Recombinant Human Intermediate conductance calcium-activated potassium channel protein 4(KCNN4)

Code CSB-CF012086HU
Size US$3587
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Product Details

Purity Greater than 85% as determined by SDS-PAGE.
Target Names KCNN4
Uniprot No. O15554
Research Area Cell Biology
Alternative Names DHS2; hIKCa1; hKCa4; hSK4; IK; IK1; IKCa1; Intermediate conductance calcium activated potassium channel protein 4; Intermediate conductance calcium-activated potassium channel protein 4; KCa3.1; KCa4; KCNN 4; Kcnn4; KCNN4_HUMAN; Potassium calcium activated channel subfamily N member 4; Potassium intermediate/small conductance calcium activated channel, subfamily N, member 4; Putative Gardos channel; SK4; SKCa 4; SKCa4
Species Homo sapiens (Human)
Source in vitro E.coli expression system
Expression Region 1-427 aa
Target Protein Sequence MGGDLVLGLGALRRRKRLLEQEKSLAGWALVLAGTGIGLMVLHAEMLWFGGCSWALYLFLVKCTISISTFLLLCLIVAFHAKEVQLFMTDNGLRDWRVALTGRQAAQIVLELVVCGLHPAPVRGPPCVQDLGAPLTSPQPWPGFLGQGEALLSLAMLLRLYLVPRAVLLRSGVLLNASYRSIGALNQVRFRHWFVAKLYMNTHPGRLLLGLTLGLWLTTAWVLSVAERQAVNATGHLSDTLWLIPITFLTIGYGDVVPGTMWGKIVCLCTGVMGVCCTALLVAVVARKLEFNKAEKHVHNFMMDIQYTKEMKESAARVLQEAWMFYKHTRRKESHAARRHQRKLLAAINAFRQVRLKHRKLREQVNSMVDISKMHMILYDLQQNLSSSHRALEKQIDTLAGKLDALTELLSTALGPRQLPEPSQQSK
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 53.7 kDa
Protein Length Full Length
Tag Info N-terminal 10xHis-tagged
Form Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
Lead Time Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA Please contact us to get it.

