ID SNX1_RAT Reviewed; 522 AA. AC Q99N27; Q56A25; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 24-JAN-2024, entry version 150. DE RecName: Full=Sorting nexin-1; GN Name=Snx1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH HGS. RX PubMed=11110793; DOI=10.1074/jbc.m004129200; RA Chin L.-S., Raynor M.C., Wei X., Chen H.-Q., Li L.; RT "Hrs interacts with sorting nexin 1 and regulates degradation of epidermal RT growth factor receptor."; RL J. Biol. Chem. 276:7069-7078(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32 AND SER-188, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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; can self-associate to form CC homodimers. The heterodimers are proposed to self-assemble into helical CC arrays on the membrane to stabilize and expand local membrane curvature CC underlying endosomal tubule formation. Thought to be a component of the CC originally described retromer complex (also called SNX-BAR retromer) CC which is a pentamer containing the heterotrimeric retromer cargo- CC selective complex (CSC), also described as vacuolar protein sorting CC subcomplex (VPS) and a heterodimeric membrane-deforming subcomplex CC formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR CC subcomplex); the respective CSC and SNX-BAR subcomplexes associate with CC low affinity. Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, CC DRD5, DENND5A, KALRN, RHOG (GDP-bound form). The interaction with SNX2 CC is reported controversially. Interacts with DNAJC13; prevented by CC presence of HGS (By similarity). Interacts with HGS (PubMed:11110793). CC {ECO:0000250|UniProtKB:Q13596}. 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 -!- 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). CC {ECO:0000250|UniProtKB:Q13596}. CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF218916; AAG59616.1; -; mRNA. DR EMBL; BC092201; AAH92201.1; -; mRNA. DR RefSeq; NP_445863.1; NM_053411.1. DR AlphaFoldDB; Q99N27; -. DR BMRB; Q99N27; -. DR SMR; Q99N27; -. DR BioGRID; 249971; 1. DR IntAct; Q99N27; 1. DR STRING; 10116.ENSRNOP00000022960; -. DR iPTMnet; Q99N27; -. DR PhosphoSitePlus; Q99N27; -. DR jPOST; Q99N27; -. DR PaxDb; 10116-ENSRNOP00000022960; -. DR Ensembl; ENSRNOT00055043863; ENSRNOP00055035848; ENSRNOG00055025415. DR Ensembl; ENSRNOT00060031611; ENSRNOP00060025676; ENSRNOG00060018363. DR Ensembl; ENSRNOT00065010286; ENSRNOP00065007518; ENSRNOG00065006647. DR GeneID; 84471; -. DR KEGG; rno:84471; -. DR UCSC; RGD:68935; rat. DR AGR; RGD:68935; -. DR CTD; 6642; -. DR RGD; 68935; Snx1. DR VEuPathDB; HostDB:ENSRNOG00000017029; -. DR eggNOG; KOG2273; Eukaryota. DR HOGENOM; CLU_022783_2_0_1; -. DR InParanoid; Q99N27; -. DR OrthoDB; 1891044at2759; -. DR PhylomeDB; Q99N27; -. DR TreeFam; TF313698; -. DR PRO; PR:Q99N27; -. DR Proteomes; UP000002494; Chromosome 8. DR Bgee; ENSRNOG00000017029; Expressed in spleen and 19 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; IEA:GOC. DR GO; GO:0043197; C:dendritic spine; ISO:RGD. DR GO; GO:0005769; C:early endosome; ISO:RGD. DR GO; GO:0031901; C:early endosome membrane; ISO:RGD. DR GO; GO:0005768; C:endosome; ISO:RGD. DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB. DR GO; GO:0098999; C:extrinsic component of postsynaptic endosome membrane; ISO:RGD. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD. DR GO; GO:0014069; C:postsynaptic density; ISO:RGD. DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:RGD. DR GO; GO:0098793; C:presynapse; ISO:RGD. DR GO; GO:0032991; C:protein-containing complex; ISO:RGD. DR GO; GO:0030904; C:retromer complex; ISO:RGD. DR GO; GO:0030905; C:retromer, tubulation complex; ISO:RGD. DR GO; GO:0031982; C:vesicle; ISO:RGD. DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:RGD. DR GO; GO:0042802; F:identical protein binding; ISO:RGD. DR GO; GO:0005158; F:insulin receptor binding; ISO:RGD. DR GO; GO:1990460; F:leptin receptor binding; ISO:RGD. DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD. DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD. DR GO; GO:1990459; F:transferrin receptor binding; ISO:RGD. DR GO; GO:0034498; P:early endosome to Golgi transport; ISO:RGD. DR GO; GO:0016197; P:endosomal transport; IEP:RGD. DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD. DR GO; GO:0072673; P:lamellipodium morphogenesis; ISS:UniProtKB. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD. DR GO; GO:0031175; P:neuron projection development; ISO:RGD. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:RGD. DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB. DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB. DR CDD; cd07665; BAR_SNX1; 1. DR CDD; cd07281; PX_SNX1; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 3.30.1520.10; Phox-like domain; 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_BAR. DR InterPro; IPR005329; Sorting_nexin_N. DR InterPro; IPR015404; Vps5_C. DR PANTHER; PTHR10555; SORTING NEXIN; 1. DR PANTHER; PTHR10555:SF129; SORTING NEXIN-1; 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; BAR/IMD domain-like; 1. DR SUPFAM; SSF64268; PX domain; 1. DR PROSITE; PS50195; PX; 1. DR Genevisible; Q99N27; RN. PE 1: Evidence at protein level; KW Acetylation; Cell projection; Endosome; Golgi apparatus; Lipid-binding; KW Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport. FT CHAIN 1..522 FT /note="Sorting nexin-1" FT /id="PRO_0000213837" FT DOMAIN 143..272 FT /note="PX" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147" FT DOMAIN 302..522 FT /note="BAR" FT REGION 1..142 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:22673903" FT MOD_RES 39 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13596" FT MOD_RES 41 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q9WV80" FT MOD_RES 48 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q13596" FT MOD_RES 58 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WV80" 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:22673903" 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" SQ SEQUENCE 522 AA; 59044 MW; F0F05664087E4D24 CRC64; MASGGGGCSA SERLPPPFPG MDPESEGAAG GSEPEAGDSD TEGEDIFTGA AAASKPQSPK KTTSLFPIKN GSKENGIHEE QDQEPQDLFA DATVELSLDS TQNNQKTMPG KTLIPHPTQE 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 HQEQANNDFF LLAELLSDYI RLLAIVRAAF DQRMKTWQRW QDAQATLQKK RESEARLLWA NKPDKLQQAK DEITEWESRV TQYERDFERI STVVRKEVTR FEKEKSKDFK NHVIKYLETL LHSQQQLAKY WEAFLPEARA IS //