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46  structures 785  species 3  interactions 7076  sequences 282  architectures

Family: PX (PF00787)

Summary: PX domain

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This is the Wikipedia entry entitled "PX domain". More...

PX domain Edit Wikipedia article

1h6h.png
PX domain of NADH oxidase (p40phox), lipid-bound
Identifiers
Symbol PX
Pfam PF00787
InterPro IPR001683
SMART PX
PROSITE PDOC50195
SCOP 1h6h
SUPERFAMILY 1h6h
OPM superfamily 60
OPM protein 1xte
CDD cd06093

The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.

This domain was first found in P40phox and p47phox domains of NADPH oxidase (phox stands for phagocytic oxidase).[1][2] It was also identified in many other proteins involved in membrane trafficking, including nexins, Phospholipase D, and phosphoinositide-3-kinases.

The PX domain is structurally conserved in eukaryotes, although amino acid sequences show little similarity.[3] PX domains interact primarily with PtdIns(3)P lipids.[4][5] However some of them bind to phosphatidic acid, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns(4,5)P2, and PtdIns(3,4,5)P3. The PX-domain can also interact with other domains and proteins.

Human proteins containing this domain[edit]

Sorting nexins contain this domain. Other examples include:

References[edit]

  1. ^ Ponting CP (November 1996). "Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?". Protein Sci. 5 (11): 2353–7. doi:10.1002/pro.5560051122. PMC 2143296. PMID 8931154. 
  2. ^ Wishart MJ, Taylor GS, Dixon JE (June 2001). "Phoxy lipids: revealing PX domains as phosphoinositide binding modules". Cell 105 (7): 817–20. doi:10.1016/S0092-8674(01)00414-7. PMID 11439176. 
  3. ^ Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D (June 2001). "Solution structure of the PX domain, a target of the SH3 domain". Nat. Struct. Biol. 8 (6): 526–30. doi:10.1038/88591. PMID 11373621. 
  4. ^ Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL (October 2002). "Binding of the PX domain of p47phox to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction". EMBO J. 21 (19): 5057–68. doi:10.1093/emboj/cdf519. PMC 129041. PMID 12356722. 
  5. ^ Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H (April 2003). "Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation". Proc. Natl. Acad. Sci. U.S.A. 100 (8): 4474–9. doi:10.1073/pnas.0735712100. PMC 153580. PMID 12672956. 

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

This is the Wikipedia entry entitled "Sorting nexin". More...

Sorting nexin Edit Wikipedia article

PX domain
PDB 1h6h EBI.jpg
Structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.[1]
Identifiers
Symbol PX
Pfam PF00787
InterPro IPR001683
SMART PX
PROSITE PDOC50195
SCOP 1h6h
SUPERFAMILY 1h6h
Sorting nexin, N-terminal domain
Identifiers
Symbol Sorting_nexin
Pfam PF03700
InterPro IPR005329
Vps5 C terminal like (BAR domain)
Identifiers
Symbol Vps5
Pfam PF09325
InterPro IPR015404
Sorting nexin, C terminal domain
Identifiers
Symbol Nexin_C
Pfam PF08628
InterPro IPR013937

Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain (a phospholipid-binding motif) or through protein-protein interactions with membrane-associated protein complexes[2][3] Some members of this family have been shown to facilitate protein sorting.

Family members[edit]

In humans, sorting nexins are transcribed from the following genes:

Genes Domain Composition
N-terminus Mid-1 Mid-2 Mid-3 C-terminus
SNX1, SNX2 Sorting_nexin_N PX BAR[4] (Vps5)
SNX4, SNX7, SNX8, SNX30 PX BAR[4] (Vsp5)
SNX5, SNX6, SNX32 PX BAR[4]
SNX9, SNX18, SNX33 SH3 PX BAR[4] (BAR_3_WASP_bdg)[5]
SNX13, SNX14, SNX19, SNX25 PXA[6] RGS PX Nexin_C
SNX15 PX MIT[7]
SNX17, SNX31 PX RA[8] FERM_M[9]
SNX23 kinesin_motor SMAD_FHA[10] PX
SNX26 PX SH3 RhoGAP
SNX27 PDZ PX - RA
SNX28 PX SH3 SH3
SNX3, SNX10, SNX11, SNX12, SNX16, SNX20, SNX21, SNX22, SNX24, SNX29 PX

Structure[edit]

Sorting nexins either consist solely of a PX domain (e.g. SNX3) or have a modular structure made up of the PX and additional domains.

A subgroup of sorting nexins (comprising, in humans, SNX1, SNX2, SNX4, SNX5, SNX6, SNX7, SNX8, SNX9, SNX18, SNX30, SNX32 and SNX33) possess a BAR domain at their C-terminus. (The BAR domain of SNXs 1, 2, 4, 7, 8 and 30 is classified by pfam as 'Vps5 C terminal like'.)

An example of a sorting nexin domain structure can be seen here for SNX1:

  1. NTD – N-terminal domain
  2. PX domain
  3. CTD – C-terminal BAR domain
Schematic diagram of the 1D structures of a representative sorting nexin, the sorting nexin 1 (SNX1). NTD = N-terminal SNX domain, PX = PX domain, CTD = C-terminal BAR domain.


