Spectrin, alpha 1

Spectrin, alpha, erythrocytic 1 (elliptocytosis 2)

PDB rendering based on 1owa.

Available structures
PDB	1OWA, 3LBX

Identifiers

Symbols

SPTA1; EL2; HPP; HS3; SPH3; SPTA

External IDs

OMIM: 182860 MGI: 98385 HomoloGene: 74460 GeneCards: SPTA1 Gene

Gene Ontology
Molecular function	• structural constituent of cytoskeleton • calcium ion binding • protein binding • actin filament binding
Cellular component	• cytoplasm • cytosol • cytosol • cell cortex • spectrin • spectrin-associated cytoskeleton • actin cytoskeleton • membrane • cortical cytoskeleton • intrinsic to internal side of plasma membrane • cuticular plate
Biological process	• porphyrin biosynthetic process • actin filament organization • axon guidance • regulation of cell shape • hemopoiesis • actin filament capping
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 1:
158.58 – 158.66 Mb

Chr 1:
176.1 – 176.18 Mb

PubMed search

[1]

[2]

Spectrin alpha chain, erythrocyte is a protein that in humans is encoded by the SPTA1 gene.^[1]

Spectrin is an actin crosslinking and molecular scaffold protein that links the plasma membrane to the actin cytoskeleton, and functions in the determination of cell shape, arrangement of transmembrane proteins, and organization of organelles. It is a tetramer made up of alpha-beta dimers linked in a head-to-head arrangement. This gene is one member of a family of alpha-spectrin genes. The encoded protein is primarily composed of 22 spectrin repeats which are involved in dimer formation. It forms weaker tetramer interactions than non-erythrocytic alpha spectrin, which may increase the plasma membrane elasticity and deformability of red blood cells. Mutations in this gene result in a variety of hereditary red blood cell disorders, including elliptocytosis type 2, pyropoikilocytosis, and spherocytic hemolytic anemia.^[1]

Interactions

Spectrin, alpha 1 has been shown to interact with Abl gene.^[2]

References

^ ^a ^b "Entrez Gene: SPTA1 spectrin, alpha, erythrocytic 1 (elliptocytosis 2)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6708.
^ Ziemnicka-Kotula, D; Xu J, Gu H, Potempska A, Kim K S, Jenkins E C, Trenkner E, Kotula L (May. 1998). "Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association of tyrosine kinases with the spectrin-based membrane skeleton". J. Biol. Chem. (UNITED STATES) 273 (22): 13681–92. doi:10.1074/jbc.273.22.13681. ISSN 0021-9258. PMID 9593709.

