PROSITE documentation PDOC51934
LRAT domain profile


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 β-sheet and three α-helices (see <PDB:4DPZ>). The longest α-helix (α3) is packed against the β-sheet, and the two other shorter α-helices are located on the sides. A highly conserved catalytic Cys, identified as the acylation site, is located near the N terminus of α3. This arrangement defines the active site location, which is embedded into a well defined groove formed by the extended loops between β1-β2, β3-β4, and the N-terminus of the α3 helix. The side chain of the Cys is packed against a β-sheet core of the domain, placing it in close proximity to a conserved His from the β2 strand. The β-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 β3 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.

Last update:

August 2020 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

LRAT, PS51934; LRAT domain profile  (MATRIX)


1AuthorsXu 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.
TitleStructural analysis of papain-like NlpC/P60 superfamily enzymes with a circularly permuted topology reveals potential lipid binding sites.
SourcePLoS One. 6:E22013-E22013(2011).
PubMed ID21799766

2AuthorsAnantharaman V. Aravind L.
TitleEvolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.
SourceGenome Biol 4:R11-R11(2003).
PubMed ID12620121

3AuthorsXue L. Rando R.R.
TitleRoles of cysteine 161 and tyrosine 154 in the lecithin-retinol acyltransferase mechanism.
SourceBiochemistry 43:6120-6126(2004).
PubMed ID15147196

4AuthorsGolczak M. Sears A.E. Kiser P.D. Palczewski K.
TitleLRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3.
SourceNat. Chem. Biol. 11:26-32(2015).
PubMed ID25383759

5AuthorsUyama T. Jin X.-H. Tsuboi K. Tonai T. Ueda N.
TitleCharacterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes.
SourceBiochim. Biophys. Acta. 1791:1114-1124(2009).
PubMed ID19615464

6AuthorsGolczak M. Kiser P.D. Sears A.E. Lodowski D.T. Blaner W.S. Palczewski K.
TitleStructural basis for the acyltransferase activity of lecithin:retinol acyltransferase-like proteins.
SourceJ. Biol. Chem. 287:23790-23807(2012).
PubMed ID22605381

7AuthorsPang X.Y. Cao J. Addington L. Lovell S. Battaile K.P. Zhang N. Rao J.L. Dennis E.A. Moise A.R.
TitleStructure/function relationships of adipose phospholipase A2 containing a cys-his-his catalytic triad.
SourceJ. Biol. Chem. 287:35260-35274(2012).
PubMed ID22923616

8AuthorsWei H. Wang L. Ren X. Yu W. Lin J. Jin C. Xia B.
TitleStructural and functional characterization of tumor suppressors TIG3 and H-REV107.
SourceFEBS. Lett. 589:1179-1186(2015).
PubMed ID25871522

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