PROSITE documentation PDOC51004Sema domain profile
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.
-------------------------------------------------------------------------------
PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Xu X. Ng S. Wu Z.-L. Nguyen D. Homburger S. Seidel-Dugan C. Ebens A. Luo Y. |
| Title | Human semaphorin K1 is glycosylphosphatidylinositol-linked and defines a new subfamily of viral-related semaphorins. | |
| Source | J. Biol. Chem. 273:22428-22434(1998). | |
| PubMed ID | 9712866 |
| 2 | Authors | Winberg M.L. Noordermeer J.N. Tamagnone L. Comoglio P.M. Spriggs M.K. Tessier-Lavigne M. Goodman C.S. |
| Title | Plexin A is a neuronal semaphorin receptor that controls axon guidance. | |
| Source | Cell 95:903-916(1998). | |
| PubMed ID | 9875845 |
| 3 | Authors | 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. |
| Title | Structure of the semaphorin-3A receptor binding module. | |
| Source | Neuron 39:589-598(2003). | |
| PubMed ID | 12925274 |
| 4 | Authors | Love C.A. Harlos K. Mavaddat N. Davis S.J. Stuart D.I. Jones E.Y. Esnouf R.M. |
| Title | The ligand-binding face of the semaphorins revealed by the high-resolution crystal structure of SEMA4D. | |
| Source | Nat. Struct. Biol. 10:843-848(2003). | |
| PubMed ID | 12958590 | |
| DOI | 10.1038/nsb977 |
| 5 | Authors | Stamos J. Lazarus R.A. Yao X. Kirchhofer D. Wiesmann C. |
| Title | Crystal structure of the HGF beta-chain in complex with the Sema domain of the Met receptor. | |
| Source | EMBO J. 23:2325-2335(2004). | |
| PubMed ID | 15167892 | |
| DOI | 10.1038/sj.emboj.7600243 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)