Reviewed, UniProtKB/Swiss-Prot P17858 (K6PL_HUMAN)

Names and origin

Protein names

Recommended name:
    6-phosphofructokinase, liver type
    EC=2.7.1.11
Alternative name(s):
    Phosphofructokinase 1
    Phosphohexokinase
    Phosphofructo-1-kinase isozyme B
      Short name=PFK-B

Gene names

Name:

PFKL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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)

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.
Pathway	Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4.
Subunit structure	Tetramer. Muscle is M4, liver is L4, and red cell is M3L, M2L2, or ML3.
Miscellaneous	In human PFK exists as a system of 3 types of subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.
Sequence similarities	Belongs to the phosphofructokinase family. Two domains subfamily.

Ontologies

Keywords
Biological process	Glycolysis
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Allosteric enzyme Direct protein sequencing
Gene Ontology (GO)
Biological process	fructose 6-phosphate metabolic process Inferred from direct assay. Source: UniProtKB glycolysis Inferred from direct assay. Source: UniProtKB protein oligomerization Inferred from direct assay. Source: UniProtKB
Cellular component	6-phosphofructokinase complex Inferred from direct assay. Source: UniProtKB
Molecular function	6-phosphofructokinase activity Inferred from direct assay. Source: UniProtKB ATP binding Inferred from direct assay. Source: UniProtKB fructose-6-phosphate binding Inferred from direct assay. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: UniProtKB kinase binding Inferred from physical interaction. Source: UniProtKB magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P17858-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P17858-2)

Also known as: a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MAAVDLEKLRASGAGKAIGVLTSGGDAQ → MCNQGRGRES...GGTSIMSRLG

