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Human Phosphatases
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Statistics

241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update:
11 Mar, 2019
last maintenance update:
01 Sep, 2023

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KCNB1

Basic Information
Phosphatases
Pathway
Interacting Proteins
Phosphorylating Kinases

Gene Name	KCNB1 (QuickGO)	Interactive visualization of KCNB1 structures (A quick tutorial to explore the interctive visulaization) Representative structure: NA
Synonyms	KCNB1
Protein Name	KCNB1
Alternative Name(s)	Potassium voltage-gated channel subfamily B member 1;Delayed rectifier potassium channel 1;DRK1;h-DRK1;Voltage-gated potassium channel subunit Kv2.1;
Protein Family	Belongs to the potassium channel family B (Shab) (TC1A12) subfamily Kv21/KCNB1 sub-subfamily
EntrezGene ID	3745 (Comparitive Toxicogenomics)
UniProt AC (Human)	Q14721 (protein sequence)
Enzyme Class	N/A
Molecular Weight	95878 Dalton
Protein Length	858 amino acids (AA)
Genome Browsers	NCBI \| ENSG00000158445 (Ensembl) \| UCSC
Crosslinking annotations	Query our ID-mapping table
Orthologues	Quest For Orthologues (QFO) \| GeneTree \| eggNOG - KOG3713 \| eggNOG - COG1226
Phosphorylation Network	Visualize

Domain organization, Expression, Diseases

Localization, Function, Catalytic activity and Sequence

Localization (UniProt annotation)
Cell membrane Perikaryon Cell projection, axon Cell projection, dendrite Membrane; Multi-pass membraneprotein Cell junction, synapse, postsynaptic cell membrane Cell junction, synapse Cell junction, synapse,synaptosome Lateral cell membrane Cell membrane, sarcolemma Note=Localizes to high-densitysomatodendritic clusters and non-clustered sites on the surface ofneocortical and hippocampal pyramidal neurons in a cortical actincytoskeleton-dependent manner (PubMed:24477962) Localizes also tohigh-density clusters in the axon initial segment (AIS), atankyrin-G-deficient sites, on the surface of neocortical andhippocampal pyramidal neurons (PubMed:24477962) KCNB1-containingAIS clusters localize either in close apposition to smoothendoplasmic reticulum cisternal organelles or with GABA-Areceptor-containing synapses of hippocampal and cortical pyramidalneurons, respectively (PubMed:24477962) Localizes to high-densityclusters on the cell surface of atrial and ventricular myocytesand at the lateral plasma membrane in epithelial cells Localizesboth to the axial and transverse tubules (T tubule) and sarcolemmain ventricular myocytes Associated with lipid raft domains Incortical neurons, apoptotic injuries induce de novo plasmamembrane insertion in a SNARE-dependent manner causing anapoptotic potassium current surge
Function (UniProt annotation)
Voltage-gated potassium channel that mediatestransmembrane potassium transport in excitable membranes,primarily in the brain, but also in the pancreas andcardiovascular system Contributes to the regulation of the actionpotential (AP) repolarization, duration and frequency ofrepetitive AP firing in neurons, muscle cells and endocrine cellsand plays a role in homeostatic attenuation of electricalexcitability throughout the brain (PubMed:23161216) Plays also arole in the regulation of exocytosis independently of itselectrical function (By similarity) Forms tetrameric potassium-selective channels through which potassium ions pass in accordancewith their electrochemical gradient The channel alternatesbetween opened and closed conformations in response to the voltagedifference across the membrane Homotetrameric channels mediate adelayed-rectifier voltage-dependent outward potassium current thatdisplay rapid activation and slow inactivation in response tomembrane depolarization (PubMed:8081723, PubMed:1283219,PubMed:10484328, PubMed:12560340, PubMed:19074135,PubMed:19717558, PubMed:24901643) Can form functionalhomotetrameric and heterotetrameric channels that contain variableproportions of KCNB2; channel properties depend on the type ofalpha subunits that are part of the channel (By similarity) Canalso form functional heterotetrameric channels with other alphasubunits that are non-conducting when expressed alone, such asKCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 andKCNV1, 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 increasedcurrent amplitude with the threshold for action potentialactivation shifted towards more negative values in hypoxic-treatedpulmonary artery smooth muscle cells (By similarity) Channelproperties are also modulated by cytoplasmic ancillary betasubunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowingactivation and inactivation rate of the delayed rectifierpotassium channels (By similarity) In vivo, membranes probablycontain a mixture of heteromeric potassium channel complexes,making it difficult to assign currents observed in intact tissuesto any particular potassium channel family member Majorcontributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system,sympathetic ganglion neurons, neuroendocrine cells, pancreaticbeta cells, cardiomyocytes and smooth muscle cells Mediates themajor part of the somatodendritic delayed-rectifier potassiumcurrent in hippocampal and cortical pyramidal neurons andsympathetic superior cervical ganglion (CGC) neurons that acts toslow down periods of firing, especially during high frequencystimulation Plays a role in the induction of long-termpotentiation (LTP) of neuron excitability in the CA3 layer of thehippocampus (By similarity) Contributes to the regulation ofglucose-induced action potential amplitude and duration inpancreatic beta cells, hence limiting calcium influx and insulinsecretion (PubMed:23161216) Plays a role in the regulation ofresting membrane potential and contraction in hypoxia-treatedpulmonary artery smooth muscle cells May contribute to theregulation of the duration of both the action potential ofcardiomyocytes and the heart ventricular repolarization QTinterval Contributes to the pronounced pro-apoptotic potassiumcurrent surge during neuronal apoptotic cell death in response tooxidative injury May confer neuroprotection in response tohypoxia/ischemic insults by suppressing pyramidal neuronshyperexcitability in hippocampal and cortical regions (Bysimilarity) Promotes trafficking of KCNG3, KCNH1 and KCNH2 to thecell surface membrane, presumably by forming heterotetramericchannels with these subunits (PubMed:12060745) Plays a role inthe calcium-dependent recruitment and release of fusion-competentvesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of thefusion machinery in a pore-independent manner (By similarity)
Catalytic Activity (UniProt annotation)
N/A
Protein Sequence
MPAGMTKHGSRSTSSLPPEPMEIVRSKACSRRVRLNVGGLAHEVLWRTLDRLPRTRLGKLRDCNTHDSLLEVCDDYSLDD NEYFFDRHPGAFTSILNFYRTGRLHMMEEMCALSFSQELDYWGIDEIYLESCCQARYHQKKEQMNEELKREAETLREREG EEFDNTCCAEKRKKLWDLLEKPNSSVAAKILAIISIMFIVLSTIALSLNTLPELQSLDEFGQSTDNPQLAHVEAVCIAWF TMEYLLRFLSSPKKWKFFKGPLNAIDLLAILPYYVTIFLTESNKSVLQFQNVRRVVQIFRIMRILRILKLARHSTGLQSL GFTLRRSYNELGLLILFLAMGIMIFSSLVFFAEKDEDDTKFKSIPASFWWATITMTTVGYGDIYPKTLLGKIVGGLCCIA GVLVIALPIPIIVNNFSEFYKEQKRQEKAIKRREALERAKRNGSIVSMNMKDAFARSIEMMDIVVEKNGENMGKKDKVQD NHLSPNKWKWTKRTLSETSSSKSFETKEQGSPEKARSSSSPQHLNVQQLEDMYNKMAKTQSQPILNTKESAAQSKPKEEL EMESIPSPVAPLPTRTEGVIDMRSMSSIDSFISCATDFPEATRFSHSPLTSLPSKTGGSTAPEVGWRGALGASGGRFVEA NPSPDASQHSSFFIESPKSSMKTNNPLKLRALKVNFMEGDPSPLLPVLGMYHDPLRNRGSAAAAVAGLECATLLDKAVLS PESSIYTTASAKTPPRSPEKHTAIAFNFEAGVHQYIDADTDDEGQLLYSVDSSPPKSLPGSTSPKFSTGTRSEKNHFESS PLPTSPKFLRQNCIYSTEALTGKGPSGQEKCKLENHISPDVRVLPGGGAHGSTRDQSI

