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Protein

Sorting nexin-3

Gene

SNX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • intralumenal vesicle formation Source: UniProtKB
  • membrane invagination Source: UniProtKB
  • negative regulation of early endosome to late endosome transport Source: UniProtKB
  • negative regulation of phagocytosis Source: UniProtKB
  • negative regulation of protein catabolic process Source: UniProtKB
  • negative regulation of protein transport Source: UniProtKB
  • negative regulation of viral entry into host cell Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • protein to membrane docking Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of Wnt signaling pathway Source: UniProtKB
  • response to bacterium Source: UniProtKB
  • Wnt signaling pathway Source: Reactome

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.

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

Microphthalmia, syndromic, 8 (MCOPS8)1 Publication
The gene represented in this entry may be involved in disease pathogenesis. A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12).
Disease descriptionA very rare congenital syndrome characterized by microcephaly, microphthalmia, ectrodactyly of the lower limbs and prognathism. Intellectual deficit has been reported. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
See also OMIM:601349

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.
MIMi601349. phenotype.
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.
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.
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

Show more details

GO - Molecular functioni

  • protein phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114263. 87 interactors.
IntActiO60493. 25 interactors.
MINTiMINT-1421811.
STRINGi9606.ENSP00000230085.

Structurei

Secondary structure

1162
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi18 – 22Combined sources5
Beta strandi29 – 34Combined sources6
Helixi44 – 46Combined sources3
Beta strandi49 – 55Combined sources7
Beta strandi63 – 69Combined sources7
Helixi71 – 84Combined sources14
Helixi97 – 100Combined sources4
Beta strandi101 – 103Combined sources3
Helixi108 – 110Combined sources3
Helixi114 – 131Combined sources18
Helixi133 – 136Combined sources4
Helixi139 – 146Combined sources8
Beta strandi147 – 149Combined sources3

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...

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.
OMAiTPSKIRQ.
OrthoDBiEOG091G0VOS.
PhylomeDBiO60493.
TreeFamiTF314980.

Family and domain databases

Gene3Di3.30.1520.10. 1 hit.
InterProiView protein in InterPro
IPR001683. Phox.
IPR036871. PX_dom_sf.
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

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: November 22, 2017
This is version 165 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families