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Protein

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4

Gene

PFKFB4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Synthesis and degradation of fructose 2,6-bisphosphate.

Catalytic activityi

Beta-D-fructose 2,6-bisphosphate + H2O = D-fructose 6-phosphate + phosphate.
ATP + D-fructose 6-phosphate = ADP + beta-D-fructose 2,6-bisphosphate.

Enzyme regulationi

The most important regulatory mechanism of these opposing activities is by phosphorylation and dephosphorylation of the enzyme.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei79 – 791Fructose 6-phosphateBy similarity
Binding sitei103 – 1031Fructose 6-phosphateBy similarity
Active sitei129 – 1291Sequence analysis
Binding sitei131 – 1311Fructose 6-phosphateBy similarity
Binding sitei137 – 1371Fructose 6-phosphateBy similarity
Active sitei159 – 1591Sequence analysis
Binding sitei173 – 1731Fructose 6-phosphateBy similarity
Binding sitei194 – 1941Fructose 6-phosphateBy similarity
Binding sitei198 – 1981Fructose 6-phosphateBy similarity
Binding sitei256 – 2561Fructose 2,6-bisphosphateBy similarity
Active sitei257 – 2571Tele-phosphohistidine intermediateBy similarity
Binding sitei263 – 2631Fructose 2,6-bisphosphateBy similarity
Binding sitei269 – 2691Fructose 2,6-bisphosphate; via amide nitrogenBy similarity
Binding sitei306 – 3061Fructose 2,6-bisphosphateBy similarity
Active sitei326 – 3261Proton donor/acceptorBy similarity
Binding sitei337 – 3371Fructose 2,6-bisphosphateBy similarity
Binding sitei351 – 3511Fructose 2,6-bisphosphateBy similarity
Binding sitei355 – 3551Fructose 2,6-bisphosphateBy similarity
Binding sitei366 – 3661Fructose 2,6-bisphosphateBy similarity
Sitei391 – 3911Transition state stabilizerBy similarity
Binding sitei392 – 3921Fructose 2,6-bisphosphateBy similarity
Binding sitei396 – 3961Fructose 2,6-bisphosphateBy similarity
Binding sitei428 – 4281ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi46 – 549ATPBy similarity
Nucleotide bindingi168 – 1736ATPBy similarity
Nucleotide bindingi348 – 3514ATPBy similarity
Nucleotide bindingi392 – 3965ATPBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-70171. Glycolysis.

Names & Taxonomyi

Protein namesi
Recommended name:
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4
Short name:
6PF-2-K/Fru-2,6-P2ase 4
Short name:
PFK/FBPase 4
Alternative name(s):
6PF-2-K/Fru-2,6-P2ase testis-type isozyme
Including the following 2 domains:
Fructose-2,6-bisphosphatase (EC:3.1.3.46)
Gene namesi
Name:PFKFB4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:8875. PFKFB4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33214.

Polymorphism and mutation databases

BioMutaiPFKFB4.
DMDMi6226609.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4694696-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4PRO_0000179970Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei444 – 4441Phosphothreonine; by PKCSequence analysis

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ16877.
MaxQBiQ16877.
PaxDbiQ16877.
PRIDEiQ16877.

PTM databases

DEPODiQ16877.
iPTMnetiQ16877.
PhosphoSiteiQ16877.

Expressioni

Gene expression databases

BgeeiQ16877.
CleanExiHS_PFKFB4.
ExpressionAtlasiQ16877. baseline and differential.
GenevisibleiQ16877. HS.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

BioGridi111231. 5 interactions.
IntActiQ16877. 3 interactions.
MINTiMINT-8247435.
STRINGi9606.ENSP00000232375.

Structurei

3D structure databases

ProteinModelPortaliQ16877.
SMRiQ16877. Positions 4-469.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2492496-phosphofructo-2-kinaseAdd
BLAST
Regioni250 – 469220Fructose-2,6-bisphosphataseAdd
BLAST

Sequence similaritiesi

In the C-terminal section; belongs to the phosphoglycerate mutase family.Curated

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiQ16877.
KOiK19030.
OMAiSPDYTNC.
OrthoDBiEOG7M3J03.
PhylomeDBiQ16877.
TreeFamiTF313541.

