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329  structures 1250  species 12  interactions 14800  sequences 391  architectures

Family: PI3_PI4_kinase (PF00454)

Summary: Phosphatidylinositol 3- and 4-kinase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Phosphoinositide 3-kinase". More...

Phosphoinositide 3-kinase Edit Wikipedia article

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Phosphatidylinositol 3- and 4-kinase Provide feedback

Some members of this family probably do not have lipid kinase activity and are protein kinases, e.g. P42345 [1].

Literature references

  1. Crespo JL, Hall MN; , Microbiol Mol Biol Rev 2002;66:579-591.: Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae. PUBMED:12456783 EPMC:12456783

  2. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S; , Science 2002;298:1912-1934.: The protein kinase complement of the human genome. PUBMED:12471243 EPMC:12471243


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000403

Phosphatidylinositol 3-kinase (PI3-kinase) (EC) [PUBMED:1322797] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) (EC) [PUBMED:8194527] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases [PUBMED:12456783].

The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases [PUBMED:8387896, PUBMED:12151228]. The catalytic domain of PI3K has the typical bilobal structure that is seen in other ATP-dependent kinases, with a small N-terminal lobe and a large C-terminal lobe. The core of this domain is the most conserved region of the PI3Ks. The ATP cofactor binds in the crevice formed by the N-and C-terminal lobes, a loop between two strands provides a hydrophobic pocket for binding of the adenine moiety, and a lysine residue interacts with the alpha-phosphate. In contrast to protein kinases, the PI3K loop which interacts with the phosphates of the ATP and is known as the glycine-rich or P-loop, contains no glycine residues. Instead, contact with the ATP -phosphate is maintained through the side chain of a conserved serine residue.

This domain is also found in a number of pseudokinases, where a lack of typical motifs at the calatytic site suggest a lack of kinase activity.

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 PKinase (CL0016), which has the following description:

This superfamily includes the Serine/Threonine- and Tyrosine- protein kinases as well as related kinases that act on non-protein substrates.

The clan contains the following 38 members:

ABC1 AceK Act-Frag_cataly Alpha_kinase APH APH_6_hur Choline_kinase CotH DUF1679 DUF2252 DUF4135 EcKinase Fam20C Fructosamin_kin FTA2 Haspin_kinase HipA_C Ins_P5_2-kin IPK IucA_IucC Kdo Kinase-like Kinase-PolyVal KIND Pan3_PK PI3_PI4_kinase PIP49_C PIP5K Pkinase Pkinase_fungal Pkinase_Tyr Pox_ser-thr_kin RIO1 Seadorna_VP7 UL97 WaaY YrbL-PhoP_reg YukC

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, 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
(41)
Full
(14800)
Representative proteomes UniProt
(22541)
NCBI
(30358)
Meta
(112)
RP15
(4206)
RP35
(8016)
RP55
(11428)
RP75
(13723)
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PP/heatmap 1                

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

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

Format an alignment

  Seed
(41)
Full
(14800)
Representative proteomes UniProt
(22541)
NCBI
(30358)
Meta
(112)
RP15
(4206)
RP35
(8016)
RP55
(11428)
RP75
(13723)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(41)
Full
(14800)
Representative proteomes UniProt
(22541)
NCBI
(30358)
Meta
(112)
RP15
(4206)
RP35
(8016)
RP55
(11428)
RP75
(13723)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   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.

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 & Pfam-B_6771 (Rlease 7.6)
Previous IDs: none
Type: Family
Sequence Ontology: SO:0100021
Author: Sonnhammer ELL , Finn RD
Number in seed: 41
Number in full: 14800
Average length of the domain: 208.30 aa
Average identity of full alignment: 22 %
Average coverage of the sequence by the domain: 13.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 25.9 25.9
Trusted cut-off 25.9 25.9
Noise cut-off 25.8 25.8
Model length: 250
Family (HMM) version: 27
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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Interactions

There are 12 interactions for this family. More...

FAT Ras PI3Ka SH2 WD40 PI3K_rbd PI3_PI4_kinase FRB_dom FATC PI3Ka PI3K_rbd PI3K_C2

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 PI3_PI4_kinase domain has been found. There are 329 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 sequence.

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