{PDOC51934}
{PS51934; LRAT}
{BEGIN}
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* LRAT domain profile *
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NlpC/P60 superfamily  papain-like enzymes play important roles in all kingdoms
of life.  Characterized  members  of  this  superfamily have diverse enzymatic
functions, such     as    peptidases,    amidases,    transglutaminases    and
acetyltransferases. This divergent superfamily consists of four main families:
P60-like, AcmB/LytN-like (see <PDOC50911>), YaeF/YiiX-like, and LRAT-like. The
latter two  families  were  predicted  to  contain a conserved catalytic triad
(Cys, His and a polar third residue) in a circularly permuted catalytic domain
where the  relative  positions of the cysteine and histidine/polar residue are
swapped in  the  primary  sequence such that the catalytic cysteine is located
near the C-terminus, instead of at the N-terminus [1].

The NlpC/P60   LRAT-type   family  includes  lecithin-retinol  acyltransferase
(LRAT), nematode  developmental  regulator  Egl-26,  class II tumor suppressor
H-rev107 and  proteins from poxviruses and animal positive-strand RNA viruses,
which share a common catalytic domain fold and the unconventional active site.
Several members   of  the  NlpC/P60  LRAT-type  family  are  able  to  act  as
transferases/esterases utilizing    glycerophospholipids    as   acyl   donors
[1,2,3,4,5].

The basic  structural  motif  of  the LRAT domain is composed of a four-strand
antiparallel beta-sheet  and three alpha-helices (see <PDB:4DPZ>). The longest
alpha-helix (alpha3)  is  packed  against  the  beta-sheet,  and the two other
shorter alpha-helices  are  located on the sides. A highly conserved catalytic
Cys, identified  as  the  acylation  site,  is  located near the N terminus of
alpha3. This  arrangement  defines the active site location, which is embedded
into a  well  defined groove formed by the extended loops between beta1-beta2,
beta3-beta4, and the N-terminus of the alpha3 helix. The side chain of the Cys
is packed  against  a  beta-sheet  core  of  the  domain,  placing it in close
proximity to  a  conserved His from the beta2 strand. The beta-sheet is spread
open on  one end allowing formation of a hydrogen bond between the His and the
Cys. The third polar residue in this catalytic triad is a polar residue in the
neighboring beta3  strand.  The  Cys residue was shown to act as a nucleophile
and form a covalent thiol-acyl intermediate in the catalytic process [6,7,8].

The profile we developed covers the entire LRAT domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2020 / First entry.

[ 1] Xu Q., Rawlings N.D., Chiu H.-J., Jaroszewski L., Klock H.E.,
     Knuth M.W., Miller M.D., Elsliger M.-A., Deacon A.M., Godzik A.,
     Lesley S.A., Wilson I.A.
     "Structural analysis of papain-like NlpC/P60 superfamily enzymes with
     a circularly permuted topology reveals potential lipid binding
     sites."
     PLoS One. 6:E22013-E22013(2011).
     PubMed=21799766; DOI=10.1371/journal.pone.0022013
[ 2] Anantharaman V., Aravind L.
     "Evolutionary history, structural features and biochemical diversity
     of the NlpC/P60 superfamily of enzymes."
     Genome Biol 4:R11-R11(2003).
     PubMed=12620121; DOI=10.1186/gb-2003-4-2-r11
[ 3] Xue L., Rando R.R.
     "Roles of cysteine 161 and tyrosine 154 in the lecithin-retinol
     acyltransferase mechanism."
     Biochemistry 43:6120-6126(2004).
     PubMed=15147196; DOI=10.1021/bi049556f
[ 4] Golczak M., Sears A.E., Kiser P.D., Palczewski K.
     "LRAT-specific domain facilitates vitamin A metabolism by domain
     swapping in HRASLS3."
     Nat. Chem. Biol. 11:26-32(2015).
     PubMed=25383759; DOI=10.1038/nchembio.1687
[ 5] Uyama T., Jin X.-H., Tsuboi K., Tonai T., Ueda N.
     "Characterization of the human tumor suppressors TIG3 and HRASLS2 as
     phospholipid-metabolizing enzymes."
     Biochim. Biophys. Acta. 1791:1114-1124(2009).
     PubMed=19615464; DOI=10.1016/j.bbalip.2009.07.001
[ 6] Golczak M., Kiser P.D., Sears A.E., Lodowski D.T., Blaner W.S.,
     Palczewski K.
     "Structural basis for the acyltransferase activity of lecithin:retinol
     acyltransferase-like proteins."
     J. Biol. Chem. 287:23790-23807(2012).
     PubMed=22605381; DOI=10.1074/jbc.M112.361550
[ 7] Pang X.Y., Cao J., Addington L., Lovell S., Battaile K.P., Zhang N.,
     Rao J.L., Dennis E.A., Moise A.R.
     "Structure/function relationships of adipose phospholipase A2
     containing a cys-his-his catalytic triad."
     J. Biol. Chem. 287:35260-35274(2012).
     PubMed=22923616; DOI=10.1074/jbc.M112.398859
[ 8] Wei H., Wang L., Ren X., Yu W., Lin J., Jin C., Xia B.
     "Structural and functional characterization of tumor suppressors TIG3
     and H-REV107."
     FEBS. Lett. 589:1179-1186(2015).
     PubMed=25871522; DOI=10.1016/j.febslet.2015.04.002

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