The reference OMIM entry for this protein is 607955

Sterile alpha motifs- and sh3 domain-containing protein 1; sash1
Kiaa0790

CLONING

By sequencing clones obtained from a size-fractionated brain cDNA library, Nagase et al. (1998) cloned SASH1, which they designated KIAA0790. The deduced protein contains 1,319 amino acids. RT-PCR ELISA detected moderate to high expression in all tissues examined, with highest expression in heart, brain, lung, ovary, and kidney. By loss of heterozygosity and in silico expression analysis to identify genes on chromosome 6q23-q25 that are downregulated in breast cancers, Zeller et al. (2003) identified SASH1. They obtained the full-length cDNA by assembling SASH1 ESTs. The deduced 1,247-amino acid protein has a calculated molecular mass of about 140 kD. SASH1 contains 2 sterile alpha modules (SAMs) and an Src homology-3 (SH3) domain. These domains are predominantly found in signaling molecules, adaptors, and scaffold proteins. SASH1 also has an N-terminal 25-residue proline-rich sequence. The mRNA has a long 3-prime untranslated region that has 2 polyadenylation signals. The human and mouse SASH1 proteins share 85% homology. Northern blot analysis detected a 4.4-kb transcript that was expressed ubiquitously, with highest levels in lung, placenta, spleen, and thymus. A 7.5-kb transcript was detected at lower levels in all tissues surveyed except brain. Using RT-PCR, Dauphinee et al. (2013) verified ubiquitous expression of Sash1 mNRA in mouse tissues. Gene-trap analysis showed that Sash1 was strongly expressed in the microvascular endothelium of all mouse organs examined.

GENE FUNCTION

By electronic Northern profiling of ESTs and RT-PCR analysis, Zeller et al. (2003) found significant downregulation of SASH1 in a majority of primary breast tumor tissues and breast cancer cell lines examined. All cell lines with deletions of chromosome 6q24.3 showed little to no SASH1 expression. Expression was reduced in 60% of breast tumors compared with normal breast tissue in a survey of 15 matched samples. A survey of 50 matched samples showed reduced expression in 74% of tumors. Expression was also reduced in a majority of lung and thyroid tumors, as well as in a few colon carcinomas. Zeller et al. (2003) did not identify mutations associated with primary breast cancers in the coding region of the SASH1 gene, and they hypothesized that other mechanisms, such as promoter methylation, may be responsible for loss of SAHS1 expression in primary and metastatic breast cancers. By proteomic analysis of lipopolysaccharide (LPS)-stimulated mouse embryonic fibroblasts, Dauphinee et al. (2013) identified Sash1 as part of the Tlr4 (603030) signaling pathway. Knockdown of SASH1 in human microvascular endothelial cells decreased NFKB (see 164011) luciferase activity in response to LPS, but not in response to TLR2 (603028), TLR3 (603029), TLR5 (603031), or other TRAF6 (602355)-dependent receptors. SASH1 knockdown also resulted in decreased production of IL6 (147620) and IL10 (124092), but it did not affect interferon-regulated genes. Coimmunoprecipitation analysis showed that residues 852 to 860 of SASH1 bound to the C-terminal region of TRAF6 containing the coiled-coil domain and that the interaction depended on LPS. SASH1 did not interact with MYD88 (602170), IRAKs (e.g., IRAK1; 300283), or other TRAF molecules. Overexpression of SASH1, in the absence of stimulation, induced autoubiquitination of TRAF6 without direct interaction of SASH1 with ubiquitin-conjugating enzymes, such as UBC13 (603679). Further coimmunoprecipitation experime ... More on the omim web site

Subscribe to this protein entry history

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

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 607955 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).