GenomeNet

Database: UniProt/SWISS-PROT
Entry: PFKAM_HUMAN
LinkDB: PFKAM_HUMAN
Original site: 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   13-FEB-2019, entry version 215.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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
RT   gene: a 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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA   Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA   Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D.,
RA   Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z.,
RA   Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H.,
RA   Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H.,
RA   Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V.,
RA   Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J.,
RA   Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A.,
RA   Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M.,
RA   Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E.,
RA   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.,
RA   Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R.,
RA   Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J.,
RA   Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C.,
RA   Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M.,
RA   Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M.,
RA   Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P.,
RA   Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L.,
RA   Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E.,
RA   Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C.,
RA   Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F.,
RA   Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M.,
RA   Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S.,
RA   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.,
RA   Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I.,
RA   Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T.,
RA   Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S.,
RA   Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D.,
RA   Kucherlapati R., Weinstock G., 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
RT   project: 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;
RA   Sharma P.M., Reddy G.R., Babior B.M., McLachlan A.;
RT   "Alternative splicing of the transcript encoding the human muscle
RT   isoenzyme 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
RT   of 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
RP   BY 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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation 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.,
RA   Buerckstuemmer T., 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
RP   BY 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   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
RT   patients with muscle phosphofructokinase deficiency.";
RL   Am. J. Hum. Genet. 54:812-819(1994).
RN   [14]
RP   VARIANT GSD7 ASP-209, VARIANTS GLN-100 AND HIS-696, AND
RP   CHARACTERIZATION OF VARIANT GSD7 ASP-209.
RX   PubMed=7825568;
RA   Raben N., Exelbert R., Spiegel R., Sherman J.B., Plotz P.,
RA   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   [15]
RP   VARIANT GSD7 CYS-686.
RX   PubMed=8889589;
RX   DOI=10.1002/(SICI)1098-1004(1996)8:3<273::AID-HUMU13>3.3.CO;2-4;
RA   Hamaguchi T., Nakajima H., Noguchi T., Nakagawa C., Kuwajima M.,
RA   Kono N., Tarui S., Matsuzawa Y.;
RT   "Novel missense mutation (W686C) of the phosphofructokinase-M gene in
RT   a Japanese patient with a mild form of glycogenosis VII.";
RL   Hum. Mutat. 8:273-275(1996).
RN   [16]
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.,
RA   Barca E., Amati A., Cassandrini D., Serlenga L., Vita G., Toscano A.;
RT   "Clinical features and new molecular findings in muscle
RT   phosphofructokinase deficiency (GSD type VII).";
RL   Neuromuscul. Disord. 22:325-330(2012).
RN   [17]
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
RT   gene.";
RL   Front. Physiol. 4:393-393(2013).
CC   -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate
CC       to 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
CC         1,6-bisphosphate + H(+); Xref=Rhea:RHEA:16109,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:32966,
CC         ChEBI:CHEBI:57634, ChEBI:CHEBI:456216; EC=2.7.1.11;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_03184};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- ACTIVITY REGULATION: Allosterically activated by ADP, AMP, or
CC       fructose 2,6-bisphosphate, and allosterically inhibited by ATP or
CC       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).
CC       Phosphofructokinase (PFK) enzyme functions as a tetramer composed
CC       of different combinations of 3 types of subunits, called PFKM
CC       (where M stands for Muscle), PFKL (Liver) and PFKP (Platelet). The
CC       composition of the PFK tetramer differs according to the tissue
CC       type it is present in. In muscles, it is composed of 4 PFKM
CC       subunits (also called M4). In the liver, the predominant form is a
CC       tetramer of PFKL subunits (L4). In erythrocytes, both PFKM and
CC       PFKL subunits randomly tetramerize to form M4, L4 and other
CC       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
CC       (via C-terminus) with HK1 (via N-terminal spermatogenic cell-
CC       specific region) (By similarity). {ECO:0000250|UniProtKB:P47857,
CC       ECO:0000255|HAMAP-Rule:MF_03184, ECO:0000305}.
CC   -!- INTERACTION:
CC       Self; NbExp=3; IntAct=EBI-514788, EBI-514788;
CC       P17858:PFKL; NbExp=6; IntAct=EBI-514788, EBI-487243;
CC       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         Note=No experimental confirmation available. Ref.4 (BAC86498)
CC         sequence is in conflict in position: 2:H->L. {ECO:0000305};
CC   -!- PTM: GlcNAcylation decreases enzyme activity. {ECO:0000250}.
CC   -!- DISEASE: Glycogen storage disease 7 (GSD7) [MIM:232800]: A
CC       metabolic disorder characterized by exercise intolerance with
CC       associated nausea and vomiting, muscle cramping, exertional
CC       myopathy and compensated hemolysis. Short bursts of intense
CC       activity are particularly difficult. Severe muscle cramps and
CC       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
CC       mutations affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: In human PFK exists as a system of 3 types of
CC       subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet)
CC       isoenzymes.
