Full text data of PFKL
PFKL
[Confidence: high (present in two of the MS resources)]
6-phosphofructokinase, liver type; 2.7.1.11 (Phosphofructo-1-kinase isozyme B; PFK-B; Phosphofructokinase 1; Phosphohexokinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
6-phosphofructokinase, liver type; 2.7.1.11 (Phosphofructo-1-kinase isozyme B; PFK-B; Phosphofructokinase 1; Phosphohexokinase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00332371
IPI00332371 6-phosphofructokinase Phosphofructokinase 1, ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate, Allosteric enzyme activated by ADP, AMP, or fructose bisphosphate and inhibited by ATP or citrate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00332371 6-phosphofructokinase Phosphofructokinase 1, ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate, Allosteric enzyme activated by ADP, AMP, or fructose bisphosphate and inhibited by ATP or citrate soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P17858
ID K6PL_HUMAN Reviewed; 780 AA.
AC P17858; Q96A64; Q96IH4; Q9BR91;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-MAR-2007, sequence version 6.
DT 22-JAN-2014, entry version 167.
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 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 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 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 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 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 [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, GLYCOSYLATION AT
RP SER-529, AND MUTAGENESIS OF THR-527 AND SER-529.
RX PubMed=22923583; DOI=10.1126/science.1222278;
RA Yi W., Clark P.M., Mason D.E., Keenan M.C., Hill C., Goddard W.A. III,
RA Peters E.C., Driggers E.M., Hsieh-Wilson L.C.;
RT "Phosphofructokinase 1 glycosylation regulates cell growth and
RT metabolism.";
RL Science 337:975-980(2012).
CC -!- FUNCTION: Catalyzes the third step of glycolysis, the
CC phosphorylation of fructose-6-phosphate (F6P) by ATP to generate
CC fructose-1,6-bisphosphate (FBP) and ADP.
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 GlcNAcylation by OGT overcomes allosteric regulation.
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 -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-487243, EBI-487243;
CC P08237:PFKM; NbExp=6; IntAct=EBI-487243, EBI-514788;
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 -!- PTM: GlcNAcylation at Ser-529 by OGT decreases enzyme activity,
CC leading to redirect glucose flux through the oxidative pentose
CC phosphate pathway. Glycosylation is stimulated by both hypoxia and
CC glucose deprivation.
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 -!- MISCELLANEOUS: Glycosylation may play a role in cancer cell
CC proliferation: inhibition of 6-phosphofructokinase activity and
CC subsequent redirection of the glucose flux through the oxidative
CC pentose phosphate pathway confers a selective growth advantage on
CC cancer cells. Moreover GlcNAcylation is observed in multiple
CC cancer cell lines and tissue samples and GlcNAcylation leads to
CC larger xenografts tunors in mice (PubMed:22923583).
CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains
CC subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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 PIR; A33639; A33639.
DR RefSeq; NP_002617.3; NM_002626.4.
DR UniGene; Hs.255093; -.
DR ProteinModelPortal; P17858; -.
DR SMR; P17858; 10-754.
DR IntAct; P17858; 10.
DR MINT; MINT-5004093; -.
DR STRING; 9606.ENSP00000269848; -.
DR BindingDB; P17858; -.
DR PhosphoSite; P17858; -.
DR DMDM; 134048493; -.
DR PaxDb; P17858; -.
DR PRIDE; P17858; -.
DR DNASU; 5211; -.
DR Ensembl; ENST00000349048; ENSP00000269848; ENSG00000141959.
DR Ensembl; ENST00000403390; ENSP00000384038; ENSG00000141959.
DR GeneID; 5211; -.
DR KEGG; hsa:5211; -.
DR UCSC; uc002zel.3; human.
DR CTD; 5211; -.
DR GeneCards; GC21P045719; -.
DR H-InvDB; HIX0016166; -.
DR HGNC; HGNC:8876; PFKL.
DR HPA; HPA030047; -.
DR MIM; 171860; gene.
DR neXtProt; NX_P17858; -.
DR PharmGKB; PA33215; -.
DR eggNOG; COG0205; -.
DR HOGENOM; HOG000200154; -.
DR HOVERGEN; HBG000976; -.
DR KO; K00850; -.
DR OMA; VQHGITN; -.
DR OrthoDB; EOG7ZSHV5; -.
DR BioCyc; MetaCyc:HS06881-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P17858; -.
