| Aspect | Summary |
|---|---|
| Target identity | Human **POMT1** corresponds to UniProt **Q9Y6A1**, an ER-associated protein O-mannosyltransferase studied together with **POMT2**; the literature consistently matches the supplied protein description and function. (pqac-00000000, pqac-00000044) |
| Enzyme reaction | POMT1 participates in the **initiation of protein O-mannosylation**, transferring **α-mannose to Ser/Thr residues** on protein substrates in the ER; this creates the initial O-Man (core M0) precursor for downstream glycan elaboration. (pqac-00000005, pqac-00000008, pqac-00000044) |
| Sugar donor | The activated donor is **dolichyl-phosphate-mannose** (**Dol-P-Man / DPM**), whereas **GDP-mannose is not used** in the mammalian POMT assay. (pqac-00000003, pqac-00000005, pqac-00000006) |
| Acceptors / substrate scope | A key physiological substrate is **α-dystroglycan (α-DG)**; newer proteomics also support POMT1/2-dependent O-mannosylation of **KIAA1549** and **SUCO**, while mammalian POMT1/2 appears to have a **narrower substrate spectrum** than yeast PMTs. (pqac-00000008, pqac-00000012, pqac-00000016, pqac-00000018) |
| Substrate specificity | POMT activity prefers **proteinaceous/structured acceptors**: short synthetic α-DG peptides failed as substrates, implying recognition depends on sequence context and/or higher-order conformation rather than a short linear motif alone. (pqac-00000008, pqac-00000018) |
| Complex requirement | **POMT1 alone is insufficient** for robust activity; **coexpression with POMT2** is required for mammalian protein O-mannosyltransferase activity, consistent with an obligatory heteromeric complex. (pqac-00000002, pqac-00000003, pqac-00000006) |
| Localization / topology | POMT1 functions in the **endoplasmic reticulum** and is detected in **microsomal membrane fractions**; family members are **integral multi-pass membrane proteins** with luminal catalytic features. (pqac-00000002, pqac-00000044, pqac-00000046) |
| Protein family classification | POMT/Pmt enzymes belong to the **GT-C fold** group and are placed in **CAZy GT39**; they are conserved eukaryotic protein O-mannosyltransferases. (pqac-00000041, pqac-00000040) |
| Key domains / motifs | Structural and sequence analyses support a **multi-pass transmembrane architecture**, a luminal **MIR domain**, and a conserved **acidic DD/DE motif** in the first luminal loop that is essential for activity; yeast Pmt1–Pmt2 structures support a conserved **11-TMH + MIR** organization relevant to human POMT1. (pqac-00000004, pqac-00000041, pqac-00000042, pqac-00000045) |
| Pathway role | POMT1/POMT2 act at the **first committed ER step** of the α-DG O-mannose pathway; downstream enzymes extend these glycans toward **matriglycan**, which is required for binding extracellular matrix ligands such as laminin. (pqac-00000020, pqac-00000022) |
| Disease link | Biallelic **POMT1 mutations** cause **dystroglycanopathies** spanning **Walker-Warburg syndrome (WWS)** to **limb-girdle muscular dystrophy (LGMD2K/LGMDR11)** via α-DG hypoglycosylation; cardiomyopathy can be part of the spectrum. (pqac-00000011, pqac-00000038, pqac-00000039) |
| Quantitative genotype-function data | Residual POMT activity correlates with phenotype severity: about **40%** residual activity was reported in an LGMD2K patient versus about **6–10%** in severe WWS cases; lymphoblast activity could be **non-detectable to 0.004 pmol/h/mg**. (pqac-00000023) |
| Clinical cohort statistics | In one biopsy-driven screen, **247** patients were evaluated, **107** showed reduced α-DG glyco-epitope labeling, and **9** had **POMT1 mutations**; a 2024 Egyptian CMD cohort reported **86% (6/7)** diagnostic yield for dystroglycanopathy cases using WES and identified **POMT1** among causal genes. (pqac-00000026, pqac-00000038, pqac-00000027) |
| Recent 2023–2024 advances | A 2024 glycoproteomics study identified **180 O-Man glycoproteins** overall and separated **POMT1/2** from TMTC/TMEM260 initiation pathways; a 2024 zebrafish **pomt1** knockout modeled dystroglycanopathy; a 2024 cardiac study linked the downstream matriglycan pathway to **t-tubule integrity** under stress. (pqac-00000016, pqac-00000017, pqac-00000022, pqac-00000048) |
| Recent quantitative pathway mapping | In the 2024 glycoproteomics dataset, investigators reported **9,026 glyco-PSMs** total, including **7,410 O-Man** and **1,614 C-Man** PSMs, and detected cadherin EC-domain O-Man on **54** unique members; these data underscore that POMT1/2 is one part of a broader but pathway-partitioned O-mannosylation landscape. (pqac-00000025, pqac-00000048) |


*Table: This table compiles the core functional annotation for human POMT1 (UniProt Q9Y6A1), including biochemical activity, localization, pathway placement, disease relevance, and recent 2023–2024 advances. It is useful as a compact evidence-backed summary for downstream gene/protein annotation work.*