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.5
	Chain	2 – 780	779	6-phosphofructokinase, liver type		PRO_0000112021
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	633	1	Phosphotyrosine Ref.6
	Modified residue	640	1	Phosphotyrosine By similarity
	Modified residue	775	1	Phosphoserine Ref.7 Ref.8
Natural variations
	Alternative sequence	1 – 28	28	MAAVD…GGDAQ → MCNQGRGRESSRGGLHVQGS CRGLSRSPQQETGFAKAPAG TDCFFHCSPGSRGQGDRKEE VTSEPGGTSIMSRLG in isoform 2.		VSP_011854
	Natural variant	81	1	G → A Ref.2		VAR_006070
	Natural variant	151	1	R → W Ref.1		VAR_006071
	Natural variant	237	1	D → V: dbSNP rs1057037.		VAR_030872
Experimental info
	Sequence conflict	27	1	A → R in CAA33597. Ref.1
	Sequence conflict	27	1	A → R in CAB46744. Ref.2
	Sequence conflict	86	1	S → T in CAB46744. Ref.2
	Sequence conflict	89	1	C → S in CAA33597. Ref.1
	Sequence conflict	89	1	C → S in CAB46744. Ref.2
	Sequence conflict	103	1	Y → N in CAB46744. Ref.2
	Sequence conflict	236	1	E → EAPPE in CAB46744. Ref.2
	Sequence conflict	386	1	K → R in CAB46744. Ref.2
	Sequence conflict	389	1	A → T in CAA33597. Ref.1
	Sequence conflict	389	1	A → T in CAB46744. Ref.2
	Sequence conflict	648	1	K → N in AAH08964. Ref.4
	Sequence conflict	648	1	K → N in AAH09919. Ref.4
	Sequence conflict	717	1	V → A in AAH08964. Ref.4
	Sequence conflict	717	1	V → A in AAH09919. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 6, 2007. Version 6. Checksum: 0D686CE074E9626D	FASTA	780	85,018
	10 20 30 40 50 60 MAAVDLEKLR ASGAGKAIGV LTSGGDAQGM NAAVRAVTRM GIYVGAKVFL IYEGYEGLVE 70 80 90 100 110 120 GGENIKQANW LSVSNIIQLG GTIIGSARCK AFTTREGRRA AAYNLVQHGI TNLCVIGGDG 130 140 150 160 170 180 SLTGANIFRS EWGSLLEELV AEGKISETTA RTYSHLNIAG LVGSIDNDFC GTDMTIGTDS 190 200 210 220 230 240 ALHRIMEVID AITTTAQSHQ RTFVLEVMGR HCGYLALVSA LASGADWLFI PEAPPEDGWE 250 260 270 280 290 300 NFMCERLGET RSRGSRLNII IIAEGAIDRN GKPISSSYVK DLVVQRLGFD TRVTVLGHVQ 310 320 330 340 350 360 RGGTPSAFDR ILSSKMGMEA VMALLEATPD TPACVVTLSG NQSVRLPLME CVQMTKEVQK 370 380 390 400 410 420 AMDDKRFDEA TQLRGGSFEN NWNIYKLLAH QKPPKEKSNF SLAILNVGAP AAGMNAAVRS 430 440 450 460 470 480 AVRTGISHGH TVYVVHDGFE GLAKGQVQEV GWHDVAGWLG RGGSMLGTKR TLPKGQLESI 490 500 510 520 530 540 VENIRIYGIH ALLVVGGFEA YEGVLQLVEA RGRYEELCIV MCVIPATISN NVPGTDFSLG 550 560 570 580 590 600 SDTAVNAAME SCDRIKQSAS GTKRRVFIVE TMGGYCGYLA TVTGIAVGAD AAYVFEDPFN 610 620 630 640 650 660 IHDLKVNVEH MTEKMKTDIQ RGLVLRNEKC HDYYTTEFLY NLYSSEGKGV FDCRTNVLGH 670 680 690 700 710 720 LQQGGAPTPF DRNYGTKLGV KAMLWLSEKL REVYRKGRVF ANAPDSACVI GLKKKAVAFS 730 740 750 760 770 780 PVTELKKDTD FEHRMPREQW WLSLRLMLKM LAQYRISMAA YVSGELEHVT RRTLSMDKGF
	Isoform 2 (a). Checksum: ADBECCB9B1FB234C	FASTA	827	90,203
	10 20 30 40 50 60 MCNQGRGRES SRGGLHVQGS CRGLSRSPQQ ETGFAKAPAG TDCFFHCSPG SRGQGDRKEE 70 80 90 100 110 120 VTSEPGGTSI MSRLGGMNAA VRAVTRMGIY VGAKVFLIYE GYEGLVEGGE NIKQANWLSV 130 140 150 160 170 180 SNIIQLGGTI IGSARCKAFT TREGRRAAAY NLVQHGITNL CVIGGDGSLT GANIFRSEWG 190 200 210 220 230 240 SLLEELVAEG KISETTARTY SHLNIAGLVG SIDNDFCGTD MTIGTDSALH RIMEVIDAIT 250 260 270 280 290 300 TTAQSHQRTF VLEVMGRHCG YLALVSALAS GADWLFIPEA PPEDGWENFM CERLGETRSR 310 320 330 340 350 360 GSRLNIIIIA EGAIDRNGKP ISSSYVKDLV VQRLGFDTRV TVLGHVQRGG TPSAFDRILS 370 380 390 400 410 420 SKMGMEAVMA LLEATPDTPA CVVTLSGNQS VRLPLMECVQ MTKEVQKAMD DKRFDEATQL 430 440 450 460 470 480 RGGSFENNWN IYKLLAHQKP PKEKSNFSLA ILNVGAPAAG MNAAVRSAVR TGISHGHTVY 490 500 510 520 530 540 VVHDGFEGLA KGQVQEVGWH DVAGWLGRGG SMLGTKRTLP KGQLESIVEN IRIYGIHALL 550 560 570 580 590 600 VVGGFEAYEG VLQLVEARGR YEELCIVMCV IPATISNNVP GTDFSLGSDT AVNAAMESCD 610 620 630 640 650 660 RIKQSASGTK RRVFIVETMG GYCGYLATVT GIAVGADAAY VFEDPFNIHD