P12382 (K6PL_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
6-phosphofructokinase, liver type
EC=2.7.1.11

Alternative name(s):
Phosphofructo-1-kinase isozyme B
Short name=PFK-B
Phosphofructokinase 1
Phosphohexokinase

Gene names

Name:	Pfkl
Synonyms:	Pfk-l, Pfkb

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	780 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the third step of glycolysis, the phosphorylation of fructose-6-phosphate (F6P) by ATP to generate fructose-1,6-bisphosphate (FBP) and ADP.
Catalytic activity	ATP + D-fructose 6-phosphate = ADP + D-fructose 1,6-bisphosphate.
Cofactor	Magnesium.
Enzyme regulation	Allosteric enzyme activated by ADP, AMP, or fructose bisphosphate and inhibited by ATP or citrate. GlcNAcylation by OGT overcomes allosteric regulation By similarity.
Pathway	Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4.
Subunit structure	Homotetramer.
Post-translational modification	GlcNAcylation at Ser-529 by OGT decreases enzyme activity, leading to redirect glucose flux through the oxidative pentose phosphate pathway. Glycosylation is stimulated by both hypoxia and glucose deprivation By similarity.
Sequence similarities	Belongs to the phosphofructokinase family. Two domains subfamily.

Ontologies

Keywords
Biological process	Glycolysis
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation Glycoprotein Phosphoprotein
Technical term	Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fructose 1,6-bisphosphate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB fructose 6-phosphate metabolic process Inferred from direct assay PubMed 8172601PubMed 9287040. Source: MGI glycolysis Inferred from direct assay PubMed 8172601PubMed 9287040. Source: MGI negative regulation of insulin secretion Inferred from direct assay PubMed 9287040. Source: MGI protein homotetramerization Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from direct assay PubMed 9287040. Source: MGI
Cellular_component	6-phosphofructokinase complex Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay PubMed 2521854. Source: MGI
Molecular_function	6-phosphofructokinase activity Inferred from direct assay PubMed 8172601PubMed 9287040. Source: MGI ATP binding Inferred from electronic annotation. Source: UniProtKB-KW fructose binding Inferred from electronic annotation. Source: Compara fructose-6-phosphate binding Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 780	779	6-phosphofructokinase, liver type		PRO_0000112022
Regions
	Nucleotide binding	35 – 39	5	ATP By similarity
	Nucleotide binding	193 – 197	5	ATP By similarity
	Nucleotide binding	210 – 226	17	ATP By similarity
Sites
	Active site	166	1	Proton acceptor By similarity
	Metal binding	224	1	Magnesium; via carbonyl oxygen By similarity
	Binding site	201	1	Substrate By similarity
	Binding site	292	1	Substrate By similarity
	Binding site	298	1	Substrate By similarity
	Binding site	301	1	Substrate By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	640	1	Phosphotyrosine Ref.6
	Modified residue	775	1	Phosphoserine Ref.7
	Glycosylation	529	1	O-linked (GlcNAc...) By similarity
Experimental info
	Sequence conflict	419	1	R → P in AAA20076. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P12382 [UniParc]. Last modified July 27, 2011. Version 4. Checksum: 0C12E2C222020B7F	FASTA	780	85,360