References[edit]

  1. ^ Bravo J, Karathanassis D, Pacold CM, et al. (October 2001). "The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate". Mol. Cell 8 (4): 829–39. doi:10.1016/S1097-2765(01)00372-0. PMID 11684018. 
  2. ^ Dixon JE, Worby CA (2002). "Sorting out the cellular functions of sorting nexins". Nat. Rev. Mol. Cell Biol. 3 (12): 919–931. doi:10.1038/nrm974. PMID 12461558. 
  3. ^ Worby CA, Dixon JE (2002). "Sorting out the cellular functions of sorting nexins". Nat. Rev. Mol. Cell Biol. 3 (12): 919–31. doi:10.1038/nrm974. PMID 12461558. 
  4. ^ a b c d Frost A, Unger VM, De Camilli P (April 2009). "The BAR domain superfamily: membrane-molding macromolecules". Cell 137 (2): 191–196. doi:10.1016/j.cell.2009.04.010. PMID 19379681. 
  5. ^ BAR_3_WASP_bdg: WASP-binding domain of Sorting nexin protein, Pfam PF10456
  6. ^ PXA: PXA domain, Pfam PF02194
  7. ^ MIT: MIT (microtubule interacting and transport) domain, Pfam PF04212
  8. ^ RA: Ras association (RalGDS/AF-6) domain, Pfam PF00788
  9. ^ FERM_M: FERM central domain, Pfam PF00373
  10. ^ SMAD_FHA: SMAD/FHA domain, IPR008984

External links[edit]


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.

PX domain Provide feedback

PX domains bind to phosphoinositides.

Literature references

  1. Ponting CP; , Protein Sci 1996;5:2353-2357.: Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? PUBMED:8931154 EPMC:8931154

  2. Wishart MJ, Taylor GS, Dixon JE; , Cell 2001;105:817-820.: Phoxy lipids: revealing PX domains as phosphoinositide binding modules. PUBMED:11439176 EPMC:11439176

  3. Karathanassis D, Stahelin RV, Bravo J, Perisic O, Pacold CM, Cho W, Williams RL; , EMBO J 2002;21:5057-5068.: Binding of the PX domain of p47(phox) to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an intramolecular interaction. PUBMED:12356722 EPMC:12356722

  4. Ago T, Kuribayashi F, Hiroaki H, Takeya R, Ito T, Kohda D, Sumimoto H; , Proc Natl Acad Sci U S A 2003;100:4474-4479.: Phosphorylation of p47phox directs phox homology domain from SH3 domain toward phosphoinositides, leading to phagocyte NADPH oxidase activation. PUBMED:12672956 EPMC:12672956

  5. Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D; , Nat Struct Biol 2001;8:526-530.: Solution structure of the PX domain, a target of the SH3 domain. PUBMED:11373621 EPMC:11373621


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001683

The PX (phox) domain [PUBMED:8931154] occurs in a variety of eukaryotic proteins and have been implicated in highly diverse functions such as cell signalling, vesicular trafficking, protein sorting and lipid modification [PUBMED:10782093, PUBMED:11736640, PUBMED:12461558]. PX domains are important phosphoinositide-binding modules that have varying lipid-binding specificities [PUBMED:11884510]. The PX domain is approximately 120 residues long [PUBMED:11373621], and folds into a three-stranded beta-sheet followed by three -helices and a proline-rich region that immediately preceeds a membrane-interaction loop and spans approximately eight hydrophobic and polar residues. The PX domain of p47phox binds to the SH3 domain in the same protein [PUBMED:11373621]. Phosphorylation of p47(phox), a cytoplasmic activator of the microbicidal phagocyte oxidase (phox), elicits interaction of p47(phox) with phoinositides. The protein phosphorylation-driven conformational change of p47(phox) enables its PX domain to bind to phosphoinositides, the interaction of which plays a crucial role in recruitment of p47(phox) from the cytoplasm to membranes and subsequent activation of the phagocyte oxidase. The lipid-binding activity of this protein is normally suppressed by intramolecular interaction of the PX domain with the C-terminal Src homology 3 (SH3) domain [PUBMED:12356722].

The PX domain is conserved from yeast to human. A recent multiple alignment of representative PX domain sequences can be found in [PUBMED:9687503], although showing relatively little sequence conservation, their structure appears to be highly conserved. Although phosphatidylinositol-3-phosphate (PtdIns(3)P) is the primary target of PX domains, binding to phosphatidic acid, phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2), phosphatidylinositol-3,5-bisphosphate (PtdIns(3,5)P2), phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2), and phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) has been reported as well. The PX-domain is also a protein-protein interaction domain [PUBMED:15263065].

Gene Ontology

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Domain organisation

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

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Alignments

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(70)
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(2076)
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  Seed
(71)
Full
(7076)
Representative proteomes NCBI
(6459)
Meta
(70)
RP15
(1382)
RP35
(2076)
RP55
(3184)
RP75
(4186)
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  Seed
(71)
Full
(7076)
Representative proteomes NCBI
(6459)
Meta
(70)
RP15
(1382)
RP35
(2076)
RP55
(3184)
RP75
(4186)
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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.

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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.

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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: Alignment kindly provided by SMART & iterated
Previous IDs: none
Type: Domain
Author: SMART
Number in seed: 71
Number in full: 7076
Average length of the domain: 114.90 aa
Average identity of full alignment: 20 %
Average coverage of the sequence by the domain: 19.35 %

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 20.9 20.9
Trusted cut-off 20.9 20.9
Noise cut-off 20.8 20.8
Model length: 113
Family (HMM) version: 19
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 3 interactions for this family. More...

PX BAR_3_WASP_bdg PB1

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 PX domain has been found. There are 46 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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