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Protein

Sorting nexin-6

Gene

SNX6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in several stages of intracellular trafficking. Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex (PubMed:19935774). 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 endosome-to-TGN transport of lysosomal enzyme receptor IGF2R (PubMed:17148574). May function as link between transport vesicles and dynactin (Probable). Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network (PubMed:20354142). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). In association with GIT1 involved in EGFR degradation. Promotes lysosomal degradation of CDKN1B (By similarity). May contribute to transcription regulation (Probable).2 PublicationsBy similarityCurated5 Publications

GO - Molecular functioni

  • dynactin binding Source: UniProtKB
  • phosphatidylinositol binding Source: GO_Central
  • protein heterodimerization activity Source: ParkinsonsUK-UCL
  • protein homodimerization activity Source: HGNC

GO - Biological processi

  • endocytosis Source: GO_Central
  • intracellular protein transport Source: UniProtKB
  • negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: HGNC
  • regulation of macroautophagy Source: ParkinsonsUK-UCL
  • retrograde transport, endosome to Golgi Source: UniProtKB
  • vesicle organization Source: GO_Central

Keywordsi

Biological processProtein transport, Transport
LigandLipid-binding

Enzyme and pathway databases

SignaLinkiQ9UNH7.

Names & Taxonomyi

Protein namesi
Recommended name:
Sorting nexin-6
Alternative name(s):
TRAF4-associated factor 2
Cleaved into the following chain:
Gene namesi
Name:SNX6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000129515.18.
HGNCiHGNC:14970. SNX6.

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

Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68R → A: Reduces interaction with SNX1. Abolishes location at endosome membranes. 1 Publication1
Mutagenesisi69Q → A: No effect on subcellular location. 1 Publication1
Mutagenesisi97R → A: No effect on subcellular location. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000129515.
PharmGKBiPA37946.

Polymorphism and mutation databases

BioMutaiSNX6.
DMDMi10720285.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232771 – 406Sorting nexin-6Add BLAST406
Initiator methionineiRemoved; alternateCombined sources
ChainiPRO_00002138462 – 406Sorting nexin-6, N-terminally processedAdd BLAST405

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei2N-acetylmethionine; in Sorting nexin-6, N-terminally processedCombined sources1
Modified residuei116PhosphoserineCombined sources1
Modified residuei194PhosphoserineCombined sources1

Post-translational modificationi

In vitro phosphorylated by PIM1; not affecting PIM1-dependent nuclear translocation (PubMed:11591366).1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9UNH7.
PaxDbiQ9UNH7.
PeptideAtlasiQ9UNH7.
PRIDEiQ9UNH7.

2D gel databases

OGPiQ9UNH7.
REPRODUCTION-2DPAGEiIPI00298111.

PTM databases

iPTMnetiQ9UNH7.
PhosphoSitePlusiQ9UNH7.
SwissPalmiQ9UNH7.

Expressioni

Gene expression databases

BgeeiENSG00000129515.
CleanExiHS_SNX6.
ExpressionAtlasiQ9UNH7. baseline and differential.
GenevisibleiQ9UNH7. HS.

Organism-specific databases

HPAiHPA049374.

Interactioni

Subunit structurei

Forms heterodimers with BAR domain-containing sorting nexins SNX1 and SNX2 (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 descibed 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, CDKN1B, TGFB receptors, BACE1, BRMS1, PIP5K1C isoform 3. Interacts with DCTN1; the association with DCTN1 is involved in movement of retromer-c ontaining vesicles toward the TGN (PubMed:11279102, PubMed:17148574, PubMed:19935774, PubMed:19619496, PubMed:20354142, PubMed:20830743, PubMed:23085988, PubMed:24610942). Interacts with CDKN1B and GIT1 (By similarity). Interacts with PIM1; translocating SNX6 to the nucleus (PubMed:11591366).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • dynactin binding Source: UniProtKB
  • protein heterodimerization activity Source: ParkinsonsUK-UCL
  • protein homodimerization activity Source: HGNC

Protein-protein interaction databases

BioGridi121852. 77 interactors.
CORUMiQ9UNH7.
DIPiDIP-37549N.
IntActiQ9UNH7. 18 interactors.
MINTiMINT-2634416.
STRINGi9606.ENSP00000355217.

