KCAB2_MOUSE
ID KCAB2_MOUSE Reviewed; 367 AA.
AC P62482; P97381; Q60942; Q64284;
DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Voltage-gated potassium channel subunit beta-2;
DE EC=1.1.1.- {ECO:0000250|UniProtKB:P62483};
DE AltName: Full=K(+) channel subunit beta-2;
DE AltName: Full=Kv-beta-2;
DE AltName: Full=Neuroimmune protein F5;
GN Name=Kcnab2; Synonyms=Ckbeta2, I2rf5, Kcnb3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH KCNA5, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Fibroblast;
RX PubMed=8576199; DOI=10.1074/jbc.271.5.2406;
RA Uebele V.N., England S.K., Chaudhary A., Tamkun M.M., Snyders D.J.;
RT "Functional differences in Kv1.5 currents expressed in mammalian cell lines
RT are due to the presence of endogenous Kv beta 2.1 subunits.";
RL J. Biol. Chem. 271:2406-2412(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INTERACTION WITH KCNA5 AND
RP KCNB2, AND FUNCTION.
RC TISSUE=Brain cortex;
RX PubMed=8824288; DOI=10.1074/jbc.271.42.26341;
RA Fink M., Duprat F., Lesage F., Heurteaux C., Romey G., Barhanin J.,
RA Lazdunski M.;
RT "A new K+ channel beta subunit to specifically enhance Kv2.2 (CDRK)
RT expression.";
RL J. Biol. Chem. 271:26341-26348(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=C57BL/6N; TISSUE=Brain, and T-cell;
RX PubMed=1573677; DOI=10.1002/jnr.490310208;
RA Cohen J.A., Arai M., Prak E.L., Brooks S.A., Young L.H., Prystowsky M.B.;
RT "Characterization of a novel mRNA expressed by neurons in mature brain.";
RL J. Neurosci. Res. 31:273-284(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF TYR-90.
RX PubMed=11825900; DOI=10.1074/jbc.m111465200;
RA McCormack K., Connor J.X., Zhou L., Ho L.L., Ganetzky B., Chiu S.Y.,
RA Messing A.;
RT "Genetic analysis of the mammalian K+ channel beta subunit Kvbeta 2
RT (Kcnab2).";
RL J. Biol. Chem. 277:13219-13228(2002).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=15720404; DOI=10.1111/j.1601-183x.2004.00094.x;
RA Connor J.X., McCormack K., Pletsch A., Gaeta S., Ganetzky B., Chiu S.Y.,
RA Messing A.;
RT "Genetic modifiers of the Kv beta2-null phenotype in mice.";
RL Genes Brain Behav. 4:77-88(2005).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT SER-20 AND SER-112,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=21357749; DOI=10.1083/jcb.201007113;
RA Vacher H., Yang J.W., Cerda O., Autillo-Touati A., Dargent B.,
RA Trimmer J.S.;
RT "Cdk-mediated phosphorylation of the Kvbeta2 auxiliary subunit regulates
RT Kv1 channel axonal targeting.";
RL J. Cell Biol. 192:813-824(2011).
RN [9]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=21209188; DOI=10.1523/jneurosci.2634-10.2011;
RA Perkowski J.J., Murphy G.G.;
RT "Deletion of the mouse homolog of KCNAB2, a gene linked to monosomy 1p36,
RT results in associative memory impairments and amygdala hyperexcitability.";
RL J. Neurosci. 31:46-54(2011).
RN [10]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-28, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Cytoplasmic potassium channel subunit that modulates the
CC characteristics of the channel-forming alpha-subunits (PubMed:8576199).
