Calcium-Binding and Regulated Proteins

Important Calcium-Binding and Regulated Proteins

Protein Name	Functions / Comments
Calbindins	refers to a family of Ca2+-binding proteins; original member identified in chickens as vitamin D-dependent calcium-binding protein and then called calbindin-D28K (encoded by the CALB1 gene); other members include calretinin (29kDa protein encoded by CALB2 gene) and calbindin-D9K (encoded by the S100G gene which is also referred to as CALB3); all members mediate Ca2+ transport across membranes; in humans the CALB1 encoded protein is involved in renal Ca2+ reabsorption; in humans the S100G (CALB3) encoded protein is required for mediating intestinal calcium absorption in response to hormonal action of calcitriol; CALB2 encodes a neural-specific Ca2+-binding protein; S100G (CALB3) is a member of the S100 family of proteins of which there are 24 members each of which function in some capacity related to the regulation of proliferation, differentiation, apoptosis, Ca2+ homeostasis, energy metabolism, inflammation and migration/invasion
Calcineurins	these proteins are components of a Ca2+-dependent serine/threonine phosphatase identified as protein phosphatase 3, PP3 (formerly PP2B); calcineurins consists of a catalytic subunit and a regulatory subunit, and a subunit of calmodulin; the catalytic subunit is encoded by one of three genes: PPP3CA (commonly called calcinuerin A, CALNA), PPP3BB (commonly called calcineurin B, CALNB), and PPP3CC (commonly called calcineurin); the regulatory subunit is encoded by one of two genes: PPP3R1 and PPP3R2; activity of the calcineurins also requires Zn2+ and Fe3+ binding to domains in the catalytic subunits; major cell types regulated by calcineurin activity are T cells, neural cells, and cardiac cells; within the brain the primary substrates for calcineurin activity are Ca2+ channels, the dephosphorylation of which leads to their inactivation, thereby modulating the release of various neurotransmitters; calcineurin is potently inhibited by the immunosuppressant drugs, cyclosporin A and FK506 (fujimycin)
Calmodulins	these proteins are regulatory subunits of numerous enzymes, particularly kinases; humans express three distinct calmodulin genes identified as CALM1, CALM2, and CALM3; the proteins possess four Ca2+-binding sites; several kinase families are known to possess calmodulin subunits: glycogen synthase-glycogen phosphorylase kinase (PHK, composed of six subunits, the δ-subunit is calmodulin), myosin light-chain kinases (four isoforms: MYLK or MLCK in smooth muscle, MYLK2 in skeletal muscle, MYLK3 in cardiac muscle, and MYLK4), and the kinases termed Ca2+/calmodulin (CaM)-dependent protein kinases (CaMK) which includes CaMKI, CaMKII, CaMKIII, and CaMKIV; CaMKIII is more commonly referred to as eEF-2 kinase (eEF-2K) involved in the regulation of protein synthesis; in addition to serving as calcium-sensing regulatory subunits of numerous kinases, calmodulins also regulate the activity of protein phosphatases (particularly PP3 as indicated above) and the nitric oxide synthases, NOS
Troponins	the troponins are actually heterotrimeric complexes of three distinct subunits: troponin C (TnC), troponin I (TnI), and troponin T (TnT); TnT and TnI exist in tissue specific isoforms with the cardiac muscle forms identified as cTnI and cTnT, whereas the skeletal muscle forms are skTnI and skTnT; TnC is the Ca2+-binding subunit whose role is to effect the Ca2+-dependent regulation of muscle contraction; TnI inhibits the ATPase activity of the actin-myosin complex of the thin filaments that control muscle fiber contraction; TnT binds tropomyosin, thereby regulating troponin complex interaction with thin filaments; measurement of plasma levels of cTnI is now considered the standard for determination of diseases/disorders related to cardiac function such as acute myocardial infarction (AMI)
PKC family	the protein kinase C (PKC) family of serine/threonine kinases is composed of several related enzymes (for a more detailed discussion go to the Signal Transduction page); PKC enzymes are divided into three subfamilies termed conventional (cPKC), novel (nPKC), and atypical (aPKC); it is only the conventional PKC subfamily of enzymes that is regulated by calcium ions