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- ***************************************
- * Carboxylesterases type-B signatures *
- ***************************************
-
- Higher eukaryotes have many distinct esterases. Among the different types are
- those which act on carboxylic esters (EC 3.1.1.-). Carboxyl-esterases have
- been classified into three categories (A, B and C) on the basis of
- differential patterns of inhibition by organophosphates. The sequence of a
- number of type-B carboxylesterases indicates [1,2,3] that the majority are
- evolutionary related. This family currently consists of the following
- proteins:
-
- - Acetylcholinesterase (EC 3.1.1.7) (AChE) from vertebrates and Drosophila.
- - Mammalian cholinesterase II (butyryl cholinesterase) (EC 3.1.1.8).
- Acetylcholinesterase and cholinesterase II are closely related enzymes that
- hydrolyze choline esters [4].
- - Mammalian liver microsomal carboxylesterases (EC 3.1.1.1).
- - Drosophila esterase 6, produced in the anterior ejaculatory duct of the
- male insect reproductive system where it plays an important role in its
- reproductive biology.
- - Drosophila esterase P.
- - Culex pipiens (mosquito) esterases B1 and B2.
- - Myzus persicae (peach-potato aphid) esterases E4 and FE4.
- - Mammalian bile-salt-activated lipase (BAL) [5], a multifunctional lipase
- which catalyzes fat and vitamin absorption. It is activated by bile salts
- in infant intestine where it helps to digest milk fats.
- - Insect juvenile hormone esterase (JH esterase) (EC 3.1.1.59).
- - Lipases (EC 3.1.1.3) from the fungi Geotrichum candidum and Candida rugosa.
- - Caenorhabditis gut esterase (gene ges-1).
- - Membrane enclosed crystal proteins from slime mold. These proteins are,
- most probably esterases; the vesicles where they are found have therefore
- been termed esterosomes.
-
- The following proteins, while having lost their catalytic activity, contain a
- domain evolutionary related to that of carboxylesterases type-B:
-
- - Thyroglobulin (TG), a glycoprotein specific to the thyroid gland, which is
- the precursor of the iodinated thyroid hormones thyroxine (T4) and triiodo
- thyronine (T3).
- - Drosophila protein neuractin (gene nrt) which may mediate or modulate cell
- adhesion between embryonic cells during development.
- - Drosophila protein glutactin (gene glt), whose function is not known.
-
- As is the case for lipases and serine proteases, the catalytic apparatus of
- esterases involves three residues (catalytic triad): a serine, a glutamate or
- aspartate and a histidine. The sequence around the active site serine is well
- conserved and can be used as a signature pattern. As a second signature
- pattern, we selected a conserved region located in the N-terminal section and
- which contains a cysteine involved in a disulfide bond.
-
- -Consensus pattern: F-G-G-x(4)-[LIVM]-x-[LIV]-x-G-x-S-[STA]-G
- [S is the active site residue]
- -Sequences known to belong to this class detected by the pattern: ALL members
- of this family with a catalytic activity.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Consensus pattern: [ED]-D-C-L-[YT]-[LIV]-[DNS]-[LIV]-[LIVFYW]-x-[PQR]
- [C is involved in a disulfide bond]
- -Sequences known to belong to this class detected by the pattern: ALL, except
- for mosquito and peach-potato aphid esterases and juvenile hormone esterases.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Note: human esterase-D, also a type-B carboxylesterase, does not seem to be
- evolutionary related.
-
- -Expert(s) to contact by email: Sussman J.
- csjoel@weizmann.weizmann.ac.il
-
- -Last update: June 1994 / Patterns and text revised.
-
- [ 1] Myers M., Richmond R.C., Oakeshott J.G.
- Mol. Biol. Evol. 5:113-119(1988).
- [ 2] Krejci E., Duval N., Chatonnet A., Vincens P., Massoulie J.
- Proc. Natl. Acad. Sci. U.S.A. 88:6647-6651(1991).
- [ 3] Cygler M., Schrag J.D., Sussman J.L., Harel M., Silman I. Gentry M.K.,
- Doctor B.P.
- Protein Sci. 2:366-382(1993).
- [ 4] Lockridge O.
- BioEssays 9:125-128(1988).
- [ 5] Wang C.-S., Hartsuck J.A.
- Biochim. Biophys. Acta 1166:1-19(1993).
-