Full text data of SNX9
SNX9
(SH3PX1, SH3PXD3A)
[Confidence: low (only semi-automatic identification from reviews)]
Sorting nexin-9 (SH3 and PX domain-containing protein 1; Protein SDP1; SH3 and PX domain-containing protein 3A)
Sorting nexin-9 (SH3 and PX domain-containing protein 1; Protein SDP1; SH3 and PX domain-containing protein 3A)
UniProt
Q9Y5X1
ID SNX9_HUMAN Reviewed; 595 AA.
AC Q9Y5X1; Q9BSI7; Q9BVM1; Q9UJH6; Q9UP20;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Sorting nexin-9;
DE AltName: Full=SH3 and PX domain-containing protein 1;
DE Short=Protein SDP1;
DE AltName: Full=SH3 and PX domain-containing protein 3A;
GN Name=SNX9; Synonyms=SH3PX1, SH3PXD3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11485546; DOI=10.1042/0264-6021:3580007;
RA Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.;
RT "A large family of endosome-localized proteins related to sorting
RT nexin 1.";
RL Biochem. J. 358:7-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ADAM9 AND ADAM15, AND
RP TISSUE SPECIFICITY.
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
RT two SH3 domain-containing proteins, endophilin I and SH3PX1.";
RL J. Biol. Chem. 274:31693-31699(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang J.S., Smith D.I.;
RT "Identification of differentially expressed genes in matched prostate
RT cancer and normal epithelial cell lines.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-595.
RA Ramanathan G., Subramaniam V.N., Hong W.;
RT "Human SDP1.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, INTERACTION WITH TNK2, IDENTIFICATION IN A COMPLEX WITH TNK2
RP AND CLATHRIN HEAVY CHAIN, AND TYROSINE PHOSPHORYLATION.
RX PubMed=11799118; DOI=10.1074/jbc.M110329200;
RA Lin Q., Lo C.G., Cerione R.A., Yang W.;
RT "The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to
RT regulate epidermal growth factor receptor degradation.";
RL J. Biol. Chem. 277:10134-10138(2002).
RN [8]
RP FUNCTION, INTERACTION WITH DNM2 AND THE AP-2 COMPLEX, IDENTIFICATION
RP IN A COMPLEX WITH THE AP-2 COMPLEX; CLATHRIN AND DNM2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12952949; DOI=10.1074/jbc.M307334200;
RA Lundmark R., Carlsson S.R.;
RT "Sorting nexin 9 participates in clathrin-mediated endocytosis through
RT interactions with the core components.";
RL J. Biol. Chem. 278:46772-46781(2003).
RN [9]
RP INTERACTION WITH TNK2, AND SUBCELLULAR LOCATION.
RX PubMed=16137687; DOI=10.1016/j.febslet.2005.07.093;
RA Yeow-Fong L., Lim L., Manser E.;
RT "SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector
RT ACK1.";
RL FEBS Lett. 579:5040-5048(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND INTERACTION
RP WITH DNM1 AND DNM2.
RX PubMed=15703209; DOI=10.1091/mbc.E04-11-1016;
RA Soulet F., Yarar D., Leonard M., Schmid S.L.;
RT "SNX9 regulates dynamin assembly and is required for efficient
RT clathrin-mediated endocytosis.";
RL Mol. Biol. Cell 16:2058-2067(2005).
RN [11]
RP SUBUNIT, SUBCELLULAR LOCATION, AND TYROSINE PHOSPHORYLATION.
RX PubMed=16316319; DOI=10.1042/BJ20050576;
RA Childress C., Lin Q., Yang W.;
RT "Dimerization is required for SH3PX1 tyrosine phosphorylation in
RT response to epidermal growth factor signalling and interaction with
RT ACK2.";
RL Biochem. J. 394:693-698(2006).
RN [12]
RP FUNCTION, INTERACTION WITH WASL, SUBCELLULAR LOCATION, SUBUNIT, AND
RP PHOSPHATIDYLINOSITOL 4,5-BISPHOSPATE BINDING.
RX PubMed=17609109; DOI=10.1016/j.devcel.2007.04.014;
RA Yarar D., Waterman-Storer C.M., Schmid S.L.;
RT "SNX9 couples actin assembly to phosphoinositide signals and is
RT required for membrane remodeling during endocytosis.";
RL Dev. Cell 13:43-56(2007).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARP3; WASL AND
RP DNM2.
RX PubMed=18388313; DOI=10.1242/jcs.016709;
RA Shin N., Ahn N., Chang-Ileto B., Park J., Takei K., Ahn S.G.,
RA Kim S.A., Di Paolo G., Chang S.;
RT "SNX9 regulates tubular invagination of the plasma membrane through
RT interaction with actin cytoskeleton and dynamin 2.";
RL J. Cell Sci. 121:1252-1263(2008).
RN [14]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL
RT (CD178) by phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP INTERACTION WITH ITCH, AND UBIQUITINATION BY ITCH.
RX PubMed=20491914; DOI=10.1111/j.1742-4658.2010.07698.x;
RA Baumann C., Lindholm C.K., Rimoldi D., Levy F.;
RT "The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an
RT unconventional substrate recognition domain.";
RL FEBS J. 277:2803-2814(2010).
RN [17]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=20427313; DOI=10.1242/jcs.064170;
RA Park J., Kim Y., Lee S., Park J.J., Park Z.Y., Sun W., Kim H.,
RA Chang S.;
RT "SNX18 shares a redundant role with SNX9 and modulates endocytic
RT trafficking at the plasma membrane.";
RL J. Cell Sci. 123:1742-1750(2010).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21048941; DOI=10.1371/journal.pone.0013763;
RA Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S.,
RA Teasdale R.D.;
RT "The SNX-PX-BAR family in macropinocytosis: the regulation of
RT macropinosome formation by SNX-PX-BAR proteins.";
RL PLoS ONE 5:E13763-E13763(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22718350; DOI=10.1242/jcs.105981;
RA Ma M.P., Chircop M.;
RT "SNX9, SNX18 and SNX33 are required for progression through and
RT completion of mitosis.";
RL J. Cell Sci. 125:4372-4382(2012).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 204-595 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3-PHOSPHATE, FUNCTION, SUBUNIT, DOMAIN,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-287; LYS-313; LYS-363;
RP 366-LYS-ARG-367; LYS-522 AND LYS-528.
