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Protein

Sorting nexin-5

Gene

SNX5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).3 Publications3 Publications

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.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processEndocytosis, Protein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
Sorting nexin-5
Gene namesi
Name:SNX5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000089006.16
HGNCiHGNC:14969 SNX5
MIMi605937 gene
neXtProtiNX_Q9Y5X3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi186 – 187FF → EE: No effect on dimerization. 1 Publication2
Mutagenesisi224K → E: Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-235, E-324, E-328 and E-330. 1 Publication1
Mutagenesisi235R → E: Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-324, E-328 and E-330. 1 Publication1
Mutagenesisi280E → A: Enables homodimerization; when associated with A-383. 1 Publication1
Mutagenesisi324K → E: Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-328 and E-330. 1 Publication1
Mutagenesisi328K → E: Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-330. 1 Publication1
Mutagenesisi330R → E: Decreaes phosphoinositide binding, including PtdIns(3,4)P2 and PtdIns(3P); when associated with E-224, E-235, E-324 and E-328. 1 Publication1
Mutagenesisi383E → A: Enables homodimerization; when associated with A-280. 1

Organism-specific databases

DisGeNETi27131
OpenTargetsiENSG00000089006
PharmGKBiPA37945

Polymorphism and mutation databases

DMDMi10720289

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002138442 – 404Sorting nexin-5Add BLAST403

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei193PhosphoserineCombined sources1
Modified residuei275N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9Y5X3
PaxDbiQ9Y5X3
PeptideAtlasiQ9Y5X3
PRIDEiQ9Y5X3
ProteomicsDBi86528

PTM databases

iPTMnetiQ9Y5X3
PhosphoSitePlusiQ9Y5X3

Expressioni

Gene expression databases

BgeeiENSG00000089006 Expressed in 221 organ(s), highest expression level in adrenal tissue
CleanExiHS_SNX5
ExpressionAtlasiQ9Y5X3 baseline and differential
GenevisibleiQ9Y5X3 HS

Organism-specific databases

HPAiCAB020679
HPA051187

Interactioni

Subunit structurei

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:19619496, PubMed:23085988, PubMed:18596235, PubMed:23602387, PubMed:24610942).2 Publications7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926243EBI-715760,EBI-743771

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118022, 57 interactors
IntActiQ9Y5X3, 24 interactors
MINTiQ9Y5X3
STRINGi9606.ENSP00000366988

Structurei

Secondary structure

1404
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9Y5X3
SMRiQ9Y5X3
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9Y5X3

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 172PXPROSITE-ProRule annotationAdd BLAST148
Domaini202 – 404BARAdd BLAST203

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni40 – 46Phosphatidylinositol bisphosphate bindingBy similarity7
Regioni99 – 105Phosphatidylinositol bisphosphate bindingBy similarity7
Regioni113 – 116Phosphatidylinositol bisphosphate bindingBy similarity4
Regioni169 – 261Interaction with DOCK11 PublicationAdd BLAST93
Regioni183 – 200Membrane-binding amphipathic helix1 PublicationAdd BLAST18

Domaini

The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.By similarity
The BAR domain is able to sense membrane curvature upon dimerization. Membrane remodeling seems to implicate insertion of an amphipatric helix (AH) in the membrane (Probable).1 Publication

Sequence similaritiesi

Belongs to the sorting nexin family.Curated

Phylogenomic databases

eggNOGiKOG1660 Eukaryota
ENOG410XPZY LUCA
GeneTreeiENSGT00930000150924
HOVERGENiHBG000716
InParanoidiQ9Y5X3
KOiK17920
OMAiHEDFIWL
OrthoDBiEOG091G08NT
PhylomeDBiQ9Y5X3
TreeFamiTF313698

