ID   FPK1_YEAST              Reviewed;         893 AA.
AC   P53739; D6W1M2;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   02-SEP-2026, entry version 204.
DE   RecName: Full=Flippase kinase 1;
DE            EC=2.7.11.1;
GN   Name=FPK1; OrderedLocusNames=YNR047W; ORFNames=N3449;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169873; DOI=10.1038/387s093;
RA   Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K.,
RA   Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K.,
RA   Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M.,
RA   Beinhauer J.D., Boskovic J., Buitrago M.J., Bussereau F., Coster F.,
RA   Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F.,
RA   Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C.,
RA   Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A.,
RA   Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H.,
RA   Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L.,
RA   Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R.,
RA   Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D.,
RA   Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A.,
RA   Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C.,
RA   Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F.,
RA   Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G.,
RA   Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M.,
RA   Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its
RT   evolutionary implications.";
RL   Nature 387:93-98(1997).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [3]
RP   FUNCTION.
RX   PubMed=11337509; DOI=10.1074/jbc.m103436200;
RA   Burchett S.A., Scott A., Errede B., Dohlman H.G.;
RT   "Identification of novel pheromone-response regulators through systematic
RT   overexpression of 120 protein kinases in yeast.";
RL   J. Biol. Chem. 276:26472-26478(2001).
RN   [4]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [5]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-414, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ADR376;
RX   PubMed=17330950; DOI=10.1021/pr060559j;
RA   Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA   Elias J.E., Gygi S.P.;
RT   "Large-scale phosphorylation analysis of alpha-factor-arrested
RT   Saccharomyces cerevisiae.";
RL   J. Proteome Res. 6:1190-1197(2007).
RN   [7]
RP   FUNCTION.
RX   PubMed=18199685; DOI=10.1091/mbc.e07-07-0646;
RA   Nakano K., Yamamoto T., Kishimoto T., Noji T., Tanaka K.;
RT   "Protein kinases Fpk1p and Fpk2p are novel regulators of phospholipid
RT   asymmetry.";
RL   Mol. Biol. Cell 19:1783-1797(2008).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-185; SER-300;
RP   SER-414 AND SER-462, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140; SER-144; SER-171;
RP   SER-175; SER-300; SER-414 AND SER-462, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
RN   [10]
RP   FUNCTION, PHOSPHORYLATION BY YPK1, AND ACTIVITY REGULATION.
RX   PubMed=19966303; DOI=10.1073/pnas.0912497106;
RA   Roelants F.M., Baltz A.G., Trott A.E., Fereres S., Thorner J.;
RT   "A protein kinase network regulates the function of aminophospholipid
RT   flippases.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:34-39(2010).
RN   [11]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=33060204; DOI=10.1074/jbc.ra120.014794;
RA   Jain B.K., Roland B.P., Graham T.R.;
RT   "Exofacial membrane composition and lipid metabolism regulates plasma
RT   membrane P4-ATPase substrate specificity.";
RL   J. Biol. Chem. 295:17997-18009(2020).
CC   -!- FUNCTION: Flippase activator that phosphorylates DNF1 and DNF2 and
CC       which is involved in the generation of phospholipid asymmetry in
CC       membranes by the inward translocation of phospholipids and in the
CC       retrieval pathway from early endosomes to the trans-Golgi network
CC       (TGN). Also phosphorylates the N-terminal half of YPK1. Involved in
CC       pheromone-response. {ECO:0000269|PubMed:11337509,
CC       ECO:0000269|PubMed:18199685, ECO:0000269|PubMed:19966303}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP +
CC         H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC         COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] +
CC         ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-
CC         COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC   -!- ACTIVITY REGULATION: Down-regulated by YKP1 phosphorylation. This
CC       effect is counteracted in the presence of mannosyl-
CC       inositolphosphorylceramide (MIPC). {ECO:0000269|PubMed:19966303}.
CC   -!- INTERACTION:
CC       P53739; P32660: DNF1; NbExp=2; IntAct=EBI-9813, EBI-3121;
CC       P53739; P12688: YPK1; NbExp=2; IntAct=EBI-9813, EBI-29473;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Cell
CC       membrane {ECO:0000269|PubMed:14562095}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:14562095}.
CC   -!- PTM: The N-terminal non-catalytic domain is phosphorylated by YPK1.
CC       {ECO:0000269|PubMed:19966303}.
CC   -!- DISRUPTION PHENOTYPE: Simultaneous knockout of KIN82 leads to decreased
CC       phosphatidylcholine and glucosylceramide transport into the cell.
CC       {ECO:0000269|PubMed:33060204}.
CC   -!- MISCELLANEOUS: Present with 752 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC       kinase family. KIN82 subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR   EMBL; Z71662; CAA96328.1; -; Genomic_DNA.
DR   EMBL; BK006947; DAA10588.1; -; Genomic_DNA.
DR   PIR; S63378; S63378.
DR   RefSeq; NP_014445.1; NM_001183224.1.
DR   AlphaFoldDB; P53739; -.
DR   SMR; P53739; -.
DR   BioGRID; 35872; 165.
DR   DIP; DIP-6427N; -.
DR   FunCoup; P53739; 364.
DR   IntAct; P53739; 13.
DR   MINT; P53739; -.
DR   STRING; 4932.YNR047W; -.
