P08237 · PFKAM_HUMAN

  • Protein
    ATP-dependent 6-phosphofructokinase, muscle type
  • Gene
    PFKM
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.

Miscellaneous

In human PFK exists as a system of 3 types of subunits, PFKM (muscle), PFKL (liver) and PFKP (platelet) isoenzymes.

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Activity regulation

Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.

Pathway

Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 3/4.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site25ATP (UniProtKB | ChEBI)
Binding site88-89ATP (UniProtKB | ChEBI)
Binding site118-121ATP (UniProtKB | ChEBI)
Binding site119Mg2+ (UniProtKB | ChEBI); catalytic
Binding site164-166substrate; ligand shared between dimeric partners; in other chain
Active site166Proton acceptor
Binding site201substrate; ligand shared between dimeric partners
Binding site208-210substrate; ligand shared between dimeric partners; in other chain
Binding site264substrate; ligand shared between dimeric partners; in other chain
Binding site292substrate; ligand shared between dimeric partners
Binding site298-301substrate; ligand shared between dimeric partners; in other chain
Binding site471beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain
Binding site528-532beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain
Binding site566beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners
Binding site573-575beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain
Binding site629beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain
Binding site655beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners
Binding site661-664beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain
Binding site735beta-D-fructose 2,6-bisphosphate (UniProtKB | ChEBI); allosteric activator; ligand shared between dimeric partners; in other chain

GO annotations

AspectTerm
Cellular Component6-phosphofructokinase complex
Cellular Componentapical plasma membrane
Cellular Componentcytosol
Cellular Componentmembrane
Cellular Componentnucleus
Cellular Componentsperm principal piece
Molecular Function6-phosphofructokinase activity
Molecular FunctionAMP binding
Molecular FunctionATP binding
Molecular Functionfructose binding
Molecular Functionfructose-6-phosphate binding
Molecular Functionidentical protein binding
Molecular Functionkinase binding
Molecular Functionmetal ion binding
Molecular Functionmonosaccharide binding
Biological Processcanonical glycolysis
Biological Processfructose 1,6-bisphosphate metabolic process
Biological Processfructose 6-phosphate metabolic process
Biological Processglucose homeostasis
Biological Processglycogen catabolic process
Biological Processglycolysis from storage polysaccharide through glucose-1-phosphate
Biological Processglycolytic process
Biological Processglycolytic process through fructose-6-phosphate
Biological Processmuscle cell cellular homeostasis
Biological Processpositive regulation of insulin secretion
Biological Processpositive regulation of transcription by RNA polymerase II

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    ATP-dependent 6-phosphofructokinase, muscle type
  • EC number
  • Short names
    ATP-PFK
    ; PFK-M
  • Alternative names
    • 6-phosphofructokinase type A
    • Phosphofructo-1-kinase isozyme A (PFK-A)
    • Phosphohexokinase

Gene names

    • Name
      PFKM
    • Synonyms
      PFKX

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P08237
  • Secondary accessions
    • J3KNX3
    • Q16814
    • Q16815
    • Q6ZTT1

Proteomes

Organism-specific databases

Disease & Variants

Involvement in disease

Glycogen storage disease 7 (GSD7)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A metabolic disorder characterized by exercise intolerance with associated nausea and vomiting, muscle cramping, exertional myopathy and compensated hemolysis. Short bursts of intense activity are particularly difficult. Severe muscle cramps and myoglobinuria develop after vigorous exercise.
  • See also
    MIM:232800
Natural variants in GSD7
Variant IDPosition(s)ChangeDescription
VAR_00606339R>Lin GSD7; Ashkenazi; dbSNP:rs121918193
VAR_00606439R>Pin GSD7; Italian; dbSNP:rs121918193
VAR_07223957G>Vin GSD7; Italian
VAR_072240180S>Cin GSD7; Italian
VAR_006066209G>Din GSD7; loss of activity shown by complementation assays in yeast; dbSNP:rs767265360
VAR_072241309D>Gin GSD7; Spanish; complete loss of enzyme activity; dbSNP:rs1169383137
VAR_006067543D>Ain GSD7; Italian; dbSNP:rs121918194
VAR_072242591D>Ain GSD7; Italian
VAR_006068686W>Cin GSD7; Japanese; dbSNP:rs121918196

