InterPro domain: IPR043936

This entry includes residues in the first 160 amino acids at the N-terminal of Hook, which is the most conserved region and necessary for dynein-dynactin interaction. It interacts with dynein light intermediate chain 1 (LIC1) [ 1 ]. This domain is also found in protein Daple [ 2 ] and Girdin [ 3 ] which are G-protein modulators involved in ciliogenesis and cilium morphology, integrity of the actin cytoskeleton, formation of actin stress fibres and lamellipodia and membrane sorting in the early endosome.

The Hook family consists of several proteins from different eukaryotic organisms, first identified in Drosophila melanogaster in which play a role in endocytic cargo sorting [ 4 ]. In Drosophila and fungi there is a single Hook gene, whereas mammals have three Hook genes, Hook1, Hook2 and Hook3. Endogenous Hook3 binds to Golgi membranes while both Hook1 and Hook2 are localised to discrete but unidentified cellular structures [ 5 , 6 ]. In mice the Hook1 gene is predominantly expressed in the testis. Hook1 function is necessary for the correct positioning of microtubule structures within the haploid germ cell. Disruption of Hook1 function in mice causes abnormal sperm head shape and fragile attachment of the flagellum to the sperm head [ 6 ].

They are a widely expressed class of dynein-associated cargo adaptor proteins which include different domains. The N-terminal part of these proteins is sufficient to form a stable complex with dynein-dynactin and includes the most conserved region within the first 160 amino acids, termed the Hook domain. This domain is followed by three coiled-coil domains, important for dimerization and activation of dynein-dynactin complex motility, and then a C-terminal domain that binds a variety of proteins specific for each Hook isoform, involved in binding to specific organelles (organelle-binding domains). All mammalian Hook isoforms form a complex with Fused Toes and the Fused Toes- and Hook-interacting protein; fungal homologues of these proteins are important for dynein-mediated early endosome transport by linking Hook to the cargo [ 7 ].

1. Assembly and activation of dynein-dynactin by the cargo adaptor protein Hook3. J. Cell Biol. 214, 309-18
2. GPCR-independent activation of G proteins promotes apical cell constriction in vivo. J. Cell Biol. 218, 1743-1763
3. A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. Dev. Cell 38, 493-506
4. Drosophila endosomal proteins hook and deep orange regulate synapse size but not synaptic vesicle recycling. J. Neurobiol. 45, 105-19
5. The Golgi-associated hook3 protein is a member of a novel family of microtubule-binding proteins. J. Cell Biol. 152, 923-34
6. The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse. Hum. Mol. Genet. 11, 1647-58