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. 2020 Jan 7;9(1):135. doi: 10.3390/cells9010135

Table 1.

PTMs of different members of TRPC as reported by traditional experimental studies.

Channel Modification Species and Accession Number Site Sequence Enzyme Cell Effect Reference
TRPC1 Phosphorylation Human
n.a.
S/T/Y n.a. PKCα HUVEC and HMEC Increased TRPC1 activity, enhanced permeability of endothelial monolayers [47]
TRPC1 Phosphorylation Rabbit
n.a.
S/T n.a. PKC Rabbit portal vein myocytes Increased TRPC1 activity, promoted PIP2-mediated SOCE [51]
TRPC1 Phosphorylation Human
P48995.2
S172
T313
SAKNKKDSLRHSRFR
SGYRRKPTCKKIMTV
PKG Porcine coronary arterial smooth muscle cell Decreased TRPC1 activity, inhibited NO-, PKG-induced smooth muscle hyperpolarization and relaxation [55]
TRPC1 Phosphorylation Human S/T/Y n.a. PKCα HUVEC Increased TRPC1 activity, promoted monocyte binding to endothelial cells and increased endothelial hyperpermeability [48]
TRPC1 Phosphorylation Rabbit
n.a.
S/T n.a. PKC Rabbit vascular smooth muscle cell Increased TRPC1 activity [52]
TRPC1 Phosphorylation Human
P48995.2
S172
T313
SAKNKKDSLRHSRFR
SGYRRKPTCKKIMTV
PKG Primary mesenteric artery endothelial cells Decreased TRPC1 activity [56]
TRPC1 Phosphorylation Rat S/T n.a. PKCα INS-1E Increased TRPC1 activity, promoted insulin secretion [54]
TRPC3 N-glycosylation Human
Q13507.3
N416
(N418 *)
EGITTLPNITVTDYP n.a. COS-M6 and HEK-293 n.a. [58,59]
TRPC3 Phosphorylation Human
Q13507.3
S712 PPFSLVPSPKSFVYF PKC HEK-293 Decreased TRPC3 activity [63]
TRPC3 Phosphorylation Human
Q13507.3
T11
S263
SPSLRRMTVMREKGR
KNDYRKLSMQCKDFV
PKG HEK-293 Decreased TRPC3 activity, abolished the SOCE mediated by TRPC3 [62,64]
TRPC3 Phosphorylation Human
Q13507.3
Y49
Y148
Y150
Y226
RFLDAAEYGNIPVVR
ELQDDDFYAYDEDGT
QDDDFYAYDEDGTRF
KGLASPAYLSLSSED
Src HEK Phosphorylation at Y226 but not others increased TRPC3 activity [61]
TRPC3 Phosphorylation Human
Q13507.3
T573 LQISLGRTVKDIFKF PKC HL-1 Coupled TRPC3 signaling to the activation of the NFAT pathway [65]
TRPC4 Phosphorylation Human
Q9UBN4.1
Y959
Y972
EEDSSIDYDLNLPDT
DTVTHEDYVTTRL
Src COS-7 Induced insertion of TRPC4 into plasma membrane and its association with NHERF [70]
TRPC4 ubiquitination Mouse
Q9QUQ5.2
N terminus n.a. AIP4 HEK-293T Promoted endocytosis of TRPC4 and reduced its basal activity [75]
TRPC4 Phosphorylation Mouse
Q9QUQ5.2
S688 KMRRKPESFGTIGRR PKG HEK-293 Increased TRPC4 activity [71]
TRPC4 Disulfide bond Mouse
Q9QUQ5.2
C549
C554
TKGLSCKGIRCEKQNN n.a. n.a. Constrained TRPC4 activity [76]
TRPC5 Phosphorylation Mouse
Q9QX29.1
T972 DGQEEQVTTRL PKC HEK-293 Accelerated desensitization of TRPC5, necessary for the association with NHERF [36,77]
TRPC5 S-nitrosylation Mouse
Q9QX29.1
C553
C558
DEPNNCKGIRCEKQNN n.a. HEK, vascular endothelial cells Increased TRPC5 activity [82]
TRPC5 Disulfide bond Human
Q9UL62.1
C553
C558
DEPNNCKGIRCEKQNN n.a. HEK-293 Constrained TRPC5 activity [79]
TRPC5 Phosphorylation Human
Q9UL62.1
S794
S796
SGGARAKSKSVSFNL PKA HEK-293 Decreased TRPC5 activity [78]
TRPC5 S-glutathionylation Human
Q9UL62.1
C176
C178
RPHQIRCNCVECVSS n.a. HEK-293,
Clonal striatal
cells
Increased TRPC5 activity, activated the calmodulin- dependent protein kinase and calpain-caspase pathway [87]
TRPC5 Disulfide bond Human
Q9UL62.1
C553
C558
DEPNNCKGIRCEKQNN n.a. HEK-293 Stabilized TRPC5 multimerization, promoted its plasma membrane insertion [80]
TRPC5 Disulfide bond Mouse
Q9QX29.1
C553
C558
DEPNNCKGIRCEKQNN n.a. n.a. Essential for TRPC5 activation [81]
TRPC6 N-glycosylation Mouse
Q61143.1
N472
N560
EGTKLLPNETSTDNA
AQSIIDANDTLKDLT
n.a. COS n.a. [6]
TRPC6 N-glycosylation Rat
Q99N78.1
N711 YVLYGVYNVTMVIVL n.a. COS n.a. [88]
TRPC6 N-glycosylation Human
Q9Y210.1
N473
N561
EGTKLLPNETSTDNA
AQSIIDANDTLKDLT
