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Protein

Sorting nexin-3

Gene

SNX3

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

Functioni

Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Also can bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:21725319, PubMed:24344282). Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes (PubMed:23237080). Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex (By similarity). In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs (PubMed:20482551).By similarity1 Publication5 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei70Phosphatidylinositol 3-phosphateBy similarity1
Binding sitei72Phosphatidylinositol 3-phosphate; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei95Phosphatidylinositol 3-phosphateBy similarity1
Binding sitei118Phosphatidylinositol 3-phosphateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processProtein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-3238698 WNT ligand biogenesis and trafficking
R-HSA-5689880 Ub-specific processing proteases

Names & Taxonomyi

Protein namesi
Recommended name:
Sorting nexin-3
Alternative name(s):
Protein SDP3
Gene namesi
Name:SNX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112335.14
HGNCiHGNC:11174 SNX3
MIMi605930 gene
neXtProtiNX_O60493

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

Cytoplasmic vesicle, Endosome

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi28F → A: Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-30 and A-32. 1 Publication1
Mutagenesisi30E → A: Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-28 and A-32. 1 Publication1
Mutagenesisi32D → A: Abolishes interaction with retromer cargo-selective subcomplex VPS26A:VPS29:VPS35; when associated with A-28 and A-30. 1 Publication1
Mutagenesisi69 – 71RRY → AAA: Abolishes binding to phosphatidylinositol 3-phosphate. 1 Publication3
Mutagenesisi71Y → A: Abolishes binding to phosphatidylinositol 3-phosphate. 1 Publication1

Keywords - Diseasei

Microphthalmia

Organism-specific databases

DisGeNETi8724
MalaCardsiSNX3
OpenTargetsiENSG00000112335
PharmGKBiPA36013

Polymorphism and mutation databases

BioMutaiSNX3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00002138402 – 162Sorting nexin-3Add BLAST161

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei43Omega-N-methylarginineCombined sources1
Modified residuei72PhosphoserineCombined sources1
Cross-linki95Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP10 (By similarity).By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO60493
MaxQBiO60493
PaxDbiO60493
PeptideAtlasiO60493
PRIDEiO60493
ProteomicsDBi49428
49429 [O60493-2]
49430 [O60493-3]
49431 [O60493-4]
TopDownProteomicsiO60493-1 [O60493-1]
O60493-2 [O60493-2]
O60493-4 [O60493-4]

2D gel databases

REPRODUCTION-2DPAGEiIPI00815770
UCD-2DPAGEiO60493

PTM databases

iPTMnetiO60493
PhosphoSitePlusiO60493

Expressioni

Gene expression databases

BgeeiENSG00000112335 Expressed in 237 organ(s), highest expression level in parietal pleura
CleanExiHS_SNX3
GenevisibleiO60493 HS

Interactioni

Subunit structurei

Interacts with VPS26A, VPS29 and VPS35; the interaction with VPS35 is direct. The association with the retromer CSC subcomplex subunits is proposed to represent a functional distinct retromer variant described as SNX3-retromer complex (PubMed:21725319, PubMed:24344282). Interacts with USP10 and SCNN1A (By similarity). Interacts with TRFC (By similarity). Interacts with SNX8; 2 molecules of SNX8 seems to associate with one molecule of SNX3 (PubMed:24866125). Interacts with PTPRU (PubMed:17622474).By similarity1 Publication4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114263, 87 interactors
IntActiO60493, 29 interactors
MINTiO60493
STRINGi9606.ENSP00000230085

Structurei

Secondary structure

1162
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO60493
SMRiO60493
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 151PXPROSITE-ProRule annotationAdd BLAST125

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni147 – 162Binds predominantly to PtdIns(P5) and weaker to PtdIns(P3) abd PtdIns(P4); involved in neurite outgrowth regulationBy similarityAdd BLAST16

Domaini

The PX domain mediates specific binding to phosphatidylinositol 3-phosphate (PtdIns(P3)).1 Publication

Sequence similaritiesi

Belongs to the sorting nexin family.Curated

Phylogenomic databases

eggNOGiKOG2527 Eukaryota
COG5391 LUCA
GeneTreeiENSGT00650000093174
HOVERGENiHBG055338
InParanoidiO60493
KOiK17918
OMAiFTKPQNL
OrthoDBiEOG091G0VOS
PhylomeDBiO60493
TreeFamiTF314980

Family and domain databases

Gene3Di3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR001683 Phox
IPR036871 PX_dom_sf
IPR039358 Sorting_nexin-like
PANTHERiPTHR10555 PTHR10555, 1 hit
PfamiView protein in Pfam
PF00787 PX, 1 hit
SMARTiView protein in SMART
SM00312 PX, 1 hit
SUPFAMiSSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS50195 PX, 1 hit

Sequences (4)i

Sequence statusi: Complete.