RX PubMed=17948057; DOI=10.1038/sj.emboj.7601889;
RA Pylypenko O., Lundmark R., Rasmuson E., Carlsson S.R., Rak A.;
RT "The PX-BAR membrane-remodeling unit of sorting nexin 9.";
RL EMBO J. 26:4788-4800(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 230-595, AND SUBUNIT.
RX PubMed=18940612; DOI=10.1016/j.str.2008.07.016;
RA Wang Q., Kaan H.Y., Hooda R.N., Goh S.L., Sondermann H.;
RT "Structure and plasticity of Endophilin and Sorting Nexin 9.";
RL Structure 16:1574-1587(2008).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 152-182 IN COMPLEX WITH
RP ALDOA.
RX PubMed=20129922; DOI=10.1074/jbc.M109.092049;
RA Rangarajan E.S., Park H., Fortin E., Sygusch J., Izard T.;
RT "Mechanism of aldolase control of sorting nexin 9 function in
RT endocytosis.";
RL J. Biol. Chem. 285:11983-11990(2010).
CC -!- FUNCTION: Involved in endocytosis and intracellular vesicle
CC trafficking, both during interphase and at the end of mitosis.
CC Required for efficient progress through mitosis and cytokinesis.
CC Required for normal formation of the cleavage furrow at the end of
CC mitosis. Plays a role in endocytosis via clathrin-coated pits, but
CC also clathrin-independent, actin-dependent fluid-phase
CC endocytosis. Plays a role in macropinocytosis. Promotes
CC internalization of TNFR. Promotes degradation of EGFR after EGF
CC signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1
CC oligomerization. Promotes activation of the Arp2/3 complex by
CC WASL, and thereby plays a role in the reorganization of the F-
CC actin cytoskeleton. Binds to membranes enriched in
CC phosphatidylinositol 4,5-bisphosphate and promotes membrane
CC tubulation. Has lower affinity for membranes enriched in
CC phosphatidylinositol 3-phosphate.
CC -!- SUBUNIT: Homodimer, and homooligomer. Heterodimer with SNX18.
CC Interacts with ITCH. Interacts (via SH3 domain) with TNK2, WASL
CC and ARP3. Identified in a complex with TNK2 and clathrin heavy
CC chains. Identified in a complex with the AP-2 complex, clathrin
CC and DNM2. Interacts (via SH3 domain) with DNM1 and DNM2.
CC Identified in an oligomeric complex containing DNM1 and SNX9.
CC Interacts with ADAM9 and ADAM15 cytoplasmic tails.
CC -!- INTERACTION:
CC Q13444:ADAM15; NbExp=2; IntAct=EBI-77848, EBI-77818;
CC Q6UW56:ATRAID; NbExp=2; IntAct=EBI-77848, EBI-723802;
CC P50570:DNM2; NbExp=2; IntAct=EBI-77848, EBI-346547;
CC B7UM88:espF (xeno); NbExp=4; IntAct=EBI-77848, EBI-2529480;
CC P48023:FASLG; NbExp=2; IntAct=EBI-77848, EBI-495538;
CC Q96J02:ITCH; NbExp=7; IntAct=EBI-77848, EBI-1564678;
CC Q8WV41:SNX33; NbExp=2; IntAct=EBI-77848, EBI-2481535;
CC Q07889:SOS1; NbExp=2; IntAct=EBI-77848, EBI-297487;
CC Q07890:SOS2; NbExp=2; IntAct=EBI-77848, EBI-298181;
CC Q17R13:TNK2 (xeno); NbExp=5; IntAct=EBI-77848, EBI-457220;
CC P0CG48:UBC; NbExp=2; IntAct=EBI-77848, EBI-3390054;
CC O00401:WASL; NbExp=2; IntAct=EBI-77848, EBI-957615;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cell membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cytoplasmic vesicle, clathrin-
CC coated vesicle. Golgi apparatus, trans-Golgi network. Cell
CC projection, ruffle. Cytoplasm. Note=Localized at sites of
CC endocytosis at the cell membrane. Detected on newly formed
CC macropinosomes. Transiently recruited to clathrin-coated pits at a
CC late stage of clathrin-coated vesicle formation. Colocalizes with
CC the actin cytoskeleton at the cell membrane.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in heart
CC and placenta, and lowest levels in thymus and peripheral blood
CC leukocytes.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched
CC in phosphatidylinositol phosphate. Has high affinity for
CC phosphatidylinositol 4,5-bisphosphate, but can also bind to
CC membranes enriched in other phosphatidylinositol phosphates.
CC -!- PTM: Ubiquitinated by ITCH.
CC -!- PTM: Phosphorylated on tyrosine residues by TNK2. Phosphorylation
CC promotes its activity in the degradation of EGFR.
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 BAR domain.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; AF121859; AAD27832.1; -; mRNA.
DR EMBL; AF131214; AAF04473.1; -; mRNA.
DR EMBL; AF172847; AAL54871.1; -; mRNA.
DR EMBL; AL035634; CAI20465.1; -; Genomic_DNA.
DR EMBL; AL139330; CAI20465.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI20465.1; JOINED; Genomic_DNA.
DR EMBL; AL139330; CAI12979.1; -; Genomic_DNA.
DR EMBL; AL035634; CAI12979.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI12979.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI15180.1; -; Genomic_DNA.
DR EMBL; AL035634; CAI15180.1; JOINED; Genomic_DNA.
DR EMBL; AL139330; CAI15180.1; JOINED; Genomic_DNA.
