Summary: Phosphoenolpyruvate carboxykinase
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Phosphoenolpyruvate carboxykinase Provide feedback
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Tari LW, Matte A, Pugazhenthi U, Goldie H, Delbaere LT; , Nat Struct Biol 1996;3:355-363.: Snapshot of an enzyme reaction intermediate in the structure of the ATP-Mg2+-oxalate ternary complex of Escherichia coli PEP carboxykinase. PUBMED:8599762 EPMC:8599762
Internal database links
|Similarity to PfamA using HHSearch:||PEPCK|
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001272
Phosphoenolpyruvate carboxykinase (PEPCK) catalyses the first committed (rate-limiting) step in hepatic gluconeogenesis, namely the reversible decarboxylation of oxaloacetate to phosphoenolpyruvate (PEP) and carbon dioxide, using either ATP or GTP as a source of phosphate. The ATP-utilising (EC) and GTP-utilising (EC) enzymes form two divergent subfamilies, which have little sequence similarity but which retain conserved active site residues. ATP-utilising PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilising PEPCKs are mainly monomers found in animals and some bacteria [PUBMED:16330239]. Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site 1 to elicit activation, while the second cation interacts at metal binding site 2 to serve as a metal-nucleotide substrate. In bacteria, fungi and plants, PEPCK is involved in the glyoxylate bypass, an alternative to the tricarboxylic acid cycle.
PEPCK helps to regulate blood glucose levels. The rate of gluconeogenesis can be controlled through transcriptional regulation of the PEPCK gene by cAMP (the mediator of glucagon and catecholamines), glucocorticoids and insulin. In general, PEPCK expression is induced by glucagon, catecholamines and glucocorticoids during periods of fasting and in response to stress, but is inhibited by (glucose-induced) insulin upon feeding [PUBMED:16126724]. With type II diabetes, this regulation system can fail, resulting in increased gluconeogenesis that in turn raises glucose levels [PUBMED:17403375].
PEPCK consists of an N-terminal and a catalytic C-terminal domain, with the active site and metal ions located in a cleft between them. Both domains have an alpha/beta topology that is partly similar to one another [PUBMED:15023367, PUBMED:8609605]. Substrate binding causes PEPCK to undergo a conformational change, which accelerates catalysis by forcing bulk solvent molecules out of the active site [PUBMED:15890557]. PCK uses an alpha/beta/alpha motif for nucleotide binding, this motif differing from other kinase domains. GTP-utilising PEPCK has a PEP-binding domain and two kinase motifs to bind GTP and magnesium.
This entry represents ATP-utilising phosphoenolpyruvate carboxykinase enzymes.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ATP binding (GO:0005524)|
|phosphoenolpyruvate carboxykinase (ATP) activity (GO:0004612)|
|Biological process||gluconeogenesis (GO:0006094)|
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|Author:||Finn RD, Bateman A|
|Number in seed:||128|
|Number in full:||2905|
|Average length of the domain:||442.70 aa|
|Average identity of full alignment:||48 %|
|Average coverage of the sequence by the domain:||86.52 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PEPCK_ATP domain has been found. There are 26 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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