Conserved Protein Domain Family
PX_SNX27

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cd06886: PX_SNX27 
The phosphoinositide binding Phox Homology domain of Sorting Nexin 27
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. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.
Statistics
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PSSM-Id: 132796
View PSSM: cd06886
Aligned: 11 rows
Threshold Bit Score: 183.381
Threshold Setting Gi: 219460910
Created: 11-Jul-2008
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
phosphoinosit..
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
  • Comment:A majority of PX domain containing proteins binds phosphatidylinositol-3-phosphate (PI3P) at this site. In some cases, other phosphoinositides, such as PI4P or PI(3,4)P2, are the preferred substrates.
  • 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                                                      ###                      ##       
NP_001026517 148 KQAVPISIPTYKHVEQNGE------KFVVYNVYMAG----RQLCSKRYREFAILHQNLKREFANFTFPRLPGKWPFSLSE 217 chicken
NP_727023    165 KRSLPISIPDYGIVNRNGE------RYIVFNIHMAG----RQLCSRRYREFANLHSLLRKEFSGFNFPKLPGKWPFQLSE 234 fruit fly
NP_956834    165 KQAVPISVPTYKHVEQSGE------KFVVYNVYMAG----RQLCSKRYREFAILHQNLKREFANFAFPKLPGKWPFSLSE 234 zebrafish
Q8K4V4       158 KQAVPISVPTYKHVEQNGE------KFVVYNVYMAG----RQLCSKRYREFAILHQNLKREFANFTFPRLPGKWPFSLSE 227 Norway rat
NP_001084727 145 KQAVPISIPTYKHVEQNGE------KFVVYNVYMAG----RQLCSKRYREFAILNQNLKREFANFTFPRLPGKWPFSLSE 214 African clawed ...
XP_780387    138 KRPVPITIPDYQHITSDGE------KYVVYNVYMAG----RLLCSHRYSEFANVHAKLKREFIDYQFPKFPGKWPFTLSD 207 purple urchin
Q93566       166 NRSLPVTIPSYNTVQDSLE------RYTVFNIHMAG----RQLGSRRYSEFVELHLALKKHFYDYCFPQLPGKWPFKLSE 235 Caenorhabditis ...
EEC14045     153 KRSLPISIPDYNWLERSGD------KFVVYNIYMAG----RHLCSRRYREFSVLHVNLRKEFPDFSFPKLPGKWPFSLSD 222 black-legged tick
XP_002228169 313 RKLVPTEFPHNLYIQNYTTaa---sTCIALRKWLFDlqreLQLTHLDMANTFFYWQTLKREFPEFPFPKMPGKWPFSLSE 389 Florida lancelet
XP_001639807 104 NQQQHKAKKQFKNYLIAGFvfisipFVTVYNIYYSG----KQICSKRYKEFSNLHSQLKKEFRDFQFPKFPGKWPFTLSE 179 starlet sea ane...
XP_002122994 131 IRRIEIDIPEYEHVEEEGS------KFVVYCIHLKG----KLVMKRRYSEFLLMYEELMKIFVEFDYPKFPSKKLFQLSE 200 Ciona intestinalis
Feature 1             #                              
NP_001026517 218 QQLDARRRGLEEYLEKVCSIRVIGESDIMQEFLSES 253 chicken
NP_727023    235 QQLDTRRRGLEQYLEKVCAVRVIAESDAVQDFLTDT 270 fruit fly
NP_956834    235 QQLDARRRGLEEYLEKVCSVRVIGESDIMQEFLSES 270 zebrafish
Q8K4V4       228 QQLDARRRGLEEYLEKVCSIRVIGESDIMQEFLSES 263 Norway rat
NP_001084727 215 QQLDARRRGLEEYLEKVCSIRIIGESDIMQEFLSES 250 African clawed frog
XP_780387    208 QQLDTRRRSLEHYIEKVSAVRAIGESDIMRDFLSTE 243 purple urchin
Q93566       236 QQLDSRRRGLEQYLEKICTIRVIAESELVQKFLMEC 271 Caenorhabditis elegans
EEC14045     223 QQLDARRRGLEQYLEKVCAIRVIAESDTMQDFLTDM 258 black-legged tick
XP_002228169 390 QQLDARRRGLEQYLEKVCSIRVIAESDVMQEFLADI 425 Florida lancelet
XP_001639807 180 HQLEARRKGLESYLQQVCSVFVIGDSVLMQDFLDDD 215 starlet sea anemone
XP_002122994 201 QQLERRRSMLETFIQETFKRRVIQECDIVMDFLKIE 236 Ciona intestinalis

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