PFKAM_HUMAN
ID PFKAM_HUMAN Reviewed; 780 AA.
AC P08237; J3KNX3; Q16814; Q16815; Q6ZTT1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=ATP-dependent 6-phosphofructokinase, muscle type {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=ATP-PFK {ECO:0000255|HAMAP-Rule:MF_03184};
DE Short=PFK-M;
DE EC=2.7.1.11 {ECO:0000255|HAMAP-Rule:MF_03184};
DE AltName: Full=6-phosphofructokinase type A;
DE AltName: Full=Phosphofructo-1-kinase isozyme A;
DE Short=PFK-A;
DE AltName: Full=Phosphohexokinase {ECO:0000255|HAMAP-Rule:MF_03184};
GN Name=PFKM; Synonyms=PFKX;
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 [GENOMIC DNA].
RC TISSUE=Muscle;
RX PubMed=1833270; DOI=10.1016/0378-1119(91)90262-a;
RA Yamasaki T., Nakajima H., Kono N., Hotta K., Yamada K., Imai E.,
RA Kuwajima M., Noguchi T., Tanaka T., Tarui S.;
RT "Structure of the entire human muscle phosphofructokinase-encoding gene: a
RT two-promoter system.";
RL Gene 104:277-282(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2526045; DOI=10.1016/0378-1119(89)90372-7;
RA Sharma P.M., Reddy G.R., Vora S., Babior B.M., McLachlan A.;
RT "Cloning and expression of a human muscle phosphofructokinase cDNA.";
RL Gene 77:177-183(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=2822475; DOI=10.1016/0014-5793(87)80519-7;
RA Nakajima H., Noguchi T., Yamasaki T., Kono N., Tanaka T., Tarui S.;
RT "Cloning of human muscle phosphofructokinase cDNA.";
RL FEBS Lett. 223:113-116(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Thymus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 272-681 (ISOFORM 2).
RC TISSUE=Muscle;
RX PubMed=2140567; DOI=10.1016/s0021-9258(19)38803-9;
RA Sharma P.M., Reddy G.R., Babior B.M., McLachlan A.;
RT "Alternative splicing of the transcript encoding the human muscle isoenzyme
RT of phosphofructokinase.";
RL J. Biol. Chem. 265:9006-9010(1990).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28.
RC TISSUE=Muscle;
RX PubMed=2526044; DOI=10.1016/0378-1119(89)90019-x;
RA Valdez B.C., Chen Z., Sosa M.G., Younathan E.S., Chang S.H.;
RT "Human 6-phosphofructo-1-kinase gene has an additional intron upstream of
RT start codon.";
RL Gene 76:167-169(1989).
RN [9]
RP REVIEW ON GSD7 VARIANTS.
RX PubMed=7550225; DOI=10.1002/humu.1380060102;
RA Raben N., Sherman J.B.;
RT "Mutations in muscle phosphofructokinase gene.";
RL Hum. Mutat. 6:1-6(1995).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-667, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP HYDROXYBUTYRYLATION AT LYS-557.
RX PubMed=29775581; DOI=10.1016/j.molcel.2018.04.011;
RA Huang H., Tang S., Ji M., Tang Z., Shimada M., Liu X., Qi S.,
RA Locasale J.W., Roeder R.G., Zhao Y., Li X.;
RT "p300-mediated lysine 2-hydroxyisobutyrylation regulates glycolysis.";
RL Mol. Cell 70:663-678(2018).
RN [14]
RP VARIANTS GSD7 PRO-39 AND ALA-543.
RX PubMed=7513946;
RA Tsujino S., Servidei S., Tonin P., Shanske S., Azan G., DiMauro S.;
RT "Identification of three novel mutations in non-Ashkenazi Italian patients
RT with muscle phosphofructokinase deficiency.";
RL Am. J. Hum. Genet. 54:812-819(1994).
RN [15]
RP VARIANT GSD7 ASP-209, VARIANTS GLN-100 AND HIS-696, AND CHARACTERIZATION OF
RP VARIANT GSD7 ASP-209.
RX PubMed=7825568;
RA Raben N., Exelbert R., Spiegel R., Sherman J.B., Plotz P., Heinisch J.J.;
RT "Functional expression of human mutant phosphofructokinase in yeast:
RT genetic defects in French Canadian and Swiss patients with
RT phosphofructokinase deficiency.";
RL Am. J. Hum. Genet. 56:131-141(1995).
RN [16]
RP VARIANT GSD7 CYS-686.
