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

Stable Identifier
Reaction [binding]
Homo sapiens
HYAL2 interacts with NHE1 to create an acidic environment
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Orthologous Events
Cite Us!