Alternative titles; symbols
HGNC Approved Gene Symbol: HOOK1
Cytogenetic location: 1p32.1 Genomic coordinates (GRCh38): 1:59,814,949-59,876,322 (from NCBI)
Hook proteins are cytosolic coiled-coil proteins that contain conserved N-terminal domains, which attach to microtubules, and more divergent C-terminal domains, which mediate binding to organelles. The Drosophila Hook protein is a component of the endocytic compartment (summary by Walenta et al., 2001).
Using homology with the Drosophila Hook gene, Kramer and Phistry (1999) identified ESTs containing the full-length human HOOK1 sequence, which they called HK1. The deduced 719-amino acid protein contains an N-terminal domain, a central coiled-coil domain, and a C-terminal domain. HOOK1 shares 33% identity with the Drosophila Hook protein, with highest conservation in the N-terminal domain.
By Western blot analysis, Walenta et al. (2001) determined that endogenous HOOK1 detected in HEK293 cells had an apparent molecular mass of about 85 kD. Endogenous HOOK1 localized to discrete punctate subcellular structures that were often closely associated with microtubules.
By subtractive hybridization to enrich for transcripts highly expressed in testis, followed by serologic expression screening with antibodies from a seminoma patient, Tureci et al. (2002) isolated HOM-TES-83. They stated that HOM-TES-83 is the likely human ortholog of fly Hook. Northern blot analysis detected high HOM-TES-83 expression in testis and much weaker expression in all other normal tissues examined.
By Western blot analysis of HEK293 immunoprecipitates, Walenta et al. (2001) determined that HOOK1 exists in a protein complex that is distinct from complexes containing HOOK2 (607824) and HOOK3 (607825). By microtubule spin-down assay, they determined that full-length HOOK1 and a C-terminal truncation mutant bound to microtubules.
The endosomal/lysosomal transmembrane protein CLN3 (607042) is mutated in Batten disease (CLN3/JNCL; 204200). Previous studies have shown that deletion of Btn1, the yeast ortholog of CLN3, leads to increased expression of Btn2, the yeast homolog of Hook1. Luiro et al. (2004) found that overexpression of CLN3 induced aggregation of Hook1 protein in HeLa cells, potentially by mediating its dissociation from the microtubules. In vitro binding assays showed a weak interaction between Hook1 and the cytoplasmic segments of CLN3. Receptor-mediated endocytosis was defective in CLN3-deficient JNCL fibroblasts, linking CLN3, Hook1 and endocytosis in the mammalian system. Coimmunoprecipitation experiments showed that Hook1 physically interacted with endocytic Rab7 (602298), Rab9 (300284), and Rab11 (605570), suggesting a role for Hook1 in membrane trafficking events. Luiro et al. (2004) suggested a link between CLN3 function, microtubule cytoskeleton, and endocytic membrane trafficking.
By proteomic analysis, Xu et al. (2008) showed that FTS (AKTIP; 608483) interacted with HOOK proteins, and that the HOOK proteins self-interacted or interacted with other HOOK proteins to form homo- or hetero-complexes. Interaction between FTS and the HOOK proteins was mediated by a conserved helix near the C termini of the HOOK proteins and by the central beta-sheet region of FTS. The Hook-FTS complex assembled further with p107-FHIP (FHIP1B; 620229) to form the 500-kD FHF complex, primarily via association of p107FHIP with FTS. The FHF complex assembled with the homotypic vacuolar protein sorting (HOPS) complex via interaction between HOOK1 of the FHF complex and VPS18 (608551) of the HOPS complex. FTS functioned to promote vesicle clustering and/or fusion by VPS18 through interaction between the FHF complex and the HOPS complex, and FTS was required for timely transit of EGF (131530) from early-to-late endocytic organelles.
By expressing a dominant-negative mammalian Rab5a (179512) mutant in rat hippocampal neurons, Guo et al. (2016) demonstrated that Rab5 regulated somatodendritic sorting of transferrin receptor (TFR, or TFRC; 190010) and glutamate receptors (see 138251). Rab5 contributed to the somatodendritic polarity of Tfr by promoting retrieval of a population of Tfr that escaped into the axon, and this Tfr retrieval by Rab5 was dependent on dynein (see 600112)-dynactin (see 601143). In the retrieval process, a mammalian FTS-HOOK-FHIP (FHF) complex containing at least Hook1, Hook3, and Fhip functioned as a Rab5 effector to link Rab5-containing carriers to dynein-dynactin. Fhip interacted directly with Rab5a in a nucleotide-dependent manner, and Hook1, Hook3, and Fhip were all required for somatodendritic sorting of Tfr.
By pull-down, immunoprecipitation, and yeast 2-hybrid analyses, Mattera et al. (2020) showed that the heterotetrameric adaptor protein complex-4 (AP4; see 607244) interacted with an FHF complex containing FHIP, FTS, HOOK1, HOOK2, and HOOK3. The interaction was mediated by direct binding between the mu-4 subunit of AP4 (AP4M1; 602296) and the HOOK1 and HOOK2 subunits of FHF. Deletion mapping revealed that 2 coiled-coiled domains in HOOK1 were necessary and sufficient for interaction with mu-4, as well as with HOOK1 and HOOK3. HOOK2 and AP4 colocalized in the perinuclear area of Hela cells. Knockdown of FHF subunits resulted in dispersal of AP4 and ATG9A (612204) from the perinuclear region toward the periphery in Hela cells, indicating that the FHF complex interacted with AP4 to mediate perinuclear distribution of AP4 and its cargo, ATG9A. Moreover, dispersal of ATG9A affected autophagy in FHF-depleted cells.
