KCNU1_HUMAN
ID KCNU1_HUMAN Reviewed; 1149 AA.
AC A8MYU2;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 127.
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=KCa5;
DE AltName: Full=Slowpoke homolog 3;
GN Name=KCNU1; Synonyms=KCNMA3, KCNMC1, SLO3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [2]
RP 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 [3]
RP X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) OF 330-1063, FUNCTION, AND PH
RP 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(+). May
CC represent 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:23129643}.
CC -!- SUBUNIT: Homotetramer; which constitutes the calcium-activated
CC potassium channel. May interact with LRRC52; this interaction may
CC change channel gating properties, such as shifting gating to more
CC negative potentials at a given pH. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Testis-specific. {ECO:0000269|PubMed:9452476}.
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 {ECO:0000250}.
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; AC124076; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS55220.1; -.
DR RefSeq; NP_001027006.2; NM_001031836.2.
DR PDB; 4HPF; X-ray; 3.40 A; A/B=330-1062.
DR PDBsum; 4HPF; -.
DR AlphaFoldDB; A8MYU2; -.
DR SMR; A8MYU2; -.
DR DIP; DIP-60091N; -.
DR STRING; 9606.ENSP00000382770; -.
DR ChEMBL; CHEMBL4524132; -.
DR GlyGen; A8MYU2; 1 site, 1 N-linked glycan (1 site).
DR iPTMnet; A8MYU2; -.
DR PhosphoSitePlus; A8MYU2; -.
DR BioMuta; KCNU1; -.
DR MassIVE; A8MYU2; -.
DR PaxDb; A8MYU2; -.
DR PeptideAtlas; A8MYU2; -.
DR PRIDE; A8MYU2; -.
DR ProteomicsDB; 2426; -.
DR Antibodypedia; 57826; 73 antibodies from 13 providers.
DR DNASU; 157855; -.
DR Ensembl; ENST00000399881.8; ENSP00000382770.3; ENSG00000215262.8.
DR GeneID; 157855; -.
DR KEGG; hsa:157855; -.
DR MANE-Select; ENST00000399881.8; ENSP00000382770.3; NM_001031836.3; NP_001027006.2.
DR UCSC; uc010lvw.5; human.
DR CTD; 157855; -.
DR DisGeNET; 157855; -.
DR GeneCards; KCNU1; -.
DR HGNC; HGNC:18867; KCNU1.
DR HPA; ENSG00000215262; Tissue enriched (testis).
DR MIM; 615215; gene.
DR neXtProt; NX_A8MYU2; -.
DR OpenTargets; ENSG00000215262; -.
DR PharmGKB; PA38727; -.
DR VEuPathDB; HostDB:ENSG00000215262; -.
DR eggNOG; KOG1420; Eukaryota.
DR GeneTree; ENSGT00940000161817; -.
DR InParanoid; A8MYU2; -.
DR OMA; ACYKRNE; -.
DR OrthoDB; 858812at2759; -.
DR PhylomeDB; A8MYU2; -.
DR TreeFam; TF314283; -.
DR PathwayCommons; A8MYU2; -.
DR Reactome; R-HSA-1300642; Sperm Motility And Taxes.
DR SignaLink; A8MYU2; -.
DR BioGRID-ORCS; 157855; 9 hits in 1058 CRISPR screens.
DR ChiTaRS; KCNU1; human.
DR GeneWiki; KCNU1; -.
DR GenomeRNAi; 157855; -.
DR Pharos; A8MYU2; Tbio.
DR PRO; PR:A8MYU2; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; A8MYU2; protein.
DR Bgee; ENSG00000215262; Expressed in sperm and 51 other tissues.
DR ExpressionAtlas; A8MYU2; baseline and differential.
DR Genevisible; A8MYU2; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005267; F:potassium channel activity; IEA:UniProtKB-KW.
DR GO; GO:0005244; F:voltage-gated ion channel activity; IEA:UniProtKB-KW.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0022414; P:reproductive process; IBA:GO_Central.
