Gene Ontology annotation through association of InterPro records with GO terms.
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity.
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt.
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods.
CNK3 and IPCEF1 produce a single protein that is required for HGF dependent Arf6 activation and migration.
-
CNKSR3 (CNK3/IPCEF1 fusion) is required for HGF-induced Arf6 activation and cell migration
"Knockdown of this protein impairs HGF-induced Arf6 activation and migration in response to HGF treatment"
-
The protein acts as a scaffold binding to cytohesin 2 (Arf6 GEF)
"IPCEF1, a scaffold that binds to cytohesin 2, is required for cytohesin-induced scattering"
-
IPCEF1 is actually the C-terminal half of CNK3
"We report here that IPCEF1 is actually the C-terminal half of CNK3"
A proteome-scale map of the human interactome network.
-
Large-scale systematic binary protein-protein interaction mapping study
"systematically screening half of the interactome space with minimal inspection bias, we more than doubled the number of high-quality binary PPIs available from the literature"
A reference map of the human binary protein interactome.
Multimodal cell maps as a foundation for structural and functional genomics.
UniProt entry for CNKSR3 (Connector enhancer of kinase suppressor of ras 3)
-
Scaffold protein coordinating ENaC-regulatory complex assembly
"Acts as a scaffold protein coordinating the assembly of an ENaC-regulatory complex (ERC)"
-
Regulates aldosterone-induced sodium transport via ENaC
"Regulates aldosterone-induced and epithelial sodium channel (ENaC)-mediated sodium transport through regulation of ENaC cell surface expression"
-
Localizes to apical plasma membrane and cytoplasm
"SUBCELLULAR LOCATION: Cytoplasm. Apical cell membrane; Peripheral membrane protein"
-
Contains SAM, CRIC, PDZ, and DUF1170 domains
"DOMAIN 7..72 SAM...DOMAIN 80..174 CRIC...DOMAIN 211..293 PDZ...DOMAIN 325..546 DUF1170"
-
PDZ domain required for ENaC and SGK1 interaction
"The PDZ domain is required for interaction with ENaC and SGK1, but not for interaction with NEDDL4 and RAF1"
-
Interacts with SCNN1A, SCNN1B, NEDD4L, RAF1, SGK1
"Interacts directly with SCNN1A (ENaC subunit alpha) and SCNN1B (ENaC subunit beta) C-terminal tails. Interacts with ENaC regulatory proteins NEDD4L, RAF1 and SGK1"
-
Up-regulated by aldosterone
"INDUCTION: Up-regulated by aldosterone (at protein level)"
-
Negatively regulates ERK1/2 cascade and peptidyl-serine phosphorylation
"negative regulation of ERK1 and ERK2 cascade; negative regulation of peptidyl-serine phosphorylation"
-
Positively regulates sodium ion transport
"positive regulation of sodium ion transport"
The role of the ENaC-regulatory complex in aldosterone-mediated sodium transport.
-
CNK3 is rapidly induced by physiological aldosterone via two functional MR binding loci near its transcription start site, supporting direct MR target gene status
"CNK3, like SGK1 and GILZ1, is rapidly induced by physiological concentrations of aldosterone, and its promoter harbors two functional MR binding loci in close vicinity to the transcription start site, suggesting a direct mode of regulation"
-
CNK3 expression is required for ENaC-mediated Na+ transport in renal epithelial cells
"CNK3 expression correlates with, and is required for, ENaC-mediated Na+ transport in renal epithelial cells"
-
CNK3 negatively regulates the Raf-1/MEK1/2/ERK1/2 MAPK cascade
"The first study addressing the mechanistic aspects of CNK3 function revealed that CNK3 expression significantly interferes with the activation of the Raf-1/MEK1/2/ERK1/2 signaling cascade"
-
CNK3 is highly expressed in connecting tubule and cortical collecting duct, the aldosterone-sensitive distal nephron
"CNK3 is highly expressed in the connecting tubule (CNT) and the cortical collecting duct (CCD), the prime target segments of aldosterone-regulated Na+ retention in the kidney"
-
Working model proposes CNK3 as a central hormone-induced scaffolding platform that assists assembly of the ENaC-regulatory complex
"Our current hypothesis involves CNK3 as a central hormone-induced scaffolding platform, that possibly aids in the assembly of the ENaC-regulatory complex, thereby promoting appropriate signal transduction"
-
CNK3 has the modular SAM-CRIC-PDZ architecture typical of scaffold proteins and lacks the PH domain present in other CNK family members
"CNK3 is the third isoform of the mammalian CNK protein family, whose members possess a modular structure and contain common protein-protein interaction domains - an N-terminal sterile α motif (SAM), followed by a conserved region in CNK (CRIC) and a PDZ domain"
-
PP2A subunits identified as abundant CNK3 binding partners, suggesting phosphoregulation integrated into CNK3-centered scaffolding
"Peptides from all three subunits of the heterotrimeric serine/threonine phosphatase PP2A were detected as the most abundant binding partners of CNK3"
Organization of the ENaC-regulatory machinery.