By immunoprecipitation and mass spectrometric analyses in 293T cell lines, Christensen et al. (2021) showed that different FHIP proteins associated with diverse cellular interactomes. Moreover, different FHIP proteins interacted with different HOOKs to generate preferential formation of different FHF complexes: FHIP1A and FHIP1B formed a complex with HOOK1 and HOOK3, FHIP2A (617312) preferentially associated with HOOK2, and FHIP2B appeared capable of forming a complex with HOOK1, HOOK2, and HOOK3. These FHF complexes associated with moving dynein/dynactin complexes, with FHIP2A preferentially interacting with HOOK2, and FHIP1B interacting with HOOK3, to form FHF complexes that associated with motile dynein/dynactin. Expression of FHIP1B or FHIP2A in human U2OS cells deficient in their respective genes revealed that FHIP1B and FHIP2A colocalized with microtubule-associated cargoes with different morphologies to determine cargo specificity of dynein. FHIP1B functioned as a RAB5-specific effector and associated with early endosomes via direct interaction with GTP-bound RAB5B. In contrast, FHIP2A formed a complex predominantly with HOOK2 to link dynein to RAB1A (RAB1; 179508)-bound endoplasmic reticulum-to-Golgi tubular intermediates.
Mendoza-Lujambio et al. (2002) determined that the mouse Hook1 gene contains 22 exons and spans more than 39 kb.
By genomic sequence analysis, Mendoza-Lujambio et al. (2002) mapped the HOOK1 gene to chromosome 1p32.1. Using FISH, they mapped the mouse Hook1 gene to chromosome 4 region C5-D2, which shows homology of synteny to human chromosome 1p32.1.
Mendoza-Lujambio et al. (2002) determined that the 'abnormal spermatozoon head shape' (azh) mutation in mice is caused by a nonfunctional Hook1 protein resulting from a deletion of exons 10 and 11 of the Hook1 gene. They found that Hook1 is predominantly expressed in haploid male germ cells. Immunohistochemical analysis revealed that Hook1 is responsible for the linkage of the microtubular manchette and the flagellum to cellular structures. Loss of Hook1 function resulted in ectopic positioning of microtubular structures within the spermatid, causing the azh phenotype.
Christensen, J. R., Kendrick, A. A., Truong, J. B., Aguilar-Maldonado, A., Adani, V., Dzieciatkowska, M., Reck-Peterson, S. L. Cytoplasmic dynein-1 cargo diversity is mediated by the combinatorial assembly of FTS-Hook-FHIP complexes. eLife 10: e74538, 2021. [PubMed: 34882091] [Full Text: https://doi.org/10.7554/eLife.74538]
Guo, X., Farias, G. G., Mattera, R., Bonifacino, J. S. Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon. Proc. Nat. Acad. Sci. 113: E5318-E5327, 2016. [PubMed: 27559088] [Full Text: https://doi.org/10.1073/pnas.1601844113]
Kramer, H., Phistry, M. Genetic analysis of hook, a gene required for endocytic trafficking in Drosophila. Genetics 151: 675-684, 1999. [PubMed: 9927460] [Full Text: https://doi.org/10.1093/genetics/151.2.675]
Luiro, K., Yliannala, K., Ahtiainen, L., Maunu, H., Jarvela, I., Kyttala, A., Jalanko, A. Interconnections of CLN3, Hook1 and Rab proteins link Batten disease to defects in the endocytic pathway. Hum. Molec. Genet. 13: 3017-3027, 2004. [PubMed: 15471887] [Full Text: https://doi.org/10.1093/hmg/ddh321]
Mattera, R., Williamson, C. D., Ren, X., Bonifacino, J. S. The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear distribution of AP-4 and its cargo ATG9A. Molec. Biol. Cell 31: 963-979, 2020. [PubMed: 32073997] [Full Text: https://doi.org/10.1091/mbc.E19-11-0658]
Mendoza-Lujambio, I., Burfeind, P., Dixkens, C., Meinhardt, A., Hoyer-Fender, S., Engel, W., Neesen, J. The Hook1 gene is non-functional in the abnormal spermatozoon head shape (azh) mutant mouse. Hum. Molec. Genet. 11: 1647-1658, 2002. [PubMed: 12075009] [Full Text: https://doi.org/10.1093/hmg/11.14.1647]
Tureci, O., Sahin, U., Koslowski, M., Buss, B., Bell, C., Ballweber, P., Zwick, C., Eberle, T., Zuber, M., Villena-Heinsen, C., Seitz, G., Pfreundschuh, M. A novel tumour associated leucine zipper protein targeting to sites of gene transcription and splicing. Oncogene 21: 3879-3888, 2002. [PubMed: 12032826] [Full Text: https://doi.org/10.1038/sj.onc.1205481]
Walenta, J. H., Didier, A. J., Liu, X., Kramer, H. The Golgi-associated Hook3 protein is a member of a novel family of microtubule-binding proteins. J. Cell Biol. 152: 923-934, 2001. [PubMed: 11238449] [Full Text: https://doi.org/10.1083/jcb.152.5.923]
Xu, L., Sowa, M. E., Chen, J., Li, X., Gygi, S. P., Harper, J. W. An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal clustering by the homotypic vacuolar protein sorting complex. Molec. Biol. Cell 19: 5059-5071, 2008. [PubMed: 18799622] [Full Text: https://doi.org/10.1091/mbc.e08-05-0473]