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WTF4_SCHKA
ID   WTF4_SCHKA              Reviewed;         337 AA.
AC   A0A218N034;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   27-SEP-2017, sequence version 1.
DT   25-MAY-2022, entry version 12.
DE   RecName: Full=Meiotic driver wtf4 {ECO:0000303|PubMed:28631612};
GN   Name=wtf4 {ECO:0000303|PubMed:28631612, ECO:0000312|EMBL:ASF62178.1};
OS   Schizosaccharomyces kambucha (Fission yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC   Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC   Schizosaccharomyces.
OX   NCBI_TaxID=204045 {ECO:0000312|EMBL:ASF62178.1};
RN   [1] {ECO:0000312|EMBL:ASF62178.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION (ISOFORMS 1 AND 2), SUBCELLULAR
RP   LOCATION (ISOFORMS 1 AND 2), ALTERNATIVE INITIATION (ISOFORMS 1 AND 2),
RP   DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 1-MET--TYR-44.
RX   PubMed=28631612; DOI=10.7554/elife.26033;
RA   Nuckolls N.L., Bravo Nunez M.A., Eickbush M.T., Young J.M., Lange J.J.,
RA   Yu J.S., Smith G.R., Jaspersen S.L., Malik H.S., Zanders S.E.;
RT   "wtf genes are prolific dual poison-antidote meiotic drivers.";
RL   Elife 6:e26033-e26033(2017).
RN   [2] {ECO:0000305}
RP   SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX   PubMed=30475921; DOI=10.1371/journal.pgen.1007836;
RA   Bravo Nunez M.A., Lange J.J., Zanders S.E.;
RT   "A suppressor of a wtf poison-antidote meiotic driver acts via mimicry of
RT   the driver's antidote.";
RL   PLoS Genet. 14:e1007836-e1007836(2018).
RN   [3] {ECO:0000305}
RP   FUNCTION (ISOFORMS 1 AND 2), INTERACTION OF ISOFORMS 1 AND 2, SUBCELLULAR
RP   LOCATION (ISOFORMS 1 AND 2), AND MUTAGENESIS OF ASN-312.
RX   PubMed=33108274; DOI=10.7554/elife.55694;
RA   Nuckolls N.L., Mok A.C., Lange J.J., Yi K., Kandola T.S., Hunn A.M.,
RA   McCroskey S., Snyder J.L., Bravo Nunez M.A., McClain M., McKinney S.A.,
RA   Wood C., Halfmann R., Zanders S.E.;
RT   "The wtf4 meiotic driver utilizes controlled protein aggregation to
RT   generate selective cell death.";
RL   Elife 9:e55694-e55694(2020).
RN   [4] {ECO:0000305}
RP   FUNCTION (ISOFORMS 1 AND 2).
RX   PubMed=32790622; DOI=10.7554/elife.57936;
RA   Bravo Nunez M.A., Sabbarini I.M., Eide L.E., Unckless R.L., Zanders S.E.;
RT   "Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe
RT   due to wtf meiotic drivers.";
RL   Elife 9:e57936-e57936(2020).
RN   [5] {ECO:0000305}
RP   SUBCELLULAR LOCATION (ISOFORMS 1 AND 2).
RX   PubMed=32032353; DOI=10.1371/journal.pgen.1008350;
RA   Bravo Nunez M.A., Sabbarini I.M., Eickbush M.T., Liang Y., Lange J.J.,
RA   Kent A.M., Zanders S.E.;
RT   "Dramatically diverse Schizosaccharomyces pombe wtf meiotic drivers all
RT   display high gamete-killing efficiency.";
RL   PLoS Genet. 16:e1008350-e1008350(2020).
CC   -!- FUNCTION: Promotes unequal transmission of alleles from the parental
CC       zygote to progeny spores by acting as poison/antidote system where the
CC       poison and antidote proteins are produced from the same locus; the
CC       poison component is trans-acting and targets all spores within an ascus
CC       whereas the antidote component is spore-specific, leading to poisoning
CC       of all progeny that do not inherit the allele.
CC       {ECO:0000269|PubMed:28631612, ECO:0000269|PubMed:32790622,
CC       ECO:0000269|PubMed:33108274}.
CC   -!- FUNCTION: [Isoform 1]: Localizes isoform 2 to the vacuole thereby
CC       facilitating its degradation. {ECO:0000269|PubMed:28631612,
CC       ECO:0000269|PubMed:32790622, ECO:0000269|PubMed:33108274}.
CC   -!- FUNCTION: [Isoform 2]: Forms toxic aggregates that disrupt spore
CC       maturation. {ECO:0000269|PubMed:28631612, ECO:0000269|PubMed:32790622,
CC       ECO:0000269|PubMed:33108274}.
