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PROSITE documentation PDOC00371 [for PROSITE entry PS00421] |
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:
These proteins share the following characteristics: they all seem to be type III membrane proteins (type III proteins are integral membrane proteins that 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.
Note:Mammalian uroplakin IA/IB, TM4SF1 (L6), TM4SF4 (il-TMP), TM4SF5, Tspan- 1, Tspan-5 are proteins that are distantly related to this family and that are not found by the above pattern.
Expert(s) to contact by email: Last update:December 2004 / Pattern and text revised.
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PROSITE method (with tools and information) covered by this documentation:
1 | Authors | Levy S. Nguyen V.Q. Andria M.L. Takahashi S. |
Title | Structure and membrane topology of TAPA-1. | |
Source | J. Biol. Chem. 266:14597-14602(1991). | |
PubMed ID | 1860863 |
2 | Authors | Tomlinson M.G. Williams A.F. Wright M.D. |
Title | Epitope mapping of anti-rat CD53 monoclonal antibodies. Implications for the membrane orientation of the Transmembrane 4 Superfamily. | |
Source | Eur. J. Immunol. 23:136-140(1993). | |
PubMed ID | 7678222 |
3 | Authors | Barclay A.N. Birkeland M.L. Brown M.H. Beyers A.D. Davis S.J. Somoza C. Williams A.F. |
Source | (In) The leucocyte antigen factsbook, Academic Press, London / San Diego, (1993). |