CC Contributes to the regulation of nerve signaling, and prevents neuronal
CC hyperexcitability (PubMed:11825900, PubMed:21209188). Promotes
CC expression of the pore-forming alpha subunits at the cell membrane, and
CC thereby increases channel activity (By similarity). Promotes potassium
CC channel closure via a mechanism that does not involve physical
CC obstruction of the channel pore (PubMed:8576199). Modulates the
CC functional properties of KCNA4 (By similarity). Modulates the
CC functional properties of KCNA5 (PubMed:8576199). Enhances KCNB2 channel
CC activity (PubMed:8824288). Modulates the functional properties of KCNA5
CC (PubMed:8576199). Binds NADPH and has NADPH-dependent aldoketoreductase
CC activity (By similarity). Has broad substrate specificity and can
CC catalyze the reduction of methylglyoxal, 9,10-phenanthrenequinone,
CC prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-
CC trans-2-nonenal (in vitro) (By similarity).
CC {ECO:0000250|UniProtKB:P62483, ECO:0000269|PubMed:11825900,
CC ECO:0000269|PubMed:21209188, ECO:0000269|PubMed:8576199,
CC ECO:0000269|PubMed:8824288}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interaction with tetrameric
CC potassium channel alpha subunits gives rise to a heterooctamer (By
CC similarity). Identified in potassium channel complexes containing
CC KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1 and KCNAB2 (By similarity).
CC Interacts with KCNA1 (By similarity). Interacts with KCNA2 (By
CC similarity). Interacts with KCNA4 and KCND3 (By similarity). Interacts
CC (in unphosphorylated form) with MAPRE1 (By similarity). Interacts with
CC KCNA5 (PubMed:8576199, PubMed:8824288). Interacts with KCNB2
CC (PubMed:8824288). Forms a ternary complex with SQSTM1 and PRKCZ (By
CC similarity). {ECO:0000250|UniProtKB:P62483,
CC ECO:0000250|UniProtKB:Q13303, ECO:0000269|PubMed:8576199,
CC ECO:0000269|PubMed:8824288}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P62483}.
CC Membrane {ECO:0000269|PubMed:21357749, ECO:0000269|PubMed:8576199};
CC Peripheral membrane protein {ECO:0000305}; Cytoplasmic side
CC {ECO:0000305}. Cell membrane {ECO:0000250|UniProtKB:P62483}; Peripheral
CC membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Cell
CC projection, axon {ECO:0000269|PubMed:11825900}. Synapse, synaptosome
CC {ECO:0000269|PubMed:21357749}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:P62483}. Note=Recruited to the cytoplasmic side
CC of the cell membrane via its interaction with pore-forming potassium
CC channel alpha subunits. Associates with microtubules when
CC unphosphorylated. {ECO:0000250|UniProtKB:P62483}.
CC -!- TISSUE SPECIFICITY: Detected in brain (PubMed:21357749). Detected at
CC basket cell terminals in cerebellum and in the juxtaparanodal region of
CC nodes of Ranvier (at protein level) (PubMed:11825900). Strongest
CC expression in brain and eye. Highest levels in brain detected in
CC brainstem and diencephalon. Strong expression also detected in lung and
CC heart. Moderate expression in kidney, T-lymphocytes and skeletal
CC muscle. {ECO:0000269|PubMed:11825900, ECO:0000269|PubMed:1573677,
CC ECO:0000269|PubMed:21357749, ECO:0000269|PubMed:8824288}.
CC -!- DEVELOPMENTAL STAGE: Not detected prior to birth, low levels of
CC expression detected from postnatal days 1 to 7. Expression reaches
CC adult levels by postnatal day 21. {ECO:0000269|PubMed:1573677}.
CC -!- DOMAIN: In contrast to KCNAB1, the shorter N-terminal domain of KCNAB2
CC cannot mediate closure of delayed rectifier potassium channels by
CC physically obstructing the pore. {ECO:0000250|UniProtKB:Q13303}.
CC -!- PTM: Phosphorylated by PRKCZ; may be regulated by incorporation in a
CC complex composed of PRKCZ and SQSTM1. {ECO:0000250|UniProtKB:P62483}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice are born at the expected Mendelian
CC rate and are fertile, but exhibit occasional seizures and have a median
CC lifespan of 255 days, which is much shorter than the 400 days typically
CC observed for heterozygotes (PubMed:11825900). The reduction in lifespan
CC depends strongly on the genetic background; median survival is 138 days
CC for B6 mice, 255 days for B6/129 mice and over 400 days for 129/SvEv
CC mice (PubMed:15720404). Mice exhibit whole body tremors after swimming
CC in cold water, which is not observed in wild-type (PubMed:11825900).