RX PubMed=8889589;
RX DOI=10.1002/(sici)1098-1004(1996)8:3<273::aid-humu13>3.0.co;2-#;
RA Hamaguchi T., Nakajima H., Noguchi T., Nakagawa C., Kuwajima M., Kono N.,
RA Tarui S., Matsuzawa Y.;
RT "Novel missense mutation (W686C) of the phosphofructokinase-M gene in a
RT Japanese patient with a mild form of glycogenosis VII.";
RL Hum. Mutat. 8:273-275(1996).
RN [17]
RP VARIANTS GSD7 VAL-57; CYS-180 AND ALA-591.
RX PubMed=22133655; DOI=10.1016/j.nmd.2011.10.022;
RA Musumeci O., Bruno C., Mongini T., Rodolico C., Aguennouz M., Barca E.,
RA Amati A., Cassandrini D., Serlenga L., Vita G., Toscano A.;
RT "Clinical features and new molecular findings in muscle phosphofructokinase
RT deficiency (GSD type VII).";
RL Neuromuscul. Disord. 22:325-330(2012).
RN [18]
RP VARIANT GSD7 GLY-309, AND CHARACTERIZATION OF VARIANT GSD7 GLY-309.
RX PubMed=24427140; DOI=10.3389/fphys.2013.00393;
RA Vives-Corrons J.L., Koralkova P., Grau J.M., Manu Pereira Mdel M.,
RA Van Wijk R.;
RT "First description of phosphofructokinase deficiency in spain:
RT identification of a novel homozygous missense mutation in the PFKM gene.";
RL Front. Physiol. 4:393-393(2013).
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.
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;
CC -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or fructose
CC 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
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: Homo- and heterotetramers (By similarity). Phosphofructokinase
CC (PFK) enzyme functions as a tetramer composed of different combinations
CC of 3 types of subunits, called PFKM (where M stands for Muscle), PFKL
CC (Liver) and PFKP (Platelet). The composition of the PFK tetramer
CC differs according to the tissue type it is present in. In muscles, it
CC is composed of 4 PFKM subunits (also called M4). In the liver, the
CC predominant form is a tetramer of PFKL subunits (L4). In erythrocytes,
CC both PFKM and PFKL subunits randomly tetramerize to form M4, L4 and
CC other combinations (ML3, M2L2, M3L). The kinetic and regulatory
CC properties of the tetrameric enzyme are dependent on the subunit
CC composition, hence can vary across tissues (Probable). Interacts (via
CC C-terminus) with HK1 (via N-terminal spermatogenic cell-specific
CC region) (By similarity). {ECO:0000250|UniProtKB:P47857,
CC ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000305}.
CC -!- INTERACTION:
CC P08237; P17858: PFKL; NbExp=6; IntAct=EBI-514788, EBI-487243;
CC P08237; P08237: PFKM; NbExp=3; IntAct=EBI-514788, EBI-514788;
CC P08237; Q8IUQ4: SIAH1; NbExp=3; IntAct=EBI-514788, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03184}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P08237-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P08237-2; Sequence=VSP_004667;
CC Name=3;
CC IsoId=P08237-3; Sequence=VSP_046125;
CC -!- PTM: GlcNAcylation decreases enzyme activity. {ECO:0000250}.
CC -!- DISEASE: Glycogen storage disease 7 (GSD7) [MIM:232800]: A metabolic
CC disorder characterized by exercise intolerance with associated nausea
CC and vomiting, muscle cramping, exertional myopathy and compensated
CC hemolysis. Short bursts of intense activity are particularly difficult.
CC Severe muscle cramps and myoglobinuria develop after vigorous exercise.
CC {ECO:0000269|PubMed:22133655, ECO:0000269|PubMed:24427140,
CC ECO:0000269|PubMed:7513946, ECO:0000269|PubMed:7825568,
CC ECO:0000269|PubMed:8889589}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of subunits,
CC PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.
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; M59741; AAA82938.1; -; Genomic_DNA.
DR EMBL; M59720; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59721; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59722; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59723; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59724; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59725; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59726; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59727; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59728; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59729; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59730; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59731; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59732; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59733; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59734; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59735; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59736; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59737; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59738; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59739; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M59740; AAA82938.1; JOINED; Genomic_DNA.
DR EMBL; M26066; AAA60068.1; -; mRNA.
DR EMBL; Y00698; CAA68692.1; -; mRNA.
DR EMBL; AK126229; BAC86498.1; -; mRNA.
DR EMBL; AC004801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC074029; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC000534; AAH00534.1; -; mRNA.
DR EMBL; BC012799; AAH12799.1; -; mRNA.
DR EMBL; BC013298; AAH13298.1; -; mRNA.
DR EMBL; BC021203; AAH21203.1; -; mRNA.
DR EMBL; J05533; AAA79220.1; -; mRNA.
DR EMBL; M24925; AAA36436.1; -; Genomic_DNA.
DR CCDS; CCDS53786.1; -. [P08237-3]
DR CCDS; CCDS86295.1; -. [P08237-2]
DR CCDS; CCDS8760.1; -. [P08237-1]
DR PIR; A91605; KIHUFM.
DR RefSeq; NP_000280.1; NM_000289.5. [P08237-1]
DR RefSeq; NP_001160158.1; NM_001166686.1. [P08237-3]
DR RefSeq; NP_001160159.1; NM_001166687.1. [P08237-1]
DR RefSeq; NP_001160160.1; NM_001166688.1. [P08237-1]
DR RefSeq; XP_005269034.1; XM_005268977.1.
DR RefSeq; XP_005269035.1; XM_005268978.2.
DR RefSeq; XP_005269036.1; XM_005268979.1. [P08237-3]
DR RefSeq; XP_011536790.1; XM_011538488.2.
DR RefSeq; XP_016874957.1; XM_017019468.1.
DR PDB; 4OMT; X-ray; 6.00 A; A=1-780.
DR PDBsum; 4OMT; -.
DR AlphaFoldDB; P08237; -.
DR SMR; P08237; -.
DR BioGRID; 111234; 180.
DR ComplexPortal; CPX-1997; 6-phosphofructokinase, M4 homotetramer.
DR ComplexPortal; CPX-2000; 6-phosphofructokinase, ML3 heterotetramer.
DR ComplexPortal; CPX-2001; 6-phosphofructokinase, M2L2 heterotetramer.
DR ComplexPortal; CPX-2002; 6-phosphofructokinase, M3L heterotetramer.
DR IntAct; P08237; 37.
DR MINT; P08237; -.
DR STRING; 9606.ENSP00000345771; -.
DR BindingDB; P08237; -.
DR ChEMBL; CHEMBL3291; -.
DR MoonProt; P08237; -.
DR GlyGen; P08237; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P08237; -.
DR MetOSite; P08237; -.
DR PhosphoSitePlus; P08237; -.
DR SwissPalm; P08237; -.
DR BioMuta; PFKM; -.
DR DMDM; 125126; -.
DR UCD-2DPAGE; P08237; -.
DR EPD; P08237; -.
DR jPOST; P08237; -.
DR MassIVE; P08237; -.
DR MaxQB; P08237; -.
DR PaxDb; P08237; -.
DR PeptideAtlas; P08237; -.
DR PRIDE; P08237; -.
DR ProteomicsDB; 52094; -. [P08237-1]
DR ProteomicsDB; 52095; -. [P08237-2]
DR Antibodypedia; 1061; 478 antibodies from 37 providers.
DR DNASU; 5213; -.
DR Ensembl; ENST00000312352.11; ENSP00000309438.7; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000340802.12; ENSP00000345771.6; ENSG00000152556.17. [P08237-3]
DR Ensembl; ENST00000359794.11; ENSP00000352842.5; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000547587.5; ENSP00000449426.1; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000550345.6; ENSP00000450369.2; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000550924.6; ENSP00000446945.2; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000551339.6; ENSP00000448253.2; ENSG00000152556.17. [P08237-1]
DR Ensembl; ENST00000551804.5; ENSP00000448177.1; ENSG00000152556.17. [P08237-2]
DR GeneID; 5213; -.
DR KEGG; hsa:5213; -.
DR MANE-Select; ENST00000359794.11; ENSP00000352842.5; NM_000289.6; NP_000280.1.
DR UCSC; uc001rrb.3; human. [P08237-1]
DR CTD; 5213; -.
DR DisGeNET; 5213; -.
DR GeneCards; PFKM; -.
DR HGNC; HGNC:8877; PFKM.
DR HPA; ENSG00000152556; Group enriched (skeletal muscle, tongue).
DR MalaCards; PFKM; -.
DR MIM; 232800; phenotype.
DR MIM; 610681; gene.
DR neXtProt; NX_P08237; -.
DR OpenTargets; ENSG00000152556; -.
DR Orphanet; 371; Glycogen storage disease due to muscle phosphofructokinase deficiency.
DR PharmGKB; PA33216; -.
DR VEuPathDB; HostDB:ENSG00000152556; -.
DR eggNOG; KOG2440; Eukaryota.
DR GeneTree; ENSGT00940000155440; -.
DR HOGENOM; CLU_011053_0_0_1; -.
DR InParanoid; P08237; -.
DR OrthoDB; 172878at2759; -.
DR PhylomeDB; P08237; -.
DR TreeFam; TF300411; -.
DR BioCyc; MetaCyc:HS07832-MON; -.
DR BRENDA; 2.7.1.11; 2681.
DR PathwayCommons; P08237; -.
DR Reactome; R-HSA-70171; Glycolysis.
DR SABIO-RK; P08237; -.
DR SignaLink; P08237; -.
DR SIGNOR; P08237; -.
DR UniPathway; UPA00109; UER00182.
DR BioGRID-ORCS; 5213; 19 hits in 1078 CRISPR screens.
DR ChiTaRS; PFKM; human.
DR GeneWiki; PFKM; -.
DR GenomeRNAi; 5213; -.
DR Pharos; P08237; Tbio.
DR PRO; PR:P08237; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P08237; protein.
DR Bgee; ENSG00000152556; Expressed in gluteal muscle and 210 other tissues.
DR ExpressionAtlas; P08237; baseline and differential.
DR Genevisible; P08237; HS.
DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:UniProtKB.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:CAFA.
DR GO; GO:0097228; C:sperm principal piece; IEA:Ensembl.
DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:UniProtKB.
DR GO; GO:0016208; F:AMP binding; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:BHF-UCL.
DR GO; GO:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0048029; F:monosaccharide binding; IBA:GO_Central.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:HGNC-UCL.
DR GO; GO:0061621; P:canonical glycolysis; IBA:GO_Central.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IBA:GO_Central.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:BHF-UCL.
DR GO; GO:0042593; P:glucose homeostasis; IEA:Ensembl.
DR GO; GO:0005980; P:glycogen catabolic process; IEA:Ensembl.
DR GO; GO:0093001; P:glycolysis from storage polysaccharide through glucose-1-phosphate; IEA:Ensembl.
DR GO; GO:0006096; P:glycolytic process; IMP:UniProtKB.
DR GO; GO:0061615; P:glycolytic process through fructose-6-phosphate; IMP:CAFA.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:CAFA.
DR CDD; cd00764; Eukaryotic_PFK; 1.
DR Gene3D; 3.40.50.460; -; 2.
DR HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR InterPro; IPR009161; 6-Pfructokinase_euk.
DR InterPro; IPR022953; ATP_PFK.
DR InterPro; IPR041914; PFK_vert-type.
DR InterPro; IPR015912; Phosphofructokinase_CS.
DR InterPro; IPR000023; Phosphofructokinase_dom.
DR InterPro; IPR035966; PKF_sf.
DR Pfam; PF00365; PFK; 2.
DR PIRSF; PIRSF000533; ATP_PFK_euk; 1.
DR PRINTS; PR00476; PHFRCTKINASE.
DR SUPFAM; SSF53784; SSF53784; 2.
DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1.
DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW ATP-binding; Cytoplasm; Disease variant; Glycogen storage disease;
KW Glycolysis; Glycoprotein; Hydroxylation; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00511"
FT CHAIN 2..780
FT /note="ATP-dependent 6-phosphofructokinase, muscle type"
FT /id="PRO_0000112016"
FT REGION 2..390
FT /note="N-terminal catalytic PFK domain 1"
FT REGION 391..401
FT /note="Interdomain linker"
FT REGION 402..780
FT /note="C-terminal regulatory PFK domain 2"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 25
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 88..89
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 118..121
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 119
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 164..166
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 201
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 208..210
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 264
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 292
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 298..301
FT /ligand="substrate"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 471
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 528..532
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 566
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 573..575
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 629
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 655
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 661..664
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT BINDING 735
FT /ligand="beta-D-fructose 2,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:58579"
FT /ligand_note="allosteric activator; ligand shared between
FT dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03184"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:P00511"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47858"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47857"
FT MOD_RES 557
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:29775581"
FT MOD_RES 667
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 775
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00511"
FT CARBOHYD 530
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MHKDEFHLKFFMCVIQSRQLVRTPQRTAGEASTSSMLIPKPPPKTDI
FT LKSLDTMDDPDTVGSIPVFKTEWIM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046125"
FT VAR_SEQ 282..312
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2140567"
FT /id="VSP_004667"
FT VARIANT 39
FT /note="R -> L (in GSD7; Ashkenazi; dbSNP:rs121918193)"
FT /id="VAR_006063"
FT VARIANT 39
FT /note="R -> P (in GSD7; Italian; dbSNP:rs121918193)"
FT /evidence="ECO:0000269|PubMed:7513946"
FT /id="VAR_006064"
FT VARIANT 57
FT /note="G -> V (in GSD7; Italian)"
FT /evidence="ECO:0000269|PubMed:22133655"
FT /id="VAR_072239"
FT VARIANT 100
FT /note="R -> Q (in dbSNP:rs2228500)"
FT /evidence="ECO:0000269|PubMed:7825568"
FT /id="VAR_006065"
FT VARIANT 180
FT /note="S -> C (in GSD7; Italian)"
FT /evidence="ECO:0000269|PubMed:22133655"
FT /id="VAR_072240"
FT VARIANT 209
FT /note="G -> D (in GSD7; loss of activity shown by
FT complementation assays in yeast; dbSNP:rs767265360)"
FT /evidence="ECO:0000269|PubMed:7825568"
FT /id="VAR_006066"
FT VARIANT 309
FT /note="D -> G (in GSD7; Spanish; complete loss of enzyme
FT activity; dbSNP:rs1169383137)"
FT /evidence="ECO:0000269|PubMed:24427140"
FT /id="VAR_072241"
FT VARIANT 543
FT /note="D -> A (in GSD7; Italian; dbSNP:rs121918194)"
FT /evidence="ECO:0000269|PubMed:7513946"
FT /id="VAR_006067"
FT VARIANT 591
FT /note="D -> A (in GSD7; Italian)"
FT /evidence="ECO:0000269|PubMed:22133655"
FT /id="VAR_072242"
FT VARIANT 686
FT /note="W -> C (in GSD7; Japanese; dbSNP:rs121918196)"
FT /evidence="ECO:0000269|PubMed:8889589"
FT /id="VAR_006068"
FT VARIANT 696
FT /note="R -> H (in dbSNP:rs41291971)"
FT /evidence="ECO:0000269|PubMed:7825568"
FT /id="VAR_006069"
FT CONFLICT 670
FT /note="P -> S (in Ref. 4; BAC86498)"
FT /evidence="ECO:0000305"
FT CONFLICT P08237-3:2
FT /note="H -> L (in Ref. 4; BAC86498)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 780 AA; 85183 MW; 769A2C01F97D1122 CRC64;
MTHEEHHAAK TLGIGKAIAV LTSGGDAQGM NAAVRAVVRV GIFTGARVFF VHEGYQGLVD
GGDHIKEATW ESVSMMLQLG GTVIGSARCK DFREREGRLR AAYNLVKRGI TNLCVIGGDG
SLTGADTFRS EWSDLLSDLQ KAGKITDEEA TKSSYLNIVG LVGSIDNDFC GTDMTIGTDS
ALHRIMEIVD AITTTAQSHQ RTFVLEVMGR HCGYLALVTS LSCGADWVFI PECPPDDDWE
EHLCRRLSET RTRGSRLNII IVAEGAIDKN GKPITSEDIK NLVVKRLGYD TRVTVLGHVQ
RGGTPSAFDR ILGSRMGVEA VMALLEGTPD TPACVVSLSG NQAVRLPLME CVQVTKDVTK
AMDEKKFDEA LKLRGRSFMN NWEVYKLLAH VRPPVSKSGS HTVAVMNVGA PAAGMNAAVR
STVRIGLIQG NRVLVVHDGF EGLAKGQIEE AGWSYVGGWT GQGGSKLGTK RTLPKKSFEQ
ISANITKFNI QGLVIIGGFE AYTGGLELME GRKQFDELCI PFVVIPATVS NNVPGSDFSV
GADTALNTIC TTCDRIKQSA AGTKRRVFII ETMGGYCGYL ATMAGLAAGA DAAYIFEEPF
TIRDLQANVE HLVQKMKTTV KRGLVLRNEK CNENYTTDFI FNLYSEEGKG IFDSRKNVLG
HMQQGGSPTP FDRNFATKMG AKAMNWMSGK IKESYRNGRI FANTPDSGCV LGMRKRALVF
QPVAELKDQT DFEHRIPKEQ WWLKLRPILK ILAKYEIDLD TSDHAHLEHI TRKRSGEAAV
