Tyrosine sulfation is a

posttranslational modification Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...

where a

sulfate The sulfate or sulphate ion is a polyatomic anion with the empirical formula . Salts, acid derivatives, and peroxides of sulfate are widely used in industry. Sulfates occur widely in everyday life. Sulfates are salts of sulfuric acid and many ...

group is added to a

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...

residue of a protein molecule. Secreted proteins and extracellular parts of membrane proteins that pass through the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles i ...

may be sulfated. Sulfation was first discovered by Bettelheim in bovine

fibrinopeptide B The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen (factor I) and are cleaved by the enzyme thrombin (factor IIa) to convert fibri ...

in 1954 and later found to be present in animals and plants but not in

prokaryote A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Con ...

s or in yeast.

Function

Sulfation plays a role in strengthening protein-protein interactions. Types of human proteins known to undergo tyrosine sulfation include adhesion molecules, G-protein-coupled receptors, coagulation factors,

serine protease inhibitor Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be i ...

s, extracellular matrix proteins, and hormones. Tyrosine O-sulfate is a stable molecule and is excreted in urine in animals. No enzymatic mechanism of tyrosine sulfate desulfation is known to exist. By knock-out of TPST genes in mice, it may be observed that tyrosine sulfation has effects on the growth of the mice, such as body weight, fecundity, and postnatal viability.

Mechanism

Sulfation is catalyzed by

tyrosylprotein sulfotransferase Tyrosylprotein sulfotransferase is an enzyme that catalyzes tyrosine sulfation. Function Tyrosylprotein sulfotransferase is the enzyme that catalyzes the sulfation reaction of protein tyrosines, a post-translational modification of prote ...

(TPST) in the

. The reaction catalyzed by TPST is a transfer of sulfate from the universal sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS) to the side-chain hydroxyl group of a tyrosine residue. Sulfation sites are tyrosine residues exposed on the surface of the protein typically surrounded by acidic residues; a detailed description of the characteristics of the sulfation site was available from

PROSITE PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformatic ...

(PROSITE pattern: PS0000

and predicted by an on-line tool named the Sulfinato

http://web.expasy.org/sulfinator/sulfinator-doc.html]. Two types of tyrosylprotein sulftotransferases (TPST-1 and TPST2) have been identified.

Regulation

There is very limited evidence that the TPST genes are subject to transcriptional regulation and tyrosine O-sulfate is very stable and cannot be easily degraded by mammalian sulfatases. Tyrosine O-sulfation is an irreversible process ''in vivo''.

Clinical Significance

It has been shown that the sulfation of Tyr1680 in

Factor VIII Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the ''F8'' gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder ...

is essential for effective binding to vWF. Thus, when this is mutated, patients may suffer mild haemophiliac symptoms due to increased turnover.

Antibody for detection of tyrosine-sulfated epitopes

In 2006, an article was published in the ''

Journal of Biological Chemistry The ''Journal of Biological Chemistry'' (''JBC'') is a weekly peer-reviewed scientific journal that was established in 1905., jbc.org Since 1925, it is published by the American Society for Biochemistry and Molecular Biology. It covers research i ...

'' describing the production and characterization of an

antibody An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of t ...

called PSG2. This antibody shows exquisite sensitivity and specificity for epitopes containing sulfotyrosine independent of the sequence context.

References

* * {{DEFAULTSORT:Tyrosine Sulfation Post-translational modification