ID K6PL_HUMAN Reviewed; 780 AA. AC P17858; Q96A64; Q96IH4; Q9BR91; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 06-MAR-2007, sequence version 6. DT 03-MAY-2011, entry version 140. DE RecName: Full=6-phosphofructokinase, liver type; DE EC=2.7.1.11; DE AltName: Full=Phosphofructo-1-kinase isozyme B; DE Short=PFK-B; DE AltName: Full=Phosphofructokinase 1; DE AltName: Full=Phosphohexokinase; GN Name=PFKL; 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 [MRNA] (ISOFORM 1), AND VARIANT TRP-151. RC TISSUE=Liver; RX MEDLINE=90126227; PubMed=2533063; RA Levanon D., Danciger E., Dafni N., Bernstein Y., Elson A., Moens W., RA Brandeis M., Groner Y.; RT "The primary structure of human liver type phosphofructokinase and its RT comparison with other types of PFK."; RL DNA 8:733-743(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT ALA-81. RX MEDLINE=90243256; PubMed=2139864; DOI=10.1016/0888-7543(90)90517-X; RA Elson A., Levanon D., Brandeis M., Dafni N., Bernstein Y., RA Danciger E., Groner Y.; RT "The structure of the human liver-type phosphofructokinase gene."; RL Genomics 7:47-56(1990). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=20289799; PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney, Lung, 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 [5] RP PROTEIN SEQUENCE OF 2-10 (ISOFORM 1). RC TISSUE=Platelet; RX MEDLINE=22608298; PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., RA Thomas G.R., Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass RT spectrometric identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [6] RP PROTEIN SEQUENCE OF 2-10; 17-35 AND 185-210, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY. RC TISSUE=Prostatic carcinoma; RA Bienvenut W.V., Gao M., Leug H., Pchelintsev N., Adams P.D.; RL Submitted (JUL-2009) to UniProtKB. RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-633, AND MASS RP SPECTROMETRY. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer RT cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, AND MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] 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). CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 1,6-bisphosphate. CC -!- COFACTOR: Magnesium. CC -!- ENZYME REGULATION: Allosteric enzyme activated by ADP, AMP, or CC fructose bisphosphate and 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 -!- SUBUNIT: Tetramer. Muscle is M4, liver is L4, and red cell is M3L, CC M2L2, or ML3. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P17858-1; Sequence=Displayed; CC Name=2; Synonyms=a; CC IsoId=P17858-2; Sequence=VSP_011854; CC Note=No experimental confirmation available; 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 family. Two domains CC subfamily. 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; X15573; CAA33597.1; -; mRNA. DR EMBL; X16911; CAB46744.1; -; Genomic_DNA. DR EMBL; X16912; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16913; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16914; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16915; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16916; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16917; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16918; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16919; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16920; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16921; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16922; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16923; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16924; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16925; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16926; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16927; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16928; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16929; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; X16930; CAB46744.1; JOINED; Genomic_DNA. DR EMBL; AP001754; BAA95561.1; -; Genomic_DNA. DR EMBL; BC006422; AAH06422.1; -; mRNA. DR EMBL; BC007536; AAH07536.1; -; mRNA. DR EMBL; BC008964; AAH08964.1; -; mRNA. DR EMBL; BC009919; AAH09919.1; -; mRNA. DR IPI; IPI00332371; -. DR IPI; IPI00925520; -. DR PIR; A33639; A33639. DR RefSeq; NP_002617.3; NM_002626.4. DR UniGene; Hs.255093; -. DR ProteinModelPortal; P17858; -. DR SMR; P17858; 15-373, 