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PROSITE documentation PDOC51004 [for PROSITE entry PS51004]
Sema domain profile


Description

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 β 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 β 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 β-strand closing the circle by providing the outermost strand (D) of the seventh (C-terminal) blade. The β-propeller is further stabilized by an extension of the N-terminus, providing an additional, fifth β-strand on the outer edge of blade 6 [3,4,5].

The profile we developed covers the entire Sema domain.

Last update:

August 2004 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

SEMA, PS51004; Sema domain profile  (MATRIX)


References

1AuthorsXu X. Ng S. Wu Z.-L. Nguyen D. Homburger S. Seidel-Dugan C. Ebens A. Luo Y.
TitleHuman semaphorin K1 is glycosylphosphatidylinositol-linked and defines a new subfamily of viral-related semaphorins.
SourceJ. Biol. Chem. 273:22428-22434(1998).
PubMed ID9712866

2AuthorsWinberg M.L. Noordermeer J.N. Tamagnone L. Comoglio P.M. Spriggs M.K. Tessier-Lavigne M. Goodman C.S.
TitlePlexin A is a neuronal semaphorin receptor that controls axon guidance.
SourceCell 95:903-916(1998).
PubMed ID9875845

3AuthorsAntipenko 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.
TitleStructure of the semaphorin-3A receptor binding module.
SourceNeuron 39:589-598(2003).
PubMed ID12925274

4AuthorsLove C.A. Harlos K. Mavaddat N. Davis S.J. Stuart D.I. Jones E.Y. Esnouf R.M.
TitleThe ligand-binding face of the semaphorins revealed by the high-resolution crystal structure of SEMA4D.
SourceNat. Struct. Biol. 10:843-848(2003).
PubMed ID12958590
DOI10.1038/nsb977

5AuthorsStamos J. Lazarus R.A. Yao X. Kirchhofer D. Wiesmann C.
TitleCrystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor.
SourceEMBO J. 23:2325-2335(2004).
PubMed ID15167892
DOI10.1038/sj.emboj.7600243



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