The domain within your query sequence starts at position 105 and ends at position 134; the E-value for the PX domain shown below is 2e-6.

DRPSTPTILGYEVMEERAKFTAFCETLEET

The domain was found using the schnipsel database

PX

PhoX homologous domain, present in p47phox and p40phox.

• SMART accession number: SM00312
• Description: Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.
• Interpro abstract (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) (PUBMED:16782399) ]. 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 neutrophil cytosol factor 1 (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 multiple alignment of representative PX domain sequences from eukaryotic proteins [ (PUBMED:9687503) ], shows relatively little sequence conservation, although 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) ].

• GO function: phosphatidylinositol binding (GO:0035091)

There are 32485 PX domains in 32392 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: signalling

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Vollert CS, Uetz P
• The phox homology (PX) domain protein interaction network in yeast.
• Mol Cell Proteomics. 2004; 3: 1053-64

The phox homology (PX) domain is a phosphoinositide-binding domain that is conserved from yeast to human. Here we show for the first time by genome-wide two-hybrid screens and in vitro binding assays that the PX domain is a bona fide protein interaction domain. The yeast PX domain-only proteins Grd19p (YOR357C) and Ypt35p (YHR105W), as well as the isolated PX domains from Mvp1p (YMR004W), Snx42p/Cvt20p/Atg20p (YDL113C), Vam7p (YGL212W), and Vps17p (YOR132W), yielded a total of 40 reproducible two-hybrid interactions. Thirty-five interactions were found for the full-length proteins of Bem1p (YBR200W), Snx42p, Snx4p/Cvt13p (YJL036W), Vam7p, Vps5p (YOR069W), and Vps17p, but these appear not to require the PX domain, because these interactions could not be reproduced with PX-only baits. Interactions of Grd19p, Vam7p, Vps5p, Vps17p, and Ypt35p with members of the Yip1p family of proteins were detected consistently and were verified by in vitro binding assays. The N-terminal cytoplasmic domain of Yip1p and Yif1p mediates these interactions with PX domains. A mutation in the lipid-binding pocket of Ypt35p that reduces lipid binding markedly does not affect these PX domain protein interactions, arguing that lipid binding uses a different interaction surface than protein binding.

• Hiroaki H, Ago T, Ito T, Sumimoto H, Kohda D
• Solution structure of the PX domain, a target of the SH3 domain.
• Nat Struct Biol. 2001; 8: 526-30

The phox homology (PX) domain is a novel protein module containing aconserved proline-rich motif. We have shown that the PX domain isolatedfrom the human p47phox protein, a soluble subunit of phagocyte NADPHoxidase, binds specifically to the C-terminal SH3 domain derived from thesame protein. The solution structure of p47 PX has an alpha + betastructure with a novel folding motif topology and reveals that theproline-rich motif is presented on the molecular surface for easyrecognition by the SH3 domain. The proline-rich motif of p47 PX in thefree state adopts a distorted left-handed polyproline type II helixconformation.

• Ponting CP
• Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains?
• Protein Sci. 1996; 5: 2353-7

Two SH3 domain-containing cytosolic components of the NADPH oxidase, p47phox and p40phox, are shown by analyses of their sequences to contain single copies of a novel class of domain, the PX (phox) domain. Homologous domains are demonstrated to be present in the Cpk class of phosphatidylinositol 3-kinase, S. cerevisiae Bem1p, and S. pombe Scd2, and a large family of human sorting nexin 1 (SNX1) homologues. The majority of these domains contains a polyproline motif, typical of SH3 domain-binding proteins. Two further findings are reported. A third NADPH oxidase subunit, p67phox, is shown to contain four tetratricopeptide repeats (TPRs) within its N-terminal RaclGTP-binding region, and a 28 residue motif in p40phox is demonstrated to be present in protein kinase C isoforms iota/lambda and zeta, and in three ZZ domain-containing proteins.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
21.28	map00565	Ether lipid metabolism
21.28	map00564	Glycerophospholipid metabolism
21.28	map04912	GnRH signaling pathway
14.89	map04070	Phosphatidylinositol signaling system
14.89	map04670	Leukocyte transendothelial migration
6.38	map04130	SNARE interactions in vesicular transport