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 3D-structure; Cell membrane; Ion channel; Ion transport; Membrane;
KW Potassium; Potassium channel; Potassium transport; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1149
FT /note="Potassium channel subfamily U member 1"
FT /id="PRO_0000349186"
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..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical; Name=Segment S2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..163
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 164..184
FT /note="Helical; Name=Segment S3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 185..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..291
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 292..312
FT /note="Helical; Name=Segment S6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 313..1149
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 711..731
FT /note="Segment S9"
FT REGION 828..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 895..915
FT /note="Segment S10"
FT REGION 1118..1149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 276..279
FT /note="Selectivity for potassium"
FT COMPBIAS 1125..1139
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 175
FT /note="D -> N (in dbSNP:rs1111125)"
FT /id="VAR_060148"
FT VARIANT 768
FT /note="W -> R (in dbSNP:rs28608091)"
FT /id="VAR_053868"
FT VARIANT 916
FT /note="N -> S (in dbSNP:rs16885577)"
FT /id="VAR_053869"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 342..349
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:4HPF"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 386..388
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 397..403
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 405..407
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 408..413
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 422..439
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 445..448
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 452..456
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 457..460
FT /evidence="ECO:0007829|PDB:4HPF"
FT TURN 466..469
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 471..473
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 475..488
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 492..498
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 512..521
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 539..549
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 585..591
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 593..597
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 598..600
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 685..690
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 697..700
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 716..720
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 732..735
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 736..739
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 745..747
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 751..755
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 757..763
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 764..767
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 771..778
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 783..788
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 791..793
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 795..800
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 815..825
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 861..864
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 868..870
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 871..878
FT /evidence="ECO:0007829|PDB:4HPF"
FT TURN 882..884
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 889..891
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 893..897
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 899..901
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 903..908
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 909..915
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 917..928
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 962..966
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 968..971
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 972..975
FT /evidence="ECO:0007829|PDB:4HPF"
FT HELIX 982..993
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 996..1003
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 1015..1020
FT /evidence="ECO:0007829|PDB:4HPF"
FT STRAND 1032..1037
FT /evidence="ECO:0007829|PDB:4HPF"
SQ SEQUENCE 1149 AA; 129543 MW; BA527F41498B6AA7 CRC64;
MFQTKLRNET WEDLPKMSCT TEIQAAFILS SFVTFFSGLI ILLIFRLIWR SVKKWQIIKG
TGIILELFTS GTIARSHVRS LHFQGQFRDH IEMLLSAQTF VGQVLVILVF VLSIGSLIIY
FINSADPVGS CSSYEDKTIP IDLVFNAFFS FYFGLRFMAA DDKIKFWLEM NSIVDIFTIP
PTFISYYLKS NWLGLRFLRA LRLLELPQIL QILRAIKTSN SVKFSKLLSI ILSTWFTAAG
FIHLVENSGD PWLKGRNSQN ISYFESIYLV MATTSTVGFG DVVAKTSLGR TFIMFFTLGS
LILFANYIPE MVELFANKRK YTSSYEALKG KKFIVVCGNI TVDSVTAFLR NFLRDKSGEI
NTEIVFLGET PPSLELETIF KCYLAYTTFI SGSAMKWEDL RRVAVESAEA CLIIANPLCS
DSHAEDISNI MRVLSIKNYD STTRIIIQIL QSHNKVYLPK IPSWNWDTGD NIICFAELKL
GFIAQGCLVP GLCTFLTSLF VEQNKKVMPK QTWKKHFLNS MKNKILTQRL SDDFAGMSFP
EVARLCFLKM HLLLIAIEYK SLFTDGFCGL ILNPPPQVRI RKNTLGFFIA ETPKDVRRAL
FYCSVCHDDV FIPELITNCG CKSRSRQHIT VPSVKRMKKC LKGISSRISG QDSPPRVSAS
TSSISNFTTR TLQHDVEQDS DQLDSSGMFH WCKPTSLDKV TLKRTGKSKY KFRNHIVACV
FGDAHSAPMG LRNFVMPLRA SNYTRKELKD IVFIGSLDYL QREWRFLWNF PQIYILPGCA
LYSGDLHAAN IEQCSMCAVL SPPPQPSSNQ TLVDTEAIMA TLTIGSLQID SSSDPSPSVS
EETPGYTNGH NEKSNCRKVP ILTELKNPSN IHFIEQLGGL EGSLQETNLH LSTAFSTGTV
FSGSFLDSLL ATAFYNYHVL ELLQMLVTGG VSSQLEQHLD KDKVYGVADS CTSLLSGRNR
CKLGLLSLHE TILSDVNPRN TFGQLFCGSL DLFGILCVGL YRIIDEEELN PENKRFVITR
PANEFKLLPS DLVFCAIPFS TACYKRNEEF SLQKSYEIVN KASQTTETHS DTNCPPTIDS
VTETLYSPVY SYQPRTNSLS FPKQIAWNQS RTNSIISSQI PLGDNAKENE RKTSDEVYDE
DPFAYSEPL
