Disease relevance of TPST1

• This indicates that TPST1 and TPST2 have distinct macromolecular substrate specificities and provides clues as to the molecular mechanism of the infertility of Tpst2(-/-) males [1].

Psychiatry related information on TPST1

• The results suggest that alcohol abuse causes enhancement in the expression of gastric mucosal tyrosylprotein sulfotransferase activity [2].

High impact information on TPST1

• The sulfation reaction is catalyzed by tyrosylprotein sulfotransferase, an integral membrane protein that recognizes tyrosine residues in exposed protein domains containing acidic amino acids [3].
• We found that CCR5 2-18 is sulfated by both TPST isoenzymes leading to a final product with four sulfotyrosine residues [4].
• Existence of distinct tyrosylprotein sulfotransferase genes: molecular characterization of tyrosylprotein sulfotransferase-2 [5].
• Tyrosylprotein sulfotransferase (TPST) is a 54- to 50-kDa integral membrane glycoprotein of the trans-Golgi network found in essentially all tissues investigated, catalyzing the tyrosine O-sulfation of soluble and membrane proteins passing through this compartment [5].
• This reaction is mediated by a Golgi enzyme activity called tyrosylprotein sulfotransferase (TPST) that catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to tyrosine residues within acidic motifs of polypeptides [6].

Biological context of TPST1

• We have also identified a cDNA that encodes a TPST in the nematode Caenorhabditis elegans that maps to the right arm of chromosome III [7].
• Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene [8].
• Patients with SDS were screened for mutations in TPST1 by sequencing of exons and intron-exon junctions [8].
• Sustained application of arterial laminar shear stress causes downregulation of TPST1 mRNA and protein expression, while TPST2 is upregulated [9].
• Shear stress-dependent downregulation of TPST1 involves tyrosine kinase, while upregulation of TPST2 is mediated by a protein kinase C-dependent pathway [corrected] [9].

Anatomical context of TPST1

• In this report we describe the purification of TPST from rat liver microsomes based on its affinity for the N-terminal 15 amino acids of PSGL-1 [6].
• Shear stress mediates tyrosylprotein sulfotransferase isoform shift in human endothelial cells [9].
• The recombinant form of the zebrafish TPST, expressed in COS-7 cells, exhibited a pH optimum at 5.75 [10].
• Treatment of PC12 cells with 2-chloroadenosine results in a dose-dependent decrease of TPST activity which is observable as early as 3 h after initiation of treatment, maximizes at 24-48 h with continuous exposure, and is readily reversible upon removal of the drug [11].
• Studies employing continuous sucrose gradient and trypsinization of the membranes demonstrate that TPST is located on the luminal side of Golgi apparatus in PC12 cells [11].

Associations of TPST1 with chemical compounds

• A 304-residue segment in the luminal domain of TPST-2 shows 75% amino acid identity to the corresponding segment of TPST-1, including conservation of the residues implicated in the binding of PAPS [5].
• By alanine mutation of these asparagine residues, we could determine that the N-linked oligosaccharides do not have an influence on Golgi retention of TPST1 [12].
• Manganese appeared to exert a stimulatory effect on the zebrafish TPST [10].
• Additionally, the activity of TPST-2, but not TPST-1, was stimulated in the presence of Mg(2+) [13].
• These results suggest that the sensitivity of TPST activity to be controlled by protein synthesis provides a mechanism for regulation of its activity by 2-chloroadenosine [11].

Other interactions of TPST1

• These results exclude TPST1 as the causative gene for SDS [8].
• 2-Chloroadenosine decreases tyrosylprotein sulfotransferase activity in the Golgi apparatus in PC12 cells. Evidence for a novel receptor [11].
• Further in vivo FRET studies using the transmembrane domain suggest that the human tyrosylprotein sulfotransferase may be functional as homodimer/oligomer in the trans-Golgi compartment [12].
• The K(m)value of tyrosylprotein sulfotransferase for statherin was 40 microM [14].

Analytical, diagnostic and therapeutic context of TPST1

• Molecular cloning and expression of human and mouse tyrosylprotein sulfotransferase-2 and a tyrosylprotein sulfotransferase homologue in Caenorhabditis elegans [7].
• Quantitative real-time PCR analysis showed that although the two TPSTs were co-expressed in all 20 human tissues examined, the levels of expression of TPST-1 and TPST-2 varied significantly among different tissues [13].
• Sequence analysis revealed that this zebrafish TPST is, at the amino acid sequence level, 66% and 60% identical to the human and mouse TPST-1 and TPST-2, respectively [10].
• By employing the reverse transcriptase-polymerase chain reaction technique in conjunction with 3' rapid amplification of cDNA ends, a full-length cDNA encoding a zebrafish (Danio rerio) tyrosylprotein sulfotransferase (TPST) was cloned and sequenced [10].
• Using poly Glu,Ala,Tyr (6:3:1; EAY) as the model substrate, human liver TPST was recovered in the microsomal fraction after differential centrifugation [15].

References