DR UniPathway; UPA00109; UER00182.
DR ChiTaRS; PFKL; human.
DR GeneWiki; PFKL; -.
DR GenomeRNAi; 5211; -.
DR NextBio; 20154; -.
DR PMAP-CutDB; P17858; -.
DR PRO; PR:P17858; -.
DR ArrayExpress; P17858; -.
DR Bgee; P17858; -.
DR CleanEx; HS_PFKL; -.
DR Genevestigator; P17858; -.
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:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolysis; IDA:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IEA:Ensembl.
DR GO; GO:0051259; P:protein oligomerization; IDA:BHF-UCL.
DR GO; GO:0009749; P:response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
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; SSF53784; 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;
KW Glycoprotein; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; 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 640 640 Phosphotyrosine (By similarity).
FT MOD_RES 775 775 Phosphoserine.
FT CARBOHYD 529 529 O-linked (GlcNAc).
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 MUTAGEN 527 527 T->A: Does not affect GlcNAcylation.
FT MUTAGEN 529 529 S->A: Prevents GlcNAcylation and enhance
FT enzyme activity.
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
//
ID K6PL_HUMAN Reviewed; 780 AA.
AC P17858; Q96A64; Q96IH4; Q9BR91;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 06-MAR-2007, sequence version 6.
DT 22-JAN-2014, entry version 167.
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 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 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 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 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 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 [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, AND MASS SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, GLYCOSYLATION AT
RP SER-529, AND MUTAGENESIS OF THR-527 AND SER-529.
RX PubMed=22923583; DOI=10.1126/science.1222278;
RA Yi W., Clark P.M., Mason D.E., Keenan M.C., Hill C., Goddard W.A. III,
RA Peters E.C., Driggers E.M., Hsieh-Wilson L.C.;
RT "Phosphofructokinase 1 glycosylation regulates cell growth and
RT metabolism.";
RL Science 337:975-980(2012).
CC -!- FUNCTION: Catalyzes the third step of glycolysis, the
CC phosphorylation of fructose-6-phosphate (F6P) by ATP to generate
CC fructose-1,6-bisphosphate (FBP) and ADP.
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 GlcNAcylation by OGT overcomes allosteric regulation.
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 -!- INTERACTION:
CC Self; NbExp=2; IntAct=EBI-487243, EBI-487243;
CC P08237:PFKM; NbExp=6; IntAct=EBI-487243, EBI-514788;
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 -!- PTM: GlcNAcylation at Ser-529 by OGT decreases enzyme activity,
CC leading to redirect glucose flux through the oxidative pentose
CC phosphate pathway. Glycosylation is stimulated by both hypoxia and
CC glucose deprivation.
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 -!- MISCELLANEOUS: Glycosylation may play a role in cancer cell
CC proliferation: inhibition of 6-phosphofructokinase activity and
CC subsequent redirection of the glucose flux through the oxidative
CC pentose phosphate pathway confers a selective growth advantage on
CC cancer cells. Moreover GlcNAcylation is observed in multiple
CC cancer cell lines and tissue samples and GlcNAcylation leads to
CC larger xenografts tunors in mice (PubMed:22923583).
CC -!- SIMILARITY: Belongs to the phosphofructokinase family. Two domains
CC subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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 PIR; A33639; A33639.
DR RefSeq; NP_002617.3; NM_002626.4.
DR UniGene; Hs.255093; -.
DR ProteinModelPortal; P17858; -.
DR SMR; P17858; 10-754.
DR IntAct; P17858; 10.
DR MINT; MINT-5004093; -.
DR STRING; 9606.ENSP00000269848; -.
DR BindingDB; P17858; -.
DR PhosphoSite; P17858; -.
DR DMDM; 134048493; -.
DR PaxDb; P17858; -.
DR PRIDE; P17858; -.
DR DNASU; 5211; -.
DR Ensembl; ENST00000349048; ENSP00000269848; ENSG00000141959.
DR Ensembl; ENST00000403390; ENSP00000384038; ENSG00000141959.
DR GeneID; 5211; -.
DR KEGG; hsa:5211; -.
DR UCSC; uc002zel.3; human.
DR CTD; 5211; -.
DR GeneCards; GC21P045719; -.
DR H-InvDB; HIX0016166; -.
DR HGNC; HGNC:8876; PFKL.