DR EMBL; BC001084; AAH01084.3; -; mRNA.
DR EMBL; BC005022; AAH05022.1; -; mRNA.
DR EMBL; AF076957; AAD43001.1; -; mRNA.
DR RefSeq; NP_057308.1; NM_016224.4.
DR UniGene; Hs.191213; -.
DR PDB; 2RAI; X-ray; 3.20 A; A/B=204-595.
DR PDB; 2RAJ; X-ray; 2.45 A; A=204-595.
DR PDB; 2RAK; X-ray; 3.00 A; A=204-595.
DR PDB; 3DYT; X-ray; 2.08 A; A=230-595.
DR PDB; 3DYU; X-ray; 4.10 A; A/B/C=230-595.
DR PDB; 3LGE; X-ray; 2.20 A; E/F/G/H=152-182.
DR PDBsum; 2RAI; -.
DR PDBsum; 2RAJ; -.
DR PDBsum; 2RAK; -.
DR PDBsum; 3DYT; -.
DR PDBsum; 3DYU; -.
DR PDBsum; 3LGE; -.
DR ProteinModelPortal; Q9Y5X1; -.
DR SMR; Q9Y5X1; 1-70, 214-595.
DR DIP; DIP-30997N; -.
DR IntAct; Q9Y5X1; 21.
DR MINT; MINT-108846; -.
DR STRING; 9606.ENSP00000376024; -.
DR PhosphoSite; Q9Y5X1; -.
DR DMDM; 12643956; -.
DR PaxDb; Q9Y5X1; -.
DR PeptideAtlas; Q9Y5X1; -.
DR PRIDE; Q9Y5X1; -.
DR DNASU; 51429; -.
DR Ensembl; ENST00000392185; ENSP00000376024; ENSG00000130340.
DR GeneID; 51429; -.
DR KEGG; hsa:51429; -.
DR UCSC; uc003qqv.1; human.
DR CTD; 51429; -.
DR GeneCards; GC06P158153; -.
DR HGNC; HGNC:14973; SNX9.
DR HPA; HPA031410; -.
DR MIM; 605952; gene.
DR neXtProt; NX_Q9Y5X1; -.
DR PharmGKB; PA37949; -.
DR eggNOG; COG5391; -.
DR HOGENOM; HOG000261633; -.
DR HOVERGEN; HBG009996; -.
DR InParanoid; Q9Y5X1; -.
DR OMA; DPWSAWN; -.
DR OrthoDB; EOG7GTT36; -.
DR PhylomeDB; Q9Y5X1; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; Q9Y5X1; -.
DR ChiTaRS; SNX9; human.
DR EvolutionaryTrace; Q9Y5X1; -.
DR GeneWiki; SNX9; -.
DR GenomeRNAi; 51429; -.
DR NextBio; 54991; -.
DR PRO; PR:Q9Y5X1; -.
DR ArrayExpress; Q9Y5X1; -.
DR Bgee; Q9Y5X1; -.
DR CleanEx; HS_SNX9; -.
DR Genevestigator; Q9Y5X1; -.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic to cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0036089; P:cleavage furrow formation; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0060988; P:lipid tube assembly; IDA:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0032461; P:positive regulation of protein oligomerization; IDA:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:UniProtKB.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR014536; Snx9_subfam.
DR InterPro; IPR019497; Sorting_nexin_WASP-bd-dom.
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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51021; BAR; FALSE_NEG.
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; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Endocytosis; Golgi apparatus; Lipid-binding; Membrane; Mitosis;
KW Phosphoprotein; Protein transport; Reference proteome; SH3 domain;
KW Transport; Ubl conjugation.
FT CHAIN 1 595 Sorting nexin-9.
FT /FTId=PRO_0000213852.
FT DOMAIN 1 62 SH3.
FT DOMAIN 250 361 PX.
FT DOMAIN 392 595 BAR.
FT REGION 201 213 Critical for tubulation activity.
FT BINDING 286 286 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 288 288 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 313 313 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 327 327 Phosphatidylinositol 4,5-bisphosphate.
FT MOD_RES 239 239 Phosphotyrosine (By similarity).
FT MOD_RES 288 288 N6-acetyllysine.
FT MUTAGEN 287 287 Y->A: Abolishes membrane tubulation
FT activity. Abolishes binding to
FT phosphatidylinositol 3-phosphate, but not
FT to phosphatidylinositol 4,5-bisphosphate;
FT when associated with A-313.
FT MUTAGEN 313 313 K->A: Abolishes binding to
FT phosphatidylinositol 3-phosphate, but not
FT to phosphatidylinositol 4,5-bisphosphate;
FT when associated with A-287.
FT MUTAGEN 363 363 K->E: Strongly reduced membrane binding.
FT MUTAGEN 366 367 KR->EE: Loss of membrane binding.
FT MUTAGEN 522 522 K->E: Abolishes membrane tubulation
FT activity; when associated with E-528.
FT MUTAGEN 528 528 K->E: Abolishes membrane tubulation
FT activity; when associated with E-522.
FT CONFLICT 89 89 Q -> H (in Ref. 5; AAH05022).
