The gamma-subunit of (Na+,K+)-ATPase: a representative example of human single transmembrane protein with a key regulatory role.
The (Na+,K+)-ATPase is a plasma membrane protein complex composed of at least three subunits (alpha,beta,gamma) that couples the exchange of three cytoplasmic Na+ ions with two extracellular K+ ions, to the hydrolysis of one molecule ofATP in most animal cells. The gamma-subunit is a 66 residue membrane protein associated with the active alpha/beta binary complex. It can be considered as an archetype of single transmembrane proteins (type I) which may play a modulatory role upon association with functional membrane partners. This paper highlights similar associations observed with other ATPases such as the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1/SERCA 2a), but also with Cl- and/or K+ currents, ionic channels (HERG, KCNQ1) and G-protein coupled receptors (adrenomedullin, CGRP and calcitonin) which are of particular interest in the cardiovascular field. Here is reviewed the assessed or suggested regulatory role of a family of small plasma/SR associated membrane proteins including gamma-subunit, phospholemman, Mat 8, KCNE (type 1, 2 and 3), RAMP (type 1, 2 and 3), sarcolipin and phospholamban, mainly found in muscular and vascular tissues. These proteins are critical in controlling important biological processes which derive from specific associations with a binding partner and particular subcellular localizations.
Berrebi-Bertran
I
I
SmithKline Beecham Laboratoires Pharmaceutiques, Saint-Grégoire, France. Isabelle_Bertrand@sbphrd.com
Robert
P
P
Camelin
J C
JC
Bril
A
A
Souchet
M
M
D020816:Amino Acid Motifs; D000818:Animals; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D012519:Sarcoplasmic Reticulum / Q000737:chemistry* / Q000201:enzymology; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D008565:Membrane Proteins; D021122:Protein Subunits; C416502:FXYD2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase