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 27-MAR-2024, entry version 244. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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; 206. 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; 43. DR MINT; P08237; -. DR STRING; 9606.ENSP00000496597; -. DR BindingDB; P08237; -. DR ChEMBL; CHEMBL3291; -. DR MoonProt; P08237; -. DR GlyCosmos; P08237; 1 site, No reported glycans. 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 CPTAC; CPTAC-2760; -. DR CPTAC; CPTAC-2761; -. DR EPD; P08237; -. DR jPOST; P08237; -. DR MassIVE; P08237; -. DR MaxQB; P08237; -. DR PaxDb; 9606-ENSP00000345771; -. DR PeptideAtlas; P08237; -. DR ProteomicsDB; 52094; -. [P08237-1] DR ProteomicsDB; 52095; -. [P08237-2] DR Pumba; P08237; -. DR Antibodypedia; 1061; 520 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 AGR; HGNC:8877; -. 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; 374214at2759; -. DR PhylomeDB; P08237; -. DR TreeFam; TF300411; -. DR BioCyc; MetaCyc:HS07832-MONOMER; -. 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; 35 hits in 1159 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 212 other cell types or tissues. DR ExpressionAtlas; P08237; baseline and differential. 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: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; 3.40.50.450; -; 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; IPR041914; PFK_vert-type. DR InterPro; IPR015912; Phosphofructokinase_CS. DR InterPro; IPR000023; Phosphofructokinase_dom. DR InterPro; IPR035966; PKF_sf. DR NCBIfam; TIGR02478; 6PF1K_euk; 1. DR PANTHER; PTHR13697:SF59; ATP-DEPENDENT 6-PHOSPHOFRUCTOKINASE, MUSCLE TYPE; 1. DR PANTHER; PTHR13697; PHOSPHOFRUCTOKINASE; 1. DR Pfam; PF00365; PFK; 2. DR PIRSF; PIRSF000533; ATP_PFK_euk; 1. DR PRINTS; PR00476; PHFRCTKINASE. DR SUPFAM; SSF53784; Phosphofructokinase; 2. DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2. DR UCD-2DPAGE; P08237; -. DR Genevisible; P08237; HS. 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 //