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

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O60493-1) [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
MAETVADTRR LITKPQNLND AYGPPSNFLE IDVSNPQTVG VGRGRFTTYE
60 70 80 90 100
IRVKTNLPIF KLKESTVRRR YSDFEWLRSE LERESKVVVP PLPGKAFLRQ
110 120 130 140 150
LPFRGDDGIF DDNFIEERKQ GLEQFINKVA GHPLAQNERC LHMFLQDEII
160
DKSYTPSKIR HA
Length:162
Mass (Da):18,762
Last modified:January 23, 2007 - v3
Checksum:i983D422FCA6E07BC
GO
Isoform 2 (identifier: O60493-2) [UniParc]FASTAAdd to basket
Also known as: SNX 3A

The sequence of this isoform differs from the canonical sequence as follows:
     55-86: Missing.

Show »
Length:130
Mass (Da):14,766
Checksum:i39DD7F3E916554AD
GO
Isoform 3 (identifier: O60493-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     87-162: VVVPPLPGKA...SYTPSKIRHA → PCLRMTSEARSHGRTWCAQNDEKLFCD

Note: No experimental confirmation available.
Show »
Length:113
Mass (Da):13,172
Checksum:iF8C0774B88153F42
GO
Isoform 4 (identifier: O60493-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     33-54: Missing.

Note: No experimental confirmation available.
Show »
Length:140
Mass (Da):16,316
Checksum:i01710ACF7D256DCA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti100 – 101QL → HF in AAC16018 (PubMed:11433298).Curated2
Sequence conflicti151D → V in BAF82165 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_01469433 – 54Missing in isoform 4. CuratedAdd BLAST22
Alternative sequenceiVSP_00619055 – 86Missing in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_01292887 – 162VVVPP…KIRHA → PCLRMTSEARSHGRTWCAQN DEKLFCD in isoform 3. 1 PublicationAdd BLAST76

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034546 mRNA Translation: AAC16040.1
AF062483 mRNA Translation: AAC16018.1
AB047360 mRNA Translation: BAB32649.1
AK289476 mRNA Translation: BAF82165.1
BT007114 mRNA Translation: AAP35778.1
CR456898 mRNA Translation: CAG33179.1
AL078596 Genomic DNA No translation available.
Z98742 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48378.1
CH471051 Genomic DNA Translation: EAW48379.1
CH471051 Genomic DNA Translation: EAW48381.1
CH471051 Genomic DNA Translation: EAW48382.1
BC008444 mRNA Translation: AAH08444.1
BC014580 mRNA Translation: AAH14580.1
BC015179 mRNA Translation: AAH15179.1
BC016863 mRNA Translation: AAH16863.1
CCDSiCCDS5064.1 [O60493-1]
CCDS5065.1 [O60493-2]
CCDS75501.1 [O60493-4]
RefSeqiNP_001287858.1, NM_001300929.1 [O60493-4]
NP_003786.1, NM_003795.5 [O60493-1]
NP_690040.1, NM_152827.3 [O60493-2]
UniGeneiHs.12102

Genome annotation databases

EnsembliENST00000230085; ENSP00000230085; ENSG00000112335 [O60493-1]
ENST00000349379; ENSP00000296991; ENSG00000112335 [O60493-4]
ENST00000368979; ENSP00000357975; ENSG00000112335 [O60493-3]
ENST00000426155; ENSP00000401779; ENSG00000112335 [O60493-2]
GeneIDi8724
KEGGihsa:8724
UCSCiuc003psh.4 human [O60493-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF034546 mRNA Translation: AAC16040.1
AF062483 mRNA Translation: AAC16018.1
AB047360 mRNA Translation: BAB32649.1
AK289476 mRNA Translation: BAF82165.1
BT007114 mRNA Translation: AAP35778.1
CR456898 mRNA Translation: CAG33179.1
AL078596 Genomic DNA No translation available.
Z98742 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48378.1
CH471051 Genomic DNA Translation: EAW48379.1
CH471051 Genomic DNA Translation: EAW48381.1
CH471051 Genomic DNA Translation: EAW48382.1
BC008444 mRNA Translation: AAH08444.1
BC014580 mRNA Translation: AAH14580.1
BC015179 mRNA Translation: AAH15179.1
BC016863 mRNA Translation: AAH16863.1
CCDSiCCDS5064.1 [O60493-1]
CCDS5065.1 [O60493-2]
CCDS75501.1 [O60493-4]
RefSeqiNP_001287858.1, NM_001300929.1 [O60493-4]
NP_003786.1, NM_003795.5 [O60493-1]
NP_690040.1, NM_152827.3 [O60493-2]
UniGeneiHs.12102

