Hyaluronan-mediated motility receptor
| HMMR | |||
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Gene ontology | |||
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| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 5: 163.46 – 163.49 Mb | Chr 11: 40.59 – 40.62 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Hyaluronan-mediated motility receptor (HMMR), also known as RHAMM (Receptor for Hyaluronan Mediated Motility) is a protein which in humans is encoded by the HMMR gene.[5] RHAMM recently has been also designated CD168 (cluster of differentiation 168).
Function
RHAMM was originally discovered as a soluble protein that altered migratory cell behavior and bound to
Golgi complex, RHAMM does not contain a membrane spanning domain nor does the mRNA transcript contain a signal sequence. RHAMM is localized inside the cell and is unconventionally exported to the cell surface in response to certain defined stimuli such as wounding and cytokines including TGF-β.[7] The precise unconventional export mechanism for transporting RHAMM to the extracellular space is still unclear but may involve transport channels or proteins, flippase activity, or exocytosis, similar to other non-conventionally exported cell surface proteins such as BFGF1,2 and epimorphin.[8]
Intracellularly, RHAMM associates with
microtubules and, working with BRCA1 and BARD1, plays a role in the regulation of mitosis,[8][9][10] and in maintaining mitotic spindle integrity.[11] RHAMM also binds directly with ERK1 and forms complexes with ERK1,2 and MEK1,[11] suggesting a role as a scaffold protein that targets these MAP kinases to the nucleus.[12]
Extracellularly, RHAMM associates with CD44, and upon binding to
hyaluronan, activates intracellular signaling pathways, mainly the MAPK pathway via ERK1,2 activation[13] Variants of RHAMM caused by alternative splicing have been observed, and alternative start codon usage has been proposed in mice and directly observed in humans.[5]
Clinical significance
RHAMM is over expressed in
MDA-MB-231.[17]
Elevated levels of RHAMM and
lung adenocarcinoma.[21]
While RHAMM has been less studied than CD44 in the process of
endothelial cells towards the tumor.[25]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000072571 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020330 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: HMMR hyaluronan-mediated motility receptor (RHAMM)".
- PMID 6185115.
- PMID 1376732.
- ^ PMID 12808028.
- S2CID 17769149.
- PMID 17922014.
- ^ PMID 20558733.
- PMID 21655434.
- PMID 1705559.
- PMID 15068665.
- PMID 10029598.
- PMID 9533523.
- PMID 24367099.
- PMID 24668563.
- PMID 24708576.
- S2CID 9302075.
- PMID 25175030.
- PMID 11024216.
- PMID 7518470.
- PMID 17392272.
- PMID 11448954.
Further reading
- Dawson SJ, White LA (May 1992). "Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin". The Journal of Infection. 24 (3): 317–320. PMID 1602151.
- Hall CL, Yang B, Yang X, Zhang S, Turley M, Samuel S, Lange LA, Wang C, Curpen GD, Savani RC, Greenberg AH, Turley EA (Jul 1995). "Overexpression of the hyaluronan receptor RHAMM is transforming and is also required for H-ras transformation". Cell. 82 (1): 19–26. S2CID 17121010.
- Pilarski LM, Miszta H, Turley EA (May 1993). "Regulated expression of a receptor for hyaluronan-mediated motility on human thymocytes and T cells". Journal of Immunology. 150 (10): 4292–4302. PMID 7683315.
- Spicer AP, Roller ML, Camper SA, McPherson JD, Wasmuth JJ, Hakim S, Wang C, Turley EA, McDonald JA (Nov 1995). "The human and mouse receptors for hyaluronan-mediated motility, RHAMM, genes (HMMR) map to human chromosome 5q33.2-qter and mouse chromosome 11". Genomics. 30 (1): 115–117. PMID 8595891.
- Wang C, Entwistle J, Hou G, Li Q, Turley EA (Oct 1996). "The characterization of a human RHAMM cDNA: conservation of the hyaluronan-binding domains". Gene. 174 (2): 299–306. PMID 8890751.
- Assmann V, Marshall JF, Fieber C, Hofmann M, Hart IR (Jun 1998). "The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells". Journal of Cell Science. 111 (12): 1685–1694. PMID 9601098.
- Pilarski LM, Pruski E, Wizniak J, Paine D, Seeberger K, Mant MJ, Brown CB, Belch AR (May 1999). "Potential role for hyaluronan and the hyaluronan receptor RHAMM in mobilization and trafficking of hematopoietic progenitor cells". Blood. 93 (9): 2918–2927. PMID 10216086.
- Assmann V, Jenkinson D, Marshall JF, Hart IR (Nov 1999). "The intracellular hyaluronan receptor RHAMM/IHABP interacts with microtubules and actin filaments". Journal of Cell Science. 112 (22): 3943–3954. PMID 10547355.
