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Gene Review

Agfg1  -  ArfGAP with FG repeats 1

Mus musculus

Synonyms: AU045498, Arf-GAP domain and FG repeat-containing protein 1, C130049H11Rik, C85612, D730048C23Rik, ...
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Disease relevance of Hrb

  • CONCLUSIONS: These aberrations, in Hrb(-/-) mouse spermatids and sperm, are reminiscent of human familial male infertility with oligoasthenoteratozoospermia syndrome [1].
  • Binding studies using an eight-residue NPF-containing peptide derived from RAB, the cellular cofactor of the HIV Rev protein, show a hydrophobic peptide-binding pocket formed by conserved tryptophan and leucine residues [2].

High impact information on Hrb


Biological context of Hrb

  • RESULTS: Hrb(-/-) male mice exhibited multiple anomalies during meiosis and spermiogenesis that produced developmentally impaired sperm with unshaped or deformed nuclei, loss in cell polarity, intracellular flagellar coiling, multinucleation, supernumerary centrioles and multiflagellation [1].
  • METHODS: Hrb(-/-) testes, epididymides, spermatids and sperm were analyzed by histology and electron microscopy [1].
  • The human genome is predicted to contain 60 RAB genes, suggesting that future work could reveal further links between Rab dysfunction and disease [5].
  • It contains characteristic signatures of RAB proteins: 4 GTP binding domains, 5 RAB specific domains, 3 RAB subfamily-specific domains, and a prenylation site. lmlrab is a single copy gene, transcribed as a 3.5 kb mRNA, highly conserved in Leishmania species, and encodes a protein doublet of approximately 75 kDa [6].

Anatomical context of Hrb

  • Here we report that the lack of an acrosome in Hrb mutant spermatids does not prevent the development of the acroplaxome [7].
  • We also show that the actin-based motor protein myosin Va and its receptor, Rab27a/b, known to be involved in vesicle transport, are present in the Golgi and Golgi-derived proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids [7].
  • The Hrb(-/-) sperm exhibited variation in head size and shape, disarranged cellular organelles, nuclear and cytoplasmic vacuolization, mitochondrial loss or scattering and no forward motility [1].
  • The antigen recognized with monoclonal antibody (mAb) Rip (Rip-antigen) has been long used as a marker of oligodendrocytes and myelin sheaths [4].

Other interactions of Hrb

  • In the Hrb mutant, myosin-Va-bound proacrosome vesicles tether to the acroplaxome, where they flatten and form a flat sac, designated pseudoacrosome [7].
  • Our findings support the interpretation that the acroplaxome provides a focal point for myosin-Va/ Rab27a/b-driven proacrosomal vesicles to accumulate, coalesce, and form an acrosome in wild-type spermatids and a pseudoacrosome in Hrb mutant spermatids [7].
  • Hrb, a protein that contains several NPF motifs (Asn-Pro-Phe) and interacts with proteins with Eps15 homology domains, is regarded as critical for the docking and/or fusion of Golgi-derived proacrosomal vesicles [7].

Analytical, diagnostic and therapeutic context of Hrb


  1. A mouse model of familial oligoasthenoteratozoospermia. Juneja, S.C., van Deursen, J.M. Hum. Reprod. (2005) [Pubmed]
  2. The EH1 domain of Eps15 is structurally classified as a member of the S100 subclass of EF-hand-containing proteins. Whitehead, B., Tessari, M., Carotenuto, A., van Bergen en Henegouwen, P.M., Vuister, G.W. Biochemistry (1999) [Pubmed]
  3. Lack of acrosome formation in Hrb-deficient mice. Kang-Decker, N., Mantchev, G.T., Juneja, S.C., McNiven, M.A., van Deursen, J.M. Science (2001) [Pubmed]
  4. Monoclonal antibody Rip specifically recognizes 2',3'-cyclic nucleotide 3'-phosphodiesterase in oligodendrocytes. Watanabe, M., Sakurai, Y., Ichinose, T., Aikawa, Y., Kotani, M., Itoh, K. J. Neurosci. Res. (2006) [Pubmed]
  5. Rab GTPases, intracellular traffic and disease. Seabra, M.C., Mules, E.H., Hume, A.N. Trends in molecular medicine. (2002) [Pubmed]
  6. Identification of a new developmentally regulated Leishmania major large RAB GTPase. Chenik, M., Chaabouni, N., Ben Achour-Chenik, Y., Ouakad, M., Lakhal-Naouar, I., Louzir, H., Dellagi, K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  7. The acroplaxome is the docking site of Golgi-derived myosin Va/Rab27a/b- containing proacrosomal vesicles in wild-type and Hrb mutant mouse spermatids. Kierszenbaum, A.L., Tres, L.L., Rivkin, E., Kang-Decker, N., van Deursen, J.M. Biol. Reprod. (2004) [Pubmed]
  8. The effect of xenoantisera on T-lymphocyte functions in the absence of complement. Rabinowitz, R., Laskov, R., Schlesinger, M. Adv. Exp. Med. Biol. (1979) [Pubmed]
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