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POMK

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Protein O-mannose kinase (POMK), formerly known as SGK196, is a type II transmembrane protein localized to the endoplasmic reticulum (ER). POMK contains a short N-terminal cytoplasmic region, a single transmembrane helix, and a C-terminal kinase domain located in the ER lumen. Biochemical and structural studies have established POMK as a glycosylation-specific kinase. Using ATP as the phosphate donor, POMK phosphorylates the C6 hydroxyl group of the mannose residue in the core M3 O-mannosyl trisaccharide, GalNAc-β3-GlcNAc-β4-Man. This phosphorylation is required for subsequent modification of α-dystroglycan: FKTN and FKRP mediate ribitol-phosphate addition, RXYLT1 (formerly TMEM5) and B4GAT1 generate the glycan structure that primes downstream extension, and LARGE1 subsequently polymerizes matriglycan. Proper phosphorylation of core M3 is therefore important for efficient matriglycan formation and the extracellular matrix-binding function of α-dystroglycan.

Fig.1 POMK is involved in the synthesis of the α-DG Laminin-Binding Modification. (OA Literature)Fig.1 Synthesis of the α-DG Laminin-Binding Modification and Enzymes Involved.1

POMK Protein Function: A Glycan-Specific Kinase at the Heart of Dystroglycan Function

POMK engages several interrelated areas of glycobiology and neuromuscular pathology:

  • α-Dystroglycan Phosphorylation and Matriglycan Assembly: POMK catalyzes the committed phosphorylation step that licenses downstream matriglycan chain assembly on αDG that is functionally critical. In the examined GalNAc-β3-GlcNAc-β4-Man trisaccharide, there comprises a phosphorylation of O-mannose residue (the initiating one) at 6-position. This phospho-mannose moiety is then extended by a phosphodiester bond to ribitol-5-phosphate repeats, which prepares the structure for LARGE-mediated polymerization of the disaccharide repeating unit Xyl-α1,3-GlcAβ1,3 that makes up the laminin-binding epitope.
  • Dystroglycan Complex Integrity: α-DG is part of the dystrophin-glycoprotein complex (DGC), a heteromultimeric structure that represents an essential mechanical link between cell 2-extracellular matrix and actin cytoskeleton. Thus, proper glycosylation of α-DG is essential for maintaining sarcolemmal stability in myofibers and physiological neuronal migration throughout cortical development. Disruption of this structural bridge by POMK deficiency results in neurogenic defects, ocular abnormalities and muscle degeneration.
  • Disease Spectrum: Variants in POMK cause a milder phenotype; classical α-dystroglycanopathy phenotypes span from mild to severe. Walker-Warburg syndrome (WWS, MDDGA12) which is associated with congenital muscular dystrophy and cobblestone lissencephaly accompanied by hydrocephalus cerebellar hypoplasia as well as eye deformities leading to death during early childhood at the most extreme end of severity.

POMK Membrane Protein Product

Explore our recombinant POMK protein products for glycobiology and muscular dystrophy-related research. As an ER-resident type II membrane protein with a luminal kinase domain, POMK presents specific considerations for construct design and protein production. Our portfolio may include full-length POMK and domain-specific or engineered research constructs according to product availability and experimental requirements. These proteins can support structural studies, investigation of POMK kinase mechanisms and substrate interactions, enzyme-related research, and antibody development and characterization. Available expression systems, construct designs, sequence variants, and functional characteristics should be determined according to the corresponding product information and supporting data.

POMK Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

POMK Stable Cell Line Product

These models are critical for the study of POMK dependent biology and therapeutic candidate evaluation. We deliver stable cell lines designed to either constitutively or inducibly express human, mouse and rat POMK as well as regulated endogenous expression of numbers of our top candidates for loss-of-function studies. These platforms are well-suited for high-throughput compound screening, α-DG glycosylation assays, laminin-binding rescue studies and kinase activity measurements to provide reliable and reproducible discoveries of POMK-mediated pathology or pharmacology.

POMK Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

POMK Recombinant Antibody Product

We offer this wide range of high-affinity recombinant antibodies for POMK, developed to meet the strict requirements of numerous research fields. These highly specific and sensitive antibodies have been produced through the advanced recombinant technologies, which also provides significant batch-to-batch reproducibility over traditionally used polyclonal antibodies. POMK Recombinant Antibodies Validation Our POMK recombinant antibodies can be used for WB, ELISA, FCM and other applications using different sample types: ER membrane preparations; whole-cell lysates; tissue sections.

POMK Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom POMK Membrane Protein and Antibody Discovery Services

In addition to our product offering, we provide custom services for protein and antibody discovery and development:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous POMK expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Will your POMK products be used for Clinical or Diagnostic use?

    POMK products and services are solely for research use only, not for clinical diagnosis or prevention treatment or cure of any disease.

  2. Do you offer stable cell lines that co-express POMK with protein O-mannosyltransferase 1 (POMT1) or dystroglycan for modeling the O-mannosylation glycan elongation pathway in a continuous system?

    We did generate stable lines co-expressing full length POMK as well as the mucin-like domain of dystroglycan from different loci. This allows the same batch to be released with validation documentation of O-mannose phosphorylation competence on a variety of dystroglycan-derived reporters, representing an uninterrupted glycosylation pathway without repeated transient transfection in one standardized cellular platform.

  3. Are your POMK antibodies cross-reactive to mouse and rat orthologs for use in translational muscular dystrophy & neurodevelopmental model studies?

    Yes, the immunogen correspond to a region that is very well conserved across mammalian species allowing detection in human, mouse and rat muscles and brain preparations without the need for additional species-specific reagents.

  4. What species variants are available?

    The catalog of POMK reagents contains mouse & rat. Additional orthologs or engineered mutants (eg, catalytically dead forms; trafficking mutants; patient-specific variants) can be custom produced upon request.

Reference
  1. Walimbe, Ameya S., et al. "POMK regulates dystroglycan function via LARGE1-mediated elongation of matriglycan." Elife 9 (2020): e61388. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.7554/eLife.61388
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