CHST4
Description
The CHST4 (carbohydrate sulfotransferase 4) is a protein-coding gene located on chromosome 16.
Carbohydrate sulfotransferase 4 is an enzyme that in humans is encoded by the CHST4 gene.
CHST4 is a sulfotransferase enzyme involved in the biosynthesis of L-selectin ligands (SELL). It catalyzes the transfer of a sulfate group from 3'-phospho-5'-adenylyl sulfate (PAPS) to the hydroxyl group at the C-6 position of the non-reducing N-acetylglucosamine (GlcNAc) residue within O-linked mucin-type glycans. This sulfation contributes to the formation of the sialyl 6-sulfo Lewis X determinant (MECA-79 epitope), which is crucial for SELL recognition. This recognition is essential for continuous lymphocyte homing into peripheral lymph nodes and antigen immune surveillance. CHST4 primarily sulfates core 2 GlcNAcbeta1-6(Galbeta1-3)GalNAcalphaSer/Thr and extended core 1 GlcNAcbeta1-3Galbeta1-3GalNAcalphaSer/Thr based O-linked glycans on CD34 and GLYCAM1 peripheral node addressins (PNAds), expressed on the lumenal side of high endothelial venules (HEVs). The interaction between SELL and PNAds triggers a multistep process involving tethering and rolling of blood lymphocytes on HEVs against blood flow, followed by chemokine signaling, integrin-mediated lymphocyte adhesion to endothelial cells, and lymphocyte transendothelial migration. CHST4 modulates rolling velocity and differentially regulates T and B lymphocyte recruitment into peripheral lymph nodes, with a major role in B lymphocyte homing. While CHST4 might be redundant in sulfating MADCAM1 and lymphocyte trafficking to mesenteric lymph nodes, it can also sulfonate core 3 GlcNAcbeta1-3GalNAc-R based glycans, as well as GlcNAcbeta1-3Galbeta1-Glc, GlcNAcbeta1-6ManOMe, and GlcNAcbeta1-2Man oligosaccharides, which might be ectopically expressed during tumorigenesis.
CHST4 is also known as GST3, GlcNAc6ST2, HECGLCNAC6ST, LSST.
Associated Diseases
- hyper-IgM syndrome type 3
- hyper-IgM syndrome type 5
- hyper-IgM syndrome type 2
- severe combined immunodeficiency due to CD70 deficiency
- immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias
- immunodeficiency 73c with defective neutrophil chemotaxis and hypogammaglobulinemia
- autoimmune lymphoproliferative syndrome type 2B
- immunodeficiency 75
