Q9Y5X3 · SNX5_HUMAN
- ProteinSorting nexin-5
- GeneSNX5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids404 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:15561769).
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) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988).
Involved in retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235).
May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387).
Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942).
Plays a role in macropinocytosis (PubMed:18854019, PubMed:21048941).
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) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988).
Involved in retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235).
May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387).
Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942).
Plays a role in macropinocytosis (PubMed:18854019, PubMed:21048941).
Features
Showing features for binding site.
GO annotations
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameSorting nexin-5
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y5X3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Early endosome membrane ; Peripheral membrane protein
Cell membrane ; Peripheral membrane protein
Cytoplasmic vesicle membrane ; Peripheral membrane protein
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 186-187 | No effect on dimerization. | ||||
Sequence: FF → EE | ||||||
Mutagenesis | 224 | Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-235, E-324, E-328 and E-330. | ||||
Sequence: K → E | ||||||
Mutagenesis | 235 | Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-324, E-328 and E-330. | ||||
Sequence: R → E | ||||||
Mutagenesis | 280 | Enables homodimerization; when associated with A-383. | ||||
Sequence: E → A | ||||||
Mutagenesis | 324 | Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-328 and E-330. | ||||
Sequence: K → E | ||||||
Mutagenesis | 328 | Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-330. | ||||
Sequence: K → E | ||||||
Mutagenesis | 330 | Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-328. | ||||
Sequence: R → E | ||||||
Mutagenesis | 383 | Enables homodimerization; when associated with A-280. | ||||
Sequence: E → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 459 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000213844 | 2-404 | UniProt | Sorting nexin-5 | |||
Sequence: AAVPELLQQQEEDRSKLRSVSVDLNVDPSLQIDIPDALSERDKVKFTVHTKTTLPTFQSPEFSVTRQHEDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEEFAKMKQELEAEYLAVFKKTVSSHEVFLQRLSSHPVLSKDRNFHVFLEYDQDLSVRRKNTKEMFGGFFKSVVKSADEVLFTGVKEVDDFFEQEKNFLINYYNRIKDSCVKADKMTRSHKNVADDYIHTAACLHSLALEEPTVIKKYLLKVAELFEKLRKVEGRVSSDEDLKLTELLRYYMLNIEAAKDLLYRRTKALIDYENSNKALDKARLKSKDVKLAEAHQQECCQKFEQLSESAKEELINFKRKRVAAFRKNLIEMSELEIKHARNNVSLLQSCIDLFKNN | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 22 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 60 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 193 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 193 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 275 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2; does not homodimerize (PubMed:23085988).
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 (Probable). Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C isoform 3. Interacts with HGS; increased by PIP5K1C isoform 3 kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2 (PubMed:16857196, PubMed:16968745, PubMed:18596235, PubMed:19619496, PubMed:23085988, PubMed:23602387, PubMed:24610942).
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 (Probable). Interacts with SNX1, SNX2, VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C isoform 3. Interacts with HGS; increased by PIP5K1C isoform 3 kinase activity and by PtdIns(3P) and/or PtdIns(3,4)P2 (PubMed:16857196, PubMed:16968745, PubMed:18596235, PubMed:19619496, PubMed:23085988, PubMed:23602387, PubMed:24610942).
