SNX5_RAT
ID SNX5_RAT Reviewed; 404 AA.
AC B1H267;
DT 08-MAR-2011, integrated into UniProtKB/Swiss-Prot.
DT 29-APR-2008, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Sorting nexin-5;
GN Name=Snx5;
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 [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [2]
RP X-RAY CRYSTALLOGRAPHY (1.47 ANGSTROMS) OF 20-180, STRUCTURE BY NMR OF
RP 20-180, DOMAIN, AND PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE BINDING.
RX PubMed=19553671; DOI=10.1074/jbc.m109.008995;
RA Koharudin L.M., Furey W., Liu H., Liu Y.J., Gronenborn A.M.;
RT "The phox domain of sorting nexin 5 lacks phosphatidylinositol 3-phosphate
RT (PtdIns(3)P) specificity and preferentially binds to phosphatidylinositol
RT 4,5-bisphosphate (PtdIns(4,5)P2).";
RL J. Biol. Chem. 284:23697-23707(2009).
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes containing phosphatidylinositol lipids. Acts
CC 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). Does not have in vitro vesicle-to-membrane remodeling
CC activity. Involved in retrograde transport of lysosomal enzyme receptor
CC IGF2R. May function as link between endosomal transport vesicles and
CC dynactin. Plays a role in the internalization of EGFR after EGF
CC stimulation. Involved in EGFR endosomal sorting and degradation; the
CC function involves PIP5K1C and is retromer-independent. Together with
CC PIP5K1C facilitates HGS interaction with ubiquitinated EGFR, which
CC initiates EGFR sorting to intraluminal vesicles (ILVs) of the
CC multivesicular body for subsequent lysosomal degradation. Involved in
CC E-cadherin sorting and degradation; inhibits PIP5K1C-mediated E-
CC cadherin degradation. Plays a role in macropinocytosis (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y5X3}.
CC -!- SUBUNIT: Forms heterodimers with BAR domain-containing sorting nexins
CC SNX1 and SNX2; does not homodimerize. 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 SNX1, SNX2,
CC VPS26A, VPS29, VPS35, DCTN1, DOCK1, MIB1, PIP5K1C. Interacts with HGS;
CC increased by PIP5K1C kinase activity and by PtdIns(3P) and/or
CC PtdIns(3,4)P2 (By similarity). {ECO:0000250|UniProtKB:Q9Y5X3}.
CC -!- SUBCELLULAR LOCATION: Endosome {ECO:0000250|UniProtKB:Q9Y5X3}. Early
CC endosome {ECO:0000250|UniProtKB:Q9Y5X3}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y5X3}; Peripheral membrane protein;
CC Cytoplasmic side. Cell membrane {ECO:0000250|UniProtKB:Q9Y5X3};
CC Peripheral membrane protein; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9Y5X3}. Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Cell
CC projection, phagocytic cup. Cell projection, ruffle. Note=Recruited to
CC the plasma membrane after EGF stimulation, which leads to increased
CC levels of phosphatidylinositol 3,4-bisphosphate (PdtIns(3,4)P2).
CC Detected on macropinosomes. Targeted to membrane ruffles in response to
CC EGFR stimulation (By similarity). {ECO:0000250|UniProtKB:Q9Y5X3}.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000269|PubMed:19553671}.
CC -!- DOMAIN: The BAR domain is able to sense membrane curvature upon
CC dimerization. Membrane remodeling seems to implicate insertion of an
CC amphipathic helix (AH) in the membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y5X3}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
CC -!- CAUTION: The selectivity for particular phosphatidylinositol lipids is
CC under debate. According to one report (PubMed:19553671), the rat
CC protein binds exclusively to phosphatidylinositol 4,5-bisphosphate,
CC while the human protein has been reported (PubMed:15561769) to bind to
CC phosphatidylinositol 3,4-bisphosphate and also to phosphatidylinositol
CC 3-phosphate. {ECO:0000305|PubMed:19553671}.
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DR EMBL; BC160883; AAI60883.1; -; mRNA.
DR RefSeq; XP_006235181.1; XM_006235119.2.
DR PDB; 3HPB; X-ray; 2.19 A; A=20-180.
