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 27-MAR-2024, entry version 154. 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, RC Pancreas, 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}. 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; 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; 7. DR DIP; DIP-60857N; -. DR IntAct; Q91VH2; 3. DR MINT; Q91VH2; -. DR STRING; 10090.ENSMUSP00000002436; -. DR iPTMnet; Q91VH2; -. DR PhosphoSitePlus; Q91VH2; -. DR SwissPalm; Q91VH2; -. DR EPD; Q91VH2; -. DR jPOST; Q91VH2; -. DR MaxQB; Q91VH2; -. DR PaxDb; 10090-ENSMUSP00000002436; -. DR ProteomicsDB; 261306; -. DR Pumba; Q91VH2; -. DR Antibodypedia; 33429; 468 antibodies from 33 providers. DR DNASU; 66616; -. DR Ensembl; ENSMUST00000002436.11; ENSMUSP00000002436.10; ENSMUSG00000002365.11. DR GeneID; 66616; -. DR KEGG; mmu:66616; -. DR UCSC; uc008afj.1; mouse. DR AGR; MGI:1913866; -. 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; 5401713at2759; -. 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 77 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 261 other cell types or tissues. DR ExpressionAtlas; Q91VH2; baseline and differential. DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB. DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell. 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:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0098793; C:presynapse; ISO: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:0065003; P:protein-containing complex assembly; ISS:UniProtKB. DR GO; GO:0006898; P:receptor-mediated endocytosis; ISS:UniProtKB. DR GO; GO:1900242; P:regulation of synaptic vesicle endocytosis; ISO:MGI. DR CDD; cd07668; BAR_SNX9; 1. DR CDD; cd07285; PX_SNX9; 1. DR CDD; cd11898; SH3_SNX9; 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 Gene3D; 2.30.30.40; SH3 Domains; 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; 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; SORTING NEXIN; 1. DR PANTHER; PTHR45827:SF2; SORTING NEXIN-9; 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; BAR/IMD domain-like; 1. DR SUPFAM; SSF64268; PX domain; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50195; PX; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q91VH2; MM. 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 //