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Protein

Sorting nexin-27

Gene

SNX27

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

Functioni

Involved in the retrograde transport from endosome to plasma membrane, a trafficking pathway that promotes the recycling of internalized transmembrane proteins. Following internalization, endocytosed transmembrane proteins are delivered to early endosomes and recycled to the plasma membrane instead of being degraded in lysosomes. SNX27 specifically binds and directs sorting of a subset of transmembrane proteins containing a PDZ-binding motif at the C-terminus: following interaction with target transmembrane proteins, associates with the retromer complex, preventing entry into the lysosomal pathway, and promotes retromer-tubule based plasma membrane recycling. SNX27 also binds with the WASH complex. Interacts with membranes containing phosphatidylinositol-3-phosphate (PtdIns(3P)). May participate in establishment of natural killer cell polarity. Recruits CYTIP to early endosomes.8 Publications

GO - Molecular functioni

  • phosphatidylinositol-3-phosphate binding Source: UniProtKB

GO - Biological processi

  • endosomal transport Source: UniProtKB
  • endosome to lysosome transport Source: Ensembl
  • establishment of natural killer cell polarity Source: UniProtKB
  • intracellular protein transport Source: UniProtKB
  • retrograde transport, endosome to plasma membrane Source: UniProtKB
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Lipid-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143376-MONOMER.

Protein family/group databases

TCDBi9.A.3.1.1. the sorting nexin27 (snx27)-retromer assembly apparatus for recycling integral membrane proteins (snx27-retromeraa) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Sorting nexin-27
Gene namesi
Name:SNX27
Synonyms:KIAA0488
ORF Names:My014
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:20073. SNX27.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: UniProtKB-SubCell
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • endosome Source: ParkinsonsUK-UCL
  • immunological synapse Source: UniProtKB
  • nucleoplasm Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi114H → A: Abolishes interaction with ADRB2, sorting and recycling of ADRB2. 1 Publication1

Organism-specific databases

DisGeNETi81609.
OpenTargetsiENSG00000143376.
PharmGKBiPA134969143.

Polymorphism and mutation databases

BioMutaiSNX27.
DMDMi166214988.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003153561 – 541Sorting nexin-27Add BLAST541

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei51PhosphoserineCombined sources1
Modified residuei62PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ96L92.
MaxQBiQ96L92.
PaxDbiQ96L92.
PeptideAtlasiQ96L92.
PRIDEiQ96L92.

PTM databases

iPTMnetiQ96L92.
PhosphoSitePlusiQ96L92.

Expressioni

Tissue specificityi

Widely expressed. Expressed in cells of hematopoietic origin (at protein level).3 Publications

Gene expression databases

BgeeiENSG00000143376.
ExpressionAtlasiQ96L92. baseline and differential.
GenevisibleiQ96L92. HS.

Organism-specific databases

HPAiHPA045816.

Interactioni

Subunit structurei

Core component of the SNX27-retromer, a multiprotein complex composed of SNX27, the WASH complex and the retromer complex. Interacts (via PDZ domain) with a number of target transmembrane proteins (via PDZ-binding motif): ABCC4, ADRB2, ARHGEF7, GRIA1, GRIA2, GRIN1, GRIN2A GRIN2C, KCNJ6, KCNJ9 and SLC2A1/GLUT1. Interacts (via the FERM-like regions) with the WASH complex. Interacts with SNX1. Interacts with CYTIP. Isoform 1 and isoform 2 directly interact with DGKZ. Isoform 1 and isoform 2 interact with HT4R isoform 5-HTA(A). Interacts with MCC.9 Publications

Protein-protein interaction databases

BioGridi123546. 71 interactors.
IntActiQ96L92. 13 interactors.
MINTiMINT-7211211.
STRINGi9606.ENSP00000357836.

Structurei

Secondary structure

1541
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi165 – 175Combined sources11
Beta strandi178 – 187Combined sources10
Beta strandi190 – 195Combined sources6
Helixi197 – 210Combined sources14
Turni211 – 213Combined sources3
Helixi229 – 246Combined sources18
Helixi250 – 253Combined sources4
Helixi256 – 261Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HASX-ray1.74A/B156-265[»]
ProteinModelPortaliQ96L92.
SMRiQ96L92.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 136PDZPROSITE-ProRule annotationAdd BLAST94
Domaini161 – 269PXPROSITE-ProRule annotationAdd BLAST109
Domaini273 – 362Ras-associatingPROSITE-ProRule annotationAdd BLAST90

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni273 – 362FERM-like region F1Add BLAST90
Regioni373 – 421FERM-like region F2Add BLAST49
Regioni425 – 525FERM-like region F3Add BLAST101

Domaini

The PDZ domain mediates binding to a subset of proteins containing a PDZ-binding motif at the C-terminus: the specificity for PDZ-binding motif is provided by the 2 residues located upstream of the canonical PDZ-binding motif (By similarity). The PDZ domain also mediates binding to the retromer complex via direct interaction with VPS26 (VPS26A or VPS26B) (PubMed:23563491).By similarity1 Publication
The PX domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns(3P)) and localization to early endosome membranes.1 Publication

