PROSITE documentation PDOC00280 [for PROSITE entry PS51407]

Lysosome-associated membrane glycoprotein family signatures and profile





Description

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.

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.

Technical section

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

LAMP_3, PS51407; Lysosome-associated membrane glycoprotein family profile  (MATRIX)

LAMP_1, PS00310; Lysosome-associated membrane glycoproteins duplicated domain signature  (PATTERN)

LAMP_2, PS00311; LAMP glycoproteins transmembrane and cytoplasmic domain signature  (PATTERN)


References

1AuthorsFukuda M.
TitleLysosomal membrane glycoproteins. Structure, biosynthesis, and intracellular trafficking.
SourceJ. Biol. Chem. 266:21327-21330(1991).
PubMed ID1939168

2AuthorsHolness C.L., da Silva R.P., Fawcett J., Gordon S., Simmons D.L.
TitleMacrosialin, a mouse macrophage-restricted glycoprotein, is a member of the lamp/lgp family.
SourceJ. Biol. Chem. 268:9661-9666(1993).
PubMed ID8486654

3Authorsde 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.
TitleA novel lysosome-associated membrane glycoprotein, DC-LAMP, induced upon DC maturation, is transiently expressed in MHC class II compartment.
SourceImmunity 9:325-336(1998).
PubMed ID9768752

4AuthorsKostich M., Fire A., Fambrough D.M.
TitleIdentification and molecular-genetic characterization of a LAMP/CD68-like protein from Caenorhabditis elegans.
SourceJ. Cell Sci. 113:2595-2606(2000).
PubMed ID10862717



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