Target Data

Function Forms a voltage-independent potassium channel that is activated by intracellular calcium
Gene References into Functions
  1. These results suggest that His358, the inhibitory histidine in KCa3.1, might coordinate a copper ion through a similar binding mode. PMID: 29953543
  2. present study was designed to evaluate in hereditary xerocytosis the functional link between mutated Piezo1 and KCNN4 PMID: 28619848
  3. this study reports cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. PMID: 29724949
  4. Expression of intermediate-conductance calmodulin/calcium-activated K+ channels 3.1 (KCa3.1) mRNA and protein was detected in all three layers of the human cornea. PMID: 29554088
  5. KCa3.1 channels are important modulators in hepatocellular homeostasis. PMID: 27354175
  6. Tumor suppressor miR-497-5p down-regulates KCa3.1 expression and contributes to the inhibition of angiosarcoma malignancy development. PMID: 27531900
  7. We identified a two-gene signature including KCNN4 and S100A14 which was related to recurrence in optimally debulked serous ovarian carcinoma patients PMID: 27270322
  8. Human arrhythmogenic calmodulin mutations impede the activation of SK2 channels in human embryonic kidney 293 cells. PMID: 27165696
  9. This study found a very substantial functional expression of KCa3.1 channels in microglia from adult epilepsy patients. PMID: 27470924
  10. Data show that RNAi-mediated knockdown of KCa3.1 and/or TRPC1 leads to a significant decrease in cell proliferation due to cell cycle arrest in the G1 phase. PMID: 27183905
  11. Higher epithelial KCNN4 expression was closely correlated with advanced TNM stages and predicted a poor prognosis in patients with pancreatic ductal adenocarcinoma. PMID: 29050937
  12. Here, the authors demonstrate that phosphorylation of His358 activates KCa3.1 by antagonizing copper-mediated inhibition of the channel. PMID: 27542194
  13. This work demonstrates the critical role of SK4 Ca(2+)-activated K(+) channels in adult pacemaker function. PMID: 28219898
  14. Blocking KCa3.1 suppresses plaque instability in advanced stages of atherosclerosis by inhibiting macrophage polarization toward an M1 phenotype. PMID: 28062499
  15. IKCa1 is overexpressed in cervical cancer tissues, and IKCa1 upregulation in cervical cancer cell linea enhances cell proliferation, partly by reducing the proportion of apoptotic cells. PMID: 28280257
  16. Findings suggest that SK4 channels are expressed in triple-negative breast cancer (TNBC) cells and are involved in the proliferation, apoptosis, migration and epithelial-mesenchymal transition processes of TNBC cells. PMID: 27124117
  17. KCa3.1 blockade protects against cisplatin-induced acute kidney injury through the attenuation of apoptosis by interference with intrinsic apoptotic and endoplasmic reticulum stress-related mediators. PMID: 26438401
  18. KCa3.1 in human immature dendritic cells play a major role in their migration and constitute an attractive target for the cell therapy optimization PMID: 27020659
  19. The results suggest that KCa3.1 activation contributes to dysfunctional tubular autophagy in diabetic nephropathy through PI3K/Akt/mTOR signaling pathways. PMID: 27029904
  20. that KCa3.1 channels are key actors in the migration capacity of neutrophils, and its inhibition did not affect other relevant cellular functions PMID: 26138196
  21. KCa3.1 and CFTR colocalize at the plasma membrane. PMID: 27092946
  22. KCNN4 inhibition differentially regulates migration of intestinal epithelial cells in inflamed vs. non-inflamed conditions in a PI3K/Akt-mediated manner. PMID: 26824610
  23. KCa3.1 protein expression was increased in asthmatic compared to healthy airway epithelium in situ, and KCa3.1 currents were larger in asthmatic compared to healthy HBECs cultured in vitro PMID: 26689552
  24. Data show that calcium-dependent potassium channel KCa3.1 operates as a positive feedback mechanism for intracellular Ca2+ increase. PMID: 26418693
  25. high KCa3.1-mRNA expression levels were indicative of low disease specific survival of ccRCC patients, short progression-free survival, and a high metastatic potential. Therefore, KCa3.1 is of prognostic value in ccRCC PMID: 25848765
  26. KCa3.1 activation in human lung mast cells is highly dependent on Ca(2+) influx through Orai1 channels, mediated via a close spatiotemporal interaction between the two channels. PMID: 26177720
  27. Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis). PMID: 26178367
  28. describes patients from 2 well-phenotyped hereditary xerocytosis (HX) kindreds, including from one of the first HX kindreds described, who lack predicted heterozygous PIEZO1-linked variants PMID: 26198474
  29. identification of a dominantly inherited missense mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis PMID: 26148990
  30. Inhibition of K(Ca)3.1 by EETs (14,15-EET), 20-HETE, and omega3 critically depended on the presence of electron double bonds and hydrophobicity within the 10 carbons preceding the carboxyl-head of the molecules. PMID: 25372486
  31. Ca2+- and KCa3.1-dependent processes facilitate "constitutive" alpha smooth muscle actin expression and Smad2/3 signalling in IPF-derived fibroblasts, and thus promote fibroblast to myofibroblast differentiation. PMID: 25476248
  32. The role and mechanisms of KCa3.1 in progressive diabetic chronic kidney disease are reviewed. PMID: 25415613
  33. The present study shows that KCNN4 is expressed at the mRNA and protein level in RA-SFs, is functionally active, and has a regulatory impact on cell proliferation and secretion of pro-inflammatory and pro-destructive mediators. PMID: 25545021
