The domain within your query sequence starts at position 951 and ends at position 1054; the E-value for the SPEC domain shown below is 2e-53.

RFFTTSVEDLLRFLADTSQLLSAVKEQDCYSLCQTRRLVHELKSKEIHLQRWRTTYALAL
EAGEKLRNTPSPETREFVDGQISRLQESWKDTELSLGEVISRLQ

The domain was found using the schnipsel database

SPEC

Spectrin repeats

• SMART accession number: SM00150
• Description: -
• 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.

There are 257395 SPEC domains in 23741 proteins in SMART's nrdb database.

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

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

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

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

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 beta chain, erythrocytic (P11277) (SMART)	OMIM:182870: Elliptocytosis-3 ; Spherocytosis-1 ; Anemia, neonatal hemolytic, fatal and near-fatal
Spectrin alpha chain, erythrocytic 1 (P02549) (SMART)	OMIM:182860: Elliptocytosis-2 ; Pyropoikilocytosis ; Spherocytosis, recessive

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	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 14 and 15 (ankyrin binding domain)
3fb2	Crystal structure of the human brain alpha spectrin repeats 15 and 16. Northeast Structural Genomics Consortium target HR5563a.
3kbt	Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK)
3kbu	Crystal structure of the ankyrin binding domain of human erythroid beta spectrin (repeats 13-15) in complex with the spectrin binding domain of human erythroid ankyrin (ZU5-ANK), EMTS derivative
3lbx	Crystal Structure of the Erythrocyte Spectrin Tetramerization Domain Complex
3pdy	Structure of the third and fourth spectrin repeats of the plakin domain of plectin
3pe0	Structure of the central region of the plakin domain of plectin
3r6n	Crystal structure of a rigid four spectrin repeat fragment of the human desmoplakin plakin domain
3uul	Crystal Structure of first N-terminal utrophin spectrin repeat
3uum	Crystal Structure of N-terminal first spectrin repeat of utrophin
3uun	Crystal Structure of N-terminal first spectrin repeat of dystrophin
4d1e	4D1E
4pd3	4PD3
5j1g	5J1G
5j1i	5J1I
5jlh	5JLH

Links (links to other resources describing this domain)

• PFAM: spectrin
• INTERPRO: IPR018159