ID   PFKA1_KOMPG             Reviewed;         989 AA.
AC   Q92448; C4R0J9;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   09-JUL-2014, sequence version 2.
DT   27-MAR-2024, entry version 122.
DE   RecName: Full=ATP-dependent 6-phosphofructokinase subunit alpha {ECO:0000255|HAMAP-Rule:MF_03184};
DE            EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE   AltName: Full=ATP-dependent 6-phosphofructokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE            Short=ATP-PFK 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE            Short=Phosphofructokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
DE   AltName: Full=Glucose-induced selective autophagy 1 protein;
DE   AltName: Full=Phosphohexokinase 1 {ECO:0000255|HAMAP-Rule:MF_03184};
GN   Name=PFK1; Synonyms=GSA1; OrderedLocusNames=PAS_chr2-1_0402;
OS   Komagataella phaffii (strain GS115 / ATCC 20864) (Yeast) (Pichia pastoris).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Phaffomycetaceae; Komagataella.
OX   NCBI_TaxID=644223;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF ASP-361.
RC   STRAIN=GS115 / ATCC 20864;
RX   PubMed=9296392; DOI=10.1242/jcs.110.16.1935;
RA   Yuan W., Tuttle D.L., Shi Y.J., Ralph G.S., Dunn W.A. Jr.;
RT   "Glucose-induced microautophagy in Pichia pastoris requires the alpha-
RT   subunit of phosphofructokinase.";
RL   J. Cell Sci. 110:1935-1945(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=GS115 / ATCC 20864;
RX   PubMed=19465926; DOI=10.1038/nbt.1544;
RA   De Schutter K., Lin Y.-C., Tiels P., Van Hecke A., Glinka S.,
RA   Weber-Lehmann J., Rouze P., Van de Peer Y., Callewaert N.;
RT   "Genome sequence of the recombinant protein production host Pichia
RT   pastoris.";
RL   Nat. Biotechnol. 27:561-566(2009).
CC   -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate to
CC       fructose 1,6-bisphosphate by ATP, the first committing step of
CC       glycolysis (By similarity). Involved in the modulation of glucose-
CC       induced microautophagy of peroxisomes independent of its ability to
CC       metabolize glucose intermediates. {ECO:0000255|HAMAP-Rule:MF_03184,
CC       ECO:0000269|PubMed:9296392}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + beta-D-fructose 6-phosphate = ADP + beta-D-fructose 1,6-
CC         bisphosphate + H(+); Xref=Rhea:RHEA:16109, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:32966, ChEBI:CHEBI:57634,
CC         ChEBI:CHEBI:456216; EC=2.7.1.11; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03184};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-
CC         Rule:MF_03184};
CC   -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or fructose
CC       2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
CC       {ECO:0000255|HAMAP-Rule:MF_03184}.
CC   -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC       phosphate and glycerone phosphate from D-glucose: step 3/4.
CC       {ECO:0000255|HAMAP-Rule:MF_03184}.
CC   -!- SUBUNIT: Heterododecamer of 4 alpha, 4 beta and 4 gamma chains. The
CC       gamma chain bridges the N-terminal halves of the alpha and beta
CC       subunits (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC   -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA) family.
CC       ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E'
CC       sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
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DR   EMBL; U73376; AAB97871.1; -; Genomic_DNA.
DR   EMBL; FN392320; CAY69023.1; -; Genomic_DNA.
DR   RefSeq; XP_002491303.1; XM_002491258.1.
DR   AlphaFoldDB; Q92448; -.
DR   SMR; Q92448; -.
DR   STRING; 644223.Q92448; -.
DR   MoonDB; Q92448; Curated.
DR   MoonProt; Q92448; -.
DR   EnsemblFungi; CAY69023; CAY69023; PAS_chr2-1_0402.
DR   GeneID; 8198870; -.
DR   KEGG; ppa:PAS_chr2-1_0402; -.
DR   eggNOG; KOG2440; Eukaryota.
DR   HOGENOM; CLU_011053_0_0_1; -.
DR   InParanoid; Q92448; -.
DR   OMA; WHNLGGS; -.
DR   OrthoDB; 374214at2759; -.
DR   UniPathway; UPA00109; UER00182.
DR   Proteomes; UP000000314; Chromosome 2.
DR   GO; GO:0005945; C:6-phosphofructokinase complex; TAS:CAFA.
DR   GO; GO:0005739; C:mitochondrion; IEA:EnsemblFungi.
DR   GO; GO:0003872; F:6-phosphofructokinase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:EnsemblFungi.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IMP:CAFA.
DR   GO; GO:0006002; P:fructose 6-phosphate metabolic process; IEA:EnsemblFungi.
DR   GO; GO:0061615; P:glycolytic process through fructose-6-phosphate; IMP:CAFA.
DR   GO; GO:0000426; P:micropexophagy; IMP:CAFA.
DR   GO; GO:0060151; P:peroxisome localization; IMP:CAFA.
DR   GO; GO:1901098; P:positive regulation of autophagosome maturation; IMP:CAFA.
DR   GO; GO:0051453; P:regulation of intracellular pH; IEA:EnsemblFungi.
DR   Gene3D; 3.10.180.90; -; 1.
DR   Gene3D; 3.40.50.450; -; 2.