DR HPA; HPA030047; -.
DR MIM; 171860; gene.
DR neXtProt; NX_P17858; -.
DR PharmGKB; PA33215; -.
DR eggNOG; COG0205; -.
DR HOGENOM; HOG000200154; -.
DR HOVERGEN; HBG000976; -.
DR KO; K00850; -.
DR OMA; VQHGITN; -.
DR OrthoDB; EOG7ZSHV5; -.
DR BioCyc; MetaCyc:HS06881-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P17858; -.
DR UniPathway; UPA00109; UER00182.
DR ChiTaRS; PFKL; human.
DR GeneWiki; PFKL; -.
DR GenomeRNAi; 5211; -.
DR NextBio; 20154; -.
DR PMAP-CutDB; P17858; -.
DR PRO; PR:P17858; -.
DR ArrayExpress; P17858; -.
DR Bgee; P17858; -.
DR CleanEx; HS_PFKL; -.
DR Genevestigator; P17858; -.
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:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0070095; F:fructose-6-phosphate binding; IDA:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006002; P:fructose 6-phosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolysis; IDA:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl.
DR GO; GO:0051289; P:protein homotetramerization; IEA:Ensembl.
DR GO; GO:0051259; P:protein oligomerization; IDA:BHF-UCL.
DR GO; GO:0009749; P:response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
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; SSF53784; 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;
KW Glycoprotein; Kinase; Magnesium; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Polymorphism; Reference proteome; 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 640 640 Phosphotyrosine (By similarity).
FT MOD_RES 775 775 Phosphoserine.
FT CARBOHYD 529 529 O-linked (GlcNAc).
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 MUTAGEN 527 527 T->A: Does not affect GlcNAcylation.
FT MUTAGEN 529 529 S->A: Prevents GlcNAcylation and enhance
FT enzyme activity.
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
//
MIM
171860
*RECORD*
*FIELD* NO
171860
*FIELD* TI
*171860 PHOSPHOFRUCTOKINASE, LIVER TYPE; PFKL
;;PFK, LIVER TYPE
*FIELD* TX
DESCRIPTION
read more
The PFKL gene encodes the liver isoform of phosphofructokinase (PFK)
(ATP:D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11). PFK
catalyzes the irreversible conversion of fructose-6-phosphate to
fructose-1,6-bisphosphate and is a key regulatory enzyme in glycolysis.
Mammalian PFK is a tetramer made up of various combinations of 3
subunits: muscle (PFKM; 610681), liver (PFKL), and platelet (PFKP;
171840), the genes for which are located on chromosomes 12q13, 21q22,
and 10p, respectively. The composition of the tetramers differs
according to the tissue type. Muscle and liver PFK are a homotetramers
of 4M and 4L subunits, respectively. Erythrocytes contain both L and M
subunits, which randomly tetramerize to form M4, L4, M3L, M2L2, and ML3
hybrid forms of the holoenzyme (Vora et al., 1980; Raben and Sherman,
1995).
CLONING
Levanon et al. (1986) isolated partial cDNA clones corresponding to the
human PFKL gene. Levanon et al. (1987) isolated overlapping cDNA clones
corresponding to the full-length human PFKL gene from a human fibroblast
cDNA library. The deduced protein has a molecular mass of 80 kD and the
PFKL mRNA is approximately 3.5 kb. Levanon et al. (1987) noted that the
L-type isoform predominates in organs with active gluconeogenesis, such
as liver and kidney. Levanon et al. (1989) stated that the human PFKL
protein contains 779 amino acids and shares approximately 90% and 68%
homology with mouse Pfkl and human PFKM, respectively.
Gehnrich et al. (1988) described the isolation and nucleotide sequencing
of mouse Pfkl cDNA and presented evidence of hormonal and nutritional
regulation of its expression.
GENE STRUCTURE
Elson et al. (1990) determined that the PFKL gene contains 22 exons and
spans approximately 28 kb.
GENE FUNCTION
Yi et al. (2012) demonstrated that the dynamic posttranslational
modification of proteins by O-linked beta-N-acetylglucosamine
(O-GlcNAcylation) is a key metabolic regulator of glucose metabolism.
O-GlcNAcylation was induced at ser529 of phosphofructokinase-1 (PFK1) in
response to hypoxia. Glycosylation inhibited PFK1 activity and
redirected glucose flux through the pentose phosphate pathway, thereby
conferring a selective growth advantage on cancer cells. Blocking
glycosylation of PFK1 at ser529 reduced cancer cell proliferation in
vitro and impaired tumor formation in vivo.
