SNX3_MOUSE
ID SNX3_MOUSE Reviewed; 162 AA.
AC O70492;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Sorting nexin-3;
DE AltName: Full=SDP3 protein;
GN Name=Snx3;
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].
RA Xu Y., Wong S.H., Zhang T., Hong W.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH USP10 AND SCNN1A.
RX PubMed=18632802; DOI=10.1152/ajprenal.00001.2008;
RA Boulkroun S., Ruffieux-Daidie D., Vitagliano J.J., Poirot O., Charles R.P.,
RA Lagnaz D., Firsov D., Kellenberger S., Staub O.;
RT "Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell
RT surface expression by deubiquitylating and stabilizing sorting nexin 3.";
RL Am. J. Physiol. 295:F889-F900(2008).
RN [3]
RP FUNCTION, PHOSPHATIDYLINOSITOL-BINDING, AND MUTAGENESIS OF LYS-152;
RP LYS-158; ARG-160 AND HIS-161.
RX PubMed=19576982; DOI=10.1016/j.cellsig.2009.06.005;
RA Mizutani R., Yamauchi J., Kusakawa S., Nakamura K., Sanbe A., Torii T.,
RA Miyamoto Y., Tanoue A.;
RT "Sorting nexin 3, a protein upregulated by lithium, contains a novel
RT phosphatidylinositol-binding sequence and mediates neurite outgrowth in
RT N1E-115 cells.";
RL Cell. Signal. 21:1586-1594(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, 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).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP TFRC AND VPS35.
RX PubMed=23416069; DOI=10.1016/j.cmet.2013.01.013;
RA Chen C., Garcia-Santos D., Ishikawa Y., Seguin A., Li L., Fegan K.H.,
RA Hildick-Smith G.J., Shah D.I., Cooney J.D., Chen W., King M.J., Yien Y.Y.,
RA Schultz I.J., Anderson H., Dalton A.J., Freedman M.L., Kingsley P.D.,
RA Palis J., Hattangadi S.M., Lodish H.F., Ward D.M., Kaplan J., Maeda T.,
RA Ponka P., Paw B.H.;
RT "Snx3 regulates recycling of the transferrin receptor and iron
RT assimilation.";
RL Cell Metab. 17:343-352(2013).
RN [7]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-43, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Phosphoinositide-binding protein required for multivesicular
CC body formation. Specifically binds phosphatidylinositol 3-phosphate
CC (PtdIns(P3)). Can also bind phosphatidylinositol 4-phosphate
CC (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and
CC phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (PubMed:19576982).
CC Plays a role in protein transport between cellular compartments.
CC Together with RAB7A facilitates endosome membrane association of the
CC retromer cargo-selective subcomplex (CSC). May act in part as component
CC of the SNX3-retromer complex which mediates the retrograde endosome-to-
CC TGN transport of WLS distinct from the SNX-BAR retromer pathway (By
CC similarity). Promotes stability and cell surface expression of
CC epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G
CC (PubMed:18632802). Not involved in EGFR degradation. Involved in the
CC regulation of phagocytosis in dendritic cells possibly by regulating
CC EEA1 recruitment to the nascent phagosomes (By similarity). Involved in
CC iron homeostasis through regulation of endocytic recycling of the
CC transferrin receptor Tfrc presuambly by delivering the
CC transferrin:transferrin receptor complex to recycling endosomes; the
CC function may involve the CSC retromer subcomplex (PubMed:23416069).
CC Involved in regulation of neurite outgrowth in primary neurons
CC (PubMed:19576982). {ECO:0000250|UniProtKB:O60493,
CC ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:23416069}.
CC -!- SUBUNIT: Interacts with VPS26A, VPS29 (By similarity). Interacts with
CC VPS35; the interaction with VPS35 is direct (PubMed:23416069). The
CC association with the retromer CSC subcomplex subunits is proposed to
CC represent a functional distinct retromer variant described as SNX3-
CC retromer complex (By similarity). Interacts with USP10 and SCNN1A
CC (PubMed:18632802). Interacts with TRFC (PubMed:23416069). Interacts
CC with SNX8; 2 molecules of SNX8 seems to associate with one molecule of
CC SNX3. Interacts with PTPRU (By similarity). Interacts with MON2 and
CC DOP1B. {ECO:0000250|UniProtKB:O60493, ECO:0000269|PubMed:18632802,
CC ECO:0000269|PubMed:23416069}.
CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:23416069}.
CC Cytoplasmic vesicle, phagosome {ECO:0000250|UniProtKB:O60493}.
CC Note=Colocalizes to clathrin-coated endosomal vesicles morphologically
CC distinct from retromer-decorated non-branched endosomal tubule
CC structures. Colocalizes with EEA1 on nascent phagosomes in dendritic
CC cells but competes with EEA1 for binding to phagosomal membrane (By
CC similarity). {ECO:0000250|UniProtKB:O60493,
CC ECO:0000269|PubMed:23416069}.