DR   Gene3D; 3.40.50.460; Phosphofructokinase domain; 2.
DR   HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR   InterPro; IPR009161; 6-Pfructokinase_euk.
DR   InterPro; IPR022953; ATP_PFK.
DR   InterPro; IPR040712; Pfk_N.
DR   InterPro; IPR015912; Phosphofructokinase_CS.
DR   InterPro; IPR000023; Phosphofructokinase_dom.
DR   InterPro; IPR035966; PKF_sf.
DR   NCBIfam; TIGR02478; 6PF1K_euk; 1.
DR   PANTHER; PTHR13697:SF57; ATP-DEPENDENT 6-PHOSPHOFRUCTOKINASE SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR13697; PHOSPHOFRUCTOKINASE; 1.
DR   Pfam; PF00365; PFK; 2.
DR   Pfam; PF18468; Pfk_N; 1.
DR   PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR   PRINTS; PR00476; PHFRCTKINASE.
DR   SUPFAM; SSF53784; Phosphofructokinase; 2.
DR   PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 1.
PE   1: Evidence at protein level;
KW   Allosteric enzyme; ATP-binding; Cytoplasm; Glycolysis; Kinase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Reference proteome; Transferase.
FT   CHAIN           1..989
FT                   /note="ATP-dependent 6-phosphofructokinase subunit alpha"
FT                   /id="PRO_0000112042"
FT   REGION          1..585
FT                   /note="N-terminal catalytic PFK domain 1"
FT   REGION          586..599
FT                   /note="Interdomain linker"
FT   REGION          600..989
FT                   /note="C-terminal regulatory PFK domain 2"
FT   ACT_SITE        361
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         220
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         283..284
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         313..316
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         314
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         359..361
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         396
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         403..405
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         460
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         487
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="2"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         493..496
FT                   /ligand="beta-D-fructose 6-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57634"
FT                   /ligand_label="1"
FT                   /ligand_note="ligand shared with subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         670
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         727..731
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         765
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="2"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         772..774
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         832
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         858
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="2"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         864..867
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   BINDING         963
FT                   /ligand="beta-D-fructose 2,6-bisphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58579"
FT                   /ligand_label="1"
FT                   /ligand_note="allosteric activator; ligand shared with
FT                   subunit beta"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT   MUTAGEN         361
FT                   /note="D->S: Abolishes catalytic activity, but not the
FT                   ability to modulate glucose-induced microautophagy of
FT                   peroxisomes."
FT                   /evidence="ECO:0000269|PubMed:9296392"
FT   CONFLICT        178
FT                   /note="S -> SK (in Ref. 1; AAB97871)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        570
FT                   /note="D -> E (in Ref. 1; AAB97871)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        914
FT                   /note="Y -> C (in Ref. 1; AAB97871)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   989 AA;  108817 MW;  6708A34ED94C9DD4 CRC64;
     MPEPSISALS FTSFVTNDDK LFEETFNFYT KLGFHATRSY VKDNRSDFEL TGISTDSIKE
     IWLESFPLSE VVETSAGREL RKPLQESVGY QSEALLGYSP YQSDGVVIKL RLSNHDLQKN
     KDLPGEVTFF TASIDKLRAK LIEIGAEIIP SEIDLVEFST KDPMGDVISF SSYPSLSSKK
     ITSPDFFLHP KKEVRSQESI VEQVKSEEGK KKIAIITSGG DAPGMNAAVR AVTRAGIFYG
     CKVYACYEGY TGLVKGGDML KELQWQDVRG LLSIGGTIIG TARSKEFRER WGRLQACYNM
     VSNGIDALVV CGGDGSLTGA DLFRNEWPEL IKELLGEGKI TKEQYETHRN LTIVGLVGSI
     DNDMCGTDST IGAYSSLERI IELVDYIDAT AASHSRAFVV EVMGRHCGWL GLMSGIATGA
     DYIFIPERPP SETNWKDDLK KVCLRHREKG RRKTTVIVAE GAIDDQLNPI TSEEVKDVLV
     EIGLDTRITR LGHVQRGGAP CAFDRFLATV QGVDAVRAVL ESTPAIPSPV ISILENKIVR
     QPLVESVAQT KTVSDAIEAK DFDKALKLRD QEFATSYESF LSVSKYDDGS YLVPESSRLN
     IAIIHVGAPT SALNPATRVA TLNSLAKGHR VFAIRNGFAG LIRHGAVREL NWIDVEDWHN
     TGGSEIGTNR SLPSDDMGTV AYYFQQYKFD GLIIIGGFEA FTALYQLDAA RAQYPIFNIP
     MCCLPATVSN NVPGTEYSLG SDTCLNTLSG YCDAVKQSAS ASRRRTFVVE VQGGYSGYLA
     SYAGLITGAL AVYTPENPIN LQTVQEDIEL LTRTYEEDDG KNRSGKIFIH NEKASKVYTT
     DLIAAIIGEA GKGRFESRTA VPGHVQQGKS PSSIDRVNAC RLAIKCCNFI EDANFQVKHN
     ANLSADERHL RFFYDDGVKT SAVSGKSSVI DDNTSVVIGI QGSEVTFTPV KQLWEKETHH
     KWRKGKNVHW EQLNIVSDLL SGRLSIRTT
//