DR   iPTMnet; P53739; -.
DR   PaxDb; 4932-YNR047W; -.
DR   PeptideAtlas; P53739; -.
DR   EnsemblFungi; YNR047W_mRNA; YNR047W; YNR047W.
DR   GeneID; 855783; -.
DR   KEGG; sce:YNR047W; -.
DR   AGR; SGD:S000005330; -.
DR   SGD; S000005330; FPK1.
DR   VEuPathDB; FungiDB:YNR047W; -.
DR   eggNOG; KOG0610; Eukaryota.
DR   HOGENOM; CLU_000288_84_2_1; -.
DR   InParanoid; P53739; -.
DR   OMA; SHRAFFK; -.
DR   OrthoDB; 432483at2759; -.
DR   BioCyc; YEAST:G3O-33354-MONOMER; -.
DR   BioGRID-ORCS; 855783; 10 hits in 13 CRISPR screens.
DR   PRO; PR:P53739; -.
DR   Proteomes; UP000002311; Chromosome XIV.
DR   RNAct; P53739; protein.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0043332; C:mating projection tip; IDA:SGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0004672; F:protein kinase activity; IDA:SGD.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:SGD.
DR   GO; GO:0045332; P:phospholipid translocation; IBA:GO_Central.
DR   GO; GO:2000370; P:positive regulation of clathrin-dependent endocytosis; IMP:SGD.
DR   GO; GO:0061092; P:positive regulation of phospholipid translocation; IGI:SGD.
DR   GO; GO:0000749; P:response to pheromone triggering conjugation with cellular fusion; IMP:SGD.
DR   CDD; cd05574; STKc_phototropin_like; 1.
DR   FunFam; 1.10.510.10:FF:000121; Serine/threonine-protein kinase nrc-2; 1.
DR   FunFam; 3.30.200.20:FF:000078; Serine/threonine-protein kinase nrc-2; 1.
DR   Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR000961; AGC-kinase_C.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR45637; FLIPPASE KINASE 1-RELATED; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Cytoplasm; Kinase; Lipid transport; Membrane;
KW   Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Serine/threonine-protein kinase; Transferase; Transport.
FT   CHAIN           1..893
FT                   /note="Flippase kinase 1"
FT                   /id="PRO_0000086154"
FT   DOMAIN          496..777
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          778..861
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   REGION          1..124
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          129..148
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          163..243
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          334..480
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          874..893
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..23
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        24..42
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        49..62
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        76..87
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        96..122
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        206..216
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        228..237
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        334..355
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        370..380
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        381..399
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        422..439
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        884..893
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        621
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         502..510
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         525
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         140
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   MOD_RES         144
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         171
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         175
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   MOD_RES         185
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MOD_RES         300
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
FT   MOD_RES         414
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17330950,
FT                   ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT   MOD_RES         462
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18407956,
FT                   ECO:0007744|PubMed:19779198"
SQ   SEQUENCE   893 AA;  100546 MW;  26AF74EE956F80DB CRC64;
     MAGHHHEHEQ ERDHEQEHEH DSLQRPTTGS ERTRSISFSK LLTRSWKRNA SSSNNMSVSS
     VNLYSDPENS RESDHNNSGS EGQSSRFSKL KSMFQSGNSS KNASAHNSSQ SSLEGDSASS
     SSKLRYVKPM TSVANASPAS PPLSPTIPET DVLQTPKMVH IDQHEHEREH SNCGSPIMLS
     SSSFSPTVAR TGTGRRRSPS TPIMPSQNSN NSSSTSAIRP NNYRHHSGSQ GFSSNNPFRE
     RAGTVRSSNP YFAYQGLPTH AMSSHDLDEG FQPYANGSGI HFLSTPTSKT NSLTNTKNLS
     NLSLNEIKEN EEVQEFNNED FFFHDIPKDL SLKDTLNGSP SRGSSKSPTI TQTFPSIIVG
     FDNEYEEDNN NDKHDEKEEQ QTTTDNKTRN LSPTKQNGKA THPRIKIPLR RAASEPNGLQ
     LASATSPTSS SARKTSGSSN INDKIPGQSV PPPNSFFPQE PSPKISDFPE PRRSRRLRTK
     SFSNKFQDIM VGPQSFEKIR LLGQGDVGKV FLVREKKTNR VYALKVLSKD EMIKRNKIKR
     VLTEQEILAT SNHPFIVTLY HSFQSEDYLY LCMEYCMGGE FFRALQTRKT KCICEDDARF
     YASEVTAALE YLHLLGFIYR DLKPENILLH QSGHIMLSDF DLSIQAKDSK VPVVKGSAQS
     TLVDTKICSD GFRTNSFVGT EEYIAPEVIR GNGHTAAVDW WTLGILIYEM LFGFTPFKGD
     NTNETFTNIL KNEVSFPNNN EISRTCKDLI KKLLTKNESK RLGCKMGAAD VKKHPFFKKV
     QWSLLRNQEP PLIPVLSEDG YDFAKLSSNK KRQTSQDSHK HLDEQEKNMF EERVEYDDEV
     SEDDPFHDFN SMSLMEQDNN SMIYGNTNSY GKIAYTPNSN RSRSNSHRTF FKR
//