Motif information from Eukaryotic Linear Motif atlas (ELM)

Gene Ontology (P: Process; F: Function and C: Component terms)

KEGG Pathway
Reactome Pathway

Pathway ID	Pathway Name	Pathway Description (KEGG)
R-HSA-1296072	Voltage gated Potassium channels.	Voltage-gated K+ channels (Kv) determine the excitability of heart, brain and skeletal muscle cells. Kv form octameric channel with alpha subunits that forms the pore of the channel and associated beta subunits. The alpha subunits associate with beta subunits with a stoichiometry of alpha4beta4.The alpha subunits have been classified into 12 families, 1-12 with several representatives from each family. Members of Kv 1-4 form both homotetramers and heterotetramers, however, members of Kv 5-12 form functional heterotetramers. Kv's are expressed in the axon, at axon nodes, somatodendritic sites and axon termini
R-HSA-381676	Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.	Glucagon-like Peptide-1 (GLP-1) is secreted by L-cells in the intestine in response to glucose and fatty acids. GLP-1 circulates to the beta cells of the pancreas where it binds a G-protein coupled receptor, GLP-1R, on the plasma membrane. The binding activates the heterotrimeric G-protein G(s), causing the alpha subunit of G(s) to exchange GDP for GTP and dissociate from the beta and gamma subunits.The activated G(s) alpha subunit interacts with Adenylyl Cyclase VIII (Adenylate Cyclase VIII, AC VIII) and activates AC VIII to produce cyclic AMP (cAMP). cAMP then has two effects: 1) cAMP activates Protein Kinase A (PKA), and 2) cAMP activates Epac1 and Epac2, two guanyl nucleotide exchange factors.Binding of cAMP to PKA causes the catalytic subunits of PKA to dissociate from the regulatory subunits and become an active kinase. PKA is known to enhance insulin secretion by closing ATP-sensitive potassium channels, closing voltage-gated potassium channels, releasing calcium from the endoplasmic reticulum, and affecting insulin secretory granules. The exact mechanisms for PKA's action are not fully known. After prolonged increases in cAMP, PKA translocates to the nucleus where it regulates the PDX-1 and CREB transcription factors, activating transcription of the insulin gene.cAMP produced by AC VIII also activates Epac1 and Epac2, which catalyze the exchange of GTP for GDP on G-proteins, notably Rap1A.. Rap1A regulates insulin secretory granules and is believed to activate the Raf/MEK/ERK mitogenic pathway leading to proliferation of beta cells. The Epac proteins also interact with RYR calcium channels on the endoplasmic reticulum, the SUR1 subunits of ATP-sensitive potassium channels, and the Piccolo:Rim2 calcium sensor at the plasma membrane