393-747. DR IntAct; P17858; 21. DR MINT; MINT-5004093; -. DR STRING; P17858; -. DR PhosphoSite; P17858; -. DR PRIDE; P17858; -. DR Ensembl; ENST00000349048; ENSP00000269848; ENSG00000141959. DR GeneID; 5211; -. DR KEGG; hsa:5211; -. DR NMPDR; fig|9606.3.peg.21069; -. DR UCSC; uc002zel.1; human. DR CTD; 5211; -. DR GeneCards; GC21P031062; -. DR HGNC; HGNC:8876; PFKL. DR HPA; HPA030047; -. DR MIM; 171860; gene. DR neXtProt; NX_P17858; -. DR PharmGKB; PA33215; -. DR eggNOG; maNOG12237; -. DR HOVERGEN; HBG000976; -. DR OMA; CKAFTTR; -. DR OrthoDB; EOG4RJG0W; -. DR PhylomeDB; P17858; -. DR BRENDA; 2.7.1.11; 247. DR Pathway_Interaction_DB; hif1_tfpathway; HIF-1-alpha transcription factor network. DR Reactome; REACT_474; Metabolism of carbohydrates. DR NextBio; 20154; -. DR PMAP-CutDB; P17858; -. DR ArrayExpress; P17858; -. DR Bgee; P17858; -. DR CleanEx; HS_PFKL; -. DR Genevestigator; P17858; -. DR GermOnline; ENSG00000141959; Homo sapiens. DR GO; GO:0005945; C:6-phosphofructokinase complex; IDA:UniProtKB. DR GO; GO:0003872; F:6-phosphofructokinase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:BHF-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0019900; F:kinase binding; IPI:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB. DR GO; GO:0006096; P:glycolysis; IDA:UniProtKB. DR GO; GO:0051259; P:protein oligomerization; IDA:BHF-UCL. DR InterPro; IPR009161; 6-phosphofructokinase_euk. DR InterPro; IPR022953; Phosphofructokinase. DR InterPro; IPR015912; Phosphofructokinase_CS. DR InterPro; IPR000023; Phosphofructokinase_dom. DR Pfam; PF00365; PFK; 2. DR PIRSF; PIRSF000533; ATP_PFK_euk; 1. DR PRINTS; PR00476; PHFRCTKINASE. DR SUPFAM; SSF53784; Ppfruckinase; 2. DR TIGRFAMs; TIGR02478; 6PF1K_euk; 1. DR PROSITE; PS00433; PHOSPHOFRUCTOKINASE; 2. PE 1: Evidence at protein level; KW Acetylation; Allosteric enzyme; Alternative splicing; ATP-binding; KW Complete proteome; Direct protein sequencing; Glycolysis; Kinase; KW Magnesium; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Polymorphism; Repeat; Transferase. FT INIT_MET 1 1 Removed. FT CHAIN 2 780 6-phosphofructokinase, liver type. FT /FTId=PRO_0000112021. FT NP_BIND 35 39 ATP (By similarity). FT NP_BIND 193 197 ATP (By similarity). FT NP_BIND 210 226 ATP (By similarity). FT ACT_SITE 166 166 Proton acceptor (By similarity). FT METAL 224 224 Magnesium; via carbonyl oxygen (By FT similarity). FT BINDING 201 201 Substrate (By similarity). FT BINDING 292 292 Substrate (By similarity). FT BINDING 298 298 Substrate (By similarity). FT BINDING 301 301 Substrate (By similarity). FT MOD_RES 2 2 N-acetylalanine. FT MOD_RES 633 633 Phosphotyrosine. FT MOD_RES 640 640 Phosphotyrosine (By similarity). FT MOD_RES 775 775 Phosphoserine. FT VAR_SEQ 1 28 MAAVDLEKLRASGAGKAIGVLTSGGDAQ -> MCNQGRGRE FT SSRGGLHVQGSCRGLSRSPQQETGFAKAPAGTDCFFHCSPG FT SRGQGDRKEEVTSEPGGTSIMSRLG (in isoform 2). FT /FTId=VSP_011854. FT VARIANT 81 81 G -> A. FT /FTId=VAR_006070. FT VARIANT 151 151 R -> W. FT /FTId=VAR_006071. FT VARIANT 237 237 D -> V (in dbSNP:rs1057037). FT /FTId=VAR_030872. FT CONFLICT 27 27 A -> R (in Ref. 1; CAA33597 and 2; FT CAB46744). FT CONFLICT 86 86 S -> T (in Ref. 2; CAB46744). FT CONFLICT 89 89 C -> S (in Ref. 1; CAA33597 and 2; FT CAB46744). FT CONFLICT 103 103 Y -> N (in Ref. 2; CAB46744). FT CONFLICT 236 236 E -> EAPPE (in Ref. 2; CAB46744). FT CONFLICT 386 386 K -> R (in Ref. 2; CAB46744). FT CONFLICT 389 389 A -> T (in Ref. 1; CAA33597 and 2; FT CAB46744). FT CONFLICT 648 648 K -> N (in Ref. 4; AAH08964/AAH09919). FT CONFLICT 717 717 V -> A (in Ref. 4; AAH08964/AAH09919). SQ SEQUENCE 780 AA; 85018 MW; 0D686CE074E9626D CRC64; MAAVDLEKLR ASGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE GGENIKQANW LSVSNIIQLG GTIIGSARCK AFTTREGRRA AAYNLVQHGI TNLCVIGGDG SLTGANIFRS EWGSLLEELV AEGKISETTA RTYSHLNIAG LVGSIDNDFC GTDMTIGTDS ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE NFMCERLGET RSRGSRLNII IIAEGAIDRN GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVTLSG NQSVRLPLME CVQMTKEVQK AMDDKRFDEA TQLRGGSFEN NWNIYKLLAH QKPPKEKSNF SLAILNVGAP AAGMNAAVRS AVRTGISHGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKGQLESI VENIRIYGIH ALLVVGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN IHDLKVNVEH MTEKMKTDIQ RGLVLRNEKC HDYYTTEFLY NLYSSEGKGV FDCRTNVLGH LQQGGAPTPF DRNYGTKLGV KAMLWLSEKL REVYRKGRVF ANAPDSACVI GLKKKAVAFS PVTELKKDTD FEHRMPREQW WLSLRLMLKM LAQYRISMAA YVSGELEHVT RRTLSMDKGF //