MAPPING
On the basis of apparent dosage effect in trisomy 21 (Down syndrome;
190685), Baikie et al. (1965) concluded that a gene for so-called 'red
cell' phosphofructokinase was on chromosome 21. In support of these
findings, Pantelakis et al. (1970) reported a 74% and 41% increase of
erythrocyte PFK activity in newborn and older children with Down
syndrome, respectively, suggesting localization of a gene to chromosome
21.
By somatic cell hybridization, Vora and Francke (1981) mapped the PFKL
gene to chromosome 21. The authors also found that the mean red cell PFK
was elevated in persons with Down syndrome. By study of dosage effects
in cases of partial monosomy or partial trisomy of chromosome 21,
Chadefaux et al. (1984) concluded that the liver-type PFK is located at
21q21-qter. This mapping was consistent with the regional assignment to
21q22 by Cox et al. (1984).
Van Keuren et al. (1986) mapped the PFKL gene to 21q22.3 by somatic cell
hamster-human hybridization. Levanon et al. (1986) confirmed the
assignment of PFKL to chromosome 21 by demonstrating hybridization of
genomic clones to the DNA from mouse-human hybrid cells containing
chromosome 21 as the only human chromosome. By linkage studies with
RFLPs, Petersen et al. (1991) confirmed the location of the gene in band
21q22.3 and determined its location relative to 15 other genes and DNA
markers.
Wang et al. (1992) found that NotI fragments occur preferentially in
band 21q22.3, suggesting that this band is unusually rich in genes,
since NotI sites occur almost exclusively in CpG islands. Furthermore,
comparison of the physical map and genetic map of that region showed a
10-fold higher than average recombination frequency. Band q22.3 is the
most telomeric band on chromosome 21. Mapping studies indicate a
concentration of genes in the telomeric regions of chromosomes, e.g.,
Xq28 and 11p15.5.
HISTORY
Although Layzer and Epstein (1972) found that patients with trisomy 21
(190685) had increased red blood cell PFK levels, they concluded that no
genes encoding the PFK subunits were located on chromosome 21. Their
conclusions were based on detailed immunostudies of the various PFK
isoforms.
*FIELD* SA
Vora et al. (1982)
*FIELD* RF
1. Baikie, A. G.; Loder, P. B.; de Grouchy, G. C.; Pitt, D. B.: Phosphohexokinase
activity of erythrocytes in Mongolism: another possible marker for
chromosome 21. Lancet 285: 412-414, 1965. Note: Originally Volume
1.
2. Chadefaux, B.; Rethore, M. O.; Allard, D.: Regional mapping of
liver type 6-phosphofructokinase isoenzyme on chromosome 21. Hum.
Genet. 68: 136-137, 1984.
3. Cox, D. R.; Kawashima, H.; Vora, S.; Epstein, C. J.: Regional
mapping of SOD-1, PRGS, and PFK-L on human chromosome 21. (Abstract) Cytogenet.
Cell Genet. 37: 441-442, 1984.
4. Elson, A.; Levanon, D.; Brandeis, M.; Dafni, N.; Bernstein, Y.;
Danciger, E.; Groner, Y.: The structure of the human liver-type phosphofructokinase
gene. Genomics 7: 47-56, 1990.
5. Gehnrich, S. C.; Gekakis, N.; Sul, H. S.: Liver (B-type) phosphofructokinase
mRNA: cloning, structure, and expression. J. Biol. Chem. 263: 11755-11759,
1988.
6. Layzer, R. B.; Epstein, C. J.: Phosphofructokinase and chromosome
21. Am. J. Hum. Genet. 24: 533-543, 1972.
7. Levanon, D.; Danciger, E.; Dafni, N.; Bernstein, Y.; Elson, A.;
Moens, W.; Brandeis, M.; Groner, Y.: The primary structure of human
liver type phosphofructokinase and its comparison with other types
of PFK. DNA 8: 733-743, 1989.
8. Levanon, D.; Danciger, E.; Dafni, N.; Groner, Y.: Construction
of a cDNA clone containing the entire coding region of the human liver-type
phosphofructokinase. Biochem. Biophys. Res. Commun. 147: 1182-1187,
1987.
