2I4K


Conserved Protein Domain Family
PX_SNX1

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cd07281: PX_SNX1 
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The phosphoinositide binding Phox Homology domain of Sorting Nexin 1
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX1 is both membrane associated and a cytosolic protein that exists as a tetramer in protein complexes. It can associate reversibly with membranes of the endosomal compartment, thereby coating these vesicles. SNX1 is a component of the retromer complex, a membrane coat multimeric complex required for endosomal retrieval of lysosomal hydrolase receptors to the Golgi. The retromer consists of a cargo-recognition subcomplex and a subcomplex formed by a dimer of sorting nexins (SNX1 and/or SNX2), which ensures efficient cargo sorting by facilitating proper membrane localization of the cargo-recognition subcomplex. SNX1 contains a Bin/Amphiphysin/Rvs (BAR) domain C-terminal to the PX domain. The PX domain of SNX1 specifically binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, while the BAR domain detects membrane curvature. Both domains help determine the specific membrane-targeting of SNX1, which is localized to a microdomain in early endosomes where it regulates cation-independent mannose-6-phosphate receptor retrieval to the trans Golgi network.
Statistics
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PSSM-Id: 132814
View PSSM: cd07281
Aligned: 3 rows
Threshold Bit Score: 260.761
Threshold Setting Gi: 147904653
Created: 23-Jan-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphoinosit..
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
  • Comment:SNX1 binds phosphatidylinositol-3-phosphate (PI3P) and PI(3,5)P2, but does not bind PI(3,4,5)P3.
  • Comment:based on the structures of phosphatidylinositol-3-phosphate bound to other members of this superfamily
  • Comment:Two basic residues are key in binding with phosphoinositides: one forms hydrogen bonds with the 3-phosphate of PI(3)P and another forms hydrogen bonds with the 4-and 5-hydroxyl groups of PI(3)P.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                 ###                                    
2I4K_A         4 LTVGITDPEKIGDGMNAYVAYKVTTQTSLPLFRSKQFAVKRRFSDFLGLYEKLSEKHSQNGFIVPPPPEKSLIGMTKVKV 83  human
NP_001084834 132 VKISVTDPEKIGDGMNAYVVYQVTTQTNLLMFKSKHFTVKRRFSDFLGLYEKLSEKHSQNGFIVAPPPEKSLIGMTKLKV 211 African clawed ...
NP_001122143 285 LNVSITNPEKVGDGMNAYMVYKVSTQTSLSMFRSKTFTVRRRFSDFLGLYEKLSEKHSQNGYIVPPPPEKSIMGMTKVKV 364 zebrafish
Feature 1                     #                              
2I4K_A        84 GKEDSSSAEFLEKRRAALERYLQRIVNHPTMLQDPDVREFLEKE 127 human
NP_001084834 212 GKEDSSSTEFLERRRASLERYLQRIVSHPSLLQDPDVREFLEKD 255 African clawed frog
NP_001122143 365 GKEDPSSAEFVERRRAALERYLQRVVSHPSLLQDPDVREFLEKE 408 zebrafish

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