Gallagher PG, Forget BG (1993). "Spectrin genes in health and disease.". Semin. Hematol. 30 (1): 4–20. PMID 8094577.
Delaunay J, Dhermy D (1993). "Mutations involving the spectrin heterodimer contact site: clinical expression and alterations in specific function.". Semin. Hematol. 30 (1): 21–33. PMID 8434258.
Snásel J, Pichová I (1997). "The cleavage of host cell proteins by HIV-1 protease.". Folia Biol. (Praha) 42 (5): 227–30. doi:10.1007/BF02818986. PMID 8997639.
Iolascon A, Miraglia del Giudice E, Perrotta S, et al. (1998). "Hereditary spherocytosis: from clinical to molecular defects.". Haematologica 83 (3): 240–57. PMID 9573679.
De Matteis MA, Morrow JS (2000). "Spectrin tethers and mesh in the biosynthetic pathway.". J. Cell. Sci. 113 ( Pt 13): 2331–43. PMID 10852813.
Delaunay J (2003). "Molecular basis of red cell membrane disorders.". Acta Haematol. 108 (4): 210–8. doi:10.1159/000065657. PMID 12432217.
Dhermy D, Schrével J, Lecomte MC (2007). "Spectrin-based skeleton in red blood cells and malaria.". Curr. Opin. Hematol. 14 (3): 198–202. doi:10.1097/MOH.0b013e3280d21afd. PMID 17414207.
Hentati A, Hu P, Asgharzadeh S, Siddique T (1993). "Dinucleotide repeat polymorphism at the human erythroid alpha spectrin (SPTA1) locus.". Hum. Mol. Genet. 1 (3): 218. doi:10.1093/hmg/1.3.218-a. PMID 1339473.
Kanzaki A, Rabodonirina M, Yawata Y, et al. (1992). "A deletional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin Tokyo (beta 220/216).". Blood 80 (8): 2115–21. PMID 1391962.
Gallagher PG, Tse WT, Coetzer T, et al. (1992). "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. 89 (3): 892–8. doi:10.1172/JCI115669. PMC 442935. PMID 1541680. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=442935.
Speicher DW, Weglarz L, DeSilva TM (1992). "Properties of human red cell spectrin heterodimer (side-to-side) assembly and identification of an essential nucleation site.". J. Biol. Chem. 267 (21): 14775–82. PMID 1634521.
Alloisio N, Wilmotte R, Morlé L, et al. (1992). "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 80 (3): 809–15. PMID 1638030.
Kotula L, Laury-Kleintop LD, Showe L, et al. (1991). "The exon-intron organization of the human erythrocyte alpha-spectrin gene.". Genomics 9 (1): 131–40. doi:10.1016/0888-7543(91)90230-C. PMID 1672285.
Coetzer TL, Sahr K, Prchal J, et al. (1991). "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. 88 (3): 743–9. doi:10.1172/JCI115371. PMC 295451. PMID 1679439. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=295451.
Sahr KE, Laurila P, Kotula L, et al. (1990). "The complete cDNA and polypeptide sequences of human erythroid alpha-spectrin.". J. Biol. Chem. 265 (8): 4434–43. PMID 1689726.
Gallagher PG, Tse WT, Marchesi SL, et al. (1993). "A defect in alpha-spectrin mRNA accumulation in hereditary pyropoikilocytosis.". Trans. Assoc. Am. Physicians 104: 32–9. PMID 1845156.
Floyd PB, Gallagher PG, Valentino LA, et al. (1991). "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 78 (5): 1364–72. PMID 1878597.
Shoeman RL, Kesselmier C, Mothes E, et al. (1991). "Non-viral cellular substrates for human immunodeficiency virus type 1 protease.". FEBS Lett. 278 (2): 199–203. doi:10.1016/0014-5793(91)80116-K. PMID 1991513.
Garbarz M, Tse WT, Gallagher PG, et al. (1991). "Spectrin Rouen (beta 220-218), a novel shortened beta-chain variant in a kindred with hereditary elliptocytosis. Characterization of the molecular defect as exon skipping due to a splice site mutation.". J. Clin. Invest. 88 (1): 76–81. doi:10.1172/JCI115307. PMC 296005. PMID 2056132. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=296005.
Tse WT, Gallagher PG, Pothier B, et al. (1991). "An insertional frameshift mutation of the beta-spectrin gene associated with elliptocytosis in spectrin nice (beta 220/216).". Blood 78 (2): 517–23. PMID 2070088.

PDB gallery

1owa: Solution Structural Studies on Human Erythrocyte Alpha Spectrin N Terminal Tetramerization Domain

Proteins of the cytoskeleton

Human

Microfilaments
(ABPs)

Myofilament

Actins	A1, A2, B, C1, G1, G2

Myosins	I (MYO1A, MYO1B, MYO1C, MYO1D, MYO1E, MYO1F, MYO1G, MYO1H) · II (MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH7B, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, MYH16) · III (MYO3A, MYO3B) · V (MYO5A, MYO5B, MYO5C) · VI (MYO6) · VII (MYO7A, MYO7B) · IX (MYO9A, MYO9B) · X (MYO10) · XV (MYO15A) · XVIII (MYO18A, MYO18B) · LC (MYL1, MYL2, MYL3, MYL4, MYL5, MYL6, MYL6B, MYL7, MYL9, MYLIP, MYLK, MYLK2, MYLL1)

