UniProtKB - Q9UNH7 (SNX6_HUMAN)
Sorting nexin-6
SNX6
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 PublicationsGO - Molecular functioni
- dynactin binding Source: UniProtKB
- phosphatidylinositol binding Source: InterPro
- protein homodimerization activity Source: HGNC-UCL
- type I transforming growth factor beta receptor binding Source: Ensembl
GO - Biological processi
- cellular response to amyloid-beta Source: ARUK-UCL
- intracellular protein transport Source: UniProtKB
- negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
- negative regulation of neuron apoptotic process Source: ARUK-UCL
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transforming growth factor beta receptor signaling pathway Source: HGNC-UCL
- regulation of macroautophagy Source: ParkinsonsUK-UCL
- retrograde transport, endosome to Golgi Source: UniProtKB
Keywordsi
Biological process | Protein transport, Transport |
Ligand | Lipid-binding |
Enzyme and pathway databases
PathwayCommonsi | Q9UNH7 |
SignaLinki | Q9UNH7 |
Names & Taxonomyi
Protein namesi | Recommended name: Sorting nexin-6Alternative name(s): TRAF4-associated factor 2 Cleaved into the following chain: |
Gene namesi | Name:SNX6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:14970, SNX6 |
MIMi | 606098, gene |
neXtProti | NX_Q9UNH7 |
VEuPathDBi | HostDB:ENSG00000129515 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Endosome
- Early endosome 3 Publications
- Early endosome membrane 1 Publication1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side Curated
Cytoplasm and Cytosol
- Cytoplasm 1 Publication
Other locations
- Cytoplasmic vesicle 1 Publication
Note: Interaction with SNX1 or SNX2 promotes location at endosome membranes (PubMed:19935774). Only a minor proportion is seen in the nucleus.1 Publication
Cytosol
- cytosol Source: GOC
Endosome
- early endosome membrane Source: UniProtKB
- endosome Source: GO_Central
- tubular endosome Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: UniProtKB
- retromer complex Source: UniProtKB
- retromer, tubulation complex Source: ParkinsonsUK-UCL
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 68 | R → A: Reduces interaction with SNX1. Abolishes location at endosome membranes. 1 Publication | 1 | |
Mutagenesisi | 69 | Q → A: No effect on subcellular location. 1 Publication | 1 | |
Mutagenesisi | 97 | R → A: No effect on subcellular location. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 58533 |
OpenTargetsi | ENSG00000129515 |
PharmGKBi | PA37946 |
Miscellaneous databases
Pharosi | Q9UNH7, Tbio |
Genetic variation databases
BioMutai | SNX6 |
DMDMi | 10720285 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000423277 | 1 – 406 | Sorting nexin-6Add BLAST | 406 | |
Initiator methioninei | Removed; alternateCombined sources | |||
ChainiPRO_0000213846 | 2 – 406 | Sorting nexin-6, N-terminally processedAdd BLAST | 405 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 2 | N-acetylmethionine; in Sorting nexin-6, N-terminally processedCombined sources | 1 | |
Modified residuei | 116 | PhosphoserineCombined sources | 1 | |
Modified residuei | 194 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | Q9UNH7 |
jPOSTi | Q9UNH7 |
MassIVEi | Q9UNH7 |
MaxQBi | Q9UNH7 |
PaxDbi | Q9UNH7 |
PeptideAtlasi | Q9UNH7 |
PRIDEi | Q9UNH7 |
ProteomicsDBi | 7568 85296 [Q9UNH7-1] |
2D gel databases
OGPi | Q9UNH7 |
REPRODUCTION-2DPAGEi | IPI00298111 |
PTM databases
