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Gene Review

Hmmr  -  hyaluronan mediated motility receptor (RHAMM)

Mus musculus

Synonyms: AA386826, CD168, Hyaluronan mediated motility receptor, Ihabp, Intracellular hyaluronic acid-binding protein, ...
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Disease relevance of Hmmr


High impact information on Hmmr

  • Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression [3].
  • Overexpression of RHAMM is transforming and is required for H-ras transformation [3].
  • The hyaluronan (HA) receptor RHAMM is an important regulator of cell growth [3].
  • The molecular mechanism underlying growth control by RHAMM and other extracellular matrix receptors remains largely unknown [3].
  • We report that soluble RHAMM induces G2/M arrest by suppressing the expression of Cdc2/Cyclin B1, a protein kinase complex essential for mitosis [3].

Biological context of Hmmr


Anatomical context of Hmmr

  • Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity [4].
  • A full-length human RHAMM cDNA clone was isolated by a combination of screening a human breast cDNA expression library with the murine RHAMM 2 cDNA as well as 5' RACE and RT-PCR using messenger RNA from human breast cell line (MCF-10A) [7].
  • RHAMM was detected in neurons of cerebral cortex and most subcortical and brainstem structures at postnatal day 1 and exhibited an adult distribution pattern by postnatal day 5 [8].
  • Immunohistochemically, RHAMM was found in the vast majority of neurons and in many oligodendrocytes throughout brain, with heterogeneous levels among cell populations, and was confined to the somata and initial processes of these cells [8].
  • We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44-ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus [9].

Associations of Hmmr with chemical compounds

  • Interestingly, we further found that the compensation for loss of the CD44 gene does not occur because of enhanced expression of the redundant gene (RHAMM), but rather because the loss of CD44 allows increased accumulation of the hyaluronic acid substrate, with which both CD44 and RHAMM engage, thus enabling augmented signaling through RHAMM [10].
  • We also found that RHAMM had an elevated level of expression in all the HCC samples we examined and it was induced during the G2/M phase of regenerating mouse hepatocytes after partial hepatectomy [11].

Regulatory relationships of Hmmr

  • Peptides corresponding to the HA-binding motif of RHAMM also suppressed TGF-beta 1-induced increases in motility rate [12].

Other interactions of Hmmr


Analytical, diagnostic and therapeutic context of Hmmr

  • One of these, RHAMM variant 4 (RHAMMv4), is transforming when overexpressed and regulates Ras signaling (Hall et al.). Here we note using flow cytometry and confocal analysis that RHAMM isoforms encoding exon 4 occur both on the cell surface and in the cytoplasm [14].
  • Comparison of cDNA clones and RT-PCR products with the genomic clones identified alternately spliced exons in both the coding and 5' noncoding regions of RHAMM [5].
  • In this study, we explored whether RHAMM is a potential target for dendritic cell (DC) immunotherapy [15].


  1. Genetic deletion of receptor for hyaluronan-mediated motility (Rhamm) attenuates the formation of aggressive fibromatosis (desmoid tumor). Tolg, C., Poon, R., Fodde, R., Turley, E.A., Alman, B.A. Oncogene (2003) [Pubmed]
  2. The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11. Spicer, A.P., Roller, M.L., Camper, S.A., McPherson, J.D., Wasmuth, J.J., Hakim, S., Wang, C., Turley, E.A., McDonald, J.A. Genomics (1995) [Pubmed]
  3. Soluble hyaluronan receptor RHAMM induces mitotic arrest by suppressing Cdc2 and cyclin B1 expression. Mohapatra, S., Yang, X., Wright, J.A., Turley, E.A., Greenberg, A.H. J. Exp. Med. (1996) [Pubmed]
  4. Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity. Hall, C.L., Wang, C., Lange, L.A., Turley, E.A. J. Cell Biol. (1994) [Pubmed]
  5. Characterization of the murine gene encoding the hyaluronan receptor RHAMM. Entwistle, J., Zhang, S., Yang, B., Wong, C., Li, Q., Hall, C.L., A, J., Mowat, M., Greenberg, A.H., Turley, E.A. Gene (1995) [Pubmed]
  6. Characterisation of the murine gene encoding the intracellular hyaluronan receptor IHABP (RHAMM). Fieber, C., Plug, R., Sleeman, J., Dall, P., Ponta, H., Hofmann, M. Gene (1999) [Pubmed]
  7. The characterization of a human RHAMM cDNA: conservation of the hyaluronan-binding domains. Wang, C., Entwistle, J., Hou, G., Li, Q., Turley, E.A. Gene (1996) [Pubmed]
  8. Identification of sequence, protein isoforms, and distribution of the hyaluronan-binding protein RHAMM in adult and developing rat brain. Lynn, B.D., Li, X., Cattini, P.A., Turley, E.A., Nagy, J.I. J. Comp. Neurol. (2001) [Pubmed]
  9. Rhamm-/- fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair. Tolg, C., Hamilton, S.R., Nakrieko, K.A., Kooshesh, F., Walton, P., McCarthy, J.B., Bissell, M.J., Turley, E.A. J. Cell Biol. (2006) [Pubmed]
  10. RHAMM, a receptor for hyaluronan-mediated motility, compensates for CD44 in inflamed CD44-knockout mice: a different interpretation of redundancy. Nedvetzki, S., Gonen, E., Assayag, N., Reich, R., Williams, R.O., Thurmond, R.L., Huang, J.F., Neudecker, B.A., Wang, F.S., Wang, F.S., Turley, E.A., Naor, D. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Integrative genomics based identification of potential human hepatocarcinogenesis-associated cell cycle regulators: RHAMM as an example. Yang, C.W., Su, J.Y., Tsou, A.P., Chau, G.Y., Liu, H.L., Chen, C.H., Chien, C.Y., Chou, C.K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  12. TGF-beta 1 stimulation of cell locomotion utilizes the hyaluronan receptor RHAMM and hyaluronan. Samuel, S.K., Hurta, R.A., Spearman, M.A., Wright, J.A., Turley, E.A., Greenberg, A.H. J. Cell Biol. (1993) [Pubmed]
  13. Spacrcan binding to hyaluronan and other glycosaminoglycans. Molecular and biochemical studies. Chen, Q., Cai, S., Shadrach, K.G., Prestwich, G.D., Hollyfield, J.G. J. Biol. Chem. (2004) [Pubmed]
  14. The hyaluronan receptor RHAMM regulates extracellular-regulated kinase. Zhang, S., Chang, M.C., Zylka, D., Turley, S., Harrison, R., Turley, E.A. J. Biol. Chem. (1998) [Pubmed]
  15. Anti-tumor activity of dendritic cells transfected with mRNA for receptor for hyaluronan-mediated motility is mediated by CD4+ T cells. Fukui, M., Ueno, K., Suehiro, Y., Hamanaka, Y., Imai, K., Hinoda, Y. Cancer Immunol. Immunother. (2006) [Pubmed]
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