The reference OMIM entry for this protein is 610963

Smg6, c. elegans, homolog of; smg6
Ever shorter telomeres 1, s. cerevisiae, homolog of, a; est1a
Kiaa0732

DESCRIPTION

SMG6 is involved in nonsense-mediated mRNA decay (Fukuhara et al., 2005).

CLONING

By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (1998) cloned SMG6, which they designated KIAA0732. RT-PCR ELISA detected high expression in brain, lung, ovary, testis, heart, and kidney and moderate expression in skeletal muscle, liver, pancreas, and spleen. By searching a database for sequences similar to S. cerevisiae Est1, Snow et al. (2003) identified SMG6, which they called EST1A. The deduced 1,388-amino acid protein has a central Est1 homology domain containing 2 tetratricopeptide repeat (TPR) motifs and a C-terminal PIN domain, which may be involved in nucleic acid binding or nuclease activity. A 7.5-kb EST1A transcript was ubiquitously expressed. Western blot analysis detected a 180-kD EST1A protein. By searching an EST database for orthologs of C. elegans Smg6, Ohnishi et al. (2003) identified SMG6. The deduced 1,419-amino acid protein contains 4 regions conserved with C. elegans Smg6. Western blot analysis detected an endogenous 170-kD SMG6 protein in HeLa cells. Cell fractionation experiments showed that SMG6 was predominantly cytosolic, but it accumulated in nuclei following treatment with a nuclear export inhibitor. Fukuhara et al. (2005) found that the TPR-containing regions of SMG5 (610962), SMG6, and SMG7 (610964) share structural similarity with 14-3-3-zeta (YWHAZ; 601288), including a conserved phosphoserine-binding site.

GENE FUNCTION

Snow et al. (2003) found that EST1A associated with telomerase activity in human cell lines and bound human TERT (187270) in rabbit reticulocyte lysates. In contrast to yeast Est1, EST1A bound TERT independently of telomerase RNA (TERC; 602322). An N-terminal region of EST1A bound yeast telomeric single-stranded DNA and, more weakly, human telomeric DNA. Transfection of human embryonic kidney cells with EST1A led to decreased average telomere length, whereas cotransfection of EST1A with TERT resulted in telomere lengths that exceeded those of cells expressing TERT alone. Transfection of EST1A with or without TERT in telomerase-negative cells resulted in no change in telomere length. Using pull-down assays, Fukuhara et al. (2005) showed that the 14-3-3-zeta-like domain of recombinant SMG6 bound to in vitro translated UPF1. Binding was impaired by mutations in the phosphoserine-binding site of SMG6. Azzalin et al. (2007) demonstrated that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. Azzalin et al. (2007) also showed that suppressors with morphogenic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated mRNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, Azzalin et al. (2007) concluded that telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.

GENE STRUCTURE

Hoff et al. (2000) identified a CpG island in the 5-prime UTR of the SMG6 gene.

MAPPING

By sequence analysis, Hoff et al. (2000) mapped the SMG6 gene to a region of chromosome 17p13.3 that frequently shows loss of heterozygosity in tumors. ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 610963 was added.

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