FT TURN 167 169
FT HELIX 215 221
FT STRAND 232 237
FT STRAND 240 243
FT STRAND 252 255
FT HELIX 257 259
FT STRAND 260 262
FT STRAND 263 266
FT STRAND 271 276
FT TURN 277 279
FT STRAND 283 286
FT HELIX 287 301
FT TURN 302 304
FT HELIX 324 339
FT HELIX 344 346
FT HELIX 348 355
FT HELIX 359 370
FT HELIX 376 382
FT STRAND 383 387
FT HELIX 392 428
FT HELIX 430 450
FT HELIX 455 457
FT HELIX 458 480
FT HELIX 482 484
FT HELIX 486 500
FT HELIX 503 518
FT HELIX 520 525
FT HELIX 531 590
SQ SEQUENCE 595 AA; 66592 MW; 963892AC1A5A9227 CRC64;
MATKARVMYD FAAEPGNNEL TVNEGEIITI TNPDVGGGWL EGRNIKGERG LVPTDYVEIL
PSDGKDQFSC GNSVADQAFL DSLSASTAQA SSSAASNNHQ VGSGNDPWSA WSASKSGNWE
SSEGWGAQPE GAGAQRNTNT PNNWDTAFGH PQAYQGPATG DDDDWDEDWD GPKSSSYFKD
SESADAGGAQ RGNSRASSSS MKIPLNKFPG FAKPGTEQYL LAKQLAKPKE KIPIIVGDYG
PMWVYPTSTF DCVVADPRKG SKMYGLKSYI EYQLTPTNTN RSVNHRYKHF DWLYERLLVK
FGSAIPIPSL PDKQVTGRFE EEFIKMRMER LQAWMTRMCR HPVISESEVF QQFLNFRDEK
EWKTGKRKAE RDELAGVMIF STMEPEAPDL DLVEIEQKCE AVGKFTKAMD DGVKELLTVG
QEHWKRCTGP LPKEYQKIGK ALQSLATVFS SSGYQGETDL NDAITEAGKT YEEIASLVAE
QPKKDLHFLM ECNHEYKGFL GCFPDIIGTH KGAIEKVKES DKLVATSKIT LQDKQNMVKR
VSIMSYALQA EMNHFHSNRI YDYNSVIRLY LEQQVQFYET IAEKLRQALS RFPVM
//
ID SNX9_HUMAN Reviewed; 595 AA.
AC Q9Y5X1; Q9BSI7; Q9BVM1; Q9UJH6; Q9UP20;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1999, sequence version 1.
DT 22-JAN-2014, entry version 122.
DE RecName: Full=Sorting nexin-9;
DE AltName: Full=SH3 and PX domain-containing protein 1;
DE Short=Protein SDP1;
DE AltName: Full=SH3 and PX domain-containing protein 3A;
GN Name=SNX9; Synonyms=SH3PX1, SH3PXD3A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11485546; DOI=10.1042/0264-6021:3580007;
RA Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.;
RT "A large family of endosome-localized proteins related to sorting
RT nexin 1.";
RL Biochem. J. 358:7-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH ADAM9 AND ADAM15, AND
RP TISSUE SPECIFICITY.
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
RT two SH3 domain-containing proteins, endophilin I and SH3PX1.";
RL J. Biol. Chem. 274:31693-31699(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang J.S., Smith D.I.;
RT "Identification of differentially expressed genes in matched prostate
RT cancer and normal epithelial cell lines.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney, and Skin;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 201-595.
RA Ramanathan G., Subramaniam V.N., Hong W.;
RT "Human SDP1.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP FUNCTION, INTERACTION WITH TNK2, IDENTIFICATION IN A COMPLEX WITH TNK2
RP AND CLATHRIN HEAVY CHAIN, AND TYROSINE PHOSPHORYLATION.
RX PubMed=11799118; DOI=10.1074/jbc.M110329200;
RA Lin Q., Lo C.G., Cerione R.A., Yang W.;
RT "The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to
RT regulate epidermal growth factor receptor degradation.";
RL J. Biol. Chem. 277:10134-10138(2002).
RN [8]
RP FUNCTION, INTERACTION WITH DNM2 AND THE AP-2 COMPLEX, IDENTIFICATION
RP IN A COMPLEX WITH THE AP-2 COMPLEX; CLATHRIN AND DNM2, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12952949; DOI=10.1074/jbc.M307334200;
RA Lundmark R., Carlsson S.R.;
RT "Sorting nexin 9 participates in clathrin-mediated endocytosis through
RT interactions with the core components.";
RL J. Biol. Chem. 278:46772-46781(2003).
RN [9]
RP INTERACTION WITH TNK2, AND SUBCELLULAR LOCATION.
RX PubMed=16137687; DOI=10.1016/j.febslet.2005.07.093;
RA Yeow-Fong L., Lim L., Manser E.;
RT "SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector
RT ACK1.";
RL FEBS Lett. 579:5040-5048(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, MASS SPECTROMETRY, AND INTERACTION
RP WITH DNM1 AND DNM2.
RX PubMed=15703209; DOI=10.1091/mbc.E04-11-1016;
RA Soulet F., Yarar D., Leonard M., Schmid S.L.;
RT "SNX9 regulates dynamin assembly and is required for efficient
RT clathrin-mediated endocytosis.";
RL Mol. Biol. Cell 16:2058-2067(2005).
RN [11]
RP SUBUNIT, SUBCELLULAR LOCATION, AND TYROSINE PHOSPHORYLATION.
RX PubMed=16316319; DOI=10.1042/BJ20050576;
RA Childress C., Lin Q., Yang W.;
RT "Dimerization is required for SH3PX1 tyrosine phosphorylation in
RT response to epidermal growth factor signalling and interaction with
RT ACK2.";
RL Biochem. J. 394:693-698(2006).
RN [12]
RP FUNCTION, INTERACTION WITH WASL, SUBCELLULAR LOCATION, SUBUNIT, AND
RP PHOSPHATIDYLINOSITOL 4,5-BISPHOSPATE BINDING.
RX PubMed=17609109; DOI=10.1016/j.devcel.2007.04.014;
RA Yarar D., Waterman-Storer C.M., Schmid S.L.;
RT "SNX9 couples actin assembly to phosphoinositide signals and is
RT required for membrane remodeling during endocytosis.";
RL Dev. Cell 13:43-56(2007).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARP3; WASL AND
RP DNM2.
RX PubMed=18388313; DOI=10.1242/jcs.016709;
RA Shin N., Ahn N., Chang-Ileto B., Park J., Takei K., Ahn S.G.,
RA Kim S.A., Di Paolo G., Chang S.;
RT "SNX9 regulates tubular invagination of the plasma membrane through
RT interaction with actin cytoskeleton and dynamin 2.";
RL J. Cell Sci. 121:1252-1263(2008).