9. Levanon, D.; Danciger, E.; Dafni, N.; Groner, Y.: Genomic clones
of the human liver-type phosphofructokinase. Biochem. Biophys. Res.
Commun. 141: 374-380, 1986.
10. Pantelakis, S. N.; Karaklis, A. G.; Alexiou, D.; Vardas, E.; Valaes,
T.: Red cell enzymes in trisomy 21. Am. J. Hum. Genet. 22: 184-193,
1970.
11. Petersen, M. B.; Slaugenhaupt, S. A.; Lewis, J. G.; Warren, A.
C.; Chakravarti, A.; Antonarakis, S. E.: A genetic linkage map of
27 markers on human chromosome 21. Genomics 9: 407-419, 1991.
12. Raben, N.; Sherman, J. B.: Mutations in muscle phosphofructokinase
gene. Hum. Mutat. 6: 1-6, 1995.
13. Van Keuren, M.; Drabkin, H.; Hart, I.; Harker, D.; Patterson,
D.; Vora, S.: Regional assignment of human liver-type 6-phosphofructokinase
to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal
anti-L antibody. Hum. Genet. 74: 34-40, 1986.
14. Vora, S.; Durham, S.; de Martinville, B.; Francke, U.: Assignment
of the genes for liver type phosphofructokinase (PFKL) to chromosome
21 and for muscle type (PFKM) to region p32-q32 of chromosome 1. (Abstract) Cytogenet.
Cell Genet. 32: 324 only, 1982.
15. Vora, S.; Francke, U.: Assignment of the human gene for liver-type
6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic
cell hybrids and monoclonal anti-L antibody. Proc. Nat. Acad. Sci. 78:
3738-3742, 1981.
16. Vora, S.; Seaman, C.; Durham, S.; Piomelli, S.: Isozymes of human
phosphofructokinase: identification and subunit structural characterization
of a new system. Proc. Nat. Acad. Sci. 77: 62-66, 1980.
17. Wang, D.; Fang, H.; Cantor, C. R.; Smith, C. L.: A contiguous
NotI restriction map of band q22.3 of human chromosome 21. Proc.
Nat. Acad. Sci. 89: 3222-3226, 1992.
18. Yi, W.; Clark, P. M.; Mason, D. E.; Keenan, M. C.; Hill, C.; Goddard,
W. A., III; Peters, E. C.; Driggers, E. M.; Hsieh-Wilson, L. C.:
Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337:
975-980, 2012.
*FIELD* CN
Ada Hamosh - updated: 9/6/2012
Cassandra L. Kniffin - reorganized: 3/8/2007
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 09/07/2012
terry: 9/6/2012
terry: 4/29/2009
carol: 3/8/2007
ckniffin: 2/26/2007
carol: 10/7/1999
mimadm: 1/14/1995
warfield: 4/12/1994
carol: 8/12/1992
carol: 8/11/1992
carol: 6/4/1992
supermim: 3/16/1992
*RECORD*
*FIELD* NO
171860
*FIELD* TI
*171860 PHOSPHOFRUCTOKINASE, LIVER TYPE; PFKL
;;PFK, LIVER TYPE
*FIELD* TX
DESCRIPTION
read more
The PFKL gene encodes the liver isoform of phosphofructokinase (PFK)
(ATP:D-fructose-6-phosphate-1-phosphotransferase, EC 2.7.1.11). PFK
catalyzes the irreversible conversion of fructose-6-phosphate to
fructose-1,6-bisphosphate and is a key regulatory enzyme in glycolysis.
Mammalian PFK is a tetramer made up of various combinations of 3
subunits: muscle (PFKM; 610681), liver (PFKL), and platelet (PFKP;
171840), the genes for which are located on chromosomes 12q13, 21q22,
and 10p, respectively. The composition of the tetramers differs
according to the tissue type. Muscle and liver PFK are a homotetramers
of 4M and 4L subunits, respectively. Erythrocytes contain both L and M
subunits, which randomly tetramerize to form M4, L4, M3L, M2L2, and ML3
hybrid forms of the holoenzyme (Vora et al., 1980; Raben and Sherman,
1995).