Sequence similaritiesi

Belongs to the sorting nexin family.Curated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation
Contains 1 Ras-associating domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IMRD. Eukaryota.
ENOG410XPAD. LUCA.
GeneTreeiENSGT00530000063147.
HOVERGENiHBG059206.
InParanoidiQ96L92.
KOiK17936.
OMAiCEQRKMV.
OrthoDBiEOG091G147N.
PhylomeDBiQ96L92.
TreeFamiTF318398.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
3.30.1520.10. 1 hit.
InterProiIPR001478. PDZ.
IPR001683. Phox.
IPR000159. RA_dom.
IPR028667. SNX27.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR12431:SF17. PTHR12431:SF17. 1 hit.
PfamiPF00595. PDZ. 1 hit.
PF00787. PX. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00312. PX. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
PS50195. PX. 1 hit.
PS50200. RA. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96L92-1) [UniParc]FASTAAdd to basket
Also known as: SNX27a

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
MADEDGEGIH PSAPHRNGGG GGGGGSGLHC AGNGGGGGGG PRVVRIVKSE
60 70 80 90 100
SGYGFNVRGQ VSEGGQLRSI NGELYAPLQH VSAVLPGGAA DRAGVRKGDR
110 120 130 140 150
ILEVNHVNVE GATHKQVVDL IRAGEKELIL TVLSVPPHEA DNLDPSDDSL
160 170 180 190 200
GQSFYDYTEK QAVPISVPRY KHVEQNGEKF VVYNVYMAGR QLCSKRYREF
210 220 230 240 250
AILHQNLKRE FANFTFPRLP GKWPFSLSEQ QLDARRRGLE EYLEKVCSIR
260 270 280 290 300
VIGESDIMQE FLSESDENYN GVSDVELRVA LPDGTTVTVR VKKNSTTDQV
310 320 330 340 350
YQAIAAKVGM DSTTVNYFAL FEVISHSFVR KLAPNEFPHK LYIQNYTSAV
360 370 380 390 400
PGTCLTIRKW LFTTEEEILL NDNDLAVTYF FHQAVDDVKK GYIKAEEKSY
410 420 430 440 450
QLQKLYEQRK MVMYLNMLRT CEGYNEIIFP HCACDSRRKG HVITAISITH
460 470 480 490 500
FKLHACTEEG QLENQVIAFE WDEMQRWDTD EEGMAFCFEY ARGEKKPRWV
510 520 530 540
KIFTPYFNYM HECFERVFCE LKWRKENIFQ MARSQQRDVA T
Length:541
Mass (Da):61,265
Last modified:January 15, 2008 - v2
Checksum:i1AA2265E463CB8DA
GO
Isoform 2 (identifier: Q96L92-3) [UniParc]FASTAAdd to basket
Also known as: SNX27b

The sequence of this isoform differs from the canonical sequence as follows:
     527-541: NIFQMARSQQRDVAT → EY

Show »
Length:528
Mass (Da):59,811
Checksum:i803D0E93E1B4A658
GO
Isoform 3 (identifier: Q96L92-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-93: Missing.
     94-104: GVRKGDRILEV → MGLSFSLFPLR

Show »
Length:448
Mass (Da):52,335
Checksum:i83DA67E659832C61
GO
Isoform 4 (identifier: Q96L92-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-309: Missing.

Note: No experimental confirmation available.
Show »
Length:232
Mass (Da):27,781
Checksum:iCFFE3A15EC60A2F2
GO

Sequence cautioni

The sequence AAG43127 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti467I → V in AAI07863 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_059851459E → K.Corresponds to variant rs11204871dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0305361 – 309Missing in isoform 4. 1 PublicationAdd BLAST309
Alternative sequenceiVSP_0305371 – 93Missing in isoform 3. 1 PublicationAdd BLAST93
Alternative sequenceiVSP_03053894 – 104GVRKGDRILEV → MGLSFSLFPLR in isoform 3. 1 PublicationAdd BLAST11
Alternative sequenceiVSP_030539527 – 541NIFQM…RDVAT → EY in isoform 2. 3 PublicationsAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY044866 mRNA. Translation: AAK97797.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73501.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73502.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73503.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17164.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17165.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17169.1.
BC012184 mRNA. Translation: AAH12184.1.
BC051817 mRNA. Translation: AAH51817.1.
BC071825 mRNA. Translation: AAH71825.1.
BC100998 mRNA. Translation: AAI00999.1.
BC100999 mRNA. Translation: AAI01000.1.
BC101000 mRNA. Translation: AAI01001.1.
BC101822 mRNA. Translation: AAI01823.1.
BC101824 mRNA. Translation: AAI01825.1.
BC107862 mRNA. Translation: AAI07863.1.
AB007957 mRNA. Translation: BAE16986.1.
AF060509 mRNA. Translation: AAG43127.1. Different initiation.
CCDSiCCDS1001.1. [Q96L92-3]
CCDS81377.1. [Q96L92-1]
RefSeqiNP_001317652.1. NM_001330723.1.
NP_112180.4. NM_030918.5. [Q96L92-3]
UniGeneiHs.192326.

