FPK1_YEAST
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 03-AUG-2022, entry version 186.
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;
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).
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). Phosphorylates also 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=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; 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=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC 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 -!- 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; 161.
DR DIP; DIP-6427N; -.
DR IntAct; P53739; 11.
DR MINT; P53739; -.
DR STRING; 4932.YNR047W; -.
DR iPTMnet; P53739; -.
DR MaxQB; P53739; -.
DR PaxDb; P53739; -.
DR PRIDE; P53739; -.
DR EnsemblFungi; YNR047W_mRNA; YNR047W; YNR047W.
DR GeneID; 855783; -.
DR KEGG; sce:YNR047W; -.
DR SGD; S000005330; FPK1.
DR VEuPathDB; FungiDB:YNR047W; -.
DR eggNOG; KOG0610; Eukaryota.
DR GeneTree; ENSGT00940000175956; -.
DR HOGENOM; CLU_000288_84_2_1; -.
DR InParanoid; P53739; -.
DR OMA; NYTEEHA; -.
DR BioCyc; YEAST:G3O-33354-MON; -.
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:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IGI:SGD.
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:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0000749; P:response to pheromone triggering conjugation with cellular fusion; IMP:SGD.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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..27
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..124
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 366..384
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..399
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 418..449
FT /note="Polar 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
