{PDOC00280}
{PS00310; LAMP_1}
{PS00311; LAMP_2}
{PS51407; LAMP_3}
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* Lysosome-associated membrane glycoprotein family signatures and profile *
***************************************************************************

Lysosome-associated membrane  glycoproteins (lamp) [1] are  integral  membrane
proteins, specific to lysosomes,  and whose exact biological  function  is not
yet clear.   Structurally,  the  lamp proteins   consist  of   two  internally
homologous  lysosome-luminal domains separated by a proline-rich hinge region;
at the C-terminal extremity there is a transmembrane region followed by a very
short cytoplasmic tail.   In each  of  the  duplicated domains, there  are two
conserved disulfide bonds. This structure is schematically  represented in the
figure below.

   +-----+            +-----+         +-----+            +-----+
   |     |            |     |         |     |            |     |
  xCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxxxCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxx
  <--------------------------><Hinge><--------------------------><TM><C>

In  mammals,  there  are two closely related types of lamp: lamp-1 and lamp-2,
which  form  major  components  of the lysosome membrane. In chicken lamp-1 is
known as LEP100.

The macrophage protein  CD68 (or macrosialin) [2] is  a  heavily  glycosylated
integral membrane  protein whose structure  consists  of  a  mucin-like domain
followed by a proline-rich hinge; a  single lamp-like domain;  a transmembrane
region and a short cytoplasmic tail.

Similar  to  CD68,  mammalian  lamp-3,  which is expressed in lymphoid organs,
dendritic cells and in lung, contains all the C-terminal regions but lacks the
N-terminal  lamp-like  region [3]. In a lamp-family protein from nematodes [4]
only the part C-terminal to the hinge is conserved.

We developed two signature patterns for this family of proteins. The first one
is  centered  on  the  first conserved cysteine of the duplicated domains. The
second  corresponds  to  a  region  that  includes the extremity of the second
domain,  the totality of the transmembrane region and the cytoplasmic tail. We
also developed a profile that covers lamp entirely.

-Consensus pattern: [STA]-C-[LIVM]-[LIVMFYW]-A-x-[LIVMFYW]-x(3)-[LIVMFYW]-
                    x(3)-Y
                    [C is involved in a disulfide bond]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for CD68s.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: C-x(2)-D-x(3,4)-[LIVM](2)-P-[LIVM]-x-[LIVM]-G-x(2)-[LIVM]-
                    x-G-[LIVM](2)-x-[LIVM](4)-A-[FY]-x-[LIVM]-x(2)-[KR]-[RH]-
                    x(1,2)-[STAG](2)-Y-[EQ]
                    [C is involved in a disulfide bond]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note:  The first pattern will fail to detect the second copy of the domain in
 lamp-2 and the first copy of chicken LEP100.

-Last update: November 2008 / Text revised; profile added.

[ 1] Fukuda M.
     "Lysosomal membrane glycoproteins. Structure, biosynthesis, and
     intracellular trafficking."
     J. Biol. Chem. 266:21327-21330(1991).
     PubMed=1939168
[ 2] Holness C.L., da Silva R.P., Fawcett J., Gordon S., Simmons D.L.
     "Macrosialin, a mouse macrophage-restricted glycoprotein, is a member
     of the lamp/lgp family."
     J. Biol. Chem. 268:9661-9666(1993).
     PubMed=8486654
[ 3] de Saint-Vis B., Vincent J., Vandenabeele S., Vanbervliet B.,
     Pin J.J., Ait-Yahia S., Patel S., Mattei M.G., Banchereau J.,
     Zurawski S., Davoust J., Caux C., Lebecque S.
     "A novel lysosome-associated membrane glycoprotein, DC-LAMP, induced
     upon DC maturation, is transiently expressed in MHC class II
     compartment."
     Immunity 9:325-336(1998).
     PubMed=9768752
[ 4] Kostich M., Fire A., Fambrough D.M.
     "Identification and molecular-genetic characterization of a
     LAMP/CD68-like protein from Caenorhabditis elegans."
     J. Cell Sci. 113:2595-2606(2000).
     PubMed=10862717

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