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_00606339in GSD7; Ashkenazi; dbSNP:rs121918193
Natural variantVAR_00606439in GSD7; Italian; dbSNP:rs121918193
Natural variantVAR_07223957in GSD7; Italian
Natural variantVAR_006065100in dbSNP:rs2228500
Natural variantVAR_072240180in GSD7; Italian
Natural variantVAR_006066209in GSD7; loss of activity shown by complementation assays in yeast; dbSNP:rs767265360
Natural variantVAR_072241309in GSD7; Spanish; complete loss of enzyme activity; dbSNP:rs1169383137
Natural variantVAR_006067543in GSD7; Italian; dbSNP:rs121918194
Natural variantVAR_072242591in GSD7; Italian
Natural variantVAR_006068686in GSD7; Japanese; dbSNP:rs121918196
Natural variantVAR_006069696in dbSNP:rs41291971

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 783 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, modified residue (large scale data), glycosylation.

TypeIDPosition(s)SourceDescription
Initiator methionine1UniProtRemoved
Modified residue2UniProtN-acetylthreonine
ChainPRO_00001120162-780UniProtATP-dependent 6-phosphofructokinase, muscle type
Modified residue (large scale data)103PRIDEPhosphotyrosine
Modified residue133UniProtPhosphoserine
Modified residue (large scale data)304PRIDEPhosphothreonine
Modified residue377UniProtPhosphoserine
Modified residue (large scale data)377PRIDEPhosphoserine
Modified residue (large scale data)398PRIDEPhosphoserine
Modified residue (large scale data)477PRIDEPhosphoserine
Glycosylation530UniProtO-linked (GlcNAc) serine
Modified residue557UniProtN6-(2-hydroxyisobutyryl)lysine
Modified residue667UniProtPhosphoserine
Modified residue (large scale data)667PRIDEPhosphoserine
Modified residue775UniProtPhosphoserine

Post-translational modification

GlcNAcylation decreases enzyme activity.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homo- and heterotetramers (By similarity).
Phosphofructokinase (PFK) enzyme functions as a tetramer composed of different combinations of 3 types of subunits, called PFKM (where M stands for Muscle), PFKL (Liver) and PFKP (Platelet). The composition of the PFK tetramer differs according to the tissue type it is present in. In muscles, it is composed of 4 PFKM subunits (also called M4). In the liver, the predominant form is a tetramer of PFKL subunits (L4). In erythrocytes, both PFKM and PFKL subunits randomly tetramerize to form M4, L4 and other combinations (ML3, M2L2, M3L). The kinetic and regulatory properties of the tetrameric enzyme are dependent on the subunit composition, hence can vary across tissues (Probable). Interacts (via C-terminus) with HK1 (via N-terminal spermatogenic cell-specific region) (By similarity).

Binary interactions

View interactors in UniProtKB
View CPX-1997 in Complex Portal

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region2-390N-terminal catalytic PFK domain 1
Region391-401Interdomain linker
Region402-780C-terminal regulatory PFK domain 2

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative splicing.

P08237-1

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.

