|SMART accession number:||SM00150|
|Interpro abstract (IPR018159):|
Spectrin repeats [(PUBMED:8266097)] are found in several proteins involved in cytoskeletal structure. These include spectrin alpha and beta subunits [(PUBMED:12672815), (PUBMED:15062087)], alpha-actinin [(PUBMED:10481917)] and dystrophin. The spectrin repeat forms a three-helix bundle. The second helix is interrupted by proline in some sequences. The repeats are defined by a characteristic tryptophan (W) residue at position 17 in helix A and a leucine (L) at 2 residues from the carboxyl end of helix C.
Click on the following links for more information.
- Evolution (species in which this domain is found)
Click on to expand nodes. To display all proteins with a SPEC domain in a specific node, click on it.
This tree shows only several representative species. The complete taxonomic breakdown of all proteins with SPEC domain is also avaliable.
Useful shortcuts: Expand all nodes or Collapse tree
Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Viel A
- Alpha-actinin and spectrin structures: an unfolding family story.
- FEBS Lett. 1999; 460: 391-4
- Display abstract
In red blood cells, the integrity of the spectrin network is essential for normal cell shape and elasticity. To understand the molecular basis for spectrin's mechanical properties, one must determine how spectrin subunits interact with each other. The newly described crystallographic structures of two consecutive homologous repeats of human alpha-actinin, a member of the spectrin superfamily, shed new light on alpha-actinin interchain binding properties. Here I present evidence that interchain binding at the tail end of the spectrin molecule is likely to occur via a mechanism similar to that observed for alpha-actinin.
- Pascual J, Castresana J, Saraste M
- Evolution of the spectrin repeat.
- Bioessays. 1997; 19: 811-7
- Display abstract
We now know that the evolution of multidomain proteins has frequently involved genetic duplication events. These, however, are sometimes difficult to trace because of low sequence similarity between duplicated segments. Spectrin, the major component of the membrane skeleton that provides elasticity to the cell, contains tandemly repeated sequences of 106 amino acid residues. The same repeats are also present in alpha-actinin, dystrophin and utrophin. Sequence alignments and phylogenetic trees of these domains allow us to interpret the evolutionary relationship between these proteins, concluding that spectrin evolved from alpha-actinin by an elongation process that included two duplications of a block of seven repeats. This analysis shows how a modular protein unit can be used in the evolution of large cytoskeletal structures.
- Wasenius VM, Narvanen O, Lehto VP, Saraste M
- Alpha-actinin and spectrin have common structural domains.
- FEBS Lett. 1987; 221: 73-6
- Display abstract
The alpha- and beta-subunits of spectrin are made of repeated homologous units of 106 residues. In the recently reported partial sequence of the chicken non-muscle alpha-actinin, a repetitive sequence homologous to the internal repeat in spectrin occurs several times. Both spectrin and alpha-actinin are components of the cytoskeletal network, the integrity of which is based on multiple and complex interactions. We suggest that the shared domain structure indicates common structural principles or interactions of spectrin and alpha-actinin and reflects their common evolution.
- Speicher DW
- The present status of erythrocyte spectrin structure: the 106-residue repetitive structure is a basic feature of an entire class of proteins.
- J Cell Biochem. 1986; 30: 245-58
- Display abstract
Spectrin, the major component of the erythroid membrane skeleton, is a long, asymmetrical rodlike protein that interacts with several other proteins to form a two-dimensional membrane skeleton. Progress in several laboratories over the past few years including substantial partial peptide and nucleotide sequence determination has greatly enhanced our knowledge of the structural properties of this large molecule (heterodimer = 465,000 daltons). The alpha and beta subunits are homologous with approximately 30% identity. They are aligned in an antiparallel side-to-side orientation with the amino- and carboxy-termini near opposite physical ends of the molecule. The predominant structural feature elucidated from sequencing this large molecule is the nearly universal occurrence in both subunits of a single type of repetitive structure. The periodicity of this homologous structure is exactly 106 amino acid residues. As many as 36 homologous, but nonidentical, repeats exist and comprise more than 90% of the mass of the heterodimer. Each of these repetitive units is folded into a triple-stranded structure that is highly helical. Peptide maps, antibody crossreactivity, peptide sequence analysis, and more recently nucleic acid sequences have defined several major properties of the erythroid molecule and related proteins in other tissues. Tissue-specific spectrins have the same 106-residue repetitive structure and show sequence homology to erythroid spectrin.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the SPEC domain.
Protein Disease Spectrin alpha chain, erythrocyte (P02549) (SMART) OMIM:182860: Elliptocytosis-2 ; Pyropoikilocytosis ; Spherocytosis, recessive Spectrin beta chain, erythrocyte (P11277) (SMART) OMIM:182870: Elliptocytosis-3 ; Spherocytosis-1 ; Anemia, neonatal hemolytic, fatal and near-fatal
- Metabolism (metabolic pathways involving proteins which contain this domain)
% proteins involved KEGG pathway ID Description 24.84 map04520 Adherens junction 24.84 map04810 Regulation of actin cytoskeleton 24.84 map04530 Tight junction 24.84 map04510 Focal adhesion 0.65 map04610 Complement and coagulation cascades
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with SPEC domain which could be assigned to a KEGG orthologous group, and not all proteins containing SPEC domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of SPEC domains in PDB
PDB code Main view Title 1aj3 Solution structure of the spectrin repeat, nmr, 20 structures 1cun Crystal structure of repeats 16 and 17 of chicken brain alpha spectrin 1g8x Structure of a genetically engineered molecular motor 1hci Crystal structure of the rod domain of alpha-actinin 1owa Solution structural studies on human erythrocyte alpha spectrin n terminal tetramerization domain 1quu Crystal structure of two central spectrin-like repeats from alpha-actinin 1s35 Crystal structure of repeats 8 and 9 of human erythroid spectrin 1sjj Cryo-em structure of chicken gizzard smooth muscle alpha- actinin 1u4q Crystal structure of repeats 15, 16 and 17 of chicken brain alpha spectrin 1u5p Crystal structure of repeats 15 and 16 of chicken brain alpha spectrin 1wlx Solution structure of the third spectrin repeat of alpha- actinin-4 2iak Crystal structure of a protease resistant fragment of the plakin domain of bullous pemphigoid antigen1 (bpag1) 2spc Crystal structure of the repetitive segments of spectrin 3edu Crystal structure of the ankyrin-binding domain of human erythroid spectrin 3edv Crystal structure of repeats 14-16 of beta2-spectrin 3f31 Crystal structure of the n-terminal region of alphaii- spectrin tetramerization domain 3f57 Crystal structure of human erythroid beta spectrin repeats and 15 (ankyrin binding domain) 3fb2 Crystal structure of the human brain alpha spectrin repeats and 16. northeast structural genomics consortium target hr5563a.
- Links (links to other resources describing this domain)
PFAM spectrin INTERPRO IPR018159