Structurei

3D structure databases

ProteinModelPortaliQ9UNH7.
SMRiQ9UNH7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 173PXAdd BLAST148
Domaini203 – 406BARCuratedAdd BLAST204

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 179Interaction with PIM11 PublicationAdd BLAST178
Regioni41 – 47Phosphatidylinositol bisphosphate bindingBy similarity7
Regioni100 – 106Phosphatidylinositol bisphosphate bindingBy similarity7
Regioni114 – 117Phosphatidylinositol bisphosphate bindingBy similarity4
Regioni182 – 199Membrane-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.
GeneTreeiENSGT00900000140943.
HOGENOMiHOG000231691.
HOVERGENiHBG000716.
InParanoidiQ9UNH7.
KOiK17920.
PhylomeDBiQ9UNH7.
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.
IPR014637. SNX5/SNX6/SNX32.
IPR028657. SNX6.
IPR015404. Vps5_C.
PANTHERiPTHR10555:SF120. PTHR10555:SF120. 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

Isoform 1 (identifier: Q9UNH7-1) [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
MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDKVKFTV
60 70 80 90 100
HTKSSLPNFK QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF
110 120 130 140 150
DASREKLQKL GEGEGSMTKE EFTKMKQELE AEYLAIFKKT VAMHEVFLCR
160 170 180 190 200
VAAHPILRRD LNFHVFLEYN QDLSVRGKNK KEKLEDFFKN MVKSADGVIV
210 220 230 240 250
SGVKDVDDFF EHERTFLLEY HNRVKDASAK SDRMTRSHKS AADDYNRIGS
260 270 280 290 300
SLYALGTQDS TDICKFFLKV SELFDKTRKI EARVSADEDL KLSDLLKYYL
310 320 330 340 350
RESQAAKDLL YRRSRSLVDY ENANKALDKA RAKNKDVLQA ETSQQLCCQK
360 370 380 390 400
FEKISESAKQ ELIDFKTRRV AAFRKNLVEL AELELKHAKG NLQLLQNCLA

VLNGDT
Length:406
Mass (Da):46,649
Last modified:May 1, 2000 - v1
Checksum:iE3659DB19C59E1BB
GO
Isoform 2 (identifier: Q9UNH7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-116: Missing.

Note: No experimental confirmation available.
Show »
Length:290
Mass (Da):33,570
Checksum:iC12EC83110C71CA8
GO

Sequence cautioni

The sequence AAD24202 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0448241 – 116Missing in isoform 2. 1 PublicationAdd BLAST116

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF121856 mRNA. Translation: AAD27829.1.
U83194 mRNA. Translation: AAD24202.1. Different initiation.
AL445363 Genomic DNA. No translation available.
AL445883 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65913.1.
CH471078 Genomic DNA. Translation: EAW65915.1.
BC001798 mRNA. Translation: AAH01798.1.
CCDSiCCDS9648.1. [Q9UNH7-2]
RefSeqiNP_067072.3. NM_021249.4. [Q9UNH7-2]
NP_689419.2. NM_152233.3.
UniGeneiHs.276523.
Hs.356647.

Genome annotation databases

EnsembliENST00000396526; ENSP00000379779; ENSG00000129515. [Q9UNH7-2]
GeneIDi58533.
KEGGihsa:58533.
UCSCiuc001wse.2. human. [Q9UNH7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSNX6_HUMAN
AccessioniPrimary (citable) accession number: Q9UNH7
Secondary accession number(s): C0H5W9, Q9Y449
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: November 22, 2017
This is version 157 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: 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. SIMILARITY comments
    Index of protein domains and families