RN [14]
RP INTERACTION WITH FASLG.
RX PubMed=19807924; DOI=10.1186/1471-2172-10-53;
RA Voss M., Lettau M., Janssen O.;
RT "Identification of SH3 domain interaction partners of human FasL
RT (CD178) by phage display screening.";
RL BMC Immunol. 10:53-53(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP INTERACTION WITH ITCH, AND UBIQUITINATION BY ITCH.
RX PubMed=20491914; DOI=10.1111/j.1742-4658.2010.07698.x;
RA Baumann C., Lindholm C.K., Rimoldi D., Levy F.;
RT "The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an
RT unconventional substrate recognition domain.";
RL FEBS J. 277:2803-2814(2010).
RN [17]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=20427313; DOI=10.1242/jcs.064170;
RA Park J., Kim Y., Lee S., Park J.J., Park Z.Y., Sun W., Kim H.,
RA Chang S.;
RT "SNX18 shares a redundant role with SNX9 and modulates endocytic
RT trafficking at the plasma membrane.";
RL J. Cell Sci. 123:1742-1750(2010).
RN [18]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=21048941; DOI=10.1371/journal.pone.0013763;
RA Wang J.T., Kerr M.C., Karunaratne S., Jeanes A., Yap A.S.,
RA Teasdale R.D.;
RT "The SNX-PX-BAR family in macropinocytosis: the regulation of
RT macropinosome formation by SNX-PX-BAR proteins.";
RL PLoS ONE 5:E13763-E13763(2010).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22718350; DOI=10.1242/jcs.105981;
RA Ma M.P., Chircop M.;
RT "SNX9, SNX18 and SNX33 are required for progression through and
RT completion of mitosis.";
RL J. Cell Sci. 125:4372-4382(2012).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 204-595 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3-PHOSPHATE, FUNCTION, SUBUNIT, DOMAIN,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-287; LYS-313; LYS-363;
RP 366-LYS-ARG-367; LYS-522 AND LYS-528.
RX PubMed=17948057; DOI=10.1038/sj.emboj.7601889;
RA Pylypenko O., Lundmark R., Rasmuson E., Carlsson S.R., Rak A.;
RT "The PX-BAR membrane-remodeling unit of sorting nexin 9.";
RL EMBO J. 26:4788-4800(2007).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 230-595, AND SUBUNIT.
RX PubMed=18940612; DOI=10.1016/j.str.2008.07.016;
RA Wang Q., Kaan H.Y., Hooda R.N., Goh S.L., Sondermann H.;
RT "Structure and plasticity of Endophilin and Sorting Nexin 9.";
RL Structure 16:1574-1587(2008).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 152-182 IN COMPLEX WITH
RP ALDOA.
RX PubMed=20129922; DOI=10.1074/jbc.M109.092049;
RA Rangarajan E.S., Park H., Fortin E., Sygusch J., Izard T.;
RT "Mechanism of aldolase control of sorting nexin 9 function in
RT endocytosis.";
RL J. Biol. Chem. 285:11983-11990(2010).
CC -!- FUNCTION: Involved in endocytosis and intracellular vesicle
CC trafficking, both during interphase and at the end of mitosis.
CC Required for efficient progress through mitosis and cytokinesis.
CC Required for normal formation of the cleavage furrow at the end of
CC mitosis. Plays a role in endocytosis via clathrin-coated pits, but
CC also clathrin-independent, actin-dependent fluid-phase
CC endocytosis. Plays a role in macropinocytosis. Promotes
CC internalization of TNFR. Promotes degradation of EGFR after EGF
CC signaling. Stimulates the GTPase activity of DNM1. Promotes DNM1
CC oligomerization. Promotes activation of the Arp2/3 complex by
CC WASL, and thereby plays a role in the reorganization of the F-
CC actin cytoskeleton. Binds to membranes enriched in
CC phosphatidylinositol 4,5-bisphosphate and promotes membrane
CC tubulation. Has lower affinity for membranes enriched in
CC phosphatidylinositol 3-phosphate.
CC -!- SUBUNIT: Homodimer, and homooligomer. Heterodimer with SNX18.
CC Interacts with ITCH. Interacts (via SH3 domain) with TNK2, WASL
CC and ARP3. Identified in a complex with TNK2 and clathrin heavy
CC chains. Identified in a complex with the AP-2 complex, clathrin
CC and DNM2. Interacts (via SH3 domain) with DNM1 and DNM2.
CC Identified in an oligomeric complex containing DNM1 and SNX9.
CC Interacts with ADAM9 and ADAM15 cytoplasmic tails.
CC -!- INTERACTION:
CC Q13444:ADAM15; NbExp=2; IntAct=EBI-77848, EBI-77818;
CC Q6UW56:ATRAID; NbExp=2; IntAct=EBI-77848, EBI-723802;
CC P50570:DNM2; NbExp=2; IntAct=EBI-77848, EBI-346547;
CC B7UM88:espF (xeno); NbExp=4; IntAct=EBI-77848, EBI-2529480;
CC P48023:FASLG; NbExp=2; IntAct=EBI-77848, EBI-495538;
CC Q96J02:ITCH; NbExp=7; IntAct=EBI-77848, EBI-1564678;
CC Q8WV41:SNX33; NbExp=2; IntAct=EBI-77848, EBI-2481535;
CC Q07889:SOS1; NbExp=2; IntAct=EBI-77848, EBI-297487;
CC Q07890:SOS2; NbExp=2; IntAct=EBI-77848, EBI-298181;
CC Q17R13:TNK2 (xeno); NbExp=5; IntAct=EBI-77848, EBI-457220;
CC P0CG48:UBC; NbExp=2; IntAct=EBI-77848, EBI-3390054;
CC O00401:WASL; NbExp=2; IntAct=EBI-77848, EBI-957615;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cell membrane; Peripheral
CC membrane protein; Cytoplasmic side. Cytoplasmic vesicle, clathrin-
CC coated vesicle. Golgi apparatus, trans-Golgi network. Cell
CC projection, ruffle. Cytoplasm. Note=Localized at sites of
CC endocytosis at the cell membrane. Detected on newly formed
CC macropinosomes. Transiently recruited to clathrin-coated pits at a
CC late stage of clathrin-coated vesicle formation. Colocalizes with
CC the actin cytoskeleton at the cell membrane.