-
CNK3 PDZ-containing scaffold characteristics make it an intriguing candidate for assembling regulatory components into a supramolecular ENaC-regulatory complex
"PDZ domain-containing scaffolding proteins can therefore function not only to bind an array of target proteins, but also to crosslink one another into complex assemblies, factors which make PDZ domain-containing scaffolds such as CNK3 intriguing candidates for the assembly of regulatory components into a large supramolecular ENaC-regulatory complex"
-
CNK3 expression interferes with Raf-1/MEK1/2/ERK1/2 activation
"The first study addressing the mechanistic aspects of CNK3 function revealed that CNK3 expression significantly interferes with the activation of the Raf-1/MEK1/2/ERK1/2 signaling cascade"
-
It remains unresolved whether CNK3 directly interacts with ENaC and whether it changes ENaC surface expression versus open probability
"although it is known that CNK3 positively regulates ENaC activity (Ziera et al., 2009), it remains to be seen if it can directly interact with and modulate the channel. It is also not known if CNK3 enhances ENaC surface expression or Po"
Aldosterone: Renal Action and Physiological Effects.
-
2023 review of aldosterone renal action discusses aldosterone-induced factors (including CNKSR3) acting via disinhibition of tonic inhibitory mechanisms rather than directly turning on transporters
"Aldosterone: Renal Action and Physiological Effects"
Scaffold protein connector enhancer of kinase suppressor of Ras isoform 3 (CNK3) coordinates assembly of a multiprotein epithelial sodium channel (ENaC)-regulatory complex.
-
CNKSR3 is an aldosterone-induced scaffold that nucleates assembly of an ENaC-regulatory complex (with Nedd4-2, GILZ1, Raf1, SGK1, 14-3-3) in cortical collecting duct cells, required for aldosterone-induced sodium reabsorption.
Deep research on CNKSR3 function
Falcon deep research on CNKSR3 function (Edison Scientific Literature, 2026-05-29).
-
CNKSR3 is positioned as an aldosterone/MR-regulated scaffold required for ENaC-mediated sodium transport in aldosterone-responsive distal nephron epithelia
"CNKSR3 is positioned as an aldosterone/mineralocorticoid receptor (MR)-regulated scaffold that is required for ENaC-mediated sodium transport in aldosterone-responsive distal nephron epithelia (connecting tubule and cortical collecting duct)"
-
CNKSR3 is not an enzyme; its function is as a regulatory adaptor shaping signaling and trafficking assemblies controlling ENaC
"CNKSR3 is not an enzyme and no catalytic reaction is attributed to it in this evidence set; rather it is a regulatory adaptor that shapes signaling and trafficking/regulatory protein assemblies controlling ENaC"
-
2024 GWAS implicates a locus near SCAF8/CNKSR3 in diabetic kidney disease, providing human genetic anchor for kidney relevance
"rs12523822 near SCAF8/CNKSR3. Reported association OR = 0.73, p = 1.3×10−8 (meta-analysis of T1D+T2D DKD; 5,226 cases vs 8,510 controls)"