CLONING
Levanon et al. (1986) isolated partial cDNA clones corresponding to the
human PFKL gene. Levanon et al. (1987) isolated overlapping cDNA clones
corresponding to the full-length human PFKL gene from a human fibroblast
cDNA library. The deduced protein has a molecular mass of 80 kD and the
PFKL mRNA is approximately 3.5 kb. Levanon et al. (1987) noted that the
L-type isoform predominates in organs with active gluconeogenesis, such
as liver and kidney. Levanon et al. (1989) stated that the human PFKL
protein contains 779 amino acids and shares approximately 90% and 68%
homology with mouse Pfkl and human PFKM, respectively.
Gehnrich et al. (1988) described the isolation and nucleotide sequencing
of mouse Pfkl cDNA and presented evidence of hormonal and nutritional
regulation of its expression.
GENE STRUCTURE
Elson et al. (1990) determined that the PFKL gene contains 22 exons and
spans approximately 28 kb.
GENE FUNCTION
Yi et al. (2012) demonstrated that the dynamic posttranslational
modification of proteins by O-linked beta-N-acetylglucosamine
(O-GlcNAcylation) is a key metabolic regulator of glucose metabolism.
O-GlcNAcylation was induced at ser529 of phosphofructokinase-1 (PFK1) in
response to hypoxia. Glycosylation inhibited PFK1 activity and
redirected glucose flux through the pentose phosphate pathway, thereby
conferring a selective growth advantage on cancer cells. Blocking
glycosylation of PFK1 at ser529 reduced cancer cell proliferation in
vitro and impaired tumor formation in vivo.
MAPPING
On the basis of apparent dosage effect in trisomy 21 (Down syndrome;
190685), Baikie et al. (1965) concluded that a gene for so-called 'red
cell' phosphofructokinase was on chromosome 21. In support of these
findings, Pantelakis et al. (1970) reported a 74% and 41% increase of
erythrocyte PFK activity in newborn and older children with Down
syndrome, respectively, suggesting localization of a gene to chromosome
21.
By somatic cell hybridization, Vora and Francke (1981) mapped the PFKL
gene to chromosome 21. The authors also found that the mean red cell PFK
was elevated in persons with Down syndrome. By study of dosage effects
in cases of partial monosomy or partial trisomy of chromosome 21,
Chadefaux et al. (1984) concluded that the liver-type PFK is located at
21q21-qter. This mapping was consistent with the regional assignment to
21q22 by Cox et al. (1984).
Van Keuren et al. (1986) mapped the PFKL gene to 21q22.3 by somatic cell
hamster-human hybridization. Levanon et al. (1986) confirmed the
assignment of PFKL to chromosome 21 by demonstrating hybridization of
genomic clones to the DNA from mouse-human hybrid cells containing
chromosome 21 as the only human chromosome. By linkage studies with
RFLPs, Petersen et al. (1991) confirmed the location of the gene in band
21q22.3 and determined its location relative to 15 other genes and DNA
markers.
Wang et al. (1992) found that NotI fragments occur preferentially in
band 21q22.3, suggesting that this band is unusually rich in genes,
since NotI sites occur almost exclusively in CpG islands. Furthermore,
comparison of the physical map and genetic map of that region showed a
10-fold higher than average recombination frequency. Band q22.3 is the
most telomeric band on chromosome 21. Mapping studies indicate a
concentration of genes in the telomeric regions of chromosomes, e.g.,
Xq28 and 11p15.5.
HISTORY
Although Layzer and Epstein (1972) found that patients with trisomy 21
(190685) had increased red blood cell PFK levels, they concluded that no
genes encoding the PFK subunits were located on chromosome 21. Their
conclusions were based on detailed immunostudies of the various PFK
isoforms.
*FIELD* SA
Vora et al. (1982)
*FIELD* RF
1. Baikie, A. G.; Loder, P. B.; de Grouchy, G. C.; Pitt, D. B.: Phosphohexokinase
activity of erythrocytes in Mongolism: another possible marker for
chromosome 21. Lancet 285: 412-414, 1965. Note: Originally Volume
1.
2. Chadefaux, B.; Rethore, M. O.; Allard, D.: Regional mapping of
liver type 6-phosphofructokinase isoenzyme on chromosome 21. Hum.
Genet. 68: 136-137, 1984.
3. Cox, D. R.; Kawashima, H.; Vora, S.; Epstein, C. J.: Regional
mapping of SOD-1, PRGS, and PFK-L on human chromosome 21. (Abstract) Cytogenet.
Cell Genet. 37: 441-442, 1984.
