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DATA
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PDOC00371
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1995-07-26
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*****************************************
* Transmembrane 4 superfamily signature *
*****************************************
Recently a number of eukaryotic cell surface antigens have been found to be
evolutionary related [1,2,3]. The proteins known to belong to this family are
listed below:
- Mammalian antigen CD9 (MIC3). A protein involved in platelet activation and
aggregation.
- Mammalian leukocyte antigen CD37, expressed on B lymphocytes.
- Mammalian leukocyte antigen CD53 (OX-44), which may be involved in growth
regulation in hematopoietic cells.
- Mammalian lysosomal membrane protein CD63 (melanoma-associated antigen
ME491) (antigen AD1).
- Human tumor-associated antigen CO-029.
- Human protein R2 (antigen C33).
- Mammalian 26 Kd cell surface protein TAPA-1, which may play an important
role in the regulation of lymphoma cell growth.
- Mink protein TI 1.
- Schistosoma mansoni and japonicum 23 Kd surface antigen (SM23 / SJ23).
These proteins share the following characteristics: they all seem to be type
II membrane proteins (type II proteins contain a N-terminal membrane-anchoring
domain which is not cleaved during biosynthesis and which functions both as a
translocation signal and as a membrane anchor); they also contain three
additional transmembrane regions, at least seven conserved cysteines residues,
and are of approximately the same size (218 to 284 residues). These proteins
are collectively know as the 'transmembrane 4 superfamily' (TM4) because they
span the plasma membrane four times. A schematic diagram of the domain
structure of these proteins is shown below.
+-+-----+-------+----+-----+-----+-----------------------------+-----+----+
| | TMa | Extra | TM2| Cyt | TM3 | Extracellular | TM4 | Cyt|
+-+-----+-------+----C-----C-----+--------CC---------C-----C---+-----C----+
*********
Cyt : cytoplasmic domain.
TMa : transmembrane anchor.
TM2 to TM4: transmembrane regions 2 to 4.
'C' : conserved cysteine.
'*' : position of the pattern.
As a signature for these proteins, we selected a conserved region that
includes two cysteines and seems to be located in a short cytoplasmic loop
between two transmembrane domains.
-Consensus pattern: [GSA]-[LIVMF](2)-G-C-x-G-[STA]-x(2)-E-x(2)-C-[LIVM](2)
-Sequences known to belong to this class detected by the pattern: ALL, except
for mink protein TI 1.
-Other sequence(s) detected in SWISS-PROT: NONE.
-Expert(s) to contact by email: Levy S.
levy@cellbio.stanford.edu
-Last update: October 1993 / Text revised.
[ 1] Levy S., Nguyen V.Q., Andria M.L., Takahashi S.
J. Biol. Chem. 266:14597-14602(1991).
[ 2] Tomlinson M.G., Williams A.F., Wright M.D.
Eur. J. Immunol. 23:136-40(1993).
[ 3] Barclay A.N., Birkeland M.L., Brown M.H., Beyers A.D., Davis S.J.,
Somoza C., Williams A.F.
The leucocyte antigen factbooks.
Academic Press, London / San Diego, (1993).