{PDOC00112}
{PS00122; CARBOXYLESTERASE_B_1}
{PS00941; CARBOXYLESTERASE_B_2}
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* Carboxylesterases type-B signatures *
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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  from
   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).
 - Duck acyl-[acyl-carrier protein] hydrolase, medium  chain (EC 3.1.2.14), an
   enzyme that may be  associated with peroxisome proliferation and may play a
   role in the production of 3-hydroxy fatty acid diester pheromones.
 - Membrane enclosed crystal  proteins from slime mold.  These  proteins  are,
   most probably  esterases;  the vesicles where they are found have therefore
   been termed esterosomes.

So far two bacterial proteins have been found to belong to this family:

 - Phenmedipham hydrolase (phenylcarbamate hydrolase), an Arthrobacter oxidans
   plasmid-encoded enzyme   (gene   pcd)  that  degrades  the  phenylcarbamate
   herbicides phenmedipham   and  desmedipham  by  hydrolyzing  their  central
   carbamate linkages.
 - Para-nitrobenzyl esterase from Bacillus subtilis (gene pnbA).

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  neurotactin  (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-[GR]-G-x(4)-[LIVM]-x-[LIV]-x-G-x-S-[STAG]-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: [EDA]-[DG]-C-L-[YTF]-[LIVT]-[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: April 2006 / Pattern revised.

[ 1] Myers M., Richmond R.C., Oakeshott J.G.
     "On the origins of esterases."
     Mol. Biol. Evol. 5:113-119(1988).
     PubMed=3163407
[ 2] Krejci E., Duval N., Chatonnet A., Vincens P., Massoulie J.
     "Cholinesterase-like domains in enzymes and structural proteins:
     functional and evolutionary relationships and identification of a
     catalytically essential aspartic acid."
     Proc. Natl. Acad. Sci. U.S.A. 88:6647-6651(1991).
     PubMed=1862088
[ 3] Cygler M., Schrag J.D., Sussman J.L., Harel M., Silman I.,
     Gentry M.K., Doctor B.P.
     "Relationship between sequence conservation and three-dimensional
     structure in a large family of esterases, lipases, and related
     proteins."
     Protein Sci. 2:366-382(1993).
     PubMed=8453375
[ 4] Lockridge O.
     "Structure of human serum cholinesterase."
     BioEssays 9:125-128(1988).
     PubMed=3067729
[ 5] Wang C.-S., Hartsuck J.A.
     "Bile salt-activated lipase. A multiple function lipolytic enzyme."
     Biochim. Biophys. Acta 1166:1-19(1993).
     PubMed=8431483

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