LKVNVEHMTE 670 680 690 700 710 720 KMKTDIQRGL VLRNEKCHDY YTTEFLYNLY SSEGKGVFDC RTNVLGHLQQ GGAPTPFDRN 730 740 750 760 770 780 YGTKLGVKAM LWLSEKLREV YRKGRVFANA PDSACVIGLK KKAVAFSPVT ELKKDTDFEH 790 800 810 820 RMPREQWWLS LRLMLKMLAQ YRISMAAYVS GELEHVTRRT LSMDKGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The primary structure of human liver type phosphofructokinase and its comparison with other types of PFK." Levanon D., Danciger E., Dafni N., Bernstein Y., Elson A., Moens W., Brandeis M., Groner Y. DNA 8:733-743(1989) [PubMed: 2533063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TRP-151. Tissue: Liver.
[2]	"The structure of the human liver-type phosphofructokinase gene." Elson A., Levanon D., Brandeis M., Dafni N., Bernstein Y., Danciger E., Groner Y. Genomics 7:47-56(1990) [PubMed: 2139864] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT ALA-81.
[3]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] 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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Kidney, Lung and Muscle.
[5]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-10 (ISOFORM 1). Tissue: Platelet.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-633, MASS SPECTROMETRY.
[7]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, MASS SPECTROMETRY.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-775, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X15573 mRNA. Translation: CAA33597.1. X16911 , X16912, X16913, X16914, X16915, X16916, X16917, X16918, X16919, X16920, X16921, X16922, X16923, X16924, X16925, X16926, X16927, X16928, X16929, X16930 Genomic DNA. Translation: CAB46744.1. AP001754 Genomic DNA. Translation: BAA95561.1. BC006422 mRNA. Translation: AAH06422.1. BC007536 mRNA. Translation: AAH07536.1. BC008964 mRNA. Translation: AAH08964.1. BC009919 mRNA. Translation: AAH09919.1.
IPI	IPI00332371. IPI00925288.
PIR	A33639.
RefSeq	NP_002617.3.
UniGene	Hs.255093
3D structure databases
HSSP	HSSP built from PDB template 3PFK based on UniProtKB P00512.
ModBase	Search...
Protein-protein interaction databases
IntAct	P17858. 13 interactions.
PTM databases
PhosphoSite	P17858.
Proteomic databases
PRIDE	P17858.
Genome annotation databases
Ensembl	ENSG00000141959. Homo sapiens. [Contig view]
GeneID	5211.
KEGG	hsa:5211.
NMPDR	fig|9606.3.peg.21069.
Organism-specific databases
GeneCards	GC21P044544.
HGNC	HGNC:8876. PFKL.
MIM	171860. gene.
PharmGKB	PA33215.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P17858.
Enzyme and pathway databases
BRENDA	2.7.1.11. 247.
Pathway_Interaction_DB	hif1_tfpathway. HIF-1-alpha transcription factor network.
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	P17858.
Bgee	P17858.
CleanEx	HS_PFKL.
GermOnline	ENSG00000141959. Homo sapiens.
Family and domain databases
InterPro	IPR009161. 6-phosphofructokinase_euk. IPR000023. Phosphofructokinase. IPR015912. Phosphofructokinase_CS. [Graphical view]
Pfam	PF00365. PFK. 2 hits. [Graphical view]
PIRSF	PIRSF000533. ATP_PFK_euk. 1 hit.
PRINTS	PR00476. PHFRCTKINASE.
ProDom	PD000707. Ppfruckinase. 2 hits. [Graphical view] [Entries sharing at least one domain]
TIGRFAMs	TIGR02478. 6PF1K_euk. 1 hit.
PROSITE	PS00433. PHOSPHOFRUCTOKINASE. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	20154.
PMAP-CutDB	P17858.
SOURCE	Search...

Entry information

Entry name

K6PL_HUMAN

Accession

Primary (citable) accession number: P17858
Secondary accession number(s): Q96A64, Q96IH4, Q9BR91

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	March 6, 2007
Last modified:	June 16, 2009
This is version 118 of the entry and version 6 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)