HMMR, Hyaluronan-mediated motility receptor, is a protein which in humans is encoded by the HMMR gene. RHAMM was originally discovered as a soluble protein that altered migratory cell behavior and bound to hyaluronan, HMMR is less well studied than the main hyaluronan (HA) receptor, CD44. In contrast to CD44 and other cell-surface receptors which contain the classical membrane spanning domain and signal sequence for secretion from the endoplasmic reticulum / Golgi complex, HMMR does not contain a membrane spanning domain nor does the mRNA transcript contain a signal sequence. HMMR normally is localized inside the cell and is only release by certain, poorly defined stimuli. The transport of HMMR to the extracellular space still is unclear but may involve transport channels or proteins, flippase activity, or exocytosis. Intracellularly, HMMR associates with microtubules and, working with BRCA1 and BARD1, plays a role in the regulation of mitosis. Extracellularly, HMMR associates with CD44, and upon binding to HA, activates intracellular signaling pathways. Variants of HMMR caused by alternative splicing have been observed, but not thoroughly studied.
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