Full text data of SNX1
SNX1
[Confidence: low (only semi-automatic identification from reviews)]
Sorting nexin-1
Sorting nexin-1
UniProt
Q13596
ID SNX1_HUMAN Reviewed; 522 AA.
AC Q13596; A6NM19; A8K6T7; H0Y2M5; O60750; O60751; Q6ZRJ8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-NOV-2001, sequence version 3.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Sorting nexin-1;
GN Name=SNX1;
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=8638121; DOI=10.1126/science.272.5264.1008;
RA Kurten R.C., Cadena D.L., Gill G.N.;
RT "Enhanced degradation of EGF receptors by a sorting nexin, SNX1.";
RL Science 272:1008-1010(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND INTERACTION WITH
RP VPS26A; VPS29; VPS35 AND SNX2.
RX PubMed=9819414;
RA Haft C.R., de la Luz Sierra M., Barr V.A., Haft D.H., Taylor S.I.;
RT "Identification of a family of sorting nexin molecules and
RT characterization of their association with receptors.";
RL Mol. Cell. Biol. 18:7278-7287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-214, AND
RP INTERACTION WITH PHOSPHATIDYLINOSITIDES.
RX PubMed=12198132; DOI=10.1074/jbc.M206986200;
RA Cozier G.E., Carlton J., McGregor A.H., Gleeson P.A., Teasdale R.D.,
RA Mellor H., Cullen P.J.;
RT "The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated
RT association of sorting nexin-1 with an early sorting endosomal
RT compartment is required for its ability to regulate epidermal growth
RT factor receptor degradation.";
RL J. Biol. Chem. 277:48730-48736(2002).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SNX2.
RX PubMed=11997453; DOI=10.1073/pnas.092142699;
RA Zhong Q., Lazar C.S., Tronchere H., Sato T., Meerloo T., Yeo M.,
RA Songyang Z., Emr S.D., Gill G.N.;
RT "Endosomal localization and function of sorting nexin 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6767-6772(2002).
RN [10]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-214
RP AND 429-LYS--ARG-431.
RX PubMed=15498486; DOI=10.1016/j.cub.2004.09.077;
RA Carlton J., Bujny M., Peter B.J., Oorschot V.M., Rutherford A.,
RA Mellor H., Klumperman J., McMahon H.T., Cullen P.J.;
RT "Sorting nexin-1 mediates tubular endosome-to-TGN transport through
RT coincidence sensing of high- curvature membranes and 3-
RT phosphoinositides.";
RL Curr. Biol. 14:1791-1800(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17101778; DOI=10.1128/MCB.00156-06;
RA Rojas R., Kametaka S., Haft C.R., Bonifacino J.S.;
RT "Interchangeable but essential functions of SNX1 and SNX2 in the
RT association of retromer with endosomes and the trafficking of mannose
RT 6-phosphate receptors.";
RL Mol. Cell. Biol. 27:1112-1124(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-39 AND SER-188,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP INTERACTION WITH SNX6.
RX PubMed=19935774; DOI=10.1038/cr.2009.130;
RA Hong Z., Yang Y., Zhang C., Niu Y., Li K., Zhao X., Liu J.J.;
RT "The retromer component SNX6 interacts with dynactin p150(Glued) and
RT mediates endosome-to-TGN transport.";
RL Cell Res. 19:1334-1349(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-237, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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 [19]
RP STRUCTURE BY NMR OF 142-269, AND SUBCELLULAR LOCATION.
RX PubMed=15673616; DOI=10.1091/mbc.E04-06-0504;
RA Zhong Q., Watson M.J., Lazar C.S., Hounslow A.M., Waltho J.P.,
RA Gill G.N.;
RT "Determinants of the endosomal localization of sorting nexin 1.";
RL Mol. Biol. Cell 16:2049-2057(2005).
CC -!- FUNCTION: May be involved in several stages of intracellular
CC trafficking. Plays a role in targeting ligand-activated EGFR to
CC the lysosomes for degradation after endocytosis from the cell
CC surface and release from the Golgi. Component of the retromer
CC complex, a complex required to retrieve lysosomal enzyme receptors
CC (IGF2R and M6PR) from endosomes to the trans-Golgi network.
CC Interacts with membranes containing phosphatidylinositol 3-
CC phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2).
CC -!- SUBUNIT: Homodimer. Self-assembles into a complex of approximately
CC 300 kDa (By similarity). Interacts with HGS (By similarity).