CC -!- TISSUE SPECIFICITY: Highly expressed in developing red cells and
CC hematopoietic tissues (PubMed:23416069). {ECO:0000269|PubMed:23416069}.
CC -!- DOMAIN: The PX domain mediates specific binding to phosphatidylinositol
CC 3-phosphate (PtdIns(P3)).
CC -!- PTM: Ubiquitinated, leading to its proteasomal degradation.
CC Deubiquitinated by USP10. {ECO:0000269|PubMed:18632802}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AF062482; AAC16017.1; -; mRNA.
DR AlphaFoldDB; O70492; -.
DR SMR; O70492; -.
DR IntAct; O70492; 1.
DR STRING; 10090.ENSMUSP00000019939; -.
DR iPTMnet; O70492; -.
DR PhosphoSitePlus; O70492; -.
DR SwissPalm; O70492; -.
DR REPRODUCTION-2DPAGE; O70492; -.
DR CPTAC; non-CPTAC-3748; -.
DR EPD; O70492; -.
DR jPOST; O70492; -.
DR MaxQB; O70492; -.
DR PaxDb; O70492; -.
DR PeptideAtlas; O70492; -.
DR PRIDE; O70492; -.
DR ProteomicsDB; 261472; -.
DR MGI; MGI:1860188; Snx3.
DR eggNOG; KOG2527; Eukaryota.
DR InParanoid; O70492; -.
DR PhylomeDB; O70492; -.
DR Reactome; R-MMU-3238698; WNT ligand biogenesis and trafficking.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR ChiTaRS; Snx3; mouse.
DR PRO; PR:O70492; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O70492; protein.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISO:MGI.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IDA:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:1905394; F:retromer complex binding; ISS:UniProtKB.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0006783; P:heme biosynthetic process; ISO:MGI.
DR GO; GO:0042541; P:hemoglobin biosynthetic process; IMP:MGI.
DR GO; GO:0070676; P:intralumenal vesicle formation; ISO:MGI.
DR GO; GO:0034499; P:late endosome to Golgi transport; IBA:GO_Central.
DR GO; GO:0010324; P:membrane invagination; ISO:MGI.
DR GO; GO:2000642; P:negative regulation of early endosome to late endosome transport; ISO:MGI.
DR GO; GO:0050765; P:negative regulation of phagocytosis; ISS:UniProtKB.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISO:MGI.
DR GO; GO:0051224; P:negative regulation of protein transport; ISO:MGI.
DR GO; GO:0046597; P:negative regulation of viral entry into host cell; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0022615; P:protein to membrane docking; ISS:UniProtKB.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IMP:MGI.
DR GO; GO:0033157; P:regulation of intracellular protein transport; IMP:MGI.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; ISO:MGI.
DR GO; GO:0033572; P:transferrin transport; IMP:MGI.
DR CDD; cd07293; PX_SNX3; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR042137; PX_SNX3_Vert.
DR Pfam; PF00787; PX; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasmic vesicle; Endosome; Isopeptide bond; Lipid-binding;
KW Methylation; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O60493"
FT CHAIN 2..162
FT /note="Sorting nexin-3"
FT /id="PRO_0000213841"
FT DOMAIN 27..151
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT REGION 147..162
FT /note="Binds predominantly to PtdIns(P5) and weaker to
FT PtdIns(P3) abd PtdIns(P4); involved in neurite outgrowth
FT regulation"
FT /evidence="ECO:0000269|PubMed:19576982"
FT BINDING 70
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 72
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 95
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 118
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 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O60493"
FT MOD_RES 43
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 72
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60493"
FT CROSSLNK 95
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O60493"
FT MUTAGEN 152
FT /note="K->A: Abolishes phosphoinositide-binding of C-
FT terminus; when associated with A-158, A-160 and A-161."
FT /evidence="ECO:0000269|PubMed:19576982"
FT MUTAGEN 158
FT /note="K->A: Abolishes phosphoinositide-binding of C-
FT terminus; when associated with A-152, A-160 and A-161."
FT /evidence="ECO:0000269|PubMed:19576982"
FT MUTAGEN 160
FT /note="R->A: Abolishes phosphoinositide-binding of C-
FT terminus; when associated with A-152, A-160 and A-161."
FT /evidence="ECO:0000269|PubMed:19576982"
FT MUTAGEN 161
FT /note="H->A: Abolishes phosphoinositide-binding of C-
FT terminus; when associated with A-152, A-158 and A-160."
FT /evidence="ECO:0000269|PubMed:19576982"
SQ SEQUENCE 162 AA; 18757 MW; 8DDF851FCA7404A5 CRC64;
MAETVADTRR LITKPQNLND AYGPPSNFLE IDVSNPQTVG VGRGRFTTYE IRVKTNLPIF
KLKESTVRRR YSDFEWLRSE LERESKVVVP PLPGKAFLRH VPFRGDDGIF DDNFIEERKQ
GLEQFINKVA GHPLAQNERC LHMFLQDEII DKSYTPSKIR HA