  34. Overexpression of CCL20 in human proximal tubular cells is inhibited by blockade of KCa3.1 under diabetic conditions through inhibition of the NF-kappaB pathway. PMID: 24733189
  35. Blood brain barrier endothelial cells exhibit KCa3.1 protein and activity. PMID: 25477223
  36. These data suggest that NO activates KCNN4 channels through the PKG but not the PKA pathways. PMID: 24826782
  37. Mg(2+) inhibits KCa3.1 via a rapid, voltage-dependent mechanism that leads to a reduction of the channel's unitary current and by reducing the open probability of the channel PMID: 24193405
  38. Tumor-associated macrophages participate in the metastasis of CRC induced by PRL-3 through secretion of IL-6 and IL-8 in a KCNN4 dependent manner. PMID: 24885636
  39. KCa3.1 confers an invasive phenotype that significantly worsens a patient's outlook with malignant glioma. PMID: 24585442
  40. These findings highlight a novel role for the KCa3.1 channel in human BSM cell phenotypic modulation. PMID: 24055799
  41. blockade of KCa3.1 attenuates diabetic renal interstitial fibrogenesis through inhibiting activation of fibroblasts PMID: 24166472
  42. The channel gating process for KCa3.1 and the S5 transmembrane segment is controlled by aromatic-aromatic interactions involving the pore helix. PMID: 24470490
  43. KCa3.1 has a role in diabetic nephropathy. (review) PMID: 24963668
  44. Our findings suggest that KCa3.1 channels play an important role in the pathogenesis of chronic AV and constitute an attractive target for the prevention of arteriopathy. PMID: 24312257
  45. Our results suggested that IKCa1 may play a role in the proliferation of human HCC, and IKCa1 blockers may represent a potential therapeutic strategy for HCC. PMID: 23392713
  46. KCa3.1 pharmacological blockade attenuated human myofibroblast proliferation, wound healing, collagen secretion and contractility in vitro, and this was associated with inhibition of TGFbeta1-dependent increases in intracellular free Ca2+. PMID: 24392001
  47. blocking KCa3.1 increases the degranulation and cytotoxicity of adherent Natural killer cells, but not of non-adherent-Natural killer cells. PMID: 24146918
  48. This study provides insight into the key molecular determinants for the high-affinity binding of peptide toxins to KCa3.1. PMID: 24138859
  49. KCa3.1 activity has an important role in glioblastoma invasiveness. PMID: 23949222
  50. Globotriaosylceramide accelerates the endocytosis and lysosomal degradation of endothelial KCa3.1 via a clathrin-dependent process, leading to endothelial dysfunction in Fabry disease. PMID: 24158513
  51. Adenosine inhibits KCa3.1 in human T cells via A2A receptor & PKAI. Comparable effects were obtained by KCa3.1 blockade with TRAM-34. Adenosine suppresses IL-2 secretion via KCa3.1 inhibition. PMID: 24227782
  52. KCa3.1 channels contribute to the regulation of glucocorticosteroid-resistant inflammatory pathways in airway smooth musclecells PMID: 23904164
  53. Explored the mechanism by which PRL-3 mediates EMT. Demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. PMID: 23572150
  54. Data indicate that Epac1-Rap1A-RhoA-ROCK signaling affects Cl- secretion via effects on the apical expression of KCNN4c channels. PMID: 23720748
  55. results provide evidence plasma from preeclampsia generates superoxide via a LOX1-NOX2-mediated pathway and downregulates endothelial KCa3.1, which may contribute to endothelial dysfunction and vasculopathy in preeclampsia PMID: 23261940
  56. KCa3.1 plays an important role in VSMC proliferation via controlling Ca(2+)-dependent signaling pathways PMID: 23609438
  57. A previously unrecognized Ca(2+)-activated intermediate K(+) conductance (IK(Ca), KCa3.1, or SK4) in young and old stage-derived human embryonic stem cell-derived cardiomyocytes, was identified. PMID: 23589888
  58. KCa3.1 in HEL cells displays a unique form of voltage dependence modulating open channel probability. PMID: 23407879
  59. K(Ca)3.1 and ClC-3 are expressed in tissue samples obtained from patients diagnosed with grade IV gliomas. Both K(Ca)3.1 and ClC-3 colocalize to the invading processes of glioma cells PMID: 23345219
  60. This study focussed on the endocytic internalization and the intracellular transport of the human isoform hK(Ca)3.1. PMID: 21465474
  61. PRL-3 promoted the proliferation of LoVo cells through upregulation of KCNN4 channels which facilitated the G2/M transition. PMID: 21725609
  62. The K(+) channel K(Ca)3.1 plays a key role in human fibrocyte migration PMID: 21872912
  63. hypoxic exercise training this intervention depresses Gardos channel-modulated erythrocyte rheological functions PMID: 21551009
  64. the N-terminal domain of K(Ca)3.1 is critical for channel trafficking to the plasma membrane PMID: 21345794
  65. Data suggest that human IK1-induced cell proliferation occurs by a direct interaction with ERK1/2 and JNK signaling pathways. PMID: 21123738
  66. Results are consistent with the notion that human K(Ca)3.1 channels are assembled from two homomeric dimers and not randomly from four independent subunits. PMID: 21228320
  67. Intermediate conductance calcium-activated potassium channel mediates vasodilation together with nitric oxide and connexin 37 in mesenteric artery. PMID: 21172909
  68. presence of mtKCa3.1 in tumor cell lines using biochemical and electrophysiological approaches PMID: 20036632
  69. hKCa3.1 might contribute to breast tumour-progression and can serve as a useful prognostic marker for breast cancer. PMID: 20712009