DR PDB; 3HPC; X-ray; 1.47 A; X=20-180.
DR PDBsum; 3HPB; -.
DR PDBsum; 3HPC; -.
DR AlphaFoldDB; B1H267; -.
DR SMR; B1H267; -.
DR STRING; 10116.ENSRNOP00000008934; -.
DR jPOST; B1H267; -.
DR PaxDb; B1H267; -.
DR PeptideAtlas; B1H267; -.
DR PRIDE; B1H267; -.
DR Ensembl; ENSRNOT00000074606; ENSRNOP00000066353; ENSRNOG00000006077.
DR GeneID; 296199; -.
DR UCSC; RGD:1310190; rat.
DR CTD; 27131; -.
DR RGD; 1310190; Snx5.
DR eggNOG; KOG1660; Eukaryota.
DR GeneTree; ENSGT00940000154632; -.
DR InParanoid; B1H267; -.
DR OMA; CAEDSTP; -.
DR OrthoDB; 1009572at2759; -.
DR PhylomeDB; B1H267; -.
DR TreeFam; TF313698; -.
DR Reactome; R-RNO-432722; Golgi Associated Vesicle Biogenesis.
DR EvolutionaryTrace; B1H267; -.
DR PRO; PR:B1H267; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000006077; Expressed in spleen and 19 other tissues.
DR Genevisible; B1H267; RN.
DR GO; GO:0005903; C:brush border; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:RGD.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031313; C:extrinsic component of endosome membrane; ISS:UniProtKB.
DR GO; GO:0070685; C:macropinocytic cup; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0030904; C:retromer complex; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0097422; C:tubular endosome; ISS:UniProtKB.
DR GO; GO:0031748; F:D1 dopamine receptor binding; IDA:RGD.
DR GO; GO:0034452; F:dynactin binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:RGD.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:RGD.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:RGD.
DR GO; GO:0007174; P:epidermal growth factor catabolic process; IDA:RGD.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0045776; P:negative regulation of blood pressure; IMP:RGD.
DR GO; GO:0006907; P:pinocytosis; ISS:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:RGD.
DR CDD; cd07291; PX_SNX5; 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; IPR042135; PX_SNX5.
DR InterPro; IPR028654; SNX5.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR45850:SF5; PTHR45850:SF5; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 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 membrane; Cell projection; Cytoplasm;
KW Cytoplasmic vesicle; Endocytosis; Endosome; Lipid-binding; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT CHAIN 2..404
FT /note="Sorting nexin-5"
FT /id="PRO_0000405693"
FT DOMAIN 25..172
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 202..404
FT /note="BAR"
FT REGION 169..261
FT /note="Interaction with DOCK1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT REGION 183..200
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT BINDING 40..46
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000269|PubMed:19553671"
FT BINDING 99..105
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000269|PubMed:19553671"
FT BINDING 113..116
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000269|PubMed:19553671"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT MOD_RES 275
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X3"
FT STRAND 30..41
FT /evidence="ECO:0007829|PDB:3HPC"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:3HPC"
FT STRAND 58..67
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 69..81
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 118..152
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:3HPC"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:3HPC"
SQ SEQUENCE 404 AA; 46793 MW; 26264759D77ECBC0 CRC64;
MAAVPELLEQ QEEDRSKLRS VSVDLNVDPS LQIDIPDALS ERDKVKFTVH TKTTLPTFQS
PEFSVTRQHE DFVWLHDTLT ETTDYAGLII PPAPTKPDFD GPREKMQKLG EGEGSMTKEE
FAKMKQELEA EYLAVFKKTV SSHEVFLQRL SSHPVLSKDR NFHVFLEYDQ DLSVRRKNTK
EMFGGFFKSV VKSADEVLFS GVKEVDDFFE QEKNFLINYY NRIKDSCAKA DKMTRSHKNV
ADDYIHTAAC LHSLALEEPT VIKKYLLKVA ELFEKLRKVE GRVSSDEDLK LTELLRYYML
NIEAAKDLLY RRTKALIDYE NSNKALDKAR LKSKDVKLAE THQQECCQKF EQLSESAKEE
LINFKRKRVA AFRKNLIEMS ELEIKHARNN VSLLQSCIDL FKNN