CC   -!- SUBUNIT: Homomer (PubMed:33108274). Forms protein aggregates
CC       (PubMed:33108274). The two isoforms can interact with each other and
CC       with themselves (PubMed:33108274). High sequence similarity is required
CC       for their interaction (By similarity). {ECO:0000250|UniProtKB:O74420,
CC       ECO:0000269|PubMed:33108274}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 1]: Spore membrane {ECO:0000255,
CC       ECO:0000269|PubMed:28631612, ECO:0000269|PubMed:30475921,
CC       ECO:0000269|PubMed:32032353, ECO:0000269|PubMed:33108274}; Multi-pass
CC       membrane protein {ECO:0000255}. Vacuole membrane {ECO:0000255,
CC       ECO:0000269|PubMed:33108274}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Contained within spores expressing the isoform and
CC       localizes isoform 2 to the vacuole. {ECO:0000269|PubMed:28631612,
CC       ECO:0000269|PubMed:30475921, ECO:0000269|PubMed:33108274}.
CC   -!- SUBCELLULAR LOCATION: [Isoform 2]: Ascus epiplasm
CC       {ECO:0000269|PubMed:28631612, ECO:0000269|PubMed:30475921,
CC       ECO:0000269|PubMed:33108274}. Cytoplasm {ECO:0000269|PubMed:28631612}.
CC       Spore membrane {ECO:0000269|PubMed:28631612,
CC       ECO:0000269|PubMed:30475921, ECO:0000269|PubMed:32032353,
CC       ECO:0000269|PubMed:33108274}; Multi-pass membrane protein
CC       {ECO:0000255}. Vacuole membrane {ECO:0000255,
CC       ECO:0000269|PubMed:33108274}; Multi-pass membrane protein
CC       {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000255,
CC       ECO:0000269|PubMed:33108274}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localizes in trans to all spores within an ascus.
CC       Localization to the spore vacuole is dependent on isoform 1.
CC       {ECO:0000269|PubMed:28631612, ECO:0000269|PubMed:30475921,
CC       ECO:0000269|PubMed:33108274}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative initiation; Named isoforms=2;
CC       Name=1; Synonyms=Antidote {ECO:0000303|PubMed:28631612}, Suppressor
CC       {ECO:0000305};
CC         IsoId=A0A218N034-1; Sequence=Displayed;
CC       Name=2; Synonyms=Poison {ECO:0000303|PubMed:28631612};
CC         IsoId=A0A218N034-2; Sequence=VSP_060931;
CC   -!- DEVELOPMENTAL STAGE: Expressed during meiosis and sporulation (at
CC       protein level). Present in spores (at protein level).
CC       {ECO:0000269|PubMed:28631612}.
CC   -!- DISRUPTION PHENOTYPE: Sensitises cells to wtf4-encoded poison.
CC       {ECO:0000269|PubMed:28631612}.
CC   -!- SIMILARITY: Belongs to the WTF family. {ECO:0000305}.
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DR   EMBL; KY652738; ASF62178.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A218N034; -.
DR   GO; GO:0072324; C:ascus epiplasm; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR   GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005773; C:vacuole; IDA:UniProtKB.
DR   GO; GO:0110134; P:meiotic drive; IDA:UniProtKB.
DR   GO; GO:0072665; P:protein localization to vacuole; IDA:UniProtKB.
DR   InterPro; IPR004982; WTF.
DR   Pfam; PF03303; WTF; 1.
PE   1: Evidence at protein level;
KW   Alternative initiation; Cytoplasm; Endoplasmic reticulum; Membrane; Toxin;
KW   Transmembrane; Transmembrane helix; Vacuole.
FT   CHAIN           1..337
FT                   /note="Meiotic driver wtf4"
FT                   /id="PRO_0000452254"
FT   TRANSMEM        89..109
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        119..139
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        149..169
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        176..196
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        210..230
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        234..254
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..33
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..44
FT                   /note="MKNKDYPLRSSMDELSTKNDNEIDLEKGPLPEYNSEDESTLPPY -> ML
FT                   (in isoform 2)"
FT                   /evidence="ECO:0000269|PubMed:28631612"
FT                   /id="VSP_060931"
FT   MUTAGEN         1..44
FT                   /note="MKNKDYPLRSSMDELSTKNDNEIDLEKGPLPEYNSEDESTLPPY->ML:
FT                   Abolishes suppressor activity."
FT                   /evidence="ECO:0000269|PubMed:28631612"
FT   MUTAGEN         312
FT                   /note="N->NAFGGIGNAFGGIGNTIGR: Loss of interaction with
FT                   wild-type isoforms."
FT                   /evidence="ECO:0000269|PubMed:33108274"
SQ   SEQUENCE   337 AA;  38171 MW;  8B400B3636ACF72E CRC64;
     MKNKDYPLRS SMDELSTKND NEIDLEKGPL PEYNSEDEST LPPYSEIWKY IKTVSEDSST
     GPTETTNPNV ERRQEFKDSH PNIYSLLRLL ISVLAVIVVF FTAWVCVNPL EKSIFGKVAF
     FVTIGITCPI LLITIFCFFE TWTQAVAQCI KVTVIFLAQC VKVTAVGLYN SREKWVVIIW
     LLWVVICYTL FLRSKFGNLN LNKALICSTC SISAALLLFL LYVRLPFWTL KHMFSGLFQV
     LGVQSCVVIV TKGLTYLFDK HIDATGYEIE ASSLFVIGNF LFFYEMECPG ALKRMPKFIR
     NGIASFLEGI GNIGRAFRGA NDNNDIPLGE MEVESEV
 
 
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