ST6Gal 1 
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Leukocyte
B Lymphocyte, Resting
35 / 50

Expression
ST6Gal 1 is expressed at low to high levels in the heart, brain, placenta, liver, lung, skeletal muscle, kidney, spleen, thymus, prostate, ovary, small intestine, colon and peripheral blood leukocyte.  The liver has the highest level of expression.  There is variable expression on the HL-60 promyelocytic leukemia cell line and Burkitt's lymphoma B cell lines.  There is high expression in mammary glands during late pregnancy and lactation and low to high expression during activation of resting B lymphocytes.  ST6Gal 1 is localized in the trans Golgi and trans Golgi network.  An active proteolytically cleaved form of the enzyme is found in body fluids such as colostrum, breast milk, blood, lymph and semen.  ST6Gal 1 is a transmembrane protein with a C-terminal catalytic domain residing in the Golgi lumen.

Structure
MOLECULAR FAMILY NAME: hST6gal 1 -->sialytransferase -->glycosyltransferase.

ST6Gal 1 names: hST6gal 1 (STgal 1) sialyltransferase 1, b-galactoside a-2,60sialyltransferase (CMP-N-acetylneuraminate b-galactoside a-2,6-sialytransferase) and EC 2.4.99.1 (2.4.99.1).

ST6Gal 1 is a type 1 glycoprotein with a C-terminal catalytic domain residing in the Golgi lumen. It is an enzyme belonging to the sialyltransferase family that transfers sialic acid.  ST6Gal 1 is comprised of 406 aa, an 1 aa-9 aa  cytoplasmic region, a 10 aa-26 aa signal-anchor region, a 27 aa-96 aa stem region, a 97 aa-403 aa catalytic domain, and an 149 aa and 161 aa N-linked glycosylation sites.

MOLECULAR MASS
Cell Type Unreduced Reduced
47 kDa 37-43 kDa

The membrane bound enzyme has a molecular weight of 47 kDa whereas the proteolytic released active enzyme is 37 kDa-43 kDa.  The membrane bound enzyme may also form an inactive dimer and can act as a galactose binding lectin.  The active monomer contains an intramolecular disulfide bond formed by 2 conserved Cys present in the large and small sialyl motifs.

POST-TRANSCRIPTIONAL MODIFICATION

The hST6Gal 1 gene comprises 7-8 exons of which 5 are coding exons.  Multiple transcripts differ only in the 5'-untranslated region.  Exon X, Y and Z are absent in the liver but exon Y and Z are present in a number of cells and tissues expressing ST6Gal mRNA.  Additional mRNA forms utilizing unique exons for the 5'-untranslated region are documented in the mouse.

POST-TRANSLATIONAL MODIFICATION

There are 2 potential N-linked glycosylation sites which have 149 aa and 161aa and for the rat, the sites have 146 aa and 158 aa. These were shown to be modified and important for activity and trafficking of the soluble rate enzyme but not the membrane-bound rat enzyme.  Modification by phosphorylation has also been reported.



Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH ST6Gal 1: No information.

Function
ST6Gal 1 is localized in trans-Golgi and trans-Golgi network in which it acts to add sialic acid to the oligosaccharide chains of the newly synthesized protein while in transit through Golgi.  The dimeric form of this enzyme is inactive and may act as a galactose-specific lectin.  The enzyme product Sia6LacNAc is a ligand of CD22, a receptor on  the B cell, and is shown to be essential in regulating the B lymphocyte activation and immune function.  NeuAc6LacNAc also plays a role in the expression of the biological activity of prolactin/growth hormone family members during rat pregnancy.

BIOCHEMICAL ACTIVITY

ST6Gal 1 transfers sialic acid from CMP-NeuAc to Galb1, 4GlcNac on N-linked glycoproteins yielding NeuAca2-6 Galb1, 4GlcNAc.  In vitro, it can also transfer sialic acid to LacNAc and LacdiNAc.  ST6Gal 1 can transfer other forms of sialic acid although Neu5Ac is believed to be the precursor of all other varieties known.  The optimal pH for this enzyme is 6.0-6.5.

DISEASE RELEVANCE AND FUNCTION OF ST6Gal 1 IN INTACT ANIMAL

ST6Gal 1 deficient mice showed symptoms of immuno-suppression which were marked with reduced serum IgM levels with attenuated antibody production to T-independent and T-dependent antigens.  The absence of the enzyme product did not effect B cell development, however these mice showed impaired B cell proliferation in response to IgM or CD40 cross-linking.  The deficiency caused an alteration in phosphotyrosine accumulation following cross-linking of the B lymphocyte antigen receptor.


Comments

MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF ST6Gal 1

Glycosylation.

SUBSTRATES
Substrate Comment
Terminal Galb 1,4 GlcNAc containing N-linked glycoproteins Terminal Galb1 1,4GlcNAc containing N-linked glycoproteins, such as prolactin
lactoferrin
fat globule membrane CD36
HB-6
CD75 (formerly CDw75)
CD75s (formally CD76)
Various milk oligosaccharides

ENZYMES WHICH MODIFY ST6Gal 1: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Antibodies

Revised June 25, 2008


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