The reference OMIM entry for this protein is 615618

Protein o-glucosyltransferase 1; poglut1
Cap10-like protein, 46-kd; clp46
Ktel motif-containing protein 1; ktelc1
Rumi, drosophila, homolog of; rumi
Chromosome 3 open reading frame 9; c3orf9

DESCRIPTION

POGLUT1 is an endoplasmic reticulum (ER) O-glucosyltransferase that adds glucose moieties to serine residues in EGF (131530)-like repeats, such as those found in the transactivating NOTCH (see NOTCH1, 190198) intracellular domain (Chu et al., 2013).

CLONING

By sequencing clones obtained from transformed CD34 (142230)-positive myelodysplastic syndrome (614286) cells, followed by EST database analysis, Teng et al. (2006) identified POGLUT1, which they designated CLP46. The transcript contains 2 variant polyadenylation signals and encodes a deduced 392-amino acid protein with a calculated molecular mass of 46.2 kD. It has a 23-amino acid N-terminal signal peptide and a C-terminal KTEL motif predicted to function as an ER retention signal. It also has a highly conserved domain similar to Cryptococcus neoformans Cap10, a lipopolysaccharide capsule-associated enzyme. CLP46 orthologs are present in vertebrates, insects, and plants. Northern blot analysis detected variable expression of a major transcript of 3.5 kb and a minor transcript of 1.9 kb in most human tissues examined. Expression was high in liver, moderate in heart, spleen, kidney, lung, and peripheral blood leukocytes, and weak in brain, skeletal muscle, and placenta. Little to no expression was detected in colon, thymus, and small intestine. Epitope-tagged CLP46 colocalized with an ER marker in transfected COS-7 cells.

GENE STRUCTURE

Teng et al. (2006) determined that the POGLUT1 gene contains 11 exons and spans over 25.7 kb.

MAPPING

By genomic sequence analysis, Teng et al. (2006) mapped the POGLUT1 gene to chromosome 3q13.33.

GENE FUNCTION

Teng et al. (2006) found that expression of CLP46 was elevated in CD34-positive MDS cells compared with normal adult bone marrow. Overexpression of CLP46 increased the rate of growth in U937 monocytic leukemia cells. Using recombinant proteins, Takeuchi et al. (2011) found that both mouse and human RUMI catalyzed the transfer of glucose from UDP-glucose onto serines within an EGF repeat from human factor VII (F7; 613878). In addition, mouse, Drosophila, and human RUMI catalyzed transfer of xylose from UDP-xylose onto serines within EGF repeats. RUMI did not use UDP-glucuronic acid. EGF repeat-16 of mouse Notch2 (600275) was modified with either O-xylose or O-glucose in RUMI-transfected cells. By examining this EGF repeat, which contains a diserine motif, Takeuchi et al. (2011) determined that properly folded EGF repeats containing the O-glucose consensus sequences (CxSxPC) were O-glycosylated by RUMI, whereas EGF repeats containing a diserine (CxSSPC) permitted RUMI-dependent O-xylosylation and O-glycosylation. Mutation of the second serine caused loss of O-xylosylation, but not O-glycosylation, at this site. Epitope-tagged human RUMI rescued the sensory organ and wing phenotypes in Rumi mutant flies, suggesting a high degree of conservation. Ma et al. (2011) found that knockdown of CLP46 in human cell lines via RNA interference had a negative effect on Notch signaling and reduced cell proliferation. Knockdown of CLP46 reduced the protein level of endogenous NOTCH1 and NOTCH intracellular domain and reduced expression of direct NOTCH1 targets and downstream effectors. Reduced Notch signaling and cell proliferation were accompanied by accumulation of the cell cycle inhibitor CDKN1B (600778) and decreased phosphorylation of the CDKN1B target RB (RB1; 614041). Ma et al. (2011) conc ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615618 was added.

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