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest levels in heart
CC and placenta, and lowest levels in thymus and peripheral blood
CC leukocytes.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched
CC in phosphatidylinositol phosphate. Has high affinity for
CC phosphatidylinositol 4,5-bisphosphate, but can also bind to
CC membranes enriched in other phosphatidylinositol phosphates.
CC -!- PTM: Ubiquitinated by ITCH.
CC -!- PTM: Phosphorylated on tyrosine residues by TNK2. Phosphorylation
CC promotes its activity in the degradation of EGFR.
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 BAR domain.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; AF121859; AAD27832.1; -; mRNA.
DR EMBL; AF131214; AAF04473.1; -; mRNA.
DR EMBL; AF172847; AAL54871.1; -; mRNA.
DR EMBL; AL035634; CAI20465.1; -; Genomic_DNA.
DR EMBL; AL139330; CAI20465.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI20465.1; JOINED; Genomic_DNA.
DR EMBL; AL139330; CAI12979.1; -; Genomic_DNA.
DR EMBL; AL035634; CAI12979.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI12979.1; JOINED; Genomic_DNA.
DR EMBL; AL391863; CAI15180.1; -; Genomic_DNA.
DR EMBL; AL035634; CAI15180.1; JOINED; Genomic_DNA.
DR EMBL; AL139330; CAI15180.1; JOINED; Genomic_DNA.
DR EMBL; BC001084; AAH01084.3; -; mRNA.
DR EMBL; BC005022; AAH05022.1; -; mRNA.
DR EMBL; AF076957; AAD43001.1; -; mRNA.
DR RefSeq; NP_057308.1; NM_016224.4.
DR UniGene; Hs.191213; -.
DR PDB; 2RAI; X-ray; 3.20 A; A/B=204-595.
DR PDB; 2RAJ; X-ray; 2.45 A; A=204-595.
DR PDB; 2RAK; X-ray; 3.00 A; A=204-595.
DR PDB; 3DYT; X-ray; 2.08 A; A=230-595.
DR PDB; 3DYU; X-ray; 4.10 A; A/B/C=230-595.
DR PDB; 3LGE; X-ray; 2.20 A; E/F/G/H=152-182.
DR PDBsum; 2RAI; -.
DR PDBsum; 2RAJ; -.
DR PDBsum; 2RAK; -.
DR PDBsum; 3DYT; -.
DR PDBsum; 3DYU; -.
DR PDBsum; 3LGE; -.
DR ProteinModelPortal; Q9Y5X1; -.
DR SMR; Q9Y5X1; 1-70, 214-595.
DR DIP; DIP-30997N; -.
DR IntAct; Q9Y5X1; 21.
DR MINT; MINT-108846; -.
DR STRING; 9606.ENSP00000376024; -.
DR PhosphoSite; Q9Y5X1; -.
DR DMDM; 12643956; -.
DR PaxDb; Q9Y5X1; -.
DR PeptideAtlas; Q9Y5X1; -.
DR PRIDE; Q9Y5X1; -.
DR DNASU; 51429; -.
DR Ensembl; ENST00000392185; ENSP00000376024; ENSG00000130340.
DR GeneID; 51429; -.
DR KEGG; hsa:51429; -.
DR UCSC; uc003qqv.1; human.
DR CTD; 51429; -.
DR GeneCards; GC06P158153; -.
DR HGNC; HGNC:14973; SNX9.
DR HPA; HPA031410; -.
DR MIM; 605952; gene.
DR neXtProt; NX_Q9Y5X1; -.
DR PharmGKB; PA37949; -.
DR eggNOG; COG5391; -.
DR HOGENOM; HOG000261633; -.
DR HOVERGEN; HBG009996; -.
DR InParanoid; Q9Y5X1; -.
DR OMA; DPWSAWN; -.
DR OrthoDB; EOG7GTT36; -.
DR PhylomeDB; Q9Y5X1; -.
DR Reactome; REACT_11123; Membrane Trafficking.
DR SignaLink; Q9Y5X1; -.
DR ChiTaRS; SNX9; human.
DR EvolutionaryTrace; Q9Y5X1; -.
DR GeneWiki; SNX9; -.
DR GenomeRNAi; 51429; -.
DR NextBio; 54991; -.
DR PRO; PR:Q9Y5X1; -.
DR ArrayExpress; Q9Y5X1; -.
DR Bgee; Q9Y5X1; -.
DR CleanEx; HS_SNX9; -.
DR Genevestigator; Q9Y5X1; -.
DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic to cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0036089; P:cleavage furrow formation; IMP:UniProtKB.
DR GO; GO:0016197; P:endosomal transport; IMP:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0060988; P:lipid tube assembly; IDA:UniProtKB.
DR GO; GO:0007067; P:mitosis; IEA:UniProtKB-KW.
DR GO; GO:0000281; P:mitotic cytokinesis; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0032461; P:positive regulation of protein oligomerization; IDA:UniProtKB.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:UniProtKB.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR014536; Snx9_subfam.
DR InterPro; IPR019497; Sorting_nexin_WASP-bd-dom.
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; SSF50044; SSF50044; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51021; BAR; FALSE_NEG.
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; Complete proteome; Cytoplasm; Cytoplasmic vesicle;
KW Endocytosis; Golgi apparatus; Lipid-binding; Membrane; Mitosis;
KW Phosphoprotein; Protein transport; Reference proteome; SH3 domain;
KW Transport; Ubl conjugation.
FT CHAIN 1 595 Sorting nexin-9.
