and hereditary elliptocytosis associated with increased levels of the spectrin alpha I/74-kilodalton tryptic peptide. Blood. 1991 Sep 1;78(5):1364-72. PMID:1878597
5. ↑ Lecomte MC, Garbarz M, Grandchamp B, Feo C, Gautero H, Devaux I, Bournier O, Galand C, d'Auriol L, Galibert F, et al.. Sp alpha I/78: a mutation of the alpha I spectrin domain in a white kindred with HE and HPP phenotypes. Blood. 1989 Aug 15;74(3):1126-33. PMID:2568862
6. ↑ Gallagher PG, Tse WT, Coetzer T, Lecomte MC, Garbarz M, Zarkowsky HS, Baruchel A, Ballas SK, Dhermy D, Palek J, et al.. A common type of the spectrin alpha I 46-50a-kD peptide abnormality in hereditary elliptocytosis and pyropoikilocytosis is associated with a mutation distant from the proteolytic cleavage site. Evidence for the functional importance of the triple helical model of spectrin. J Clin Invest. 1992 Mar;89(3):892-8. PMID:1541680 doi:http://dx.doi.org/10.1172/JCI115669
7. ↑ Dalla Venezia N, Alloisio N, Forissier A, Denoroy L, Aymerich M, Vives-Corrons JL, Besalduch J, Besson I, Delaunay J. Elliptopoikilocytosis associated with the alpha 469 His-->Pro mutation in spectrin Barcelona (alpha I/50-46b). Blood. 1993 Sep 1;82(5):1661-5. PMID:8364215
8. ↑ Morle L, Roux AF, Alloisio N, Pothier B, Starck J, Denoroy L, Morle F, Rudigoz RC, Forget BG, Delaunay J, et al.. Two elliptocytogenic alpha I/74 variants of the spectrin alpha I domain. Spectrin Culoz (GGT----GTT; alpha I 40 Gly----Val) and spectrin Lyon (CTT----TTT; alpha I 43 Leu---Phe). J Clin Invest. 1990 Aug;86(2):548-54. PMID:2384601 doi:http://dx.doi.org/10.1172/JCI114743
9. ↑ Alloisio N, Wilmotte R, Morle L, Baklouti F, Marechal J, Ducluzeau MT, Denoroy L, Feo C, Forget BG, Kastally R, et al.. Spectrin Jendouba: an alpha II/31 spectrin variant that is associated with elliptocytosis and carries a mutation distant from the dimer self-association site. Blood. 1992 Aug 1;80(3):809-15. PMID:1638030
10. ↑ Morle L, Morle F, Roux AF, Godet J, Forget BG, Denoroy L, Garbarz M, Dhermy D, Kastally R, Delaunay J. Spectrin Tunis (Sp alpha I/78), an elliptocytogenic variant, is due to the CGG----TGG codon change (Arg----Trp) at position 35 of the alpha I domain. Blood. 1989 Aug 1;74(2):828-32. PMID:2568861
11. ↑ Perrotta S, Miraglia del Giudice E, Alloisio N, Sciarratta G, Pinto L, Delaunay J, Cutillo S, Iolascon A. Mild elliptocytosis associated with the alpha 34 Arg-->Trp mutation in spectrin Genova (alpha I/74). Blood. 1994 Jun 1;83(11):3346-9. PMID:8193371
12. ↑ Perrotta S, Iolascon A, De Angelis F, Pagano L, Colonna G, Cutillo S, Miraglia del Giudice E. Spectrin Anastasia (alpha I/78): a new spectrin variant (alpha 45 Arg-->Thr) with moderate elliptocytogenic potential. Br J Haematol. 1995 Apr;89(4):933-6. PMID:7772539
13. ↑ Floyd PB, Gallagher PG, Valentino LA, Davis M, Marchesi SL, Forget BG. Heterogeneity of the molecular basis of hereditary pyropoikilocytosis and hereditary elliptocytosis associated with increased levels of the spectrin alpha I/74-kilodalton tryptic peptide. Blood. 1991 Sep 1;78(5):1364-72. PMID:1878597