4. Elson, A.; Levanon, D.; Brandeis, M.; Dafni, N.; Bernstein, Y.;
Danciger, E.; Groner, Y.: The structure of the human liver-type phosphofructokinase
gene. Genomics 7: 47-56, 1990.
5. Gehnrich, S. C.; Gekakis, N.; Sul, H. S.: Liver (B-type) phosphofructokinase
mRNA: cloning, structure, and expression. J. Biol. Chem. 263: 11755-11759,
1988.
6. Layzer, R. B.; Epstein, C. J.: Phosphofructokinase and chromosome
21. Am. J. Hum. Genet. 24: 533-543, 1972.
7. Levanon, D.; Danciger, E.; Dafni, N.; Bernstein, Y.; Elson, A.;
Moens, W.; Brandeis, M.; Groner, Y.: The primary structure of human
liver type phosphofructokinase and its comparison with other types
of PFK. DNA 8: 733-743, 1989.
8. Levanon, D.; Danciger, E.; Dafni, N.; Groner, Y.: Construction
of a cDNA clone containing the entire coding region of the human liver-type
phosphofructokinase. Biochem. Biophys. Res. Commun. 147: 1182-1187,
1987.
9. Levanon, D.; Danciger, E.; Dafni, N.; Groner, Y.: Genomic clones
of the human liver-type phosphofructokinase. Biochem. Biophys. Res.
Commun. 141: 374-380, 1986.
10. Pantelakis, S. N.; Karaklis, A. G.; Alexiou, D.; Vardas, E.; Valaes,
T.: Red cell enzymes in trisomy 21. Am. J. Hum. Genet. 22: 184-193,
1970.
11. Petersen, M. B.; Slaugenhaupt, S. A.; Lewis, J. G.; Warren, A.
C.; Chakravarti, A.; Antonarakis, S. E.: A genetic linkage map of
27 markers on human chromosome 21. Genomics 9: 407-419, 1991.
12. Raben, N.; Sherman, J. B.: Mutations in muscle phosphofructokinase
gene. Hum. Mutat. 6: 1-6, 1995.
13. Van Keuren, M.; Drabkin, H.; Hart, I.; Harker, D.; Patterson,
D.; Vora, S.: Regional assignment of human liver-type 6-phosphofructokinase
to chromosome 21q22.3 by using somatic cell hybrids and a monoclonal
anti-L antibody. Hum. Genet. 74: 34-40, 1986.
14. Vora, S.; Durham, S.; de Martinville, B.; Francke, U.: Assignment
of the genes for liver type phosphofructokinase (PFKL) to chromosome
21 and for muscle type (PFKM) to region p32-q32 of chromosome 1. (Abstract) Cytogenet.
Cell Genet. 32: 324 only, 1982.
15. Vora, S.; Francke, U.: Assignment of the human gene for liver-type
6-phosphofructokinase isozyme (PFKL) to chromosome 21 by using somatic
cell hybrids and monoclonal anti-L antibody. Proc. Nat. Acad. Sci. 78:
3738-3742, 1981.
16. Vora, S.; Seaman, C.; Durham, S.; Piomelli, S.: Isozymes of human
phosphofructokinase: identification and subunit structural characterization
of a new system. Proc. Nat. Acad. Sci. 77: 62-66, 1980.
17. Wang, D.; Fang, H.; Cantor, C. R.; Smith, C. L.: A contiguous
NotI restriction map of band q22.3 of human chromosome 21. Proc.
Nat. Acad. Sci. 89: 3222-3226, 1992.
18. Yi, W.; Clark, P. M.; Mason, D. E.; Keenan, M. C.; Hill, C.; Goddard,
W. A., III; Peters, E. C.; Driggers, E. M.; Hsieh-Wilson, L. C.:
Phosphofructokinase 1 glycosylation regulates cell growth and metabolism. Science 337:
975-980, 2012.
*FIELD* CN
Ada Hamosh - updated: 9/6/2012
Cassandra L. Kniffin - reorganized: 3/8/2007
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
alopez: 09/07/2012
terry: 9/6/2012
terry: 4/29/2009
carol: 3/8/2007
ckniffin: 2/26/2007
carol: 10/7/1999
mimadm: 1/14/1995
warfield: 4/12/1994
carol: 8/12/1992
carol: 8/11/1992
carol: 6/4/1992
supermim: 3/16/1992