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2MXCNMR-A2-162[»]
2YPSX-ray2.60A/B/C/D24-155[»]
5F0JX-ray2.70C1-162[»]
5F0LX-ray3.20C1-162[»]
5F0MX-ray3.10C1-162[»]
5F0PX-ray2.78C1-162[»]
ProteinModelPortaliO60493
SMRiO60493
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114263, 87 interactors
IntActiO60493, 29 interactors
MINTiO60493
STRINGi9606.ENSP00000230085

PTM databases

iPTMnetiO60493
PhosphoSitePlusiO60493

Polymorphism and mutation databases

BioMutaiSNX3

2D gel databases

REPRODUCTION-2DPAGEiIPI00815770
UCD-2DPAGEiO60493

Proteomic databases

EPDiO60493
MaxQBiO60493
PaxDbiO60493
PeptideAtlasiO60493
PRIDEiO60493
ProteomicsDBi49428
49429 [O60493-2]
49430 [O60493-3]
49431 [O60493-4]
TopDownProteomicsiO60493-1 [O60493-1]
O60493-2 [O60493-2]
O60493-4 [O60493-4]

Protocols and materials databases

DNASUi8724
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000230085; ENSP00000230085; ENSG00000112335 [O60493-1]
ENST00000349379; ENSP00000296991; ENSG00000112335 [O60493-4]
ENST00000368979; ENSP00000357975; ENSG00000112335 [O60493-3]
ENST00000426155; ENSP00000401779; ENSG00000112335 [O60493-2]
GeneIDi8724
KEGGihsa:8724
UCSCiuc003psh.4 human [O60493-1]

Organism-specific databases

CTDi8724
DisGeNETi8724
EuPathDBiHostDB:ENSG00000112335.14
GeneCardsiSNX3
H-InvDBiHIX0006117
HGNCiHGNC:11174 SNX3
MalaCardsiSNX3
MIMi605930 gene
neXtProtiNX_O60493
OpenTargetsiENSG00000112335
PharmGKBiPA36013
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2527 Eukaryota
COG5391 LUCA
GeneTreeiENSGT00650000093174
HOVERGENiHBG055338
InParanoidiO60493
KOiK17918
OMAiFTKPQNL
OrthoDBiEOG091G0VOS
PhylomeDBiO60493
TreeFamiTF314980

Enzyme and pathway databases

ReactomeiR-HSA-3238698 WNT ligand biogenesis and trafficking
R-HSA-5689880 Ub-specific processing proteases

Miscellaneous databases

ChiTaRSiSNX3 human
GeneWikiiSNX3
GenomeRNAii8724
PROiPR:O60493
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112335 Expressed in 237 organ(s), highest expression level in parietal pleura
CleanExiHS_SNX3
GenevisibleiO60493 HS

Family and domain databases

Gene3Di3.30.1520.10, 1 hit
InterProiView protein in InterPro
IPR001683 Phox
IPR036871 PX_dom_sf
IPR039358 Sorting_nexin-like
PANTHERiPTHR10555 PTHR10555, 1 hit
PfamiView protein in Pfam
PF00787 PX, 1 hit
SMARTiView protein in SMART
SM00312 PX, 1 hit
SUPFAMiSSF64268 SSF64268, 1 hit
PROSITEiView protein in PROSITE
PS50195 PX, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSNX3_HUMAN
AccessioniPrimary (citable) accession number: O60493
Secondary accession number(s): A8K0B1
, E1P5E4, E1P5E5, O60718, Q4TT29, Q4TT31, Q5JXJ7, Q5JXJ8, Q96AP9, Q9C0J5, Q9NU45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 23, 2007
Last modified: October 10, 2018
This is version 172 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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