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   24-JAN-2024, entry version 155.
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).
RN   [10]
RP   MUTAGENESIS OF HIS-720.
RX   PubMed=35551387; DOI=10.1093/humrep/deac102;
RA   Liu R., Yan Z., Fan Y., Qu R., Chen B., Li B., Wu L., Wu H., Mu J.,
RA   Zhao L., Wang W., Dong J., Zeng Y., Li Q., Wang L., Sang Q., Zhang Z.,
RA   Kuang Y.;
RT   "Bi-allelic variants in KCNU1 cause impaired acrosome reactions and male
RT   infertility.";
RL   Hum. Reprod. 37:1394-1405(2022).
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; 10090-ENSMUSP00000096457; -.
DR   ProteomicsDB; 268968; -.
DR   ABCD; O54982; 1 sequenced antibody.
DR   DNASU; 16532; -.
DR   GeneID; 16532; -.
DR   KEGG; mmu:16532; -.
DR   AGR; MGI:1202300; -.
DR   CTD; 157855; -.
DR   MGI; MGI:1202300; Kcnu1.
DR   eggNOG; KOG1420; Eukaryota.
DR   InParanoid; O54982; -.
DR   OrthoDB; 2902976at2759; -.
DR   PhylomeDB; O54982; -.
DR   Reactome; R-MMU-1300642; Sperm Motility And Taxes.
DR   BioGRID-ORCS; 16532; 1 hit in 79 CRISPR screens.
DR   ChiTaRS; Kcnu1; mouse.
DR   PRO; PR:O54982; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; O54982; Protein.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0034702; C:monoatomic ion channel complex; 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:0051649; P:establishment of localization in cell; IMP:MGI.
DR   GO; GO:0071805; P:potassium ion transmembrane transport; IBA:GO_Central.
DR   GO; GO:0006813; P:potassium ion transport; IMP:MGI.
DR   GO; GO:0050821; P:protein stabilization; IMP:MGI.
DR   GO; GO:0022414; P:reproductive process; IMP:MGI.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 2.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR003929; K_chnl_BK_asu.
DR   InterPro; IPR047871; K_chnl_Slo-like.
DR   InterPro; IPR048735; Slowpoke-like_C.
DR   PANTHER; PTHR10027; CALCIUM-ACTIVATED POTASSIUM CHANNEL ALPHA CHAIN; 1.
DR   PANTHER; PTHR10027:SF23; POTASSIUM CHANNEL SUBFAMILY U MEMBER 1; 1.
DR   Pfam; PF03493; BK_channel_a; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   Pfam; PF21014; Slowpoke_C; 1.
DR   PRINTS; PR01449; BKCHANNELA.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 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"
FT   MUTAGEN         720
FT                   /note="H->R: Homozygous males are infertile. In mutant
FT                   sperm, the protein is barely detectable by Western blot."
FT                   /evidence="ECO:0000269|PubMed:35551387"
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
//