CC The whole body tremors observed after swimming in cold water differ
CC between mouse strains; the observed differences are largely due to
CC differences in the decrease of the core body temperature
CC (PubMed:15720404). Mice lacking both KCNAB1 and KCNAB2 have a median
CC survival of 114 days instead of the 255 days observed for mice lacking
CC only KCNAB2, but show no aggravation of the whole body tremors observed
CC after swimming in cold water (PubMed:15720404). Mice lacking KCNAB2
CC show subtle deficits in associative learning and aberrant excitability
CC of neurons from the lateral amygdala (PubMed:21209188).
CC {ECO:0000269|PubMed:11825900, ECO:0000269|PubMed:15720404,
CC ECO:0000269|PubMed:21209188}.
CC -!- SIMILARITY: Belongs to the shaker potassium channel beta subunit
CC family. {ECO:0000305}.
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DR EMBL; L48983; AAB00829.1; -; mRNA.
DR EMBL; U65592; AAB37263.1; -; mRNA.
DR EMBL; U31908; AAA75174.1; -; mRNA.
DR EMBL; BC039178; AAH39178.1; -; mRNA.
DR CCDS; CCDS19000.1; -.
DR RefSeq; NP_001239585.1; NM_001252656.1.
DR RefSeq; NP_034728.2; NM_010598.3.
DR RefSeq; XP_017175485.1; XM_017319996.1.
DR AlphaFoldDB; P62482; -.
DR SMR; P62482; -.
DR BioGRID; 200884; 14.
DR IntAct; P62482; 8.
DR MINT; P62482; -.
DR STRING; 10090.ENSMUSP00000125058; -.
DR iPTMnet; P62482; -.
DR PhosphoSitePlus; P62482; -.
DR SwissPalm; P62482; -.
DR EPD; P62482; -.
DR jPOST; P62482; -.
DR MaxQB; P62482; -.
DR PaxDb; P62482; -.
DR PeptideAtlas; P62482; -.
DR PRIDE; P62482; -.
DR ProteomicsDB; 269182; -.
DR ABCD; P62482; 3 sequenced antibodies.
DR Antibodypedia; 4538; 165 antibodies from 23 providers.
DR DNASU; 16498; -.
DR Ensembl; ENSMUST00000105648; ENSMUSP00000101273; ENSMUSG00000028931.
DR Ensembl; ENSMUST00000160884; ENSMUSP00000125058; ENSMUSG00000028931.
DR GeneID; 16498; -.
DR KEGG; mmu:16498; -.
DR UCSC; uc008wal.2; mouse.
DR CTD; 8514; -.
DR MGI; MGI:109239; Kcnab2.
DR VEuPathDB; HostDB:ENSMUSG00000028931; -.
DR eggNOG; KOG1575; Eukaryota.
DR GeneTree; ENSGT00940000157867; -.
DR InParanoid; P62482; -.
DR OMA; PPYSLFW; -.
DR OrthoDB; 1106773at2759; -.
DR PhylomeDB; P62482; -.
DR TreeFam; TF324563; -.
DR Reactome; R-MMU-1296072; Voltage gated Potassium channels.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 16498; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Kcnab2; mouse.
DR PRO; PR:P62482; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P62482; protein.
DR Bgee; ENSMUSG00000028931; Expressed in dentate gyrus of hippocampal formation granule cell and 175 other tissues.
DR ExpressionAtlas; P62482; baseline and differential.
DR Genevisible; P62482; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0043194; C:axon initial segment; IDA:MGI.
DR GO; GO:0043679; C:axon terminus; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0044224; C:juxtaparanode region of axon; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005874; C:microtubule; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:1990031; C:pinceau fiber; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0034705; C:potassium channel complex; ISS:UniProtKB.
DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISO:MGI.
DR GO; GO:0004033; F:aldo-keto reductase (NADP) activity; ISS:UniProtKB.
DR GO; GO:0015459; F:potassium channel regulator activity; ISS:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IEA:InterPro.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IGI:MGI.
DR GO; GO:0070995; P:NADPH oxidation; ISS:UniProtKB.
DR GO; GO:0050905; P:neuromuscular process; IMP:UniProtKB.
DR GO; GO:0098900; P:regulation of action potential; IBA:GO_Central.
DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISS:UniProtKB.
DR GO; GO:2000008; P:regulation of protein localization to cell surface; ISS:UniProtKB.
DR Gene3D; 3.20.20.100; -; 1.
DR InterPro; IPR005983; K_chnl_volt-dep_bsu_KCNAB.
DR InterPro; IPR005399; K_chnl_volt-dep_bsu_KCNAB-rel.
DR InterPro; IPR005401; K_chnl_volt-dep_bsu_KCNAB2.
DR InterPro; IPR023210; NADP_OxRdtase_dom.
DR InterPro; IPR036812; NADP_OxRdtase_dom_sf.
DR PANTHER; PTHR43150; PTHR43150; 1.
DR Pfam; PF00248; Aldo_ket_red; 1.
DR PRINTS; PR01579; KCNAB2CHANEL.
DR PRINTS; PR01577; KCNABCHANNEL.
DR SUPFAM; SSF51430; SSF51430; 1.
DR TIGRFAMs; TIGR01293; Kv_beta; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Ion channel; Ion transport; Membrane; Methylation; NADP; Oxidoreductase;
KW Phosphoprotein; Potassium; Potassium transport; Reference proteome;
KW Synapse; Synaptosome; Transport; Voltage-gated channel.
FT CHAIN 1..367
FT /note="Voltage-gated potassium channel subunit beta-2"
FT /id="PRO_0000148747"
FT ACT_SITE 90
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 56..57
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 63
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 85
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 90
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 188..189
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 214
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 243..248
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 254
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT BINDING 323..329
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P62483"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13303"
FT MOD_RES 20
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21357749"
FT MOD_RES 28
FT /note="Asymmetric dimethylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 28
FT /note="Omega-N-methylarginine; alternate"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 31
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13303"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21357749"
FT MOD_RES 124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13303"
FT MUTAGEN 90
FT /note="Y->F: No detectable phenotype."
FT /evidence="ECO:0000269|PubMed:11825900"
FT CONFLICT 64
FT /note="I -> L (in Ref. 2; AAB37263)"
FT /evidence="ECO:0000305"
FT CONFLICT 99..100
FT /note="LG -> FR (in Ref. 3; AAA75174)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="A -> G (in Ref. 2; AAB37263)"
FT /evidence="ECO:0000305"
FT CONFLICT 266
FT /note="S -> L (in Ref. 3; AAA75174)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 367 AA; 41021 MW; 5303FD1411B324FC CRC64;
MYPESTTGSP ARLSLRQTGS PGMIYSTRYG SPKRQLQFYR NLGKSGLRVS CLGLGTWVTF
GGQITDEMAE HLMTLAYDNG INLFDTAEVY AAGKAEVVLG NIIKKKGWRR SSLVITTKIF
WGGKAETERG LSRKHIIEGL KASLERLQLE YVDVVFANRP DPNTPMEETV RAMTHVINQG
MAMYWGTSRW SSMEIMEAYS VARQFNLIPP ICEQAEYHMF QREKVEVQLP ELFHKIGVGA
MTWSPLACGI VSGKYDSGIP PYSRASLKGY QWLKDKILSE EGRRQQAKLK ELQAIAERLG
CTLPQLAIAW CLRNEGVSSV LLGASNAEQL MENIGAIQVL PKLSSSIVHE IDSILGNKPY
SKKDYRS
