SNX1_MOUSE
ID SNX1_MOUSE Reviewed; 522 AA.
AC Q9WV80; Q9EQZ9;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Sorting nexin-1;
GN Name=Snx1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Thymus;
RA Takahara K., Omatsu Y., Maeda Y., Shimoyama S., Inaba K.;
RT "Complete sequence of mouse sorting nexin 1 (Snx1) cDNA.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBUNIT.
RC STRAIN=C57BL/6J;
RX PubMed=11726276; DOI=10.1093/oxfordjournals.jbchem.a003047;
RA Nakamura N., Sun-Wada G.H., Yamamoto A., Wada Y., Futai M.;
RT "Association of mouse sorting nexin 1 with early endosomes.";
RL J. Biochem. 130:765-771(2001).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=12388759; DOI=10.1091/mbc.e02-03-0145;
RA Schwarz D.G., Griffin C.T., Schneider E.A., Yee D., Magnuson T.;
RT "Genetic analysis of sorting nexins 1 and 2 reveals a redundant and
RT essential function in mice.";
RL Mol. Biol. Cell 13:3588-3600(2002).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-39; THR-41; SER-58
RP AND SER-188, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes containing phosphatidylinositol 3-phosphate
CC (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
CC Acts in part as component of the retromer membrane-deforming SNX-BAR
CC subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo
CC proteins from endosomes to the trans-Golgi network (TGN) and is
CC involved in endosome-to-plasma membrane transport for cargo protein
CC recycling. The SNX-BAR subcomplex functions to deform the donor
CC membrane into a tubular profile called endosome-to-TGN transport
CC carrier (ETC). Can sense membrane curvature and has in vitro vesicle-
CC to-membrane remodeling activity. Involved in retrograde endosome-to-TGN
CC transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1). Plays
CC a role in targeting ligand-activated EGFR to the lysosomes for
CC degradation after endocytosis from the cell surface and release from
CC the Golgi. Involvement in retromer-independent endocytic trafficking of
CC P2RY1 and lysosomal degradation of protease-activated receptor-1/F2R.
CC Promotes KALRN- and RHOG-dependent but retromer-independent membrane
CC remodeling such as lamellipodium formation; the function is dependent
CC on GEF activity of KALRN. Required for endocytosis of DRD5 upon agonist
CC stimulation but not for basal receptor trafficking (By similarity).
CC {ECO:0000250|UniProtKB:Q13596}.
CC -!- SUBUNIT: Predominantly forms heterodimers with BAR domain-containing
CC sorting nexins SNX5, SNX6 and SNX32 (By similarity). Can self-associate
CC to form homodimers (PubMed:11726276). The heterodimers are proposed to
CC self-assemble into helical arrays on the membrane to stabilize and
CC expand local membrane curvature underlying endosomal tubule formation.
CC Thought to be a component of the originally described retromer complex
CC (also called SNX-BAR retromer) which is a pentamer containing the
CC heterotrimeric retromer cargo-selective complex (CSC), also described
CC as vacuolar protein sorting subcomplex (VPS) and a heterodimeric
CC membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or
CC SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR
CC subcomplexes associate with low affinity. Interacts with SNX5, SNX6,
CC SNX32, VPS26A, VPS29, VPS35, DRD5, DENND5A, KALRN, RHOG (GDP-bound
CC form). The interaction with SNX2 is reported controversially. Interacts
CC with DNAJC13; prevented by presence of HGS. Interacts with HGS (By
CC similarity). {ECO:0000250|UniProtKB:Q13596,
CC ECO:0000250|UniProtKB:Q99N27}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:Q13596};
CC Peripheral membrane protein; Cytoplasmic side. Golgi apparatus, trans-
CC Golgi network membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cell projection,
CC lamellipodium {ECO:0000250|UniProtKB:Q13596}. Note=Enriched on tubular
CC elements of the early endosome membrane. Binds preferentially to highly
CC curved membranes enriched in phosphatidylinositol 3-phosphate
CC (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
CC Colocalized with SORT1 to tubular endosomal membrane structures called
CC endosome-to-TGN transport carriers (ETCs) which are budding from early
CC endosome vacuoles just before maturing into late endosome vacuoles.
CC Colocalized with F-actin at the leading edge of lamellipodia in a
CC KALRN-dependent manner. {ECO:0000250|UniProtKB:Q13596}.
CC -!- DOMAIN: The BAR domain is able to sense membrane curvature upon
CC dimerization. Membrane remodeling seems to implicate insertion of a N-
CC terminal amphipathic helix (AH) in the membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q13596}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian ratio and are fertile. Mice lacking both Snx1 and
CC Snx2 die during embryonic development, around 9.5 and 11.5 dpc.
CC {ECO:0000269|PubMed:12388759}.
CC -!- MISCELLANEOUS: Binds phosphatidylinositol 3-phosphate (PtdIns-(3)P) and
CC phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2) in liposome-
CC based assays. Can bind PtdIns(3,4,5)P3 in protein:lipid overlay assays,
CC but not in liposome-based assays (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AF154120; AAD38805.1; -; mRNA.