CC   -!- SIMILARITY: Belongs to the phosphofructokinase type A (PFKA)
CC       family. ATP-dependent PFK group I subfamily. Eukaryotic two domain
CC       clade "E" sub-subfamily. {ECO:0000255|HAMAP-Rule:MF_03184}.
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   UniGene; Hs.75160; -.
DR   PDB; 4OMT; X-ray; 6.00 A; A=1-780.
DR   PDBsum; 4OMT; -.
DR   ProteinModelPortal; P08237; -.
DR   SMR; P08237; -.
DR   BioGrid; 111234; 74.
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; 29.
DR   MINT; P08237; -.
DR   STRING; 9606.ENSP00000345771; -.
DR   BindingDB; P08237; -.
DR   ChEMBL; CHEMBL3291; -.
DR   MoonProt; P08237; -.
DR   iPTMnet; P08237; -.
DR   PhosphoSitePlus; P08237; -.
DR   BioMuta; PFKM; -.
DR   DMDM; 125126; -.
DR   UCD-2DPAGE; P08237; -.
DR   EPD; P08237; -.
DR   jPOST; P08237; -.
DR   MaxQB; P08237; -.
DR   PaxDb; P08237; -.
DR   PeptideAtlas; P08237; -.
DR   PRIDE; P08237; -.
DR   ProteomicsDB; 52094; -.
DR   ProteomicsDB; 52095; -. [P08237-2]
DR   DNASU; 5213; -.
DR   Ensembl; ENST00000312352; ENSP00000309438; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000340802; ENSP00000345771; ENSG00000152556. [P08237-3]
DR   Ensembl; ENST00000359794; ENSP00000352842; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000547587; ENSP00000449426; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000550345; ENSP00000450369; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000550924; ENSP00000446945; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000551339; ENSP00000448253; ENSG00000152556. [P08237-1]
DR   Ensembl; ENST00000551804; ENSP00000448177; ENSG00000152556. [P08237-2]
DR   GeneID; 5213; -.
DR   KEGG; hsa:5213; -.
DR   UCSC; uc001rrb.3; human. [P08237-1]
DR   CTD; 5213; -.
DR   DisGeNET; 5213; -.
DR   EuPathDB; HostDB:ENSG00000152556.15; -.
DR   GeneCards; PFKM; -.
DR   HGNC; HGNC:8877; PFKM.
DR   HPA; HPA002117; -.
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   eggNOG; KOG2440; Eukaryota.
DR   eggNOG; COG0205; LUCA.
DR   GeneTree; ENSGT00940000155440; -.
DR   HOGENOM; HOG000200154; -.
DR   HOVERGEN; HBG000976; -.
DR   InParanoid; P08237; -.
DR   KO; K00850; -.
DR   OMA; KQYDELC; -.
DR   OrthoDB; 172878at2759; -.
DR   PhylomeDB; P08237; -.
DR   TreeFam; TF300411; -.
DR   BioCyc; MetaCyc:HS07832-MONOMER; -.
DR   Reactome; R-HSA-70171; Glycolysis.
DR   SABIO-RK; P08237; -.
DR   UniPathway; UPA00109; UER00182.
DR   ChiTaRS; PFKM; human.
DR   GeneWiki; PFKM; -.
DR   GenomeRNAi; 5213; -.
DR   PMAP-CutDB; P08237; -.
DR   PRO; PR:P08237; -.
DR   Proteomes; UP000005640; Chromosome 12.
DR   Bgee; ENSG00000152556; Expressed in 238 organ(s), highest expression level in muscle of leg.
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:0005634; C:nucleus; IDA:CAFA.
DR   GO; GO:0097228; C:sperm principal piece; IBA:GO_Central.
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.
DR   GO; GO:0042803; F:protein homodimerization activity; 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:0006007; P:glucose catabolic process; IBA:GO_Central.
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   GO; GO:0051259; P:protein complex oligomerization; IDA:BHF-UCL.
DR   HAMAP; MF_03184; Phosphofructokinase_I_E; 1.
DR   InterPro; IPR009161; 6-Pfructokinase_euk.
DR   InterPro; IPR022953; ATP_PFK.
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; Complete proteome; Cytoplasm; Disease mutation;
KW   Glycogen storage disease; Glycolysis; Glycoprotein; Kinase; Magnesium;
KW   Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Transferase.
FT   INIT_MET      1      1       Removed. {ECO:0000250|UniProtKB:P00511}.