Family and domain databases

Gene3Di3.40.50.1240. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERiPTHR10606. PTHR10606. 1 hit.
PfamiPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PRINTSiPR00991. 6PFRUCTKNASE.
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q16877-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MASPRELTQN PLKKIWMPYS NGRPALHACQ RGVCMTNCPT LIVMVGLPAR
60 70 80 90 100
GKTYISKKLT RYLNWIGVPT REFNVGQYRR DVVKTYKSFE FFLPDNEEGL
110 120 130 140 150
KIRKQCALAA LRDVRRFLSE EGGHVAVFDA TNTTRERRAT IFNFGEQNGY
160 170 180 190 200
KTFFVESICV DPEVIAANIV QVKLGSPDYV NRDSDEATED FMRRIECYEN
210 220 230 240 250
SYESLDEDLD RDLSYIKIMD VGQSYVVNRV ADHIQSRIVY YLMNIHVTPR
260 270 280 290 300
SIYLCRHGES ELNLKGRIGG DPGLSPRGRE FAKSLAQFIS DQNIKDLKVW
310 320 330 340 350
TSQMKRTIQT AEALGVPYEQ WKVLNEIDAG VCEEMTYEEI QDNYPLEFAL
360 370 380 390 400
RDQDKYRYRY PKGESYEDLV QRLEPVIMEL ERQENVLVIC HQAVMRCLLA
410 420 430 440 450
YFLDKAAEQL PYLKCPLHTV LKLTPVAYGC KVESIFLNVA AVNTHRDRPQ
460
NVDISRPPEE ALVTVPAHQ
Length:469
Mass (Da):54,040
Last modified:January 23, 2007 - v6
Checksum:i7E190C3C0A197D9F
GO
Isoform 2 (identifier: Q16877-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     330-364: Missing.

Show »
Length:434
Mass (Da):49,708
Checksum:i223B1A32CE970560
GO
Isoform 3 (identifier: Q16877-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: Missing.

Show »
Length:435
Mass (Da):50,203
Checksum:i814E51B938C76DA4
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti181 – 1811N → K in a breast cancer sample; somatic mutation. 1 Publication
VAR_036075

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 3434Missing in isoform 3. 2 PublicationsVSP_056621Add
BLAST
Alternative sequencei330 – 36435Missing in isoform 2. 1 PublicationVSP_056530Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY756062 mRNA. Translation: AAV28717.1.
AY756064 mRNA. Translation: AAV28719.1.
D49818 mRNA. Translation: BAA18921.1.
AY714243 mRNA. Translation: AAU14998.1.
AF108765 mRNA. Translation: AAD09427.1.
AY786551 Genomic DNA. Translation: AAV65753.1.
AC134772 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64890.1.
BC010269 mRNA. Translation: AAH10269.1.
CCDSiCCDS2771.1. [Q16877-1]
PIRiJC5871.
RefSeqiNP_001304063.1. NM_001317134.1.
NP_001304064.1. NM_001317135.1.
NP_001304065.1. NM_001317136.1.
NP_001304066.1. NM_001317137.1. [Q16877-2]
NP_001304067.1. NM_001317138.1.
NP_004558.1. NM_004567.3. [Q16877-1]
UniGeneiHs.476217.

Genome annotation databases

EnsembliENST00000232375; ENSP00000232375; ENSG00000114268. [Q16877-1]
ENST00000383734; ENSP00000373240; ENSG00000114268. [Q16877-2]
GeneIDi5210.
KEGGihsa:5210.
UCSCiuc003ctv.4. human. [Q16877-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY756062 mRNA. Translation: AAV28717.1.
AY756064 mRNA. Translation: AAV28719.1.
D49818 mRNA. Translation: BAA18921.1.
AY714243 mRNA. Translation: AAU14998.1.
AF108765 mRNA. Translation: AAD09427.1.
AY786551 Genomic DNA. Translation: AAV65753.1.
AC134772 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64890.1.
BC010269 mRNA. Translation: AAH10269.1.
CCDSiCCDS2771.1. [Q16877-1]
PIRiJC5871.
RefSeqiNP_001304063.1. NM_001317134.1.
NP_001304064.1. NM_001317135.1.
NP_001304065.1. NM_001317136.1.
NP_001304066.1. NM_001317137.1. [Q16877-2]
NP_001304067.1. NM_001317138.1.
NP_004558.1. NM_004567.3. [Q16877-1]
UniGeneiHs.476217.

3D structure databases

ProteinModelPortaliQ16877.
SMRiQ16877. Positions 4-469.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111231. 5 interactions.
IntActiQ16877. 3 interactions.
MINTiMINT-8247435.
STRINGi9606.ENSP00000232375.

