DegronMD - Q9NZV8(KCND2)

FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient (PubMed:10551270, PubMed:15454437, PubMed:14695263, PubMed:14623880, PubMed:14980201, PubMed:16934482, PubMed:24811166, PubMed:24501278). The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11507158). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation (PubMed:15454437, PubMed:14623880, PubMed:14980201, PubMed:19171772, PubMed:24501278, PubMed:24811166). Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity). {ECO:0000250|UniProtKB:Q63881, ECO:0000250|UniProtKB:Q9Z0V2, ECO:0000269|PubMed:10551270, ECO:0000269|PubMed:10729221, ECO:0000269|PubMed:11507158, ECO:0000269|PubMed:14623880, ECO:0000269|PubMed:14695263, ECO:0000269|PubMed:14980201, ECO:0000269|PubMed:15454437, ECO:0000269|PubMed:16934482, ECO:0000269|PubMed:19171772, ECO:0000269|PubMed:24501278, ECO:0000269|PubMed:24811166}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D612N	TCGA-EE-A2GS	SKCM	TCGA	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.D612N	TCGA-JW-A5VL	CESC	TCGA	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.D612N	TCGA-V5-AASV	ESCA	TCGA	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.D612N	DO49976	CESC	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.D612N	DO222880	MELA	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.D612N	DO37465	SKCM	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.P601Q	TCGA-ER-A2NF	SKCM	TCGA	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation altering degron motif	0.5924
p.P601Q	DO47451	SKCM	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation altering degron motif	0.5924
p.E615K	TCGA-OD-A75X	SKCM	TCGA	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.0833
p.E615K	DO48601	SKCM	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.0833
p.P603L	DO222884	COCA	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation altering degron motif	0.7582
p.T606I	DO50450	ESAD	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation altering degron motif	0.7078
p.D612Y	DO229027	LICA	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.1667
p.P601T	DO220891	MELA	ICGC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation altering degron motif	0.5919
p.Q590P	SIDM01582	Gastric Carcinoma	GDSC	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.0556
p.Q590P	ACH-000507	Gastric Cancer	CCLE	IPTPPVT	DEG_SCF_FBW7_1	600:606	Mutation rewiring degron network	0.0556

DegronMD: protein-targeted degradation, mutation and drug response to degrons

KCND2

UniProt ID: Q9NZV8

Entrez ID: 3751

Protein name: Potassium voltage-gated channel subfamily D member 2 (Voltage-gated potassium channel subunit Kv4.2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for KCND2 in