The reference OMIM entry for this protein is 604570

Shroom family member 3; shroom3
Shroom, mouse, homolog of; shrm
Kiaa1481

CLONING

Using gene trap mutagenesis, Hildebrand and Soriano (1999) identified a mutation in mice that caused exencephaly, acrania, facial clefting, and spina bifida, all of which could be attributed to failed neural tube closure. This mutation was designated 'shroom' (shrm), because the neural folds 'mushroom' outward and do not converge at the dorsal midline. By 5-prime RACE and library screening, the cDNA for the trapped gene was cloned. Sequence analysis indicated there are at least 2 shrm transcripts that encode 2 different putative protein products. The longest predicted transcript, shrmL, encodes a protein of 1,986 amino acids, while the second transcript, shrmS, encodes a protein of 1,808 amino acids that lacks the N-terminal 177 amino acids of shrmL. Shrm is a PDZ domain-containing protein related to Xenopus Apx and human APXL (SHROOM2; 300103). By sequencing clones obtained from a size-fractionated fetal brain cDNA library, Nagase et al. (2000) cloned SHRM, which they designated KIAA1481. The deduced protein shares significant identity with human APXL. RT-PCR ELISA detected highest expression of SHRM in liver, followed by kidney, ovary, cerebellum, and spinal cord. Intermediate expression was found in all other tissues and brain regions examined except skeletal muscle, where there was little to no expression.

GENE FUNCTION

Hildebrand and Soriano (1999) found that Shrm is involved at several levels in regulating aspects of cytoarchitecture. First, endogenous shrm localized to adherens junctions and the cytoskeleton. Second, ectopically expressed Shrm altered the subcellular distribution of F-actin. Third, Shrm directly bound F-actin. Finally, cytoskeletal polarity within the neuroepithelium was perturbed in mutant embryos. In concert, these observations suggested that Shrm is a critical determinant of the cellular architecture required for proper neurulation. In experiments in Xenopus, Lee et al. (2007) showed that SHROOM3 is necessary and sufficient to induce a redistribution of the microtubule regulator gamma-tubulin (see 191135). They found that this change in gamma-tubulin distribution underlies the assembly of aligned arrays of microtubules that drive apicobasal cell elongation. They concluded that Shroom family proteins govern epithelial cell behaviors by coordinating the assembly of both microtubule and actin cytoskeletons. Hildebrand (2005) found that Shroom localized to the apical junctional complex in Madin-Darby canine kidney cells. Overexpression of Shroom resulted in altered cell morphology with apical constriction and altered apical cell-cell alignment. Targeting the C-terminal domain of Shroom to the apical plasma membrane produced similar changes. The neural epithelia of Schroom-mutant mouse embryos showed a marked reduction in the apical position of myosin IIB (MYH10; 160776), whereas the positions of nectin-3 (PVRL3; 607147) and Zo1 (TJP1; 601009) were unaltered. Hildebrand (2005) concluded that Shroom facilitates the subapical distribution of nonmuscle myosin IIB, which in turn regulates the tissue rigidity and cell shape changes required for neural tube closure.

MAPPING

By analyzing a human-rodent hybrid panel, Nagase et al. (2000) mapped the SHRM gene to chromosome 4. ... More on the omim web site

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Oct. 27, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

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

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604570 was added.