GALNT1 Human
Description
Structure and Biochemical Properties
GALNT1 consists of four domains:
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N-terminal transmembrane domain for Golgi apparatus localization
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Stem region
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Catalytic domain containing GT1 and Gal/GalNAc transferase motifs
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C-terminal ricin/lectin-like domain for substrate recognition
Recombinant human GALNT1 (rhGALNT1) is produced as a 559-amino acid protein (Gly41-Phe559) with an N-terminal 6-His tag, exhibiting enzymatic activity confirmed via phosphatase-coupled assays . Its substrate specificity favors non-glycosylated or monoglycosylated peptides, classifying it as an "early transferase" in hierarchical O-glycosylation .
Normal Physiological Roles
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Initiates O-glycosylation of extracellular matrix (ECM) proteins (e.g., laminin, collagen IV)
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Regulates bone formation via glycosylation of osteopontin and bone sialoprotein
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Essential for cardiac valve development by modulating versican cleavage and BMP/MAPK signaling
Pathological Roles in Cancer
GALNT1 is dysregulated in multiple cancers, driving malignancy through:
Substrate Landscape and Glycosylation Preferences
A 2022 proteomics study identified 412 novel GALNT1 substrates across human cell lines, revealing:
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Residue preference: Thr > Ser (3:1 ratio)
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Sequence context: Proline enrichment at +3/+4 positions relative to glycosylation sites
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Key pathways affected:
Diagnostic Potential
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AUC = 0.91 for distinguishing gastric cancer vs. normal tissue (TCGA data)
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Correlates with advanced tumor stage (p < 0.001) and lymph node metastasis
Therapeutic Targeting
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Knockdown effects:
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Pharmacological inhibition: Preclinical studies targeting GALNT1-mediated glycosylation show reduced tumor angiogenesis and EMT .
Expression Patterns and Regulation
| Tissue | Expression Level | Localization |
|---|---|---|
| Liver | High | Cytoplasmic |
| Breast | Variable | Nuclear membrane |
| Heart valves | Developmental | ECM |
Transcript variants utilize alternative polyadenylation signals, enabling tissue-specific regulation .
Evolutionary and Comparative Insights
Product Specs
Belonging to the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family, Polypeptide N-Acetylgalactosaminyltransferase 1 (Galnt1) is an enzyme. Galnt1 catalyzes the first step in O-linked oligosaccharide biosynthesis, which involves transferring an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Galnt1 is also known to be involved in the glycosylation of proteins such as osteopontin and bone sialoprotein, which are crucial for bone formation.
Produced in Sf9 Insect cells, GALNT1 is a single, glycosylated polypeptide chain that consists of 528 amino acids (41-559a.a.) and has a molecular weight of 60.4kDa. A 9 amino acid His tag is present at the C-Terminus of GALNT1, which is purified using proprietary chromatographic techniques.
A clear, colorless solution that has been sterilized by filtration.
The GALNT1 protein solution has a concentration of 1mg/ml and is supplied in a buffer containing 20mM Tris-HCl (pH 8.0), 0.1M NaCl, and 10% glycerol.
If the entire vial is to be used within 2-4 weeks, it should be stored at 4°C. For longer-term storage, the solution should be frozen at -20°C. The addition of a carrier protein (0.1% HSA or BSA) is recommended for long-term storage. Repeated freeze-thaw cycles should be avoided.
Analysis by SDS-PAGE has determined that the purity is greater than 90.0%.
The specific activity, defined as the amount of enzyme required to transfer 1.0 picomole of GalNAc from UDP-GalNAc to peptide EA2 per minute at a pH of 8.0 and a temperature of 37°C, is greater than 300 pmol/min/ug.
Polypeptide N-acetylgalactosaminyltransferase 1, GALNT1, GALNAC-T1
Sf9, Insect cells.
ADPGLPAGDV LEPVQKPHEG PGEMGKPVVI PKEDQEKMKE MFKINQFNLM ASEMIALNRS
LPDVRLEGCK TKVYPDNLPT TSVVIVFHNE AWSTLLRTVH SVINRSPRHM IEEIVLVDDA
SERDFLKRPL ESYVKKLKVP VHVIRMEQRS GLIRARLKGA AVSKGQVITF LDAHCECTVG
WLEPLLARIK HDRRTVVCPI IDVISDDTFE YMAGSDMTYG GFNWKLNFRW YPVPQREMDR
RKGDRTLPVR TPTMAGGLFS IDRDYFQEIG TYDAGMDIWG GENLEISFRI WQCGGTLEIV
TCSHVGHVFR KATPYTFPGG TGQIINKNNR RLAEVWMDEF KNFFYIISPG VTKVDYGDIS
SRVGLRHKLQ CKPFSWYLEN IYPDSQIPRH YFSLGEIRNV ETNQCLDNMA RKENEKVGIF
NCHGMGGNQV FSYTANKEIR TDDLCLDVSK LNGPVTMLKC HHLKGNQLWE YDPVKLTLQH
VNSNQCLDKA TEEDSQVPSI RDCNGSRSQQ WLLRNVTLPE IFHHHHHH.
Product Science Overview
Polypeptide N-Acetylgalactosaminyltransferase 1 (GALNT1) is an enzyme that plays a crucial role in the process of glycosylation, specifically in the initiation of mucin-type O-linked glycosylation. This enzyme is part of the larger family of glycosyltransferases, which are responsible for transferring sugar moieties to proteins and lipids, thus modifying their function and activity.
GALNT1 catalyzes the transfer of N-acetyl-D-galactosamine (GalNAc) from UDP-GalNAc to serine or threonine residues on target polypeptides. This reaction is essential for the biosynthesis of O-glycans, which are important components of glycoproteins. The systematic name of this enzyme is UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyl-transferase .
The glycosylation process mediated by GALNT1 is critical for various biological functions, including protein folding, stability, and cell signaling. Aberrant glycosylation patterns have been associated with numerous diseases, including cancer. For instance, changes in the glycosylation of mucin proteins, which are substrates for GALNT1, have been linked to the progression of breast cancer .
Human recombinant GALNT1 is produced using recombinant DNA technology, which involves inserting the gene encoding GALNT1 into a suitable expression system, such as bacteria or mammalian cells. This allows for the large-scale production of the enzyme for research and therapeutic purposes. Recombinant GALNT1 is used in various studies to understand its role in glycosylation and its potential as a therapeutic target.
Research on GALNT1 has provided insights into its role in health and disease. For example, studies have shown that GALNT1 is involved in the glycosylation of oncoproteins like mucin 1 (MUC1), which is upregulated in many cancers . Understanding the function of GALNT1 and its substrates can lead to the development of novel therapeutic strategies for cancer treatment.