Family and domain databases

Gene3Di1.20.1270.60, 1 hit
3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR001683 Phox
IPR036871 PX_dom_sf
IPR028654 SNX5
IPR014637 SNX5/SNX6/SNX32
IPR039358 Sorting_nexin-like
IPR015404 Vps5_C
PANTHERiPTHR10555 PTHR10555, 1 hit
PTHR10555:SF6 PTHR10555:SF6, 1 hit
PfamiView protein in Pfam
PF00787 PX, 1 hit
PF09325 Vps5, 1 hit
PIRSFiPIRSF036924 Snx5_Snx6, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS50195 PX, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9Y5X3-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAVPELLQQ QEEDRSKLRS VSVDLNVDPS LQIDIPDALS ERDKVKFTVH
60 70 80 90 100
TKTTLPTFQS PEFSVTRQHE DFVWLHDTLI ETTDYAGLII PPAPTKPDFD
110 120 130 140 150
GPREKMQKLG EGEGSMTKEE FAKMKQELEA EYLAVFKKTV SSHEVFLQRL
160 170 180 190 200
SSHPVLSKDR NFHVFLEYDQ DLSVRRKNTK EMFGGFFKSV VKSADEVLFT
210 220 230 240 250
GVKEVDDFFE QEKNFLINYY NRIKDSCVKA DKMTRSHKNV ADDYIHTAAC
260 270 280 290 300
LHSLALEEPT VIKKYLLKVA ELFEKLRKVE GRVSSDEDLK LTELLRYYML
310 320 330 340 350
NIEAAKDLLY RRTKALIDYE NSNKALDKAR LKSKDVKLAE AHQQECCQKF
360 370 380 390 400
EQLSESAKEE LINFKRKRVA AFRKNLIEMS ELEIKHARNN VSLLQSCIDL

FKNN
Length:404
Mass (Da):46,816
Last modified:November 1, 1999 - v1
Checksum:i87A85620AF827EC6
GO
Isoform 2 (identifier: Q9Y5X3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     18-126: LRSVSVDLNV...TKEEFAKMKQ → VRSSQPQTPG...FFLKLSSASW
     127-404: Missing.

Show »
Length:126
Mass (Da):13,349
Checksum:iF04391B429CE2D7A
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5QPE5Q5QPE5_HUMAN
Sorting nexin-5
SNX5
269Annotation score:
A0A087WUY5A0A087WUY5_HUMAN
Sorting nexin-5
SNX5
170Annotation score:
Q5QPE4Q5QPE4_HUMAN
Sorting nexin-5
SNX5
230Annotation score:
U3KQL0U3KQL0_HUMAN
Sorting nexin 5 isoform 2
SNX5
31Annotation score:
U3KQP5U3KQP5_HUMAN
Sorting nexin-5
SNX5
55Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti279V → L (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05638618 – 126LRSVS…AKMKQ → VRSSQPQTPGRAALRAPGSL HSFPCASIGRGCSPPSPARE APVRPGRPLSLVFTEGCPGE SLWMSRILLGQNQRRGTLAP AQAPVPSGLGEMISGDPGMF FLKLSSASW in isoform 2. 2 PublicationsAdd BLAST109
Alternative sequenceiVSP_056387127 – 404Missing in isoform 2. 2 PublicationsAdd BLAST278

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF121855 mRNA Translation: AAD27828.1
BT007191 mRNA Translation: AAP35855.1
AK001793 mRNA Translation: BAA91914.1
AK123903 mRNA Translation: BAG53980.1
AL121585 Genomic DNA No translation available.
BC000100 mRNA No translation available.
CH471133 Genomic DNA Translation: EAX10264.1
CH471133 Genomic DNA Translation: EAX10265.1
CH471133 Genomic DNA Translation: EAX10266.1
CH471133 Genomic DNA Translation: EAX10268.1
BC093623 mRNA Translation: AAH93623.1
BC093980 mRNA Translation: AAH93980.1
BC143274 mRNA Translation: AAI43275.1
CCDSiCCDS13130.1 [Q9Y5X3-1]
RefSeqiNP_055241.1, NM_014426.3 [Q9Y5X3-1]
NP_689413.1, NM_152227.2 [Q9Y5X3-1]
UniGeneiHs.316890