GlyGeni | Q9UNH7, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9UNH7 |
MetOSitei | Q9UNH7 |
PhosphoSitePlusi | Q9UNH7 |
SwissPalmi | Q9UNH7 |
Expressioni
Gene expression databases
Bgeei | ENSG00000129515, Expressed in placenta and 222 other tissues |
ExpressionAtlasi | Q9UNH7, baseline and differential |
Genevisiblei | Q9UNH7, HS |
Organism-specific databases
HPAi | ENSG00000129515, Low tissue specificity |
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 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, 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 PublicationsBinary interactionsi
Q9UNH7
GO - Molecular functioni
- dynactin binding Source: UniProtKB
- protein homodimerization activity Source: HGNC-UCL
- type I transforming growth factor beta receptor binding Source: Ensembl
Protein-protein interaction databases
BioGRIDi | 121852, 169 interactors |
CORUMi | Q9UNH7 |
DIPi | DIP-37549N |
IntActi | Q9UNH7, 52 interactors |
MINTi | Q9UNH7 |
STRINGi | 9606.ENSP00000355217 |
Miscellaneous databases
RNActi | Q9UNH7, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 26 – 173 | PXPROSITE-ProRule annotationAdd BLAST | 148 | |
Domaini | 203 – 406 | BARCuratedAdd BLAST | 204 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 179 | Interaction with PIM11 PublicationAdd BLAST | 178 | |
Regioni | 41 – 47 | Phosphatidylinositol bisphosphate bindingBy similarity | 7 | |
Regioni | 100 – 106 | Phosphatidylinositol bisphosphate bindingBy similarity | 7 | |
Regioni | 114 – 117 | Phosphatidylinositol bisphosphate bindingBy similarity | 4 | |
Regioni | 182 – 199 | Membrane-binding amphipathic helix1 PublicationAdd BLAST | 18 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1660, Eukaryota |
GeneTreei | ENSGT00940000154940 |
InParanoidi | Q9UNH7 |
OrthoDBi | 1009572at2759 |
PhylomeDBi | Q9UNH7 |
TreeFami | TF313698 |
Family and domain databases
CDDi | cd07292, PX_SNX6, 1 hit |
Gene3Di | 1.20.1270.60, 1 hit 3.30.1520.10, 1 hit |
InterProi | View protein in InterPro IPR027267, AH/BAR_dom_sf IPR001683, PX_dom IPR036871, PX_dom_sf IPR042136, PX_SNX6 IPR014637, SNX5/SNX6/SNX32 IPR028657, SNX6 IPR015404, Vps5_C |
PANTHERi | PTHR45850:SF4, PTHR45850:SF4, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF09325, Vps5, 1 hit |
PIRSFi | PIRSF036924, Snx5_Snx6, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0A0MRI2 | A0A0A0MRI2_HUMAN | Sorting nexin | SNX6 hCG_2013610 | 418 | Annotation score: | ||
G3V5X9 | G3V5X9_HUMAN | Sorting nexin-6 | SNX6 | 227 | Annotation score: | ||
H0YJF8 | H0YJF8_HUMAN | Sorting nexin-6 | SNX6 | 144 | Annotation score: | ||
G3V5U2 | G3V5U2_HUMAN | Sorting nexin-6 | SNX6 | 132 | Annotation score: | ||
G3V4Z5 | G3V4Z5_HUMAN | Sorting nexin-6 | SNX6 | 157 | Annotation score: | ||
G3V2U1 | G3V2U1_HUMAN | Sorting nexin-6 | SNX6 | 120 | Annotation score: | ||
G3V589 | G3V589_HUMAN | Sorting nexin-6 | SNX6 | 20 | Annotation score: |
Sequence cautioni
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044824 | 1 – 116 | Missing in isoform 2. 1 PublicationAdd BLAST | 116 |
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 |
CCDSi | CCDS41942.1 [Q9UNH7-1] CCDS9648.1 [Q9UNH7-2] |
RefSeqi | NP_067072.3, NM_021249.4 [Q9UNH7-2] NP_689419.2, NM_152233.3 [Q9UNH7-1] |
Genome annotation databases
Ensembli | ENST00000362031; ENSP00000355217; ENSG00000129515 ENST00000396526; ENSP00000379779; ENSG00000129515 [Q9UNH7-2] |
GeneIDi | 58533 |
KEGGi | hsa:58533 |