CC Component of the retromer complex composed of VPS26 (VPS26A or
CC VPS26B), VPS29, VPS35, SNX1 and SNX2. Interacts with SNX6.
CC -!- SUBCELLULAR LOCATION: Endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Golgi apparatus, trans-Golgi network
CC membrane; Peripheral membrane protein; Cytoplasmic side
CC (Potential). Early endosome membrane; Peripheral membrane protein;
CC Cytoplasmic side. Note=Enriched on tubular elements of the early
CC endosome membrane. Binds preferentially to highly curved membranes
CC enriched in phosphatidylinositol 3-phosphate (PtdIns(3P)) or
CC phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13596-1; Sequence=Displayed;
CC Name=1A;
CC IsoId=Q13596-2; Sequence=VSP_006189;
CC Name=3;
CC IsoId=Q13596-3; Sequence=VSP_044823;
CC Note=No experimental confirmation available;
CC -!- MISCELLANEOUS: Binds phosphatidylinositol 3-phosphate (PtdIns-
CC (3)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2)
CC in liposome-based assays. Can bind PtdIns(3,4,5)P3 in
CC protein:lipid overlay assays, but not in liposome-based assays.
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 BAR domain.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
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DR EMBL; U53225; AAA98672.1; -; mRNA.
DR EMBL; AF065483; AAC17182.1; -; mRNA.
DR EMBL; AF065484; AAC17183.1; -; mRNA.
DR EMBL; BT006983; AAP35629.1; -; mRNA.
DR EMBL; AK128179; BAC87312.1; -; mRNA.
DR EMBL; AK291752; BAF84441.1; -; mRNA.
DR EMBL; AC021541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77663.1; -; Genomic_DNA.
DR EMBL; CH471082; EAW77665.1; -; Genomic_DNA.
DR EMBL; BC000357; AAH00357.1; -; mRNA.
DR PIR; G02522; G02522.
DR RefSeq; NP_001229862.1; NM_001242933.1.
DR RefSeq; NP_003090.2; NM_003099.4.
DR RefSeq; NP_683758.1; NM_148955.3.
DR UniGene; Hs.188634; -.
DR PDB; 2I4K; NMR; -; A=142-269.
DR PDB; 4FZS; X-ray; 2.80 A; A/B=301-522.
DR PDBsum; 2I4K; -.
DR PDBsum; 4FZS; -.
DR ProteinModelPortal; Q13596; -.
DR SMR; Q13596; 142-269.
DR DIP; DIP-398N; -.
DR IntAct; Q13596; 10.
DR MINT; MINT-4135098; -.
DR STRING; 9606.ENSP00000369638; -.
DR PhosphoSite; Q13596; -.
DR DMDM; 17380569; -.
DR PaxDb; Q13596; -.
DR PRIDE; Q13596; -.
DR DNASU; 6642; -.
DR Ensembl; ENST00000261889; ENSP00000261889; ENSG00000028528.
DR Ensembl; ENST00000559844; ENSP00000453785; ENSG00000028528.
DR Ensembl; ENST00000561026; ENSP00000453567; ENSG00000028528.
DR GeneID; 6642; -.
DR KEGG; hsa:6642; -.
DR UCSC; uc010uio.2; human.
DR CTD; 6642; -.
DR GeneCards; GC15P064875; -.
DR HGNC; HGNC:11172; SNX1.
DR HPA; HPA047373; -.
DR MIM; 601272; gene.
DR neXtProt; NX_Q13596; -.
DR PharmGKB; PA36011; -.
DR eggNOG; COG5391; -.
DR HOVERGEN; HBG000618; -.
DR InParanoid; Q13596; -.
DR OMA; PQPTYEE; -.
DR OrthoDB; EOG7HHWSB; -.
DR ChiTaRS; SNX1; human.
DR EvolutionaryTrace; Q13596; -.
DR GeneWiki; SNX1; -.
DR GenomeRNAi; 6642; -.
DR NextBio; 25881; -.
DR PRO; PR:Q13596; -.
DR ArrayExpress; Q13596; -.
DR Bgee; Q13596; -.
DR CleanEx; HS_SNX1; -.
DR Genevestigator; Q13596; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0034498; P:early endosome to Golgi transport; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR005329; Sorting_nexin_N.
DR InterPro; IPR015404; Vps5_C.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF03700; Sorting_nexin; 1.
DR Pfam; PF09325; Vps5; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51021; BAR; FALSE_NEG.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Endosome; Golgi apparatus; Lipid-binding; Membrane; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT CHAIN 1 522 Sