KCNU1_MOUSE
ID KCNU1_MOUSE Reviewed; 1121 AA.
AC O54982;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Potassium channel subfamily U member 1;
DE AltName: Full=Calcium-activated potassium channel subunit alpha-3;
DE AltName: Full=Calcium-activated potassium channel, subfamily M subunit alpha-3;
DE AltName: Full=Pore-forming subunit of the sperm-specific alkalization activated K(+) current;
DE Short=KSper;
DE AltName: Full=Slowpoke homolog 3;
DE Short=mSlo3;
DE AltName: Full=pH-sensitive maxi potassium channel;
GN Name=Kcnu1; Synonyms=Kcnma3, Ksper, Slo3;
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, AND TISSUE SPECIFICITY.
RX PubMed=9452476; DOI=10.1074/jbc.273.6.3509;
RA Schreiber M., Wei A., Yuan A., Gaut J., Saito M., Salkoff L.;
RT "Slo3, a novel pH-sensitive K+ channel from mammalian spermatocytes.";
RL J. Biol. Chem. 273:3509-3516(1998).
RN [2]
RP FUNCTION.
RX PubMed=11696614; DOI=10.1085/jgp.118.5.589;
RA Shi J., Cui J.;
RT "Intracellular Mg(2+) enhances the function of BK-type Ca(2+)-activated
RT K(+) channels.";
RL J. Gen. Physiol. 118:589-606(2001).
RN [3]
RP FUNCTION.
RX PubMed=11723163; DOI=10.1085/jgp.118.6.711;
RA Moss B.L., Magleby K.L.;
RT "Gating and conductance properties of BK channels are modulated by the S9-
RT S10 tail domain of the alpha subunit. A study of mSlo1 and mSlo3 wild-type
RT and chimeric channels.";
RL J. Gen. Physiol. 118:711-734(2001).
RN [4]
RP FUNCTION.
RX PubMed=15201331; DOI=10.1523/jneurosci.1296-04.2004;
RA Xia X.-M., Zhang X., Lingle C.J.;
RT "Ligand-dependent activation of Slo family channels is defined by
RT interchangeable cytosolic domains.";
RL J. Neurosci. 24:5585-5591(2004).
RN [5]
RP FUNCTION.
RX PubMed=16940555; DOI=10.1085/jgp.200609552;
RA Zhang X., Zeng X., Lingle C.J.;
RT "Slo3 K+ channels: voltage and pH dependence of macroscopic currents.";
RL J. Gen. Physiol. 128:317-336(2006).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF PHE-279.
RX PubMed=16940554; DOI=10.1085/jgp.200609551;
RA Zhang X., Zeng X., Xia X.-M., Lingle C.J.;
RT "pH-regulated Slo3 K+ channels: properties of unitary currents.";
RL J. Gen. Physiol. 128:301-315(2006).
RN [7]
RP FUNCTION, IDENTIFICATION AS KSPER, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=21427226; DOI=10.1073/pnas.1100240108;
RA Zeng X.H., Yang C., Kim S.T., Lingle C.J., Xia X.M.;
RT "Deletion of the Slo3 gene abolishes alkalization-activated K+ current in
RT mouse spermatozoa.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:5879-5884(2011).
RN [8]
RP INTERACTION WITH LRRC52, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=22084117; DOI=10.1073/pnas.1111104108;
RA Yang C., Zeng X.H., Zhou Y., Xia X.M., Lingle C.J.;
RT "LRRC52 (leucine-rich-repeat-containing protein 52), a testis-specific
RT auxiliary subunit of the alkalization-activated Slo3 channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:19419-19424(2011).
RN [9]
RP FUNCTION, AND PH DEPENDENCE.
RX PubMed=23129643; DOI=10.1073/pnas.1215078109;
RA Leonetti M.D., Yuan P., Hsiung Y., Mackinnon R.;
RT "Functional and structural analysis of the human SLO3 pH- and voltage-gated
RT K+ channel.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19274-19279(2012).
CC -!- FUNCTION: Testis-specific potassium channel activated by both
CC intracellular pH and membrane voltage that mediates export of K(+).
CC Represents the primary spermatozoan K(+) current. In contrast to
CC KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for
CC fertility. May play an important role in sperm osmoregulation required
CC for the acquisition of normal morphology and motility when faced with
CC osmotic challenges, such as those experienced after mixing with seminal
CC fluid and entry into the vagina. {ECO:0000269|PubMed:11696614,
CC ECO:0000269|PubMed:11723163, ECO:0000269|PubMed:15201331,
CC ECO:0000269|PubMed:16940554, ECO:0000269|PubMed:16940555,
CC ECO:0000269|PubMed:21427226, ECO:0000269|PubMed:23129643,
CC ECO:0000269|PubMed:9452476}.
CC -!- SUBUNIT: Homotetramer; which constitutes the calcium-activated
CC potassium channel. May interact with LRRC52; this interaction may
CC change some channel gating properties, such as shifting gating to more
CC negative potentials at a given pH.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22084117};
CC Multi-pass membrane protein {ECO:0000269|PubMed:22084117}.
CC -!- TISSUE SPECIFICITY: Testis-specific. Mainly expressed in spermatocytes.
CC {ECO:0000269|PubMed:21427226, ECO:0000269|PubMed:9452476}.
CC -!- DEVELOPMENTAL STAGE: Very low expression levels in testis before
CC postnatal day 25 (P25). Levels strongly increase between P25 and P30,
CC and then remain high from P30 through P150.
CC {ECO:0000269|PubMed:22084117}.
CC -!- DOMAIN: The S4 segment, which is characterized by a series of
CC positively charged amino acids at every third position, is part of the
CC voltage-sensor. {ECO:0000250}.
CC -!- DOMAIN: The pore-forming domain (also referred as P region) is imbedded
CC into the membrane, and forms the selectivity filter of the pore. It
CC contains the signature sequence of potassium channels that displays
CC selectivity to potassium (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The RCK N-terminal domain mediates the homotetramerization,
CC thereby promoting the assembly of monomers into functional potassium
CC channel. {ECO:0000250}.
CC -!- DOMAIN: The C-terminal cytosolic region confers the pH-dependence.
CC -!- DISRUPTION PHENOTYPE: Mutant males are infertile, but their sperm
CC retains some fertility within in vitro fertilization assays.
CC Spermatozoa exhibit a higher incidence of morphological abnormalities
CC as compared to wild-type, accentuated by hypotonic challenge and
CC deficits in motility, in the absence of bicarbonate.
CC {ECO:0000269|PubMed:21427226}.
CC -!- SIMILARITY: Belongs to the potassium channel family. Calcium-activated
CC (TC 1.A.1.3) subfamily. KCa5.1/KCNU1 sub-subfamily. {ECO:0000305}.
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DR EMBL; AF039213; AAB99742.2; -; mRNA.
DR CCDS; CCDS52530.1; -.
DR PIR; T42383; T42383.
DR RefSeq; NP_032458.3; NM_008432.3.
DR AlphaFoldDB; O54982; -.
DR SMR; O54982; -.
DR STRING; 10090.ENSMUSP00000096457; -.
DR TCDB; 1.A.1.3.5; the voltage-gated ion channel (vic) superfamily.
DR PhosphoSitePlus; O54982; -.
DR PaxDb; O54982; -.
DR PRIDE; O54982; -.
DR ProteomicsDB; 268968; -.
DR ABCD; O54982; 1 sequenced antibody.
DR DNASU; 16532; -.
DR GeneID; 16532; -.
DR KEGG; mmu:16532; -.
DR CTD; 157855; -.
DR MGI; MGI:1202300; Kcnu1.
DR eggNOG; KOG1420; Eukaryota.
DR InParanoid; O54982; -.
DR OrthoDB; 858812at2759; -.
DR PhylomeDB; O54982; -.
DR Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR BioGRID-ORCS; 16532; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Kcnu1; mouse.
DR PRO; PR:O54982; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O54982; protein.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005267; F:potassium channel activity; IMP:MGI.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI.
DR GO; GO:0006813; P:potassium ion transport; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; IMP:MGI.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0022414; P:reproductive process; IMP:MGI.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR003929; K_chnl_BK_asu.
DR Pfam; PF03493; BK_channel_a; 1.
