DegronMD - Q14721(KCNB1)

FUNCTION: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216). Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity). Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:8081723, PubMed:1283219, PubMed:10484328, PubMed:12560340, PubMed:19074135, PubMed:19717558, PubMed:24901643). Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, PubMed:11852086, PubMed:12060745, PubMed:19074135, PubMed:19717558, PubMed:24901643). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity). Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity). Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216). Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity). Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745). Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity). {ECO:0000250|UniProtKB:P15387, ECO:0000250|UniProtKB:Q03717, ECO:0000269|PubMed:10484328, ECO:0000269|PubMed:11852086, ECO:0000269|PubMed:12060745, ECO:0000269|PubMed:12560340, ECO:0000269|PubMed:1283219, ECO:0000269|PubMed:19074135, ECO:0000269|PubMed:19717558, ECO:0000269|PubMed:23161216, ECO:0000269|PubMed:24901643, ECO:0000269|PubMed:8081723}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.P521H	TCGA-55-7907	LUAD	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.2778
p.P521H	DO25396	LUAD	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.2778
p.S519C	TCGA-86-8073	LUAD	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7541
p.S519C	DO23624	LUAD	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7541
p.S519F	TCGA-95-7947	LUAD	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7982
p.S519F	DO26404	LUAD	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7982
p.P774L	TCGA-AQ-A04H	BRCA	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1944
p.P774L	DO3340	BRCA	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1944
p.S792L	TCGA-AX-A05Z	UCEC	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.0833
p.S792L	TCGA-EY-A1GI	UCEC	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.0833
p.S792L	DO222762	COCA	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.0833
p.S792L	DO40884	UCEC	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.0833
p.S792L	DO41211	UCEC	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.0833
p.T788M	TCGA-B5-A0JY	UCEC	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788M	DO43041	UCEC	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.P512L	TCGA-D3-A3C8	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.25
p.P512L	DO47636	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.25
p.S517L	TCGA-D3-A8GR	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	TCGA-EE-A2M6	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	TCGA-GN-A266	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	DO9876	COAD	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	DO222514	MELA	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	DO37432	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	DO37976	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	DO51247	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	SIDM00781	Colorectal Carcinoma	GDSC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	SIDM00780	Colorectal Carcinoma	GDSC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	ACH-000967	Colon/Colorectal Cancer	CCLE	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	ACH-001199	Colon/Colorectal Cancer	CCLE	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S517L	SNU-C2B	large intestine	COSMIC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation altering degron motif	0.7667
p.S511F	TCGA-EO-A3B0	UCEC	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.2222
p.S511F	DO219773	UCEC	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.2222
p.E508K	TCGA-ER-A194	SKCM	TCGA	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.1389
p.E508K	DO47646	SKCM	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.1389
p.P779S	TCGA-ER-A3PL	SKCM	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation altering degron motif	0.6752
p.P779S	DO37495	SKCM	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation altering degron motif	0.6752
p.P784S	TCGA-FS-A1ZK	SKCM	TCGA	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.3056
p.P784S	DO37474	SKCM	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.3056
p.G510R	DO222734	ESCA	ICGC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.1944
p.P784T	DO229026	LICA	ICGC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.3056
p.S773N	SIDM02050	Colorectal Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1667
p.G789E	SIDM00450	Acute Myeloid Leukemia	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1667
p.G789E	ACH-000218	Leukemia	CCLE	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1667
p.G789E	PL-21	haematopoietic and lymphoid tissue	COSMIC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1667
p.T788K	SIDM01259	B-Lymphoblastic Leukemia	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788K	SIDM01144	Gastric Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788K	SIDM00988	Kidney Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788K	SIDM01695	Acute Myeloid Leukemia	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788K	SIDM01463	Endometrial Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T788K	SIDM00159	Biliary Tract Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation blocking phosphorylation signal	0.6389
p.T782A	SIDM00516	Melanoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation altering degron motif	0.7139
p.T782A	ACH-002166	Skin Cancer	CCLE	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation altering degron motif	0.7139
p.T782A	MZ7-mel	skin	COSMIC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation altering degron motif	0.7139
p.D771E	SIDM00534	Colorectal Carcinoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1111
p.D771E	ACH-000986	Colon/Colorectal Cancer	CCLE	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1111
p.D771E	HT-115	large intestine	COSMIC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation rewiring degron network	0.1111
p.K776R	SIDM01780	B-Cell Non-Hodgkin's Lymphoma	GDSC	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation substituting flanking lysine	0.3611
p.K776R	ACH-000388	Lymphoma	CCLE	PGSTS	DEG_SPOP_SBC_1	779:783	Mutation substituting flanking lysine	0.3611
p.V526I	SIDM01766	Chondrosarcoma	GDSC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.1389
p.V526I	SIDM01778	B-Cell Non-Hodgkin's Lymphoma	GDSC	ARSSS	DEG_SPOP_SBC_1	515:519	Mutation rewiring degron network	0.1389

Kaplan plot for KCNB1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

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

KCNB1

UniProt ID: Q14721

Entrez ID: 3745

Protein name: Potassium voltage-gated channel subfamily B member 1 (Delayed rectifier potassium channel 1) (DRK1) (h-DRK1) (Voltage-gated potassium channel subunit Kv2.1)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for KCNB1 in