n.a. HEK-293 Decreased TRPC6 constitutive activity [59]
TRPC6 Phosphorylation n.a. Y n.a. src COS-7 Increased TRPC6 activity [96]
TRPC6 Phosphorylation Rat
Q99N78.1
S768 VPFNLVPSPKSLLYL PKC PC12D Decreased TRPC6 activity, required for protein complex formation upon activation of the M1 muscarinic acetylcholine receptor [113]
TRPC6 Phosphorylation Mouse
Q61143.1
T69 RLTHRRQTILREKGR PKG HEK-293 and A7r5 Decreased TRPC6 activity [86]
TRPC6 Phosphorylation Mouse
Q61143.1
S448 KFVAHAASFTIFLGL PKC HEK-293T and A7r5 Decreased TRPC6 activity, reduced vasopressin-induced Ca2+ entry [107]
TRPC6 Phosphorylation Mouse
Q61143.1
T69 RLTHRRQTILREKGR PKG NRVM Decreased TRPC6 activity, suppressed NFAT activation, prevented cardiac hypertrophy [100,102]
TRPC6 Phosphorylation Human
Q9Y210.1
T70
S322
RLAHRRQTVLREKGR
KNDYKKLSMQCKDFV
PKG NRVM and AMVM Decrease TRPC6 activity, suppressed NFAT activation, prevented cardiac hypertrophy [101]
TRPC6 Phosphorylation Mouse
Q61143.1
T69 RLTHRRQTILREKGR PKA RAoSMC Decreased TRPC6 activity, attenuated angiotensin II-induced vasoconstriction [104]
TRPC6 Phosphorylation Mouse
Q61143.1
S814 KKFGISGSHEDLSKF n.a., but not casein kinase II HEK-293 No effect on TRPC6 activity [112]
TRPC6 Phosphorylation Mouse
Q61143.1
S281 NAYKGLASPAYLSLS ERK1/2 HEK-293 and Rat Glomerular mesangial cell Increased TRPC6 activity, necessary for cAMP-induced Ca2+ influx [98]
TRPC6 Phosphorylation Mouse
Q61143.1
Y284 KGLASPAYLSLSSED Src HEK-293T, podocyte Enhanced plasma membrane trafficking of TRPC6 [109]
TRPC6 Phosphorylation Mouse
Q61143.1
S28
T69
AGTRRNESQDYLLMD
RLTHRRQTILREKGR
PKA HEK-293 S28 but not T69 decreased TRPC6 activity [105]
TRPC6 Phosphorylation Mouse
Q61143.1
T69 RLTHRRQTILREKGR cGKI MLEC and HDMEC Decreased TRPC6 activity, prevented endothelial cell hyperpermeability responses to hyperforin [106]
TRPC6 Phosphorylation Mouse
Q61143.1
T487 RQLFRMKTSCFSWME CaMKII HEK293 and A7r5 Increased TRPC6 activity, enhanced arginine vasopressin-induced cation current in smooth muscle cells [97]
TRPC6 Phosphorylation Mouse
Q61143.1
T69
S321
RLTHRRQTILREKGR
KNDYKKLSMQCKDFV
PKG Murine podocyte Decreased TRPC6 activity, reduced podocyte motility [108]
TRPC6 Phosphorylation Dog T n.a. n.a. Canine heart left ventricle Decreased TRPC6 activity, underpinned the tadalafil-caused delay of dystrophic cardiomyopathy onset [103]
TRPC6 Phosphorylation Human
Q9Y210.1
S4
S13, S14
S814
MSQSPAFGPRR
AFGPRRGSSPRGAAG
KKLGILGSHEDLSKL
MAPK
Cdk-5
HEK-293T S14 enhanced TRPC6 plasma membrane trafficking and constitutive activity [110]
TRPC6 N-glycosylation Human
Q9Y210.1
N473
N561
EGTKLLPNETSTDNA
AQSIIDANDTLKDLT
n.a. TRex293, podocyte Required for channel activity, ERK activation and cytotoxicity of the GOF TRPC6 mutant (R895C) [89]
TRPC7 Phosphorylation Mouse Q9WVC5.1 T15 KNMQRRHTTLREKGR cGKI COS-7 and HEK-293T Decreased TRPC7 activity [115]
TRPC7 Phosphorylation Mouse Q9WVC5.1 S714 APFNLVPSPKSFYYL PKC MEF Decreased TRPC7 activity, regulated cytoskeleton organization and myofibroblast phenotype [116]

* Denotes PTM sites reported in the original papers but they are actually the same sites as indicated in the table. INS-1E: rat insulinoma cells. HUVEC: human umbilical vein endothelial cells. HMEC: human microvessel endothelial cells. COS: African green monkey kidney fibroblast-like cell line. HEK: human embryonic kidney cell line. HL-1: murine atrial myocytes. Hela: human cervix epithelia cell line. PC12D: rat adrenal gland cell line. NRVM: neonatal rat ventricular myocyte. AMVM: adult mouse ventricular myocyte. RAoSMC: rat aortic smooth muscle cell. MLEC: mouse microvascular lung endothelial cell. HDMEC: human dermal microvascular endothelial cell. Cdk-5: cyclin-dependent kinase 5. MEF: murine embryonic fibroblasts. A7r5: vascular smooth muscle cell line.