FT /FTId=PRO_0000213852.
FT DOMAIN 1 62 SH3.
FT DOMAIN 250 361 PX.
FT DOMAIN 392 595 BAR.
FT REGION 201 213 Critical for tubulation activity.
FT BINDING 286 286 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 288 288 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 313 313 Phosphatidylinositol 4,5-bisphosphate.
FT BINDING 327 327 Phosphatidylinositol 4,5-bisphosphate.
FT MOD_RES 239 239 Phosphotyrosine (By similarity).
FT MOD_RES 288 288 N6-acetyllysine.
FT MUTAGEN 287 287 Y->A: Abolishes membrane tubulation
FT activity. Abolishes binding to
FT phosphatidylinositol 3-phosphate, but not
FT to phosphatidylinositol 4,5-bisphosphate;
FT when associated with A-313.
FT MUTAGEN 313 313 K->A: Abolishes binding to
FT phosphatidylinositol 3-phosphate, but not
FT to phosphatidylinositol 4,5-bisphosphate;
FT when associated with A-287.
FT MUTAGEN 363 363 K->E: Strongly reduced membrane binding.
FT MUTAGEN 366 367 KR->EE: Loss of membrane binding.
FT MUTAGEN 522 522 K->E: Abolishes membrane tubulation
FT activity; when associated with E-528.
FT MUTAGEN 528 528 K->E: Abolishes membrane tubulation
FT activity; when associated with E-522.
FT CONFLICT 89 89 Q -> H (in Ref. 5; AAH05022).
FT TURN 167 169
FT HELIX 215 221
FT STRAND 232 237
FT STRAND 240 243
FT STRAND 252 255
FT HELIX 257 259
FT STRAND 260 262
FT STRAND 263 266
FT STRAND 271 276
FT TURN 277 279
FT STRAND 283 286
FT HELIX 287 301
FT TURN 302 304
FT HELIX 324 339
FT HELIX 344 346
FT HELIX 348 355
FT HELIX 359 370
FT HELIX 376 382
FT STRAND 383 387
FT HELIX 392 428
FT HELIX 430 450
FT HELIX 455 457
FT HELIX 458 480
FT HELIX 482 484
FT HELIX 486 500
FT HELIX 503 518
FT HELIX 520 525
FT HELIX 531 590
SQ SEQUENCE 595 AA; 66592 MW; 963892AC1A5A9227 CRC64;
MATKARVMYD FAAEPGNNEL TVNEGEIITI TNPDVGGGWL EGRNIKGERG LVPTDYVEIL
PSDGKDQFSC GNSVADQAFL DSLSASTAQA SSSAASNNHQ VGSGNDPWSA WSASKSGNWE
SSEGWGAQPE GAGAQRNTNT PNNWDTAFGH PQAYQGPATG DDDDWDEDWD GPKSSSYFKD
SESADAGGAQ RGNSRASSSS MKIPLNKFPG FAKPGTEQYL LAKQLAKPKE KIPIIVGDYG
PMWVYPTSTF DCVVADPRKG SKMYGLKSYI EYQLTPTNTN RSVNHRYKHF DWLYERLLVK
FGSAIPIPSL PDKQVTGRFE EEFIKMRMER LQAWMTRMCR HPVISESEVF QQFLNFRDEK
EWKTGKRKAE RDELAGVMIF STMEPEAPDL DLVEIEQKCE AVGKFTKAMD DGVKELLTVG
QEHWKRCTGP LPKEYQKIGK ALQSLATVFS SSGYQGETDL NDAITEAGKT YEEIASLVAE
QPKKDLHFLM ECNHEYKGFL GCFPDIIGTH KGAIEKVKES DKLVATSKIT LQDKQNMVKR
VSIMSYALQA EMNHFHSNRI YDYNSVIRLY LEQQVQFYET IAEKLRQALS RFPVM
//
MIM
605952
*RECORD*
*FIELD* NO
605952
*FIELD* TI
*605952 SORTING NEXIN 9; SNX9
;;SH3 DOMAIN- AND PX DOMAIN-CONTAINING PROTEIN; SH3PX1
read more*FIELD* TX
DESCRIPTION
Members of the sorting nexin protein family, such as SNX9, contain a
phospholipid-binding module called the phox homology (PX) domain. SNX9
functions in clathrin (see 118955)-mediated endocytosis and
clathrin-independent, actin (see 102610)-dependent fluid-phase
endocytosis (Yarar et al., 2007).
CLONING
By use of a yeast 2-hybrid screen, Howard et al. (1999) identified 2 SH3
domain-containing proteins, endophilin-1 (SH3GL2; 604465) and SNX9, that
interact with the cytoplasmic domains of metalloprotease disintegrins
ADAM9 (602713) and ADAM15 (605548). The 595-amino acid SNX9 protein
contains an N-terminal SH3 domain, followed by a PX domain and a
C-terminal coiled-coil domain. Northern blot analysis detected wide
expression of 4.4- and 3.1-kb transcripts, with high levels in heart and
placenta and relatively low levels in thymus and peripheral blood
leukocytes.
GENE FUNCTION
Howard et al. (1999) determined that binding of the SH3 domain of SNX9
to ADAM9 and ADAM15 required the C-terminal proline-rich region of the
ADAM9 and ADAM15 cytoplasmic tails. Both SNX9 and SH3GL2 preferentially
bound the precursors, but not the processed forms, of ADAM9 and ADAM15.
Using green monkey kidney cells, Yarar et al. (2007) showed that SNX9
was required for clathrin-independent, actin-dependent fluid-phase
endocytosis. SNX9 directly regulated F-actin nucleation through N-WASP
(WASL; 605056) and the ARP2 (ACTR2; 604221)/ARP3 (ACTR3; 604222)
complex, and this activity was synergistically enhanced by
phosphatidylinositol(4,5)bisphosphate-containing liposomes. Yarar et al.