Genome annotation databases

EnsembliENST00000368843; ENSP00000357836; ENSG00000143376. [Q96L92-3]
ENST00000458013; ENSP00000400333; ENSG00000143376. [Q96L92-1]
GeneIDi81609.
KEGGihsa:81609.
UCSCiuc001eyn.2. human. [Q96L92-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY044866 mRNA. Translation: AAK97797.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73501.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73502.1.
AL391335, AL589765 Genomic DNA. Translation: CAH73503.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17164.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17165.1.
AL589765, AL391335 Genomic DNA. Translation: CAI17169.1.
BC012184 mRNA. Translation: AAH12184.1.
BC051817 mRNA. Translation: AAH51817.1.
BC071825 mRNA. Translation: AAH71825.1.
BC100998 mRNA. Translation: AAI00999.1.
BC100999 mRNA. Translation: AAI01000.1.
BC101000 mRNA. Translation: AAI01001.1.
BC101822 mRNA. Translation: AAI01823.1.
BC101824 mRNA. Translation: AAI01825.1.
BC107862 mRNA. Translation: AAI07863.1.
AB007957 mRNA. Translation: BAE16986.1.
AF060509 mRNA. Translation: AAG43127.1. Different initiation.
CCDSiCCDS1001.1. [Q96L92-3]
CCDS81377.1. [Q96L92-1]
RefSeqiNP_001317652.1. NM_001330723.1.
NP_112180.4. NM_030918.5. [Q96L92-3]
UniGeneiHs.192326.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4HASX-ray1.74A/B156-265[»]
ProteinModelPortaliQ96L92.
SMRiQ96L92.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123546. 71 interactors.
IntActiQ96L92. 13 interactors.
MINTiMINT-7211211.
STRINGi9606.ENSP00000357836.

Protein family/group databases

TCDBi9.A.3.1.1. the sorting nexin27 (snx27)-retromer assembly apparatus for recycling integral membrane proteins (snx27-retromeraa) family.

PTM databases

iPTMnetiQ96L92.
PhosphoSitePlusiQ96L92.

Polymorphism and mutation databases

BioMutaiSNX27.
DMDMi166214988.

Proteomic databases

EPDiQ96L92.
MaxQBiQ96L92.
PaxDbiQ96L92.
PeptideAtlasiQ96L92.
PRIDEiQ96L92.

Protocols and materials databases

DNASUi81609.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000368843; ENSP00000357836; ENSG00000143376. [Q96L92-3]
ENST00000458013; ENSP00000400333; ENSG00000143376. [Q96L92-1]
GeneIDi81609.
KEGGihsa:81609.
UCSCiuc001eyn.2. human. [Q96L92-1]

Organism-specific databases

CTDi81609.
DisGeNETi81609.
GeneCardsiSNX27.
HGNCiHGNC:20073. SNX27.
HPAiHPA045816.
MIMi611541. gene.
neXtProtiNX_Q96L92.
OpenTargetsiENSG00000143376.
PharmGKBiPA134969143.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMRD. Eukaryota.
ENOG410XPAD. LUCA.
GeneTreeiENSGT00530000063147.
HOVERGENiHBG059206.
InParanoidiQ96L92.
KOiK17936.
OMAiCEQRKMV.
OrthoDBiEOG091G147N.
PhylomeDBiQ96L92.
TreeFamiTF318398.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000143376-MONOMER.

Miscellaneous databases

ChiTaRSiSNX27. human.
GeneWikiiSNX27.
GenomeRNAii81609.
PROiQ96L92.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000143376.
ExpressionAtlasiQ96L92. baseline and differential.
GenevisibleiQ96L92. HS.

Family and domain databases

Gene3Di2.30.42.10. 1 hit.
3.30.1520.10. 1 hit.
InterProiIPR001478. PDZ.
IPR001683. Phox.
IPR000159. RA_dom.
IPR028667. SNX27.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR12431:SF17. PTHR12431:SF17. 1 hit.
PfamiPF00595. PDZ. 1 hit.
PF00787. PX. 1 hit.
PF00788. RA. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 1 hit.
SM00312. PX. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 1 hit.
SSF54236. SSF54236. 1 hit.
SSF64268. SSF64268. 1 hit.
PROSITEiPS50106. PDZ. 1 hit.
PS50195. PX. 1 hit.
PS50200. RA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSNX27_HUMAN
AccessioniPrimary (citable) accession number: Q96L92
Secondary accession number(s): Q32Q36
, Q4AEJ5, Q5VWB0, Q5VWB1, Q5VWB2, Q6IPP6, Q86UB1, Q96D79, Q9H3K8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: January 15, 2008
Last modified: November 30, 2016
This is version 128 of the entry and version 2 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.