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26  structures 2608  species 1  interaction 2905  sequences 5  architectures

Family: PEPCK_ATP (PF01293)

Summary: Phosphoenolpyruvate carboxykinase

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Phosphoenolpyruvate carboxykinase Provide feedback

No Pfam abstract.

Literature references

  1. 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

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.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan PEP-carboxyk (CL0374), which has the following description:

This includes the PEP carboxykinase C-terminal domain and HPr kinase HprK C-terminal domain families.

The clan contains the following 3 members:

Hpr_kinase_C PEPCK PEPCK_ATP

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(128)
Full
(2905)
Representative proteomes NCBI
(2097)
Meta
(1598)
RP15
(226)
RP35
(436)
RP55
(591)
RP75
(690)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(128)
Full
(2905)
Representative proteomes NCBI
(2097)
Meta
(1598)
RP15
(226)
RP35
(436)
RP55
(591)
RP75
(690)
Alignment:
Format:
Order:
Sequence:
Gaps:
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Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(128)
Full
(2905)
Representative proteomes NCBI
(2097)
Meta
(1598)
RP15
(226)
RP35
(436)
RP55
(591)
RP75
(690)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: none
Type: Family
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.5 25.5
Trusted cut-off 25.8 25.6
Noise cut-off 25.4 25.4
Model length: 467
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

PEPCK_ATP

Structures

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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