MANE-Selecti | ENST00000362031.10; ENSP00000355217.5; NM_152233.4; NP_689419.3 |
UCSCi | uc001wse.2, human [Q9UNH7-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS41942.1 [Q9UNH7-1] CCDS9648.1 [Q9UNH7-2] |
RefSeqi | NP_067072.3, NM_021249.4 [Q9UNH7-2] NP_689419.2, NM_152233.3 [Q9UNH7-1] |
3D structure databases
SMRi | Q9UNH7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 121852, 169 interactors |
CORUMi | Q9UNH7 |
DIPi | DIP-37549N |
IntActi | Q9UNH7, 52 interactors |
MINTi | Q9UNH7 |
STRINGi | 9606.ENSP00000355217 |
PTM databases
GlyGeni | Q9UNH7, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q9UNH7 |
MetOSitei | Q9UNH7 |
PhosphoSitePlusi | Q9UNH7 |
SwissPalmi | Q9UNH7 |
Genetic variation databases
BioMutai | SNX6 |
DMDMi | 10720285 |
2D gel databases
OGPi | Q9UNH7 |
REPRODUCTION-2DPAGEi | IPI00298111 |
Proteomic databases
EPDi | Q9UNH7 |
jPOSTi | Q9UNH7 |
MassIVEi | Q9UNH7 |
MaxQBi | Q9UNH7 |
PaxDbi | Q9UNH7 |
PeptideAtlasi | Q9UNH7 |
PRIDEi | Q9UNH7 |
ProteomicsDBi | 7568 85296 [Q9UNH7-1] |
Protocols and materials databases
Antibodypediai | 23146, 308 antibodies from 28 providers |
DNASUi | 58533 |
Genome annotation databases
Ensembli | ENST00000362031; ENSP00000355217; ENSG00000129515 ENST00000396526; ENSP00000379779; ENSG00000129515 [Q9UNH7-2] |
GeneIDi | 58533 |
KEGGi | hsa:58533 |
MANE-Selecti | ENST00000362031.10; ENSP00000355217.5; NM_152233.4; NP_689419.3 |
UCSCi | uc001wse.2, human [Q9UNH7-1] |
Organism-specific databases
CTDi | 58533 |
DisGeNETi | 58533 |
GeneCardsi | SNX6 |
HGNCi | HGNC:14970, SNX6 |
HPAi | ENSG00000129515, Low tissue specificity |
MIMi | 606098, gene |
neXtProti | NX_Q9UNH7 |
OpenTargetsi | ENSG00000129515 |
PharmGKBi | PA37946 |
VEuPathDBi | HostDB:ENSG00000129515 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1660, Eukaryota |
GeneTreei | ENSGT00940000154940 |
InParanoidi | Q9UNH7 |
OrthoDBi | 1009572at2759 |
PhylomeDBi | Q9UNH7 |
TreeFami | TF313698 |
Enzyme and pathway databases
PathwayCommonsi | Q9UNH7 |
SignaLinki | Q9UNH7 |
Miscellaneous databases
BioGRID-ORCSi | 58533, 45 hits in 1047 CRISPR screens |
ChiTaRSi | SNX6, human |
GenomeRNAii | 58533 |
Pharosi | Q9UNH7, Tbio |
PROi | PR:Q9UNH7 |
RNActi | Q9UNH7, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000129515, Expressed in placenta and 222 other tissues |
ExpressionAtlasi | Q9UNH7, baseline and differential |
Genevisiblei | Q9UNH7, HS |
Family and domain databases
CDDi | cd07292, PX_SNX6, 1 hit |
Gene3Di | 1.20.1270.60, 1 hit 3.30.1520.10, 1 hit |
InterProi | View protein in InterPro IPR027267, AH/BAR_dom_sf IPR001683, PX_dom IPR036871, PX_dom_sf IPR042136, PX_SNX6 IPR014637, SNX5/SNX6/SNX32 IPR028657, SNX6 IPR015404, Vps5_C |
PANTHERi | PTHR45850:SF4, PTHR45850:SF4, 1 hit |
Pfami | View protein in Pfam PF00787, PX, 1 hit PF09325, Vps5, 1 hit |
PIRSFi | PIRSF036924, Snx5_Snx6, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit SSF64268, SSF64268, 1 hit |
PROSITEi | View protein in PROSITE PS50195, PX, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SNX6_HUMAN | |
Accessioni | Q9UNH7Primary (citable) accession number: Q9UNH7 Secondary accession number(s): C0H5W9, Q9Y449 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | May 1, 2000 | |
Last modified: | February 23, 2022 | |
This is version 185 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 14
Human chromosome 14: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families