FT   CHAIN         2    780       ATP-dependent 6-phosphofructokinase,
FT                                muscle type.
FT                                /FTId=PRO_0000112016.
FT   NP_BIND      88     89       ATP. {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   NP_BIND     118    121       ATP. {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   REGION        2    390       N-terminal catalytic PFK domain 1.
FT   REGION      164    166       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      208    210       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      298    301       Substrate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      391    401       Interdomain linker.
FT   REGION      402    780       C-terminal regulatory PFK domain 2.
FT   REGION      528    532       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      573    575       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   REGION      661    664       Allosteric activator fructose 2,6-
FT                                bisphosphate binding. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   ACT_SITE    166    166       Proton acceptor. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   METAL       119    119       Magnesium; catalytic. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING      25     25       ATP; via amide nitrogen.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     201    201       Substrate; shared with dimeric partner.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     264    264       Substrate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     292    292       Substrate; shared with dimeric partner.
FT                                {ECO:0000255|HAMAP-Rule:MF_03184}.
FT   BINDING     471    471       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     566    566       Allosteric activator fructose 2,6-
FT                                bisphosphate; shared with dimeric
FT                                partner. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     629    629       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     655    655       Allosteric activator fructose 2,6-
FT                                bisphosphate; shared with dimeric
FT                                partner. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   BINDING     735    735       Allosteric activator fructose 2,6-
FT                                bisphosphate. {ECO:0000255|HAMAP-
FT                                Rule:MF_03184}.
FT   MOD_RES       2      2       N-acetylthreonine.
FT                                {ECO:0000250|UniProtKB:P00511}.
FT   MOD_RES     133    133       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P47858}.
FT   MOD_RES     377    377       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P47857}.
FT   MOD_RES     667    667       Phosphoserine.
FT                                {ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     775    775       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P00511}.
FT   CARBOHYD    530    530       O-linked (GlcNAc) serine. {ECO:0000250}.
FT   VAR_SEQ       1      1       M -> MHKDEFHLKFFMCVIQSRQLVRTPQRTAGEASTSSM
FT                                LIPKPPPKTDILKSLDTMDDPDTVGSIPVFKTEWIM (in
FT                                isoform 3).
FT                                {ECO:0000303|PubMed:14702039}.
FT                                /FTId=VSP_046125.
FT   VAR_SEQ     282    312       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:2140567}.
FT                                /FTId=VSP_004667.
FT   VARIANT      39     39       R -> L (in GSD7; Ashkenazi;
FT                                dbSNP:rs121918193).
FT                                /FTId=VAR_006063.
FT   VARIANT      39     39       R -> P (in GSD7; Italian;
FT                                dbSNP:rs121918193).
FT                                {ECO:0000269|PubMed:7513946}.
FT                                /FTId=VAR_006064.
FT   VARIANT      57     57       G -> V (in GSD7; Italian).
FT                                {ECO:0000269|PubMed:22133655}.
FT                                /FTId=VAR_072239.
FT   VARIANT     100    100       R -> Q (in dbSNP:rs2228500).
FT                                {ECO:0000269|PubMed:7825568}.
FT                                /FTId=VAR_006065.
FT   VARIANT     180    180       S -> C (in GSD7; Italian).
FT                                {ECO:0000269|PubMed:22133655}.
FT                                /FTId=VAR_072240.
FT   VARIANT     209    209       G -> D (in GSD7; loss of activity shown
FT                                by complementation assays in yeast;
FT                                dbSNP:rs767265360).
FT                                {ECO:0000269|PubMed:7825568}.
FT                                /FTId=VAR_006066.
FT   VARIANT     309    309       D -> G (in GSD7; Spanish; complete loss
FT                                of enzyme activity; dbSNP:rs1169383137).
FT                                {ECO:0000269|PubMed:24427140}.
FT                                /FTId=VAR_072241.
FT   VARIANT     543    543       D -> A (in GSD7; Italian;
FT                                dbSNP:rs121918194).
FT                                {ECO:0000269|PubMed:7513946}.
FT                                /FTId=VAR_006067.
FT   VARIANT     591    591       D -> A (in GSD7; Italian).
FT                                {ECO:0000269|PubMed:22133655}.
FT                                /FTId=VAR_072242.
FT   VARIANT     686    686       W -> C (in GSD7; Japanese;
FT                                dbSNP:rs121918196).
FT                                {ECO:0000269|PubMed:8889589}.
FT                                /FTId=VAR_006068.
FT   VARIANT     696    696       R -> H (in dbSNP:rs41291971).
FT                                {ECO:0000269|PubMed:7825568}.
FT                                /FTId=VAR_006069.
FT   CONFLICT    670    670       P -> S (in Ref. 4; BAC86498).
FT                                {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
//
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