. 2020 Dec 15;10(12):425. doi: 10.3390/membranes10120425

Table 2.

Expression, localization, and biological functions of CRAC channel components and K_Ca2+ channels individually as well as complexed either with each other or with accessory proteins. This table depicts the expression, localization, and biological functions of CRAC and K_Ca2+ ion channels in normal and related cancer tissue. Moreover, disease-related mutations of the proteins are summarized.

Channel Type or Channel-Protein Complexes	Expression Level		Localization		Associated Mutation	Biological Function		Ref
	Normal Tissue	Cancer Tissue	Normal Tissue	Cancer Tissue		Normal Tissue	Cancer Tissue
Orai1 channels	low	high (reduced in prostate cancer)	Ubiquitously expressed in a diversity of tissues Heart brain kidney lung skeletal muscle and other organs	Renal carcinoma Breast Melanoma Glioma Esophageal squamous cell carcinoma Pancreatic adenocarcinoma Prostate	A137V (colorectal tumor) M139V (stomach carcinoma) S159L (uterine carcinoma) G183D (glioblastoma) G247S (neck carcinoma)	Involved in Ca²⁺ signaling indispensable role in the immune system	Proliferation Migration Increased cell survival Tumor growth progression metastasis	[61,132,251,252,253]
Orai1-SPCA2	-	high	-	Breast	n.d.	Separately involved in cell Ca²⁺ signaling	Activation of Ras–ERK pathway, involved in proliferation and cell cycle Tumorigenesis Cell growth	[254,255]
Orai2 channels	low	high	brain and at lower levels in the spleen, lung, and small intestine	Parathyroid tumors Prostate	n.d.	Involved in Ca²⁺ signaling	Proliferation	[256,257]
Orai3 channels	low	high	wide tissue expression including the heart, brain, kidney, lung, skeletal muscle, and other organs	Breast Prostate Renal carcinoma Lung adenocarcinoma	n.d.	Involved in Ca²⁺ signaling	Proliferation Invasion Increased cell survival Tumor growth progression Apoptosis	[59,258,259]
STIM1	low	high	Ubiquitously expressed in a diversity of tissues, such as heart, skeletal muscle, and the central nervous system	Breast Lung adenocarcinoma Glioblastoma Colorectal, gastric, cervical cancer renal carcinoma hepatocellular carcinoma	A79T, E87Q, W350L, G446C/V (lung adenocarcinoma) S116N (Glioblastoma)	Involved in Ca²⁺ signaling indispensable role in the immune system	Migration Invasion Increased cell survival	[260,261,262,263,264]
STIM2	low	high	diverse primary lymphocytes such as T_h, T_C, and B-cells	Glioblastoma Prostate Melanoma Colorectal cancer	n.d.	Involved in Ca²⁺ signaling	Migration Invasion	[265,266,267]
SK channels	low	high	Neuronal tissues, colon, corpus cavernosum, adrenal gland, brain, prostate, bladder, liver, and heart	Breast Colon Medulloblastoma Melanoma Glioma Leukemia cells	n.d.	Synaptic function. Firing in pacemaker neurons. Control the pattern of single spike firing of dopamine neurons	Migration, proliferation tumor cell dissemination, and metastasis	[38,268,269,270]
SK3-Orai1	low	high	guinea pig gall bladder smooth muscle	Breast	n.d	Involved in Ca²⁺ signaling regulate muscle contraction	Migration Ca²⁺-dependent invasive process Bone metastasis Constitutive Ca²⁺ entry	[34,44]
SK3-SigmaR1-Orai1	-	high	-	Breast Colorectal	n.d.	Involved in Ca²⁺ signaling	Migration Ca²⁺-dependent invasive process Bone metastasis Constitutive Ca²⁺ entry	[271]
SK3-TRPC1-Orai1	-	high	-	Colon	n.d.	Involved in Ca²⁺ signaling	Migration activation of the Akt pathway SOCE amplification Constitutive Ca²⁺ entry	[272]
SK3-cAMP-Orai1	-	high	-	Breast	n.d.	Involved in Ca²⁺ signaling	Migration Constitutive Ca²⁺ entry Bone metastasis	[36].
IK channels	low	high	Blood, microglial endothelial and epithelial cells trachea, prostate, placenta and salivary glands. presence in excitable cells such as central neurons and cardiomyocytes	Prostate Breast Glioblastoma Endometrial, hepatocellular, and cervical carcinoma	n.d.	Immune responses of B and T cells Secretion in epithelial tissues	Tumor cell signaling including cell cycle progression Proliferation, Migration and the Epithelial-Mesenchymal Transition	[19,42,273,274,275]
BK channels	low	high	Skeletal muscles Nervous system, Smooth muscle cells	Prostate Breast Glioblastoma Neuroblastoma	n.d.	Regulation of calcium signaling related processes	Proliferation, migration, metastasis, apoptosis	[276,277,278]