InterPro domain: IPR000782

The FAS1 (fasciclin-like) domain is an extracellular module of about 140 amino acid residues. It has been suggested that the FAS1 domain represents an ancient cell adhesion domain common to plants and animals [ 1 ]; related FAS1 domains are also found in bacteria [ 2 ].

The crystal structure of FAS1 domains 3 and 4 of fasciclin I from Drosophila melanogaster (Fruit fly) has been determined, revealing a novel domain fold consisting of a seven-stranded beta wedge and at least five alpha helices; two well-ordered N-acetylglucosamine groups attached to a conserved asparagine are located in the interface region between the two FAS1 domains [ 3 ]. Fasciclin I is an insect neural cell adhesion molecule involved in axonal guidance that is attached to the membrane by a GPI-anchored protein.

FAS1 domains are present in many secreted and membrane-anchored proteins. These proteins are usually GPI anchored and consist of: (i) a single FAS1 domain, (ii) a tandem array of FAS1 domains, or (iii) FAS1 domain(s) interspersed with other domains.

Proteins known to contain a FAS1 domain include:

• Fasciclin I (4 FAS1 domains).
• Human TGF-beta induced Ig-H3 (BIgH3) protein (4 FAS1 domains), where the FAS1 domains mediate cell adhesion through an interaction with alpha3/beta1 integrin; mutation in the FAS1 domains result in corneal dystrophy [ 4 ].
• Volvox major cell adhesion protein (2 FAS1 domains) [ 5 ].
• Arabidopsis fasciclin-like arabinogalactan proteins (2 FAS1 domains) [ 5 ].
• Mammalian stabilin protein, a family of fasciclin-like hyaluronan receptor homologues (7 FAS1 domains)[ 6 ].
• Human extracellular matrix protein periostin (4 FAS1 domains).
• Bacterial immunogenic protein MPT70 (1 FAS1 domain) [ 7 ].

The FAS1 domains of both human periostin ( Q15063 ) and BIgH3 ( Q15582 ) proteins were found to contain vitamin K-dependent gamma-carboxyglutamate residues [ 8 ]. Gamma-carboxyglutamate residues are more commonly associated with GLA domains ( IPR000294 ), where they occur through post-translational modification catalysed by the vitamin K-dependent enzyme gamma-glutamylcarboxylase.

1. Algal-CAMs: isoforms of a cell adhesion molecule in embryos of the alga Volvox with homology to Drosophila fasciclin I. EMBO J. 13, 4212-22
2. Relationship of secretion pattern and MPB70 homology with osteoblast-specific factor 2 to osteitis following Mycobacterium bovis BCG vaccination. Infect. Immun. 63, 672-5
3. Novel fold revealed by the structure of a FAS1 domain pair from the insect cell adhesion molecule fasciclin I. Structure 11, 197-203
4. Identification of motifs for cell adhesion within the repeated domains of transforming growth factor-beta-induced gene, betaig-h3. J. Biol. Chem. 275, 30907-15
5. Putative fasciclin-like arabinogalactan-proteins (FLA) in wheat (Triticum aestivum) and rice (Oryza sativa): identification and bioinformatic analyses. Mol. Genet. Genomics 276, 478-94
6. Stabilin-1 localizes to endosomes and the trans-Golgi network in human macrophages and interacts with GGA adaptors. J. Leukoc. Biol. 76, 1151-61
7. Cloning and sequencing of a unique antigen MPT70 from Mycobacterium tuberculosis H37Rv and expression in BCG using E. coli-mycobacteria shuttle vector. Scand. J. Immunol. 41, 281-7
8. Periostin, a member of a novel family of vitamin K-dependent proteins, is expressed by mesenchymal stromal cells. J. Biol. Chem. 283, 17991-8001