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The FCH domain is a short conserved region of around 60 amino acids first described as a region of homology between FER and CIP4 proteins [1]. Many proteins containing an FCH domain are involved in the regulation of cytoskeletal rearrangements, vesicular transport and endocytosis. In the CIP4 protein the FCH domain binds to microtubules [2]. The FCH domain is always found N-terminally and is followed by a coiled-coil region.

Proteins containing an FCH domain can be divided in 3 classes [3]:

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 homolog 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.

The profile we developed covers the entire FCH domain.

August 2002 / First entry.

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

FCH, PS50133; FCH domain profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE

• Domain architecture view of Swiss-Prot proteins matching PS50133 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS50133 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS50133 • Scan Swiss-Prot/TrEMBL entries against PS50133 • view ligand binding statistics

Matching PDB structures: 2EFK 2EFL 2V0O 2X3V ... [ALL]

1	Authors	Aspenstrom P.
	Title	A Cdc42 target protein with homology to the non-kinase domain of FER has a potential role in regulating the actin cytoskeleton.
	Source	Curr. Biol. 7:479-487(1997).
	PubMed ID	9210375

2	Authors	Tian L., Nelson D.L., Stewart D.M.
	Title	Cdc42-interacting protein 4 mediates binding of the Wiskott-Aldrich syndrome protein to microtubules.
	Source	J. Biol. Chem. 275:7854-7861(2000).
	PubMed ID	10713100

3	Authors	Greer P.
	Title	Closing in on the biological functions of Fps/Fes and Fer.
	Source	Nat. Rev. Mol. Cell Biol. 3:278-289(2002).
	PubMed ID	11994747
	DOI	10.1038/nrm783

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