{PDOC00398}
{PS00497; TYROSINASE_1}
{PS00498; TYROSINASE_2}
{BEGIN}
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* Tyrosinase signatures *
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Tyrosinase (EC 1.14.18.1) [1] is  a  copper  monooxygenases that catalyzes the
hydroxylation of  monophenols and the oxidation  of  o-diphenols to o-quinols.
This enzyme, found in prokaryotes as well as in eukaryotes, is involved in the
formation of pigments such as melanins and other polyphenolic compounds.

Tyrosinase binds two copper ions (CuA and CuB). Each of the two copper ion has
been shown [2] to be bound by three conserved histidines residues. The regions
around these copper-binding ligands are well conserved and also shared by some
hemocyanins, which are copper-containing oxygen carriers from the hemolymph of
many molluscs and arthropods [3,4].

At least two proteins related to tyrosinase are known to exist in mammals:

 - TRP-1 (TYRP1) [5], which is responsible for  the conversion of 5,6-dihydro-
   xyindole-2-carboxylic acid (DHICA) to indole-5,6-quinone-2-carboxylic acid.
 - TRP-2 (TYRP2) [6], which is  the  melanogenic enzyme DOPAchrome tautomerase
   (EC 5.3.3.12) that catalyzes the conversion of DOPAchrome to DHICA.   TRP-2
   differs from tyrosinases and TRP-1 in that  it binds  two zinc ions instead
   of copper [7].

Other proteins that belong to this family are:

 - Plants polyphenol oxidases (PPO) (EC 1.10.3.1) which catalyze the oxidation
   of mono- and o-diphenols to o-diquinones [8].
 - Caenorhabditis elegans hypothetical protein C02C2.1.

We have  derived  two  signature patterns for tyrosinase and related proteins.
The first one contains two of the histidines that bind CuA, and is  located in
the N-terminal section of tyrosinase.  The second pattern contains a histidine
that binds CuB, that pattern is located in the central section of the enzyme.

-Consensus pattern: H-x(4,5)-F-[LIVMFTP]-x-[FW]-H-R-x(2)-[LVMT]-x(3)-E
                    [The 2 H's are copper ligands]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: D-P-x-F-[LIVMFYW]-x(2)-H-x(3)-D
                    [H is a copper ligand]
-Sequences known to belong to this class detected by the pattern: ALL the
 tyrosinases as well as all the hemocyanins.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: April 2006 / Pattern revised.

[ 1] Lerch K.
     "Protein and active-site structure of tyrosinase."
     Prog. Clin. Biol. Res. 256:85-98(1988).
     PubMed=3130643
[ 2] Jackman M.P., Hajnal A., Lerch K.
     "Albino mutants of Streptomyces glaucescens tyrosinase."
     Biochem. J. 274:707-713(1991).
     PubMed=1901488
[ 3] Linzen B.
     "Blue blood: structure and evolution of hemocyanin."
     Naturwissenschaften 76:206-211(1989).
     PubMed=2664531
[ 4] Lang W.H., van Holde K.E.
     "Cloning and sequencing of Octopus dofleini hemocyanin cDNA: derived
     sequences of functional units Ode and Odf."
     Proc. Natl. Acad. Sci. U.S.A. 88:244-248(1991).
     PubMed=1898774
[ 5] Kobayashi T., Urabe K., Winder A., Jimenez-Cervantes C., Imokawa G.,
     Brewington T., Solano F., Garcia-Borron J.C., Hearing V.J.
     "Tyrosinase related protein 1 (TRP1) functions as a DHICA oxidase in
     melanin biosynthesis."
     EMBO J. 13:5818-5825(1994).
     PubMed=7813420
[ 6] Jackson I.J., Chambers D.M., Tsukamoto K., Copeland N.G.,
     Gilbert D.J., Jenkins N.A., Hearing V.
     "A second tyrosinase-related protein, TRP-2, maps to and is mutated at
     the mouse slaty locus."
     EMBO J. 11:527-535(1992).
     PubMed=1537334
[ 7] Solano F., Martinez-Liarte J.H., Jimenez-Cervantes C.,
     Garcia-Borron J.C., Lozano J.A.
     "Dopachrome tautomerase is a zinc-containing enzyme."
     Biochem. Biophys. Res. Commun. 204:1243-1250(1994).
     PubMed=7980602
[ 8] Cary J.W., Lax A.R., Flurkey W.H.
     "Cloning and characterization of cDNAs coding for Vicia faba
     polyphenol oxidase."
     Plant Mol. Biol. 20:245-253(1992).
     PubMed=1391768

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