Genome annotation databases

EnsembliENST00000377759; ENSP00000366988; ENSG00000089006 [Q9Y5X3-1]
ENST00000377768; ENSP00000366998; ENSG00000089006 [Q9Y5X3-1]
ENST00000606557; ENSP00000475510; ENSG00000089006 [Q9Y5X3-2]
GeneIDi27131
KEGGihsa:27131
UCSCiuc002wqc.5 human [Q9Y5X3-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF121855 mRNA Translation: AAD27828.1
BT007191 mRNA Translation: AAP35855.1
AK001793 mRNA Translation: BAA91914.1
AK123903 mRNA Translation: BAG53980.1
AL121585 Genomic DNA No translation available.
BC000100 mRNA No translation available.
CH471133 Genomic DNA Translation: EAX10264.1
CH471133 Genomic DNA Translation: EAX10265.1
CH471133 Genomic DNA Translation: EAX10266.1
CH471133 Genomic DNA Translation: EAX10268.1
BC093623 mRNA Translation: AAH93623.1
BC093980 mRNA Translation: AAH93980.1
BC143274 mRNA Translation: AAI43275.1
CCDSiCCDS13130.1 [Q9Y5X3-1]
RefSeqiNP_055241.1, NM_014426.3 [Q9Y5X3-1]
NP_689413.1, NM_152227.2 [Q9Y5X3-1]
UniGeneiHs.316890

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SYSX-ray2.40C257-265[»]
5TGHX-ray2.80A/C/E/G22-170[»]
5TGIX-ray1.98A/B22-170[»]
5TGJX-ray2.60A/C22-170[»]
5WY2X-ray1.90A/C20-180[»]
ProteinModelPortaliQ9Y5X3
SMRiQ9Y5X3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118022, 57 interactors
IntActiQ9Y5X3, 24 interactors
MINTiQ9Y5X3
STRINGi9606.ENSP00000366988

PTM databases

iPTMnetiQ9Y5X3
PhosphoSitePlusiQ9Y5X3

Polymorphism and mutation databases

DMDMi10720289

Proteomic databases

EPDiQ9Y5X3
PaxDbiQ9Y5X3
PeptideAtlasiQ9Y5X3
PRIDEiQ9Y5X3
ProteomicsDBi86528

Protocols and materials databases

DNASUi27131
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377759; ENSP00000366988; ENSG00000089006 [Q9Y5X3-1]
ENST00000377768; ENSP00000366998; ENSG00000089006 [Q9Y5X3-1]
ENST00000606557; ENSP00000475510; ENSG00000089006 [Q9Y5X3-2]
GeneIDi27131
KEGGihsa:27131
UCSCiuc002wqc.5 human [Q9Y5X3-1]

Organism-specific databases

CTDi27131
DisGeNETi27131
EuPathDBiHostDB:ENSG00000089006.16
GeneCardsiSNX5
HGNCiHGNC:14969 SNX5
HPAiCAB020679
HPA051187
MIMi605937 gene
neXtProtiNX_Q9Y5X3
OpenTargetsiENSG00000089006
PharmGKBiPA37945
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1660 Eukaryota
ENOG410XPZY LUCA
GeneTreeiENSGT00930000150924
HOVERGENiHBG000716
InParanoidiQ9Y5X3
KOiK17920
OMAiHEDFIWL
OrthoDBiEOG091G08NT
PhylomeDBiQ9Y5X3
TreeFamiTF313698

Enzyme and pathway databases

ReactomeiR-HSA-432722 Golgi Associated Vesicle Biogenesis

Miscellaneous databases

ChiTaRSiSNX5 human
EvolutionaryTraceiQ9Y5X3
GeneWikiiSNX5
GenomeRNAii27131
PROiPR:Q9Y5X3
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000089006 Expressed in 221 organ(s), highest expression level in adrenal tissue
CleanExiHS_SNX5
ExpressionAtlasiQ9Y5X3 baseline and differential
GenevisibleiQ9Y5X3 HS

Family and domain databases

Gene3Di1.20.1270.60, 1 hit
3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR001683 Phox
IPR036871 PX_dom_sf
IPR028654 SNX5
IPR014637 SNX5/SNX6/SNX32
IPR039358 Sorting_nexin-like
IPR015404 Vps5_C
PANTHERiPTHR10555 PTHR10555, 1 hit
PTHR10555:SF6 PTHR10555:SF6, 1 hit
PfamiView protein in Pfam
PF00787 PX, 1 hit
PF09325 Vps5, 1 hit
PIRSFiPIRSF036924 Snx5_Snx6, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS50195 PX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSNX5_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5X3
Secondary accession number(s): B7ZKN3
, D3DW26, Q52LC4, Q7KZN0, Q9BWP0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 164 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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