  • Length
    780
  • Mass (Da)
    85,183
  • Last updated
    2007-01-23 v2
  • Checksum
    769A2C01F97D1122
MTHEEHHAAKTLGIGKAIAVLTSGGDAQGMNAAVRAVVRVGIFTGARVFFVHEGYQGLVDGGDHIKEATWESVSMMLQLGGTVIGSARCKDFREREGRLRAAYNLVKRGITNLCVIGGDGSLTGADTFRSEWSDLLSDLQKAGKITDEEATKSSYLNIVGLVGSIDNDFCGTDMTIGTDSALHRIMEIVDAITTTAQSHQRTFVLEVMGRHCGYLALVTSLSCGADWVFIPECPPDDDWEEHLCRRLSETRTRGSRLNIIIVAEGAIDKNGKPITSEDIKNLVVKRLGYDTRVTVLGHVQRGGTPSAFDRILGSRMGVEAVMALLEGTPDTPACVVSLSGNQAVRLPLMECVQVTKDVTKAMDEKKFDEALKLRGRSFMNNWEVYKLLAHVRPPVSKSGSHTVAVMNVGAPAAGMNAAVRSTVRIGLIQGNRVLVVHDGFEGLAKGQIEEAGWSYVGGWTGQGGSKLGTKRTLPKKSFEQISANITKFNIQGLVIIGGFEAYTGGLELMEGRKQFDELCIPFVVIPATVSNNVPGSDFSVGADTALNTICTTCDRIKQSAAGTKRRVFIIETMGGYCGYLATMAGLAAGADAAYIFEEPFTIRDLQANVEHLVQKMKTTVKRGLVLRNEKCNENYTTDFIFNLYSEEGKGIFDSRKNVLGHMQQGGSPTPFDRNFATKMGAKAMNWMSGKIKESYRNGRIFANTPDSGCVLGMRKRALVFQPVAELKDQTDFEHRIPKEQWWLKLRPILKILAKYEIDLDTSDHAHLEHITRKRSGEAAV

P08237-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

P08237-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-1: M → MHKDEFHLKFFMCVIQSRQLVRTPQRTAGEASTSSMLIPKPPPKTDILKSLDTMDDPDTVGSIPVFKTEWIM

Computationally mapped potential isoform sequences

There are 16 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A2R8Y891A0A2R8Y891_HUMANPFKM883
H0YHB8H0YHB8_HUMANPFKM41
F8VZI0F8VZI0_HUMANPFKM694
F8VZQ1F8VZQ1_HUMANPFKM161
F8VZ53F8VZ53_HUMANPFKM59
F8VX13F8VX13_HUMANPFKM156
F8VYK8F8VYK8_HUMANPFKM149
F8VVE3F8VVE3_HUMANPFKM165
F8VW30F8VW30_HUMANPFKM116
F8VUB8F8VUB8_HUMANPFKM141
F8VTQ3F8VTQ3_HUMANPFKM854
F8VTT5F8VTT5_HUMANPFKM176
F8VSF7F8VSF7_HUMANPFKM102
F8VSF5F8VSF5_HUMANPFKM73
F8VP00F8VP00_HUMANPFKM176
F8VNZ1F8VNZ1_HUMANPFKM125

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0461251in isoform 3
Sequence conflict2In isoform P08237-3; in Ref. 4; BAC86498
Alternative sequenceVSP_004667282-312in isoform 2
Sequence conflict670in Ref. 4; BAC86498

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M59741
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59720
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59721
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59722
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59723
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59724
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59725
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59726
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59727
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59728
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59729
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59730
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59731
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59732
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59733
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59734
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59735
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59736
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59737
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59738
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59739
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M59740
EMBL· GenBank· DDBJ
AAA82938.1
EMBL· GenBank· DDBJ
Genomic DNA
M26066
EMBL· GenBank· DDBJ
AAA60068.1
EMBL· GenBank· DDBJ
mRNA
Y00698
EMBL· GenBank· DDBJ
CAA68692.1
EMBL· GenBank· DDBJ
mRNA
AK126229
EMBL· GenBank· DDBJ
BAC86498.1
EMBL· GenBank· DDBJ
mRNA
AC004801
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC074029
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC000534
EMBL· GenBank· DDBJ
AAH00534.1
EMBL· GenBank· DDBJ
mRNA
BC012799
EMBL· GenBank· DDBJ
AAH12799.1
EMBL· GenBank· DDBJ
mRNA
BC013298
EMBL· GenBank· DDBJ
AAH13298.1
EMBL· GenBank· DDBJ
mRNA
BC021203
EMBL· GenBank· DDBJ
AAH21203.1
EMBL· GenBank· DDBJ
mRNA
J05533
EMBL· GenBank· DDBJ
AAA79220.1
EMBL· GenBank· DDBJ
mRNA
M24925
EMBL· GenBank· DDBJ
AAA36436.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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