SNX9_MOUSE
ID SNX9_MOUSE Reviewed; 595 AA.
AC Q91VH2;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Sorting nexin-9;
GN Name=Snx9;
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 TISSUE=Mammary tumor;
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 INTERACTION WITH ADAM9 AND ADAM15.
RX PubMed=10531379; DOI=10.1074/jbc.274.44.31693;
RA Howard L., Nelson K.K., Maciewicz R.A., Blobel C.P.;
RT "Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two
RT SH3 domain-containing proteins, endophilin I and SH3PX1.";
RL J. Biol. Chem. 274:31693-31699(1999).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [4]
RP IDENTIFICATION BY 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-200, AND IDENTIFICATION BY
RP 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, INTERACTION WITH FCHSD1, AND TISSUE SPECIFICITY.
RX PubMed=23437151; DOI=10.1371/journal.pone.0056516;
RA Cao H., Yin X., Cao Y., Jin Y., Wang S., Kong Y., Chen Y., Gao J.,
RA Heller S., Xu Z.;
RT "FCHSD1 and FCHSD2 are expressed in hair cell stereocilia and cuticular
RT plate and regulate actin polymerization in vitro.";
RL PLoS ONE 8:E56516-E56516(2013).
RN [7]
RP STRUCTURE BY NMR OF 1-70.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the SH3 domain from mouse sorting nexin-9.";
RL Submitted (OCT-2007) to the PDB data bank.
CC -!- FUNCTION: Involved in endocytosis and intracellular vesicle
CC trafficking, both during interphase and at the end of mitosis. Required
CC for efficient progress through mitosis and cytokinesis. Required for
CC normal formation of the cleavage furrow at the end of mitosis. Plays a
CC role in endocytosis via clathrin-coated pits, but also clathrin-
CC independent, actin-dependent fluid-phase endocytosis. Plays a role in
CC macropinocytosis. Promotes internalization of TNFR. Promotes
CC degradation of EGFR after EGF signaling. Stimulates the GTPase activity
CC of DNM1. Promotes DNM1 oligomerization. Promotes activation of the
CC Arp2/3 complex by WASL, and thereby plays a role in the reorganization
CC of the F-actin cytoskeleton (PubMed:23437151). Binds to membranes
CC enriched in phosphatidylinositol 4,5-bisphosphate and promotes membrane
CC tubulation. Has lower affinity for membranes enriched in
CC phosphatidylinositol 3-phosphate (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:23437151}.
CC -!- SUBUNIT: Homodimer, and homooligomer. Heterodimer with SNX18. Interacts
CC with ITCH. Interacts (via SH3 domain) with TNK2, WASL and ACTR3.
CC Identified in a complex with TNK2 and clathrin heavy chains. Identified
CC in a complex with the AP-2 complex, clathrin and DNM2. Interacts (via
CC SH3 domain) with DNM1 and DNM2. Identified in an oligomeric complex
CC containing DNM1 and SNX9 (By similarity). Interacts with FCHSD1
CC (PubMed:23437151). Interacts with ADAM9 and ADAM15 cytoplasmic tails
CC (PubMed:10531379). {ECO:0000250, ECO:0000269|PubMed:10531379,
CC ECO:0000269|PubMed:23437151}.
CC -!- INTERACTION:
CC Q91VH2; Q01968: OCRL; Xeno; NbExp=2; IntAct=EBI-8429356, EBI-6148898;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cytoplasmic vesicle,
CC clathrin-coated vesicle {ECO:0000250}. Golgi apparatus, trans-Golgi
CC network {ECO:0000250}. Cell projection, ruffle {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Note=Localized at sites of endocytosis at the cell
CC membrane. Detected on newly formed macropinosomes. Transiently
CC recruited to clathrin-coated pits at a late stage of clathrin-coated
CC vesicle formation (By similarity). Colocalizes with the actin
CC cytoskeleton at the cell membrane (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected in inner ear vestibula and in the
CC cuticular plate of cochlear hair cells (at protein level).
CC {ECO:0000269|PubMed:23437151}.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol phosphate. Has high affinity for
CC phosphatidylinositol 4,5-bisphosphate, but can also bind to membranes
CC enriched in other phosphatidylinositol phosphates.
CC {ECO:0000250|UniProtKB:Q9Y5X1}.
CC -!- PTM: Phosphorylated on tyrosine residues by TNK2. Phosphorylation
CC promotes its activity in the degradation of EGFR (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated by ITCH. {ECO:0000250|UniProtKB:Q9Y5X1}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; BC014814; AAH14814.1; -; mRNA.
DR CCDS; CCDS57041.1; -.
DR RefSeq; NP_079940.2; NM_025664.5.
DR PDB; 2ENM; NMR; -; A=1-70.
DR PDBsum; 2ENM; -.
DR AlphaFoldDB; Q91VH2; -.
DR SMR; Q91VH2; -.
DR BioGRID; 211598; 4.
DR DIP; DIP-60857N; -.
DR IntAct; Q91VH2; 3.
DR MINT; Q91VH2; -.
DR STRING; 10090.ENSMUSP00000002436; -.
DR iPTMnet; Q91VH2; -.
DR PhosphoSitePlus; Q91VH2; -.
DR EPD; Q91VH2; -.
DR jPOST; Q91VH2; -.
DR MaxQB; Q91VH2; -.
DR PaxDb; Q91VH2; -.
DR PRIDE; Q91VH2; -.
DR ProteomicsDB; 261306; -.
DR Antibodypedia; 33429; 418 antibodies from 33 providers.
DR DNASU; 66616; -.
