SNX5_MOUSE
ID SNX5_MOUSE Reviewed; 404 AA.
AC Q9D8U8; Q543N9;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Sorting nexin-5;
GN Name=Snx5;
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 [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Head, Medulla oblongata, Pancreas, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18854019; DOI=10.1186/1471-2121-9-58;
RA Lim J.P., Wang J.T., Kerr M.C., Teasdale R.D., Gleeson P.A.;
RT "A role for SNX5 in the regulation of macropinocytosis.";
RL BMC Cell Biol. 9:58-58(2008).
RN [4]
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).
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 (By similarity). Plays a role in macropinocytosis
CC (PubMed:18854019). {ECO:0000250|UniProtKB:Q9Y5X3,
CC ECO:0000269|PubMed:18854019}.
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 -!- INTERACTION:
CC Q9D8U8; P0DJI4: incE; Xeno; NbExp=4; IntAct=EBI-643385, EBI-22303778;
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) (By
CC similarity). Detected on macropinosomes (PubMed:18854019). Targeted to
CC membrane ruffles in response to EGFR stimulation (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y5X3, ECO:0000269|PubMed:18854019}.
CC -!- TISSUE SPECIFICITY: Detected in macrophages (at protein level).
CC {ECO:0000269|PubMed:18854019}.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000250}.
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}.
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; AK007676; BAB25180.1; -; mRNA.
DR EMBL; AK029463; BAC26460.1; -; mRNA.
DR EMBL; AK031873; BAC27587.1; -; mRNA.
DR EMBL; AK049129; BAC33558.1; -; mRNA.
DR EMBL; AK159904; BAE35468.1; -; mRNA.
DR EMBL; AK169786; BAE41365.1; -; mRNA.
DR EMBL; BC002242; AAH02242.1; -; mRNA.
DR CCDS; CCDS16815.1; -.
DR RefSeq; NP_001186117.1; NM_001199188.1.
DR RefSeq; NP_077187.1; NM_024225.5.
DR PDB; 5TP1; X-ray; 2.31 A; A/B/C/D=20-180.
DR PDBsum; 5TP1; -.
DR AlphaFoldDB; Q9D8U8; -.
DR SMR; Q9D8U8; -.
DR BioGRID; 213273; 21.
DR IntAct; Q9D8U8; 3.
DR MINT; Q9D8U8; -.
DR STRING; 10090.ENSMUSP00000105657; -.
DR iPTMnet; Q9D8U8; -.
DR PhosphoSitePlus; Q9D8U8; -.
DR SwissPalm; Q9D8U8; -.
DR EPD; Q9D8U8; -.
DR jPOST; Q9D8U8; -.
DR MaxQB; Q9D8U8; -.
DR PaxDb; Q9D8U8; -.
DR PRIDE; Q9D8U8; -.
DR ProteomicsDB; 261395; -.
DR Antibodypedia; 24488; 227 antibodies from 33 providers.
DR DNASU; 69178; -.
DR Ensembl; ENSMUST00000028909; ENSMUSP00000028909; ENSMUSG00000027423.
DR Ensembl; ENSMUST00000110030; ENSMUSP00000105657; ENSMUSG00000027423.
DR GeneID; 69178; -.
DR KEGG; mmu:69178; -.
DR UCSC; uc008mqq.3; mouse.
DR CTD; 27131; -.
DR MGI; MGI:1916428; Snx5.
DR VEuPathDB; HostDB:ENSMUSG00000027423; -.
DR eggNOG; KOG1660; Eukaryota.
DR GeneTree; ENSGT00940000154632; -.
DR HOGENOM; CLU_040966_0_0_1; -.
DR InParanoid; Q9D8U8; -.
DR OMA; CAEDSTP; -.
DR OrthoDB; 1009572at2759; -.
DR PhylomeDB; Q9D8U8; -.
DR TreeFam; TF313698; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR BioGRID-ORCS; 69178; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Snx5; mouse.
DR PRO; PR:Q9D8U8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9D8U8; protein.
DR Bgee; ENSMUSG00000027423; Expressed in stroma of bone marrow and 287 other tissues.
DR Genevisible; Q9D8U8; MM.
DR GO; GO:0005903; C:brush border; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
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:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0070685; C:macropinocytic cup; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0001891; C:phagocytic cup; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0034452; F:dynactin binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0080025; F:phosphatidylinositol-3,5-bisphosphate binding; ISO:MGI.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; ISO:MGI.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; ISO:MGI.
DR GO; GO:0007174; P:epidermal growth factor catabolic process; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0045776; P:negative regulation of blood pressure; ISO:MGI.
DR GO; GO:0006907; P:pinocytosis; ISS:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISO:MGI.
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; 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_0000213845"
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:0000250|UniProtKB:B1H267"
FT BINDING 99..105
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 113..116
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
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 31..34
FT /evidence="ECO:0007829|PDB:5TP1"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:5TP1"
FT STRAND 44..53
FT /evidence="ECO:0007829|PDB:5TP1"
FT STRAND 61..68
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 69..80
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 100..111
FT /evidence="ECO:0007829|PDB:5TP1"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:5TP1"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 121..151
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:5TP1"
FT HELIX 160..167
FT /evidence="ECO:0007829|PDB:5TP1"
FT TURN 172..177
FT /evidence="ECO:0007829|PDB:5TP1"
SQ SEQUENCE 404 AA; 46797 MW; C24D8C78F753FAFC CRC64;
MAAVPELLEQ QEEDRSKLRS VSVDLNVDPS LQIDIPDALS ERDKVKFTVH TKTTLSTFQS
PEFSVTRQHE DFVWLHDTLT ETTDYAGLII PPAPTKPDFD GPREKMQKLG EGEGSMTKEE
FAKMKQELEA EYLAVFKKTV STHEVFLQRL 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