DR EMBL; AB019214; BAB20283.1; -; mRNA.
DR RefSeq; NP_062701.2; NM_019727.2.
DR PDB; 7D6D; EM; 9.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-522.
DR PDB; 7D6E; EM; 10.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=1-522.
DR PDBsum; 7D6D; -.
DR PDBsum; 7D6E; -.
DR AlphaFoldDB; Q9WV80; -.
DR SMR; Q9WV80; -.
DR BioGRID; 207981; 22.
DR IntAct; Q9WV80; 1.
DR STRING; 10090.ENSMUSP00000034946; -.
DR iPTMnet; Q9WV80; -.
DR PhosphoSitePlus; Q9WV80; -.
DR SwissPalm; Q9WV80; -.
DR EPD; Q9WV80; -.
DR jPOST; Q9WV80; -.
DR MaxQB; Q9WV80; -.
DR PaxDb; Q9WV80; -.
DR PeptideAtlas; Q9WV80; -.
DR PRIDE; Q9WV80; -.
DR ProteomicsDB; 261597; -.
DR DNASU; 56440; -.
DR GeneID; 56440; -.
DR KEGG; mmu:56440; -.
DR CTD; 6642; -.
DR MGI; MGI:1928395; Snx1.
DR eggNOG; KOG2273; Eukaryota.
DR InParanoid; Q9WV80; -.
DR OrthoDB; 947320at2759; -.
DR PhylomeDB; Q9WV80; -.
DR BioGRID-ORCS; 56440; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Snx1; mouse.
DR PRO; PR:Q9WV80; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9WV80; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043197; C:dendritic spine; IDA:SynGO-UCL.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0031901; C:early endosome membrane; ISO:MGI.
DR GO; GO:0005768; C:endosome; IDA:MGI.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0098999; C:extrinsic component of postsynaptic endosome membrane; IDA:SynGO-UCL.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; IDA:SynGO-UCL.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
DR GO; GO:0098793; C:presynapse; IDA:SynGO-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0030905; C:retromer, tubulation complex; ISO:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:1990460; F:leptin receptor binding; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
DR GO; GO:0034498; P:early endosome to Golgi transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISO:MGI.
DR GO; GO:0072673; P:lamellipodium morphogenesis; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:MGI.
DR GO; GO:0031175; P:neuron projection development; IDA:SynGO-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR CDD; cd07281; PX_SNX1; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR034901; PX_SNX1.
DR InterPro; IPR028660; SNX1.
DR InterPro; IPR005329; Sorting_nexin_N.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR10555:SF129; PTHR10555:SF129; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF03700; Sorting_nexin; 1.
DR Pfam; PF09325; Vps5; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell projection; Endosome; Golgi apparatus;
KW Lipid-binding; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..522
FT /note="Sorting nexin-1"
FT /id="PRO_0000213836"
FT DOMAIN 143..272
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 302..522
FT /note="BAR"
FT REGION 1..144
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..298
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT COMPBIAS 55..70
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..129
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 186
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 188
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 214
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 238
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 41
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 48
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT MOD_RES 58
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 237
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT CONFLICT 31
FT /note="A -> G (in Ref. 2; BAB20283)"
FT /evidence="ECO:0000305"
FT CONFLICT 117
FT /note="S -> P (in Ref. 2; BAB20283)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="S -> C (in Ref. 2; BAB20283)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="Missing (in Ref. 2; BAB20283)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="S -> F (in Ref. 2; BAB20283)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 522 AA; 58952 MW; 1EFC06B3EA551311 CRC64;
MASGGGGCSA SERLPPPFPG MDPESEGAAG ASEPEAGDSD TEGEDIFTGA AAATKPQSPK
KTTSLFPIKN GSKENGIHED QDQEPQDLFA DATVELSLDS TQNNQKTMPG KTLTSHSPQE
ATNSPKPQPS YEELEEEEQE DQFDLTVGIT DPEKIGDGMN AYVAYKVTTQ TSLPMFRSRQ
FAVKRRFSDF LGLYEKLSEK HSQNGFIVPP PPEKSLIGMT KVKVGKEDSS SAEFLEKRRA
ALERYLQRIV NHPTMLQDPD VREFLEKEEL PRAVGTQALS GAGLLKMFNK ATDAVSKMTI
KMNESDIWFE EKLQEVECEE QRLRKLHAVV ETLVNHRKEL ALNTALFAKS LAMLGSSEDN
TALSRALSQL AEVEEKIEQL HQEQANNDSF LLAELLSDYI RLLAIVRAAF DQRMKTWQRW
QDAQATLQKK RESEARLLWA NKPDKLQQAK DEITEWESRV TQYERDFERI STVVRKEVTR
FEKEKSKDFK NHVMKYLETL LHSQQQLAKY WEAFLPEAKA IS