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with PX domain which could be assigned to a KEGG orthologous group, and not all proteins containing PX domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of PX domains in PDB

PDB code	Title
1gd5	SOLUTION STRUCTURE OF THE PX DOMAIN FROM HUMAN P47PHOX NADPH OXIDASE
1h6h	Structure of the PX domain from p40phox bound to phosphatidylinositol 3-phosphate
1kmd	SOLUTION STRUCTURE OF THE VAM7P PX DOMAIN
1kq6	p47phox PX domain
1o7k	human p47 PX domain complex with sulphates
1ocs	Crystal structure of the yeast PX-doamin protein Grd19p (sorting nexin3) complexed to phosphatidylinosytol-3-phosphate.
1ocu	Crystal structure of the yeast PX-domain protein Grd19p (sorting nexin 3) complexed to phosphatidylinosytol-3-phospahte.
1xte	crystal structure of CISK-PX domain
1xtn	crystal structure of CISK-PX domain with sulfates
2ar5	Crystal structure of the mammalian C2alpha-PI3 Kinase PX-domain
2csk	Solution structure of PX domain from human SNX12
2czo	Solution Structure of the PX Domain of Bem1p
2dyb	The crystal structure of human p40(phox)
2ett	Solution Structure of Human Sorting Nexin 22 PX Domain
2i4k	Solution Structure of the PX domain of Sorting Nexin 1
2iwl	Structure of the PX Domain of Phosphoinositide 3-Kinase-C2alpha
2l73	Structure of the NOXO1b PX domain
2mxc	2MXC
2rai	The PX-BAR membrane remodeling unit of Sorting Nexin 9
2raj	SO4 bound PX-BAR membrane remodeling unit of Sorting Nexin 9
2rak	PI(3)P bound PX-BAR membrane remodeling unit of Sorting Nexin 9
2rea	Crystal structures of C2ALPHA-PI3 kinase PX-domain domain indicate conformational change associated with ligand binding.
2red	Crystal structures of C2ALPHA-PI3 kinase PX-domain domain indicate conformational change associated with ligand binding.
2v14	Kinesin 16B Phox-homology domain (KIF16B)
2v6v	The structure of the Bem1p PX domain
2wwe	Crystal structure of the phox homology domain of human phosphoinositide-3-kinase-C2-gamma
2yps	Crystal structure of the PX domain of human sorting nexin 3
3dyt	Crystal structure of Snx9PX-BAR (230-595), C2221
3dyu	Crystal structure of Snx9PX-BAR (230-595), H32
3fog	Crystal structure of the PX domain of sorting nexin-17 (SNX17)
3hpb	Crystal structure of SNX5-PX domain in P212121 space group
3hpc	Crystal structure of SNX5-PX domain in P21 space group
3iq2	Human sorting nexin 7, phox homology (PX) domain
3lui	Crystal structure of the SNX17 PX domain with bound sulphate
3p0c	Nischarin PX-domain
4akv	Crystal structure of human sorting nexin 33 (SNX33)
4az9	Crystal structure of phox homology domain of human sorting nexin 24
4bgj	Crystal structure of the phox-homology domain of human sorting nexin 14
4has	Crystal structure of PX domain of human sorting nexin SNX27
4ikb	Crystal structure of SNX11 PX domain
4ikd	Crystal structure of SNX11 PX domain
4on3	4ON3
4oxw	4OXW
4p2i	4P2I
4p2j	4P2J
4pqo	4PQO
4pqp	4PQP
4pzg	4PZG

Links (links to other resources describing this domain)

• INTERPRO: IPR001683
• PFAM: PX