DR Ensembl; ENSMUST00000002436; ENSMUSP00000002436; ENSMUSG00000002365.
DR GeneID; 66616; -.
DR KEGG; mmu:66616; -.
DR UCSC; uc008afj.1; mouse.
DR CTD; 51429; -.
DR MGI; MGI:1913866; Snx9.
DR VEuPathDB; HostDB:ENSMUSG00000002365; -.
DR eggNOG; KOG2528; Eukaryota.
DR GeneTree; ENSGT00940000156557; -.
DR HOGENOM; CLU_021494_2_0_1; -.
DR InParanoid; Q91VH2; -.
DR OMA; FDSAPMR; -.
DR OrthoDB; 811995at2759; -.
DR PhylomeDB; Q91VH2; -.
DR TreeFam; TF314082; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR BioGRID-ORCS; 66616; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Snx9; mouse.
DR EvolutionaryTrace; Q91VH2; -.
DR PRO; PR:Q91VH2; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q91VH2; protein.
DR Bgee; ENSMUSG00000002365; Expressed in ileal epithelium and 257 other tissues.
DR ExpressionAtlas; Q91VH2; baseline and differential.
DR Genevisible; Q91VH2; MM.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0071933; F:Arp2/3 complex binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0036089; P:cleavage furrow formation; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; ISS:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:MGI.
DR GO; GO:0060988; P:lipid tube assembly; ISS:UniProtKB.
DR GO; GO:0000281; P:mitotic cytokinesis; ISS:UniProtKB.
DR GO; GO:0097320; P:plasma membrane tubulation; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0051044; P:positive regulation of membrane protein ectodomain proteolysis; ISO:MGI.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:UniProtKB.
DR CDD; cd07668; BAR_SNX9; 1.
DR CDD; cd07285; PX_SNX9; 1.
DR CDD; cd11898; SH3_SNX9; 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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR028644; SNX9.
DR InterPro; IPR037425; SNX9_BAR.
DR InterPro; IPR014536; Snx9_fam.
DR InterPro; IPR037426; SNX9_PX.
DR InterPro; IPR035558; SNX9_SH3.
DR InterPro; IPR019497; Sorting_nexin_WASP-bd-dom.
DR PANTHER; PTHR45827:SF2; PTHR45827:SF2; 1.
DR Pfam; PF10456; BAR_3_WASP_bdg; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PIRSF; PIRSF027744; Snx9; 1.
DR SMART; SM00312; PX; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cell cycle; Cell division; Cell membrane;
KW Cell projection; Cytoplasm; Cytoplasmic vesicle; Endocytosis;
KW Golgi apparatus; Lipid-binding; Membrane; Mitosis; Phosphoprotein;
KW Protein transport; Reference proteome; SH3 domain; Transport;
KW Ubl conjugation.
FT CHAIN 1..595
FT /note="Sorting nexin-9"
FT /id="PRO_0000213853"
FT DOMAIN 1..62
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 250..360
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 392..595
FT /note="BAR"
FT REGION 89..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..213
FT /note="Critical for tubulation activity"
FT /evidence="ECO:0000250"
FT COMPBIAS 89..106
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 122..148
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 286
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X1"
FT BINDING 288
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X1"
FT BINDING 327
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-4,5-bisphosphate)"
FT /ligand_id="ChEBI:CHEBI:58456"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X1"
FT MOD_RES 121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X1"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 239
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455"
FT MOD_RES 288
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5X1"
FT STRAND 3..9
FT /evidence="ECO:0007829|PDB:2ENM"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:2ENM"
FT STRAND 27..33
FT /evidence="ECO:0007829|PDB:2ENM"
FT STRAND 36..43
FT /evidence="ECO:0007829|PDB:2ENM"
FT STRAND 49..53
FT /evidence="ECO:0007829|PDB:2ENM"
FT TURN 54..56
FT /evidence="ECO:0007829|PDB:2ENM"
FT STRAND 57..60
FT /evidence="ECO:0007829|PDB:2ENM"
SQ SEQUENCE 595 AA; 66546 MW; 3D5568476F2D816D CRC64;
MATKARVMYD FAAEPGNNEL TVTEGEIITV TNPNVGGGWL EGKNNKGEQG LVPTDYVEIL
PNDGKDPFSC GNSVADQAFL DSLTASTAQT NSSSANSNNQ VGGGNDPWTA WNAPKPGNWD
SSDAWGSRTD GTSAQRNSSA NNWDTGFGHP QAYQGPATGD DDEWDEDWDD PKSSSPYFKD
SEPAEAGGIQ RGNSRAGASS MKLPLNKFPG FAKPGMEQYL LAKQLAKPKE KIAIIVGDYG
PMWVYPTSTF DCVVADPRKG SKMYGLKSYI EYQLTPTNTN RSVNHRYKHF DWLYERLLVK
FGSAIPIPSL PDKQVTGRFE EEFIKMRMER LQAWMTRMCR HPVVSESEVF QQFLNFRDEK
EWKTGKRKAE KDELVGVMIF STMEPEAPDL DLIEIEQKCD AVGKFTKAMD DGVKELLTVG
QEHWKRCTGP LPKEYQKIGK ALQSLAAVFS SSGYQGETDL NDAITEAGKT YEEIASLVAE
QPKKDLHFLM ECNHEYKGFL GCFPDIIGAH KGAIEKVKES DKLVATSKIT PQDKQTMVKR
VGTMSYALQA EMNHFHSNRI YDYNSVIRLY LEQQVQFYET IAEKLRQALS RFPVM