- Lokeshwar VB, Selzer MG (Sep 2000). "Differences in hyaluronic acid-mediated functions and signaling in arterial, microvessel, and vein-derived human endothelial cells". The Journal of Biological Chemistry. 275 (36): 27641–27649. PMID 10882722.
- Lynn BD, Li X, Cattini PA, Nagy JI (Jun 2001). "Sequence, protein expression and extracellular-regulated kinase association of the hyaladherin RHAMM (receptor for hyaluronan mediated motility) in PC12 cells". Neuroscience Letters. 306 (1–2): 49–52. S2CID 38778150.
- Lynn BD, Turley EA, Nagy JI (Jul 2001). "Subcellular distribution, calmodulin interaction, and mitochondrial association of the hyaluronan-binding protein RHAMM in rat brain". Journal of Neuroscience Research. 65 (1): 6–16. S2CID 23843138.
- Savani RC, Cao G, Pooler PM, Zaman A, Zhou Z, DeLisser HM (Sep 2001). "Differential involvement of the hyaluronan (HA) receptors CD44 and receptor for HA-mediated motility in endothelial cell function and angiogenesis". The Journal of Biological Chemistry. 276 (39): 36770–36778. PMID 11448954.
- Akiyama Y, Jung S, Salhia B, Lee S, Hubbard S, Taylor M, Mainprize T, Akaishi K, van Furth W, Rutka JT (Jun 2001). "Hyaluronate receptors mediating glioma cell migration and proliferation". Journal of Neuro-Oncology. 53 (2): 115–127. S2CID 33691799.
- Greiner J, Ringhoffer M, Taniguchi M, Schmitt A, Kirchner D, Krähn G, Heilmann V, Gschwend J, Bergmann L, Döhner H, Schmitt M (Sep 2002). "Receptor for hyaluronan acid-mediated motility (RHAMM) is a new immunogenic leukemia-associated antigen in acute and chronic myeloid leukemia". Experimental Hematology. 30 (9): 1029–1035. PMID 12225794.
- Rein DT, Roehrig K, Schöndorf T, Lazar A, Fleisch M, Niederacher D, Bender HG, Dall P (Mar 2003). "Expression of the hyaluronan receptor RHAMM in endometrial carcinomas suggests a role in tumour progression and metastasis". Journal of Cancer Research and Clinical Oncology. 129 (3): 161–164. S2CID 22224158.
- Maxwell CA, Keats JJ, Crainie M, Sun X, Yen T, Shibuya E, Hendzel M, Chan G, Pilarski LM (Jun 2003). "RHAMM is a centrosomal protein that interacts with dynein and maintains spindle pole stability". Molecular Biology of the Cell. 14 (6): 2262–2276. PMID 12808028.
- Aziz KA (Aug 2003). "CD44 mediates polymorphonuclear leukocyte motility on hyaluronan". Saudi Medical Journal. 24 (8): 827–831. PMID 12939665.
- Maxwell CA, Keats JJ, Belch AR, Pilarski LM, Reiman T (Feb 2005). "Receptor for hyaluronan-mediated motility correlates with centrosome abnormalities in multiple myeloma and maintains mitotic integrity". Cancer Research. 65 (3): 850–860. S2CID 15463595.
- Yamasaki C, Tashiro S, Nishito Y, Sueda T, Igarashi K (Mar 2005). "Dynamic cytoplasmic anchoring of the transcription factor Bach1 by intracellular hyaluronic acid binding protein IHABP". Journal of Biochemistry. 137 (3): 287–296. PMID 15809329.
- Pujana MA, Han JD, Starita LM, Stevens KN, Tewari M, Ahn JS, Rennert G, Moreno V, Kirchhoff T, Gold B, Assmann V, Elshamy WM, Rual JF, Levine D, Rozek LS, Gelman RS, Gunsalus KC, Greenberg RA, Sobhian B, Bertin N, Venkatesan K, Ayivi-Guedehoussou N, Solé X, Hernández P, Lázaro C, Nathanson KL, Weber BL, Cusick ME, Hill DE, Offit K, Livingston DM, Gruber SB, Parvin JD, Vidal M (Nov 2007). "Network modeling links breast cancer susceptibility and centrosome dysfunction". Nature Genetics. 39 (11): 1338–1349. PMID 17922014.
- Kalmyrzaev B, Pharoah PD, Easton DF, Ponder BA, Dunning AM (Dec 2008). "Hyaluronan-mediated motility receptor gene single nucleotide polymorphisms and risk of breast cancer". Cancer Epidemiology, Biomarkers & Prevention. 17 (12): 3618–3620. PMID 19064580.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.