| Literature References | 1. FRANK, M.
MAL, a proteolipid in glycosphingolipid enriched domains: functional
implications in myelin and beyond.
PROG.NEUROBIOL. 60(6) 531-544 (2000).
2. CHEONG, K.H., ZACCHETTI, D., SCHNEEBERGER, E.E. AND SIMONS, K.
VIP17/MAL, a lipid raft-associated protein, is involved in apical transport
in MDCK cells.
PROC.NATL.ACAD.SCI.U.S.A. 90 6242-6248 (1999).
3. MILLAN, J. AND ALONSO, M.A.
MAL, a novel integral membrane protein of human T lymphocytes, associates
with glycosylphosphatidylinositol-anchored proteins and Src-like tyrosine
kinases.
EUR.J.IMMUNOL. 28(11) 3675-3684 (1998).
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| Documentation | Myelin is a product of myelinating cells: Schawnn cells in the peripheral
nervous system (PNS) and oligodendrocytes in the central nervous system
(CNS). The processes of these myelinating cells wrap around axon segments
to form a sheath. This sheath possesses insulating properties, allowing
rapid propagation of action potentials (the electrical signal propagated by
nerve cells) between the myelinating cell intervening nodes. Without myelin
insulation, axons would need a 10-30-fold increase in diameter to achieve
comparable conduction velocities.
At the onset of myelination, during development, large amounts of myelin-
specific lipids and proteins are synthesised and transported to the
developing myelin sheath. The major protein component of PNS and CNS
myelin differs between the 2 nervous systems. However, some of the minor
protein components, including the 4 transmembrane (TM)-domain-containing
myelin and lymphocyte protein (MAL), are found in both systems. Outside
the nervous system, MAL is also found in T-cells and some epithelial cells
(e.g., kidney, stomach and thyroid) [1].
Glycosphingolipids are enriched in both epithelial cells and myelin, and
are believed to decrease the permeability of lipid membranes to small
molecules and increase the ability for membrane curvature. MAL co-purifies
with glycosphingolipids in detergent-insoluble domains, suggesting a
possible interaction. In Madin Darby Canine Kidney (MDCK) cells, MAL is
found mainly in transport vesicles, and recent studies suggest that MAL is
required for efficient vesicular transport of proteins across apical cell
membranes [2]. In myelinating cells, MAL appears to play a similar role,
interacting with glycosphingolipids to decrease membrane permeability;
however, here this property most likely manifests itself as an improved
insulating ability of the myelin [1]. In lymphocytes, however, MAL appears
to act as a TM-linker protein in T-cell signal transduction, linking the
cell surface glycosyl phosphatidylinositol anchored protein CD59 to the
intracellular tyrosine kinase Lck [3].
MALPROTEIN is a 4-element fingerprint that provides a signature for the
myelin and lymphocyte protein family. The fingerprint was derived from an
initial alignment of 5 sequences: the motifs were drawn from conserved
regions spanning the full alignment length: motifs 1 and 2 lie in the 1st
and 2nd TM domains, respectively; motif 3 spans the C-terminal portion of
the 1st cytoplasmic loop and the N-terminal portion of the 3rd TM domain;
and motif 4 lies in the 4th TM domain. Two iterations on SPTR40_20f were
required to reach convergence, at which point a true set comprising 11
sequences was identified. A single partial match was also found, Q9D2R2,
which lacks a substantial portion of TM domains 1-3.
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