Q9D8U8 · SNX5_MOUSE

  • Protein
    Sorting nexin-5
  • Gene
    Snx5
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol lipids. Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC). Does not have in vitro vesicle-to-membrane remodeling activity. Involved in retrograde transport of lysosomal enzyme receptor IGF2R. May function as link between endosomal transport vesicles and dynactin. Plays a role in the internalization of EGFR after EGF stimulation. Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C and is retromer-independent. Together with PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation. Involved in E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By similarity).
Plays a role in macropinocytosis (PubMed:18854019).

Caution

The selectivity for particular phosphatidylinositol lipids is under debate. According to one report (PubMed:19553671), the rat protein binds exclusively to phosphatidylinositol 4,5-bisphosphate, while the human protein has been reported (PubMed:15561769) to bind to phosphatidylinositol 3,4-bisphosphate and also to phosphatidylinositol 3-phosphate.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site40-46phosphatidylinositol bisphosphate (UniProtKB | ChEBI)
Binding site99-105phosphatidylinositol bisphosphate (UniProtKB | ChEBI)
Binding site113-116phosphatidylinositol bisphosphate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentbrush border
Cellular Componentcytoplasmic side of early endosome membrane
Cellular Componentcytoplasmic side of plasma membrane
Cellular Componentcytosol
Cellular Componentendosome
Cellular Componentmacropinocytic cup
Cellular Componentperinuclear region of cytoplasm
Cellular Componentphagocytic cup
Cellular Componentretromer complex
Cellular Componentruffle
Cellular Componenttubular endosome
Molecular FunctionD1 dopamine receptor binding
Molecular Functiondynactin binding
Molecular Functionphosphatidylinositol binding
Molecular Functionphosphatidylinositol-3,5-bisphosphate binding
Molecular Functionphosphatidylinositol-4-phosphate binding
Molecular Functionphosphatidylinositol-5-phosphate binding
Biological Processepidermal growth factor catabolic process
Biological Processintracellular protein transport
Biological Processnegative regulation of blood pressure
Biological Processpinocytosis
Biological Processpositive regulation of DNA-templated transcription
Biological Processpositive regulation of insulin receptor signaling pathway
Biological Processretrograde transport, endosome to Golgi

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Sorting nexin-5

Gene names

    • Name
      Snx5

Organism names

  • Taxonomic identifier
  • Strains
    • C57BL/6J
    • NOD
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q9D8U8
  • Secondary accessions
    • Q543N9

Proteomes

Organism-specific databases

Subcellular Location

Endosome
Early endosome
Early endosome membrane
; Peripheral membrane protein
Cell membrane
; Peripheral membrane protein
Cytoplasmic vesicle membrane ; Peripheral membrane protein
Note: Recruited to the plasma membrane after EGF stimulation, which leads to increased levels of phosphatidylinositol 3,4-bisphosphate (PdtIns(3,4)P2) (By similarity).
Detected on macropinosomes (PubMed:18854019).
Targeted to membrane ruffles in response to EGFR stimulation (By similarity).

Keywords

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00002138452-404Sorting nexin-5
Modified residue193Phosphoserine
Modified residue275N6-acetyllysine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in macrophages (at protein level).

Gene expression databases

Interaction

Subunit

Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2; does not homodimerize. The heterodimers are proposed to self-assemble into helical arrays on the membrane to stabilize and expand local membrane curvature underlying endosomal tubule formation. Thought to be a component of the originally described retromer complex (also called SNX-BAR retromer) which is a pentamer containing the heterotrimeric retromer cargo-selective complex (CSC), also described as vacuolar protein sorting subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes associate with low affinity. Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C. Interacts with HGS; increased by PIP5K1C kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2 (By similarity).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
XENO Q9D8U8incE P0DJI44EBI-643385, EBI-22303778

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for domain, region.

TypeIDPosition(s)Description
Domain25-172PX
Region169-261Interaction with DOCK1
Region183-200Membrane-binding amphipathic helix
Domain202-404BAR

Domain

The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipathic helix (AH) in the membrane (By similarity).

Sequence similarities

Belongs to the sorting nexin family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    404
  • Mass (Da)
    46,797
  • Last updated
    2001-06-01 v1
  • Checksum
    C24D8C78F753FAFC
MAAVPELLEQQEEDRSKLRSVSVDLNVDPSLQIDIPDALSERDKVKFTVHTKTTLSTFQSPEFSVTRQHEDFVWLHDTLTETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEEFAKMKQELEAEYLAVFKKTVSTHEVFLQRLSSHPVLSKDRNFHVFLEYDQDLSVRRKNTKEMFGGFFKSVVKSADEVLFSGVKEVDDFFEQEKNFLINYYNRIKDSCAKADKMTRSHKNVADDYIHTAACLHSLALEEPTVIKKYLLKVAELFEKLRKVEGRVSSDEDLKLTELLRYYMLNIEAAKDLLYRRTKALIDYENSNKALDKARLKSKDVKLAETHQQECCQKFEQLSESAKEELINFKRKRVAAFRKNLIEMSELEIKHARNNVSLLQSCIDLFKNN

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK007676
EMBL· GenBank· DDBJ
BAB25180.1
EMBL· GenBank· DDBJ
mRNA
AK029463
EMBL· GenBank· DDBJ
BAC26460.1
EMBL· GenBank· DDBJ
mRNA
AK031873
EMBL· GenBank· DDBJ
BAC27587.1
EMBL· GenBank· DDBJ
mRNA
AK049129
EMBL· GenBank· DDBJ
BAC33558.1
EMBL· GenBank· DDBJ
mRNA
AK159904
EMBL· GenBank· DDBJ
BAE35468.1
EMBL· GenBank· DDBJ
mRNA
AK169786
EMBL· GenBank· DDBJ
BAE41365.1
EMBL· GenBank· DDBJ
mRNA
BC002242
EMBL· GenBank· DDBJ
AAH02242.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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