(2007) concluded that SNX9 physically couples F-actin nucleation to
plasma membrane remodeling during endocytosis.
Posor et al. (2013) showed that the BAR domain protein SNX9 is a
phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) effector at
clathrin-coated pits in clathrin-mediated endocytosis. Timed formation
of PI(3,4)P2 by class 2 phosphatidylinositol-3-kinase C2A (PI3KC2A;
603601) is required for selective enrichment of SNX9 at late-stage
endocytic intermediates.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX9
gene to chromosome 6 (TMAP WI-19319).
*FIELD* RF
1. Howard, L.; Nelson, K. K.; Maciewicz, R. A.; Blobel, C. P.: Interaction
of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing
proteins, endophilin I and SH3PX1. J. Biol. Chem. 274: 31693-31699,
1999.
2. Posor, Y.; Eichhorn-Gruenig, M.; Puchkov, D.; Schoneberg, J.; Ullrich,
A.; Lampe, A.; Muller, R.; Zarbakhsh, S.; Gulluni, F.; Hirsch, E.;
Krauss, M.; Schultz, C.; Schmoranzer, J.; Noe, F.; Haucke, V.: Spatiotemporal
control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499:
233-237, 2013.
3. Yarar, D.; Waterman-Storer, C. M.; Schmid, S. L.: SNX9 couples
actin assembly to phosphoinositide signals and is required for membrane
remodeling during endocytosis. Dev. Cell 13: 43-56, 2007.
*FIELD* CN
Ada Hamosh - updated: 08/29/2013
Patricia A. Hartz - updated: 8/23/2007
Carol A. Bocchini - updated: 5/24/2001
*FIELD* CD
Carol A. Bocchini: 5/21/2001
*FIELD* ED
alopez: 08/29/2013
mgross: 8/31/2007
terry: 8/23/2007
mcapotos: 5/24/2001
carol: 5/24/2001
mcapotos: 5/24/2001
carol: 5/23/2001
*RECORD*
*FIELD* NO
605952
*FIELD* TI
*605952 SORTING NEXIN 9; SNX9
;;SH3 DOMAIN- AND PX DOMAIN-CONTAINING PROTEIN; SH3PX1
read more*FIELD* TX
DESCRIPTION
Members of the sorting nexin protein family, such as SNX9, contain a
phospholipid-binding module called the phox homology (PX) domain. SNX9
functions in clathrin (see 118955)-mediated endocytosis and
clathrin-independent, actin (see 102610)-dependent fluid-phase
endocytosis (Yarar et al., 2007).
CLONING
By use of a yeast 2-hybrid screen, Howard et al. (1999) identified 2 SH3
domain-containing proteins, endophilin-1 (SH3GL2; 604465) and SNX9, that
interact with the cytoplasmic domains of metalloprotease disintegrins
ADAM9 (602713) and ADAM15 (605548). The 595-amino acid SNX9 protein
contains an N-terminal SH3 domain, followed by a PX domain and a
C-terminal coiled-coil domain. Northern blot analysis detected wide
expression of 4.4- and 3.1-kb transcripts, with high levels in heart and
placenta and relatively low levels in thymus and peripheral blood
leukocytes.
GENE FUNCTION
Howard et al. (1999) determined that binding of the SH3 domain of SNX9
to ADAM9 and ADAM15 required the C-terminal proline-rich region of the
ADAM9 and ADAM15 cytoplasmic tails. Both SNX9 and SH3GL2 preferentially
bound the precursors, but not the processed forms, of ADAM9 and ADAM15.
Using green monkey kidney cells, Yarar et al. (2007) showed that SNX9
was required for clathrin-independent, actin-dependent fluid-phase
endocytosis. SNX9 directly regulated F-actin nucleation through N-WASP
(WASL; 605056) and the ARP2 (ACTR2; 604221)/ARP3 (ACTR3; 604222)
complex, and this activity was synergistically enhanced by
phosphatidylinositol(4,5)bisphosphate-containing liposomes. Yarar et al.
(2007) concluded that SNX9 physically couples F-actin nucleation to
plasma membrane remodeling during endocytosis.
Posor et al. (2013) showed that the BAR domain protein SNX9 is a
phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2) effector at
clathrin-coated pits in clathrin-mediated endocytosis. Timed formation
of PI(3,4)P2 by class 2 phosphatidylinositol-3-kinase C2A (PI3KC2A;
603601) is required for selective enrichment of SNX9 at late-stage
endocytic intermediates.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX9
gene to chromosome 6 (TMAP WI-19319).
*FIELD* RF
1. Howard, L.; Nelson, K. K.; Maciewicz, R. A.; Blobel, C. P.: Interaction
of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing
proteins, endophilin I and SH3PX1. J. Biol. Chem. 274: 31693-31699,
1999.
2. Posor, Y.; Eichhorn-Gruenig, M.; Puchkov, D.; Schoneberg, J.; Ullrich,
A.; Lampe, A.; Muller, R.; Zarbakhsh, S.; Gulluni, F.; Hirsch, E.;
Krauss, M.; Schultz, C.; Schmoranzer, J.; Noe, F.; Haucke, V.: Spatiotemporal
control of endocytosis by phosphatidylinositol-3,4-bisphosphate. Nature 499:
233-237, 2013.
3. Yarar, D.; Waterman-Storer, C. M.; Schmid, S. L.: SNX9 couples
actin assembly to phosphoinositide signals and is required for membrane
remodeling during endocytosis. Dev. Cell 13: 43-56, 2007.
*FIELD* CN
Ada Hamosh - updated: 08/29/2013
Patricia A. Hartz - updated: 8/23/2007
Carol A. Bocchini - updated: 5/24/2001
*FIELD* CD
Carol A. Bocchini: 5/21/2001
*FIELD* ED
alopez: 08/29/2013
mgross: 8/31/2007
terry: 8/23/2007
mcapotos: 5/24/2001
carol: 5/24/2001
mcapotos: 5/24/2001
carol: 5/23/2001