{PDOC51004}
{PS51004; SEMA}
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* Sema domain profile *
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The 500  amino  acid Sema domain is a receptor recognition and binding module,
which is found near the N-terminus of the eukaryotic and viral proteins:

 - Semaphorins,  a  large  group  of  secreted,  transmembrane,  or GPI-linked
   proteins, some  of  which  are known to act as repulsive axon guidance cues
   during development or to be involved in immune function,
 - Plexins, receptors for multiple classes of semaphorins,
 - MET-hepatocyte growth factor (or scatter-factor) receptor.

The Sema  domain  can be found associated with other domains such as PSI, IPT,
Ig-like and TSP1 (see <PDOC50092>) [1,2].

The Sema  domain  is  characterized  by  a conserved set of cysteine residues,
which form  four  disulfide  bonds to stabilize the structure. The Sema domain
fold is a variation of the beta propeller topology, with seven blades radially
arranged around  a  central axis (see <PDB:1Q47>). Each blade contains a four-
stranded (strands  A  to  D) antiparallel beta sheet. The inner strand of each
blade (A) lines the channel at the center of the propeller, with strands B and
C of  the  same  repeat  radiating  outward,  and  strand D of the next repeat
forming the  outer edge of the blade. The large size of the Sema domain is not
due to  a  single inserted domain but results from the presence of additionnal
secondary structure  elements  inserted in most of the blades. The Sema domain
uses a  'loop  and  hook' system to close the circle between the first and the
last blades.  The blades are constructed sequentially with an N-terminal beta-
strand closing the circle by providing the outermost strand (D) of the seventh
(C-terminal) blade.  The  beta-propeller is further stabilized by an extension
of the  N-terminus,  providing  an  additional, fifth beta-strand on the outer
edge of blade 6 [3,4,5].

The profile we developed covers the entire Sema domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: August 2004 / First entry.

[ 1] Xu X., Ng S., Wu Z.-L., Nguyen D., Homburger S., Seidel-Dugan C.,
     Ebens A., Luo Y.
     "Human semaphorin K1 is glycosylphosphatidylinositol-linked and
     defines a new subfamily of viral-related semaphorins."
     J. Biol. Chem. 273:22428-22434(1998).
     PubMed=9712866
[ 2] Winberg M.L., Noordermeer J.N., Tamagnone L., Comoglio P.M.,
     Spriggs M.K., Tessier-Lavigne M., Goodman C.S.
     "Plexin A is a neuronal semaphorin receptor that controls axon
     guidance."
     Cell 95:903-916(1998).
     PubMed=9875845
[ 3] Antipenko A., Himanen J.-P., van Leyen K., Nardi-Dei V., Lesniak J.,
     Barton W.A., Rajashankar K.R., Lu M., Hoemme C., Puschel A.W.,
     Nikolov D.B.
     "Structure of the semaphorin-3A receptor binding module."
     Neuron 39:589-598(2003).
     PubMed=12925274
[ 4] Love C.A., Harlos K., Mavaddat N., Davis S.J., Stuart D.I.,
     Jones E.Y., Esnouf R.M.
     "The ligand-binding face of the semaphorins revealed by the
     high-resolution crystal structure of SEMA4D."
     Nat. Struct. Biol. 10:843-848(2003).
     PubMed=12958590; DOI=10.1038/nsb977
[ 5] Stamos J., Lazarus R.A., Yao X., Kirchhofer D., Wiesmann C.
     "Crystal structure of the HGF beta-chain in complex with the Sema
     domain of the Met receptor."
     EMBO J. 23:2325-2335(2004).
     PubMed=15167892; DOI=10.1038/sj.emboj.7600243

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