DR Pfam; PF00520; Ion_trans; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Ion channel; Ion transport; Membrane; Potassium;
KW Potassium channel; Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1121
FT /note="Potassium channel subfamily U member 1"
FT /id="PRO_0000349188"
FT TOPO_DOM 1..24
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 25..45
FT /note="Helical; Name=Segment S0"
FT /evidence="ECO:0000255"
FT TOPO_DOM 46..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical; Name=Segment S1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..137
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 187..188
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 189..209
FT /note="Helical; Voltage-sensor; Name=Segment S4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 210..226
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 227..247
FT /note="Helical; Name=Segment S5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 248..259
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT INTRAMEM 260..282
FT /note="Pore-forming; Name=P region"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..290
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..311
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 312..1121
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 339..482
FT /note="RCK N-terminal"
FT REGION 480..500
FT /note="Segment S7"
FT REGION 537..557
FT /note="Segment S8"
FT REGION 716..736
FT /note="Segment S9"
FT REGION 836..858
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 900..920
FT /note="Segment S1"
FT REGION 1052..1076
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..279
FT /note="Selectivity for potassium"
FT COMPBIAS 1052..1075
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 279
FT /note="F->Y: Does not induce any change in single channel
FT conductance or variance in open current levels."
FT /evidence="ECO:0000269|PubMed:16940554"
SQ SEQUENCE 1121 AA; 126870 MW; 4D7E0425B97B47A1 CRC64;
MSQTLLDSLN QKELTETSCT IEIQAAFILS SLATFFGGLI ILFLFRIALK SSRSWKYVKG
PRGLLELFSS RRIEANPLRK LYFHGVFRQR IEMLLSAQTV VGQVLVILVF VLSIGSLVIY
FINSMDPVRR CSSYEDKIVH GDLSFNAFFS FYFGLRFWAA EDKIKFWLEM NSIVDIFTIP
PTFISYYLKS NWLGLRFLRA LRLLELPKIL QILQVIKTSN SVKLSKLLSI VISTWFTAAG
FLHLVENSGD PWLNGRNSQT MSYFESIYLV TATMSTVGFG DVVAKTSLGR IFIVFFTLGS
LILFANYIPE MVELFSTRKK YTKPYEAVKG KKFIVVCGNI TVDSVTAFLR NFLHWKSGEI
NIEIVFLGET LPCLELETLL KCHTSCTNFV CGTALKFEDL KRVAVENSEA CLILANHFCS
DLHDEDNSNI MRVLSIKNYY PQTRVIIQIL QSQNKVFLSK IPNWDWSAGD NILCFAELKL
GFIAQGCLVP GLCTFLTTLF IEQNQKVFPK HPWQKHFLNG LKNKILTQRL SNDFVGMTFP
QVSRLCFVKL NLMLIAIQHK PFFHSCCTLI LNPSSQVRLN KDTLGFFIAD SSKAVKRAFF
YCSNCHSDVC NPELIGKCNC KIKSRQQLIA PTIMVMKSSL TDFTTSSHIH ASMSTEIHTC
FSREQPSLIT ITTNRPTTND TVDDTDMLDS SGMFHWCRAM PLDKVVLKRS EKAKHEFQNH
IVVCVFGDAQ CTLVGLRNFV MPLRASNYTR QELKDIVFIG SLEYFQREWR FLRNFPKIHI
MPGSALYMGD LIAVNVEQCS MCVILATPYK ALSSQILVDT EAIMATLNIQ SLRITSPTPG
SSKSEVKPSS AFDSKERKQR YKQIPILTEL KNPSNIHFIE QMGGLDGMLK GTSLHLSTSF
STGAVFSDTF LDSLLATSFY NYHVVELLQM LVTGGISSEM EHYLVKEKPY KTTDDYEAIK
SGRTRCKLGL LSLDQTVLSG INPRKTFGQL FCGSLDNFGI LCVGLYRMID EEEPSQEHKR
FVITRPSNEC HLLPSDLVFC AIPFNTTCGK SDSSPSIQAQ NNSTNATTPL AQGSNFFDSH
HADESHDLYP VDDTGERWSQ HHHSRVYPLD TLDASDIVQE K