(Microbial infection) Interacts with human cytomegalovirus proteins UL35 and UL35A; these interactions inhibit the ability of USP7 to form nuclear bodies.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y5X3 | APPBP2 Q92624 | 3 | EBI-715760, EBI-743771 | |
BINARY | Q9Y5X3 | SNX1 Q13596 | 5 | EBI-715760, EBI-2822329 | |
BINARY | Q9Y5X3 | SNX2 O60749 | 3 | EBI-715760, EBI-1046690 | |
BINARY | Q9Y5X3-2 | APPBP2 Q92624 | 3 | EBI-12229025, EBI-743771 | |
BINARY | Q9Y5X3-2 | BANP Q8N9N5-2 | 3 | EBI-12229025, EBI-11524452 | |
BINARY | Q9Y5X3-2 | PSMB8 P28062-2 | 3 | EBI-12229025, EBI-372312 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 25-172 | PX | ||||
Sequence: LNVDPSLQIDIPDALSERDKVKFTVHTKTTLPTFQSPEFSVTRQHEDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEEFAKMKQELEAEYLAVFKKTVSSHEVFLQRLSSHPVLSKDRNFHVFLEYDQDL | ||||||
Region | 169-261 | Interaction with DOCK1 | ||||
Sequence: DQDLSVRRKNTKEMFGGFFKSVVKSADEVLFTGVKEVDDFFEQEKNFLINYYNRIKDSCVKADKMTRSHKNVADDYIHTAACLHSLALEEPTV | ||||||
Region | 183-200 | Membrane-binding amphipathic helix | ||||
Sequence: FGGFFKSVVKSADEVLFT | ||||||
Domain | 202-404 | BAR | ||||
Sequence: VKEVDDFFEQEKNFLINYYNRIKDSCVKADKMTRSHKNVADDYIHTAACLHSLALEEPTVIKKYLLKVAELFEKLRKVEGRVSSDEDLKLTELLRYYMLNIEAAKDLLYRRTKALIDYENSNKALDKARLKSKDVKLAEAHQQECCQKFEQLSESAKEELINFKRKRVAAFRKNLIEMSELEIKHARNNVSLLQSCIDLFKNN |
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 (Probable).
Sequence similarities
Belongs to the sorting nexin family.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q9Y5X3-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length404
- Mass (Da)46,816
- Last updated1999-11-01 v1
- Checksum87A85620AF827EC6
Q9Y5X3-2
- Name2
Computationally mapped potential isoform sequences
There are 5 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
U3KQP5 | U3KQP5_HUMAN | SNX5 | 55 | ||
U3KQL0 | U3KQL0_HUMAN | SNX5 | 31 | ||
A0A087WUY5 | A0A087WUY5_HUMAN | SNX5 | 170 | ||
Q5QPE4 | Q5QPE4_HUMAN | SNX5 | 230 | ||
Q5QPE5 | Q5QPE5_HUMAN | SNX5 | 269 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056386 | 18-126 | in isoform 2 | |||
Sequence: LRSVSVDLNVDPSLQIDIPDALSERDKVKFTVHTKTTLPTFQSPEFSVTRQHEDFVWLHDTLIETTDYAGLIIPPAPTKPDFDGPREKMQKLGEGEGSMTKEEFAKMKQ → VRSSQPQTPGRAALRAPGSLHSFPCASIGRGCSPPSPAREAPVRPGRPLSLVFTEGCPGESLWMSRILLGQNQRRGTLAPAQAPVPSGLGEMISGDPGMFFLKLSSASW | ||||||
Alternative sequence | VSP_056387 | 127-404 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 279 | in Ref. 3 | ||||
Sequence: V → L |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF121855 EMBL· GenBank· DDBJ | AAD27828.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007191 EMBL· GenBank· DDBJ | AAP35855.1 EMBL· GenBank· DDBJ | mRNA | ||
AK001793 EMBL· GenBank· DDBJ | BAA91914.1 EMBL· GenBank· DDBJ | mRNA | ||
AK123903 EMBL· GenBank· DDBJ | BAG53980.1 EMBL· GenBank· DDBJ | mRNA | ||
AL121585 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC000100 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
CH471133 EMBL· GenBank· DDBJ | EAX10264.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471133 EMBL· GenBank· DDBJ | EAX10265.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471133 EMBL· GenBank· DDBJ | EAX10266.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471133 EMBL· GenBank· DDBJ | EAX10268.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC093623 EMBL· GenBank· DDBJ | AAH93623.1 EMBL· GenBank· DDBJ | mRNA | ||
BC093980 EMBL· GenBank· DDBJ | AAH93980.1 EMBL· GenBank· DDBJ | mRNA | ||
BC143274 EMBL· GenBank· DDBJ | AAI43275.1 EMBL· GenBank· DDBJ | mRNA |