Reactome | HA:HAR:HYAL2 binds to SLC9A1:p-CHP:Ca2+

HA:HAR:HYAL2 binds to SLC9A1:p-CHP:Ca2+

Stable Identifier

R-HSA-2160884

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

HYAL2 interacts with NHE1 to create an acidic environment

ReviewStatus

5/5

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Hyaluronidases are only active in acidic environments. HYAL2 can interact with the Na+-H+ exchanger (SLC9A1, NHE1) which can create an acidic microenvironment in the caveolae. Extracellular Na+ ions are exchanged for protons which creates the acidic conditions required for the activity of HYAL2 (Bourguignon et al. 2004). The interaction of calcineurin homologous protein 1 (CHP1) with SLC9A1 is essential for the maintenance of, or increasing, the pH sensitivity of SLC9A1 thus CHP1 can regulate SLC9A1 activity (Lin & Barber 1996, Pang et al. 2004, Mishima et al. 2007). CHP1 depletion in Xenopus oocytes results in a dramatic reduction (>90%) in the Na+-H+ exchange activity of SLC9A1 (Pang et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
15090545	CD44 interaction with Na+-H+ exchanger (NHE1) creates acidic microenvironments leading to hyaluronidase-2 and cathepsin B activation and breast tumor cell invasion Singleton, PA, Gilad, E, Diedrich, F, Stern, R, Bourguignon, LY	J Biol Chem	2004
11350981	Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers Su, X, Pang, T, Shigekawa, M, Wakabayashi, S	J. Biol. Chem.	2001
8901634	A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange Barber, DL, Lin, X	Proc. Natl. Acad. Sci. U.S.A.	1996
15035633	Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements Shigekawa, M, Wakabayashi, S, Hisamitsu, T, Pang, T, Mori, H	Biochemistry	2004
17050540	Solution structure of the cytoplasmic region of Na+/H+ exchanger 1 complexed with essential cofactor calcineurin B homologous protein 1 Mishima, M, Wakabayashi, S, Kojima, C	J. Biol. Chem.	2007