  70. These results are the first to demonstrate that plasma membrane-associated KCa3.1 is targeted for lysosomal degradation via a Rab7 and ESCRT-dependent pathway. PMID: 20720181
  71. Our data implicate the role of KCNN4 in ileal Crohn Disease. PMID: 20407432
  72. IK1 channels are present in biliary epithelial cells and contribute to ATP-stimulated secretion through a P2Y-IP3 receptor pathway. PMID: 20501432
  73. Data demonstrate that bestrophin 1 is localized in the endoplasmic reticulum (ER), where it interacts with the ER-Ca(2+) sensor and can enhance Ca(2+) signaling and activation of Ca(2+)-dependent Cl(-) (TMEM16A) and K(+) (SK4) channels. PMID: 19823864
  74. functional role of the intermediate conductance Ca(2+)-activated K(+) channel, hIK1, in HaCaT keratinocytes PMID: 12421833
  75. trafficking depends upon a C-terminal leucine zipper PMID: 12493744
  76. arachidonic acid (AA) interacts with the pore-lining amino acids, Thr(250) and Val(275) in hIK1, conferring inhibition of hIK1 by AA PMID: 12609997
  77. Ca2+-activated Cl- secretion in native human airway epithelia requires activation of Ca2+-dependent basolateral K+ channels (hSK4). PMID: 12612194
  78. SK4 is the gene that codes for the Gardos channel in red blood cells. This channel is important pathophysiologically, because it represents the major pathway for cell shrinkage via KCl and water loss that occurs in sickle cell disease. PMID: 12773623
  79. K(Ca) channels presenting the pharmacology of SK4 channels are present on both apical and basolateral membranes, but it is the basolateral SK4-like channels that play a major role in calcium-dependent chloride secretion in 16HBE14o- cells. PMID: 14724753
  80. the NH(2) terminus of hIK1 contains overlapping leucine zipper and dileucine motifs essential for channel assembly and trafficking to the plasma membrane PMID: 14754884
  81. activation of Gardos channel at different oxygen tensions is correlated with changes in passive and active calcium transport and sensitivity to calcium PMID: 15039018
  82. stochastic Ca2+ permeabilization rather than Gardos-channel variation is the main determinant selecting which sickle cells dehydrate through Gardos channels in each sickling episode PMID: 15339840
  83. We present in this work a structural model of the open IKCa (KCa3.1) channel derived by homology modeling from the MthK channel structure, and used this model to compute the transmembrane potential profile along the channel pore. PMID: 15452196
  84. first demonstration that gating of the iKCa1 potassium channel is regulated by beta2-adrenoceptors PMID: 15817638
  85. Results describe the subcellular distribution of the canine (cIK1) and the human (hIK1) channel protein in different migrating cells. PMID: 15965951
  86. phosphatidylinositol 3-phosphate and these 14 amino acids regulate KCa3.1 channel activity by recruiting an as yet to be defined regulatory subunit that is required for Ca2+ gating of KCa3.1 PMID: 16251351
  87. H441 cells express KCNN4 and cellular potassium conductance is important to the control of Na(+) absorption in respiratory epithelium PMID: 16766578
  88. KCa3.1 channels are a part of the signaling complex that forms at the IS upon antigen presentation. PMID: 17151145
  89. We show that nucleoside diphosphate kinase B (NDPK-B), a mammalian histidine kinase, functions downstream of PI(3)P to activate KCa3.1 by phosphorylating histidine 358 in the carboxyl terminus of KCa3.1. PMID: 17157250
  90. Increased activity of IKCa1 channel is necessary for the development of endometrial cancer. PMID: 17310992
  91. S6 transmembrane segment of the open KCa3.1 channel contains two functional domains delimited by V282 with MTSEA and MTSET binding leading to a channel inhibition at V275, T278, and V282 and to a steep channel activation at positions A283 and A286 PMID: 17353352
  92. KCNN4 activity decines sharply throughout the lifespan of human red blood cells. PMID: 17470662
  93. The G(alphas)-coupled adenosine A2A receptor closes KCa3.1, providing a clearly defined mechanism by which adenosine inhibits human lung mast cell migration and degranulation. PMID: 17474152
  94. KCa3.1 channels are important in human airway smooth muscle cell proliferation. PMID: 17585114
  95. SK4 channels activity, underlying the Ca(2+)-dependent K(+) permeability was in particular increased by IL-13 PMID: 17762175
  96. KCNN4 channels, possibly in parallel with volume-sensitive outwardly rectifying Cl channels, effect regulatory volume decrease in lens epithelial cells. PMID: 18184876
  97. KCa3.1 channels are not immobilized at the front but move in a diffuse way throughout the plasma membrane of migrating cells. PMID: 18287336
  98. IK1 channel activity appears to mediate, at least in part, the response of epidermoid cancer cells to cisplatin treatment. PMID: 18367588
  99. KCa3.1 channels play a critical role in transcellular chloride secretion and net fluid transport into the kidney cysts of patients with ADPKD by maintaining PMID: 18547995
  100. KCa3.1 contributes to atherogenesis in mice and humans PMID: 18688283

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Involvement in disease Dehydrated hereditary stomatocytosis 2 (DHS2)
Subcellular Location Cell membrane, Multi-pass membrane protein
Protein Families Potassium channel KCNN family, KCa3.1/KCNN4 subfamily
Tissue Specificity Widely expressed in non-excitable tissues.
Database Links

HGNC: 6293

OMIM: 602754

KEGG: hsa:3783

STRING: 9606.ENSP00000262888

UniGene: Hs.10082

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