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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).
-