PTM databases

DEPODiQ16877.
iPTMnetiQ16877.
PhosphoSiteiQ16877.

Polymorphism and mutation databases

BioMutaiPFKFB4.
DMDMi6226609.

Proteomic databases

EPDiQ16877.
MaxQBiQ16877.
PaxDbiQ16877.
PRIDEiQ16877.

Protocols and materials databases

DNASUi5210.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000232375; ENSP00000232375; ENSG00000114268. [Q16877-1]
ENST00000383734; ENSP00000373240; ENSG00000114268. [Q16877-2]
GeneIDi5210.
KEGGihsa:5210.
UCSCiuc003ctv.4. human. [Q16877-1]

Organism-specific databases

CTDi5210.
GeneCardsiPFKFB4.
HGNCiHGNC:8875. PFKFB4.
MIMi605320. gene.
neXtProtiNX_Q16877.
PharmGKBiPA33214.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0234. Eukaryota.
COG0406. LUCA.
GeneTreeiENSGT00390000018751.
HOGENOMiHOG000181112.
HOVERGENiHBG005628.
InParanoidiQ16877.
KOiK19030.
OMAiSPDYTNC.
OrthoDBiEOG7M3J03.
PhylomeDBiQ16877.
TreeFamiTF313541.

Enzyme and pathway databases

BRENDAi2.7.1.105. 2681.
3.1.3.46. 2681.
ReactomeiR-HSA-70171. Glycolysis.

Miscellaneous databases

ChiTaRSiPFKFB4. human.
GeneWikiiPFKFB4.
GenomeRNAii5210.
NextBioi20150.
PROiQ16877.
SOURCEiSearch...

Gene expression databases

BgeeiQ16877.
CleanExiHS_PFKFB4.
ExpressionAtlasiQ16877. baseline and differential.
GenevisibleiQ16877. HS.

Family and domain databases

Gene3Di3.40.50.1240. 1 hit.
3.40.50.300. 1 hit.
InterProiIPR003094. 6Pfruct_kin.
IPR013079. 6Phosfructo_kin.
IPR013078. His_Pase_superF_clade-1.
IPR029033. His_PPase_superfam.
IPR027417. P-loop_NTPase.
IPR001345. PG/BPGM_mutase_AS.
[Graphical view]
PANTHERiPTHR10606. PTHR10606. 1 hit.
PfamiPF01591. 6PF2K. 1 hit.
PF00300. His_Phos_1. 1 hit.
[Graphical view]
PRINTSiPR00991. 6PFRUCTKNASE.
SMARTiSM00855. PGAM. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
SSF53254. SSF53254. 1 hit.
PROSITEiPS00175. PG_MUTASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Hypoxia induces transcription of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-4 gene via hypoxia-inducible factor-1alpha activation."
    Minchenko O., Opentanova I., Minchenko D., Ogura T., Esumi H.
    FEBS Lett. 576:14-20(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), ALTERNATIVE SPLICING.
  2. Sakakibara R.
    Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  3. "Alternative splicing of human 6-phosphofructo-2-kinase/fructose-2,6-phosphatase 4 in melanoma cells."
    Minchenko O.H., Opentanova I.L., Minchenko D.O., Kurashima Y., Esumi H.
    Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING.
  4. "Cloning, expression and chromosomal localization of a human testis 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene."
    Manzano A., Perez J.X., Nadal M., Estivill X., Lange A., Bartrons R.
    Gene 229:83-89(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Testis.
  5. "Specific expression of pfkfb4 gene in spermatogonia germ cells and analysis of its 5'-flanking region."
    Gomez M., Manzano A., Navarro-Sabate A., Duran J., Obach M., Perales J.C., Bartrons R.
    FEBS Lett. 579:357-362(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "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] (ISOFORM 1).
    Tissue: Placenta.
  9. "Cloning of cDNA encoding for a novel isozyme of fructose 6-phosphate, 2-kinase/fructose 2,6-bisphosphatase from human placenta."
    Sakai A., Kato M., Fukasawa M., Ishiguro M., Furuya E., Sakakibara R.
    J. Biochem. 119:506-511(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 357-469 (ISOFORM 1).
    Tissue: Placenta.
  10. Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-181.

Entry informationi

Entry nameiF264_HUMAN
AccessioniPrimary (citable) accession number: Q16877
Secondary accession number(s): Q5S3G5, Q5XLC2, Q64EX5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 23, 2007
Last modified: March 16, 2016
This is version 154 of the entry and version 6 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.