{PDOC52033}
{PS52033; CYSTATIN_LXN}
{BEGIN}
**********************************************
* Latexin (LXN)-type cystatin domain profile *
**********************************************

Latexin (LXN),  or  tissue carboxypeptidase inhibitor (TCI), is the only known
mammalian carboxypeptidase  inhibitor  (CPI).  LTX  has no detectable sequence
similarity with  plant  and  parasite inhibitors, but it is related to a human
putative tumor suppressor protein, TIG1.  TIG1 is larger than latexin, and the
additional residues are thought to encode a membrane anchor at the N terminus.
Other proteins  with  sequence  identity  to  latexin  are  found  in  chicken
(ovocalyxin-32) and   Xenopus,   but   no   related  proteins  were  found  in
nonvertebrates. Chicken  ovocalyxin-32  is  a  protein  involved  in egg shell
production [1,2].

The structure  of  LXN  shows  no  structural  relationship  with  other CPIs.
Furthermore, despite  a lack of detectable sequence duplication, the structure
incorporates two  topologically  analogous  domains related by pseudo two-fold
symmetry. Each domain comprises a curved five-stranded antiparallel beta sheet
wrapped around an alpha helix (see <PDB:1WNH>). These domains share a cystatin
fold architecture   found   in   proteins  that  inhibit  cysteine  proteases,
suggesting an  evolutionary and possibly functional relationship. LXN may have
evolved from  an  ancestral  cystatin-like  protein as a consequence of a gene
duplication event. The LXN-type cystatin domains are packed against each other
through the  helices  and  linked by a connecting segment encompassing a third
alpha-helix. The  two  domains  are  arranged so that there is a cleft in this
part of the structure that can accommodate a peptide chain [1,2].

The profile  we developed covers the LXN-type cystatin domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2023 / First entry.

[ 1] Aagaard A., Listwan P., Cowieson N., Huber T., Ravasi T., Wells C.A.,
     Flanagan J.U., Kellie S., Hume D.A., Kobe B., Martin J.L.
     "An inflammatory role for the mammalian carboxypeptidase inhibitor
     latexin:  relationship to cystatins and the tumor suppressor TIG1."
     Structure 13:309-317(2005).
     PubMed=15698574; DOI=10.1016/j.str.2004.12.013
[ 2] Pallares I., Bonet R., Garcia-Castellanos R., Ventura S., Aviles F.X.,
     Vendrell J., Gomis-Rueth F.X.
     "Structure of human carboxypeptidase A4 with its endogenous protein
     inhibitor,  latexin."
     Proc. Natl. Acad. Sci. U. S. A. 102:3978-3983(2005).
     PubMed=15738388; DOI=10.1073/pnas.0500678102

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}