FCH domain is a short conserved region of around 60 amino acids first described as a region of homology between FER and CIP4 proteins [ (PUBMED:9210375) ]. In the CIP4 protein the FCH domain binds to microtubules [ (PUBMED:10713100) ]. The FCH domain is always found N-terminally and is followed by a coiled-coil region. The FCH and coiled-coil domains are structurally similar to Bin/amphiphysin/RVS (BAR) domains [ (PUBMED:18525024) ]. They are alpha-helical membrane-binding modules that function in endocytosis, regulation of the actin cytoskeleton and signalling [ (PUBMED:18525024) ].
Proteins containing an FCH domain can be divided in 3 classes [ (PUBMED:11994747) ]:
A subfamily of protein kinases usually associated with an SH2 domain:
Fps/fes (Fujimani poultry sarcoma/feline sarcoma) proto-oncogenes. They are non-receptor protein-tyrosine kinases preferentially expressed in myeloid lineage. The viral oncogene has an unregulated kinase activity which abrogates the need for cytokines and influences differentiation of haematopoietic progenitor cells.
Fes related protein (fer). It is an ubiquitously expressed homologue of Fes.
Adaptor proteins usually associated with a C-terminal SH3 domain:
Schizosaccharomyces pombe CDC15 protein. It mediates cytoskeletal rearrangements required for cytokinesis. It is essential for viability.
CD2 cytoplasmic domain binding protein.
Mammalian Cdc42-interacting protein 4 (CIP4). It may act as a link between Cdc42 signaling and regulation of the actin cytoskeleton.
Mammalian PACSIN proteins. A family of cytoplasmic phosphoproteins playing a role in vesicle formation and transport.
A subfamily of Rho-GAP proteins:
Mammalian RhoGAP4 proteins. They may down-regulate Rho-like GTPases in hematopoietic cells.
Yeast hypothetical protein YBR260C.
Caenorhabditis elegans hypothetical protein ZK669.1.
Family alignment:
There are 9693 FCH domains in 9691 proteins in SMART's nrdb database.
Click on the following links for more information.
Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing FCH domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with FCH domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing FCH domain in the selected taxonomic class.
Cellular role (predicted cellular role)
Binding / catalysis: unknown
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
A Cdc42 target protein with homology to the non-kinase domain of FER has a potential role in regulating the actin cytoskeleton.
Curr Biol. 1997; 7: 479-87
Display abstract
BACKGROUND: Members of the Rho family of small GTPases have been shown to have a diverse role in cell signalling events. They were originally identified as proteins that, by regulating the assembly of the actin cytoskeleton, are important determinants of cell morphology, and have recently been shown to be involved in transcriptional activation by the JNK/SAPK signalling pathway. In order to understand the mechanisms underlying the effects of Rho GTPases on these processes, the yeast two-hybrid system has been used to identify proteins that bind to an activated mutant of Cdc42, a Rho-family member. RESULTS: A cDNA encoding a previously unidentified Cdc42 target protein, CIP4, which is 545 amino-acids long and contains an SH3 domain at its carboxyl terminus, was cloned from a human B-cell library. The amino terminus of CIP4 bears resemblance to the non-kinase domain of the FER and Fes/Fps family of tyrosine kinases. In addition, similarities to a number of proteins with roles in regulating the actin cytoskeleton were noticed. CIP4 binds to activated Cdc42 in vitro and in vivo and overexpression of CIP4 in Swiss 3T3 fibroblasts reduces the amount of stress fibres in these cells. Moreover, coexpression of activated Cdc42 and CIP4 leads to clustering of CIP4 to a large number of foci at the dorsal side of the cells. CONCLUSIONS: CIP4 is a downstream target of activated GTP-bound Cdc42, and is similar in sequence to proteins involved in signalling and cytoskeletal control. Together, these findings suggest that CIP4 may act as a link between Cdc42 signalling and regulation of the actin cytoskeleton.
Metabolism (metabolic pathways involving proteins which contain this domain)
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with FCH domain which could be assigned to a KEGG orthologous group, and not all proteins containing FCH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