Other	Tropomodulin (1, 2, 3, 4) · Troponin (T 1 2 3, C 1 2, I 1 2 3) · Tropomyosin (1, 2, 3, 4) Actinin (1, 2, 3, 4) · Arp2/3 complex · actin depolymerizing factors (Cofilin (1, 2) · Destrin) · Gelsolin · Profilin (1, 2) · Titin

Other

Wiskott-Aldrich syndrome protein · Fibrillin · Filamin (FLNA, FLNB, FLNC) · Espin · TRIOBP

IFs

Type 1/2
(Keratin,
Cytokeratin)

Epithelial keratins (soft alpha-keratins)	type I/chromosome 17 (10, 12, 13, 14, 15, 16, 17, 19, 20) · chromosome 12 (18) · none (21) type II/chromosome 12 (1, 2A, 3, 4, 5, 6A, 6B, 7, 8, 9)

Hair keratins (hard alpha-keratins)	type I/chromosome 17 (31, 32, 33A, 33B, 34, 35, 36, 37, 38) type II/chromosome 12 (81, 82, 83, 84, 85, 86)

Ungrouped alpha	chromosome 17 (23, 24, 25, 26, 27, 28, 39, 40) chromosome 12 (71, 72, 73, 74, 75, 76, 77, 78, 79, 80)

Not alpha	Beta-keratin

Type 3

Desmin, GFAP, Peripherin, Vimentin

Type 4

Internexin, Nestin, Neurofilament (NEFL, NEFM, NEFH), Synemin, Syncoilin

Type 5

Lamin A, B

Microtubules/
MAPs

Kinesins	KIF1A, KIF1B, KIF2A, KIF2C, KIF3B, KIF3C, KIF4A, KIF4B, KIF5A, KIF5B, KIF5C, KIF6, KIF7, KIF9, KIF11, KIF12, KIF13A, KIF13B, KIF14, KIF15, KIF16B, KIF17, KIF18A, KIF18B, KIF19, KIF20A, KIF20B, KIF21A, KIF21B, KIF22, KIF23, KIF24, KIF25, KIF26A, KIF26B, KIF27, KIFC1, KIFC2, KIFC3

Dyneins	axonemal: DNAH1, DNAH2, DNAH3, DNAH5, DNAH6, DNAH7, DNAH8, DNAH9, DNAH10, DNAH11, DNAH12, DNAH13, DNAH14, DNAH17, DNAI1, DNAI2, DNALI1, DNAL1, DNAL4 cytoplasmic: DYNC1H1, DYNC2H1, DYNC1I1, DYNC1I2, DYNC1LI1, DYNC1LI2, DYNC2LI1, DYNLL1, DYNLL2, DYNLRB1, DYNLRB2, DYNLT1, DYNLT3

Other	Tau protein · Dynactin (DCTN1) · Tubulins (TUBA1A, TUBA1B, TUBA1C, TUBA3C, TUBA3D, TUBA3E, TUBA4A, TUBA8) · Stathmin · Tektin (TEKT1, TEKT2, TEKT3, TEKT4, TEKT5) · Dynamin (DNM1, DNM2, DNM3)

Catenins

Alpha catenin · Beta catenin (APC) · Plakoglobin (gamma catenin) · Delta catenin · GAN

Membrane

Dystrophin (Dystroglycan) · Utrophin · Ankyrin (ANK1, ANK2, ANK3) · Spectrin (SPTA1, SPTAN1, SPTB, SPTBN1, SPTBN2, SPTBN4, SPTBN5)

Other

plakin (Desmoplakin, Plectin) · Talin (TLN1) · Vinculin · Plakophilin (PKP1, PKP2)

Nonhuman

Major sperm proteins · Prokaryotic cytoskeleton (Crescentin, FtsZ, MreB)

see also cytoskeletal defects
B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)

Spectrin, alpha 1

Interactions

References

Further reading