Embryonal fyn-associated substrate is a protein that in humans is encoded by the EFS gene. It is also known as CASS3.
History and discovery
EFS (Embryonal Fyn-associated Substrate), also known as SIN (Src INteracting or Signal Integrating protein) was originally identified using cDNA library screening of mouse embryonal libraries for proteins containing SH3-interacting domains, or interacting with the SRC SH3 domain, in two independent studies by Ishino et al. in 1995 and Alexandropoulos et al. in 1996.
In humans, the 561 amino acid EFS protein acts as a scaffolding protein for cell signaling based on interactions with SRC, FAK, and other proteins, and has been linked to roles in the function of the immune system, and the development of cancer.
Gene
The chromosomal location of the EFS gene is 14q11.2 and its genomic coordinates are 14:23356400-23365633 on the reverse strand in GRChB38p2 (Genome Reference Consortium Human Build 38 patch release 2). According to the Human Genome Organization (HUGO) Gene Nomenclature Committee (HGNC) its approved symbol is EFS and its synonyms are "Cas scaffolding protein family member 3", CASS3, EFS1, EFS2, HEFS and SIN. The official Gene IDs assigned to EFS are 16898 (HGNC), 10278 (Entrez Gene) and ENSG00000100842 (Ensembl).
In humans, at least three transcript variants are known for EFS: isoform 1, containing 6 exons end encoding the full-length protein with 561 amino acids; isoform 2, containing 5 exons and encoding a shorter protein (468 amino acids in length); and isoform 3, containing 6 exons and encoding the shortest protein (392 amino acids).
Little is known about the transcriptional regulation of EFS, but several transcriptional regulators for EFS have been proposed based on consensus binding sites in its promoter region for ATF (Activating transcription factor), NF-κβ, NF-κβ1, GATA-3, C/EBPα (CCAAT/enhancer-binding protein alpha), glucocorticoid receptors α and β, and p53. Expression of isoforms 1 and 2 has been detected in multiple tissues, with maximal expression in the placenta, and the embryonal central nervous system, heart, testes and lungs. Although its expression has been reported as lower in thymus and lymphocytes, functional studies of EFS to date have best defined it as important for immune system function. One screen for implantation-related genes regulated by progesterone found that EFS was downregulated by 17β-estradiol and progesterone in explants of late proliferative phase endometrium.
Protein family
EFS is a member of the CAS (Crk-Associated Substrate) family of proteins. In humans and mammals, this group consists of four members: p130Cas/BCAR1, NEDD9/HEF1, CASS4 and EFS. There are no paraloguous genes for this family in yeasts and fungi, diploblasts and nematodes such as C. elegans. A single ancestral member is found in Drosophila.