	10 20 30 40 50 60 MATVDLEKLR MSGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE 70 80 90 100 110 120 GGENIKPANW LSVSNIIQLG GTIIGSARCK AFTTREGRLA AAYNLLQHGI TNLCVIGGDG 130 140 150 160 170 180 SLTGANIFRN EWGSLLEELV KEGKISESTA QNYAHLTIAG LVGSIDNDFC GTDMTIGTDS 190 200 210 220 230 240 ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE 250 260 270 280 290 300 NFMCERLGET RSRGSRLNII IIAEGAIDRH GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ 310 320 330 340 350 360 RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVSLSG NQSVRLPLME CVQVTKDVQK 370 380 390 400 410 420 AMDEERFDEA IQLRGRSFEN NWKIYKLLAH QKVSKEKSNF SLAILNVGAP AAGMNAAVRS 430 440 450 460 470 480 AVRTGISEGH TVYIVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKPHLEAI 490 500 510 520 530 540 VENLRTYNIH ALLVIGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG 550 560 570 580 590 600 SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN 610 620 630 640 650 660 IHDLKANVEH MTEKMKTDIQ RGLVLRNEKC HEHYTTEFLY NLYSSEGRGV FDCRTNVLGH 670 680 690 700 710 720 LQQGGAPTPF DRNYGTKLGV KAMLWVSEKL RDVYRKGRVF ANAPDSACVI GLRKKVVAFS 730 740 750 760 770 780 PVTELKKETD FEHRMPREQW WLNLRLMLKM LAHYRISMAD YVSGELEHVT RRTLSIDKGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Liver (B-type) phosphofructokinase mRNA. Cloning, structure, and expression." Gehnrich S.C., Gekakis N., Sul H.S. J. Biol. Chem. 263:11755-11759(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Cerebellum, Head and Pituitary.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Czech II. Tissue: Mammary tumor.
[5]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 130-141; 257-269; 367-374; 655-672 AND 716-726, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[6]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-640, MASS SPECTROMETRY. Tissue: Brain.
[7]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J03928 mRNA. Translation: AAA20076.1. AK030511 mRNA. Translation: BAC26997.1. AK036318 mRNA. Translation: BAC29382.1. AK081313 mRNA. Translation: BAC38193.1. AK159328 mRNA. Translation: BAE34994.1. CH466553 Genomic DNA. Translation: EDL31763.1. BC020097 mRNA. Translation: AAH20097.1.
IPI	IPI00554862.
PIR	A31070.
RefSeq	NP_032852.2. NM_008826.4.
UniGene	Mm.269649.
3D structure databases
ProteinModelPortal	P12382.
SMR	P12382. Positions 10-754.
ModBase	Search...
Protein-protein interaction databases
IntAct	P12382. 6 interactions.
MINT	MINT-135975.
PTM databases
PhosphoSite	P12382.
Proteomic databases
PaxDb	P12382.
PRIDE	P12382.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020522; ENSMUSP00000020522; ENSMUSG00000020277.
GeneID	18641.
KEGG	mmu:18641.
Organism-specific databases
CTD	5211.
MGI	MGI:97547. Pfkl.
Phylogenomic databases
eggNOG	COG0205.
GeneTree	ENSGT00390000013209.
HOGENOM	HOG000200154.
HOVERGEN	HBG000976.
InParanoid	Q8VDX7.
KO	K00850.
OMA	PISSSYV.
OrthoDB	EOG4RJG0W.
Enzyme and pathway databases
SABIO-RK	P12382.
UniPathway	UPA00109; UER00182.
Gene expression databases
ArrayExpress	P12382.
Bgee	P12382.
CleanEx	MM_PFKL.
Genevestigator	P12382.
GermOnline	ENSMUSG00000020277. Mus musculus.
Family and domain databases
InterPro	IPR009161. 6-phosphofructokinase_euk. IPR022953. Phosphofructokinase. IPR015912. Phosphofructokinase_CS. IPR000023. Phosphofructokinase_dom. [Graphical view]
Pfam	PF00365. PFK. 2 hits. [Graphical view]
PIRSF	PIRSF000533. ATP_PFK_euk. 1 hit.
PRINTS	PR00476. PHFRCTKINASE.
SUPFAM	SSF53784. Ppfruckinase. 2 hits.
TIGRFAMs	TIGR02478. 6PF1K_euk. 1 hit.
PROSITE	PS00433. PHOSPHOFRUCTOKINASE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	294626.
SOURCE	Search...

Entry information

Entry name

K6PL_MOUSE

Accession

Primary (citable) accession number: P12382
Secondary accession number(s): Q8VDX7

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 127 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program