The reference OMIM entry for this protein is 606214

Spectrin, beta, nonerythrocytic, 4; sptbn4
Spectrin, beta-iv
Quivering, mouse, homolog of; qv

Spectrins (e.g., SPTA1; 182860) are rod-shaped proteins that are part of the lattice-like cytoskeleton under the erythrocyte membrane. This meshwork is critical for the maintenance of plasma membrane shape and lipid asymmetry, as revealed by mutant spectrins in diseases such as elliptocytosis (see 182860) and spherocytosis (see 182870). Although originally identified in erythrocytes, spectrins have also been found in the membranes of intracellular organelles, such as the Golgi, lysosomes, and secretory vesicles. The spectrin molecule is a tetramer consisting of 2 alpha and 2 beta subunits, in which the N terminus of an alpha subunit is tightly connected with the C terminus of a beta subunit to form a heterodimer. Spectrin repeats contain approximately 106 amino acids. Alpha subunits have 20 spectrin repeats, while beta subunits have 17.

CLONING

By screening a size-fractionated adult brain cDNA library for cDNAs with the potential to encode large proteins, Nagase et al. (2000) isolated a partial cDNA encoding SPTBN4, which they called KIAA1642. RT-PCR analysis detected ubiquitous expression of SPTBN4, with relatively high levels in adult and fetal brain, low levels in lung, liver, pancreas, and spleen, and intermediate levels in the other tissues tested and in specific brain regions. Using a yeast 2-hybrid screen of a brain cDNA library with the cytoplasmic domain of ICA512 (PTPRN; 601773) as bait, followed by probing a brain cDNA library, PCR, and genomic sequence analysis, Berghs et al. (2000) isolated cDNAs encoding SPTBN4 and several splice variants. Sequence analysis predicted that the full-length 2,559-amino acid SPTBN4 protein, designated sigma-1, contains 2 N-terminal calponin homology domains, which mediate interactions with actin; 16 complete spectrin repeats; 1 partial spectrin repeat; a unique proline-rich, basic domain containing 4 ERQES repeats; numerous SH3 binding sites; and a C-terminal pleckstrin homology domain. An insertion in exon 17 termed exon 17b yields a 1,302-residue splice variant, sigma-2, which terminates in spectrin repeat 9, and another variant, sigma-3, which begins at exon 17b to generate a 1,307-amino acid protein. Variant sigma-4 has an insertion in exon 30 termed exon 30b that introduces 42 amino acids and a stop codon, resulting in a 2,149-amino acid protein that lacks the ERQES and pleckstrin homology domains. Binding analysis indicated that the C terminus of SPTBN4 binds to PTPRN and only weakly to an active tyrosine phosphatase mutant of PTPRN and to PHOGRIN (601698). Northern blot analysis revealed expression of 9.0-, 5.1-, and 3.1-kb SPTBN4 transcripts that were predominantly expressed in brain. Western blot analysis showed expression of 250- and 160-kD proteins in rat brain and human pancreatic islets, as well as a 140-kD protein in rat brain only. Phosphatase treatment indicated that the 160-kD protein is phosphorylated, probably in the ERQES domain, which modifies its interaction with cytoskeletal and membrane proteins. Immunocytochemistry and confocal microscopy demonstrated coexpression of PTPRN and SPTBN4 in both insulin-secreting beta cells and glucagon-secreting alpha cells. In situ hybridization and immunocytochemistry suggested coexpression of SPTBN4 and ankyrin-G (ANK3; 600465) in rat brain. Tse et al. (2001) cloned SPTBN4, which they termed SPTBN3, as well as a splice variant, sigma-5, encoding a 678-amino acid protein. Whole-mount in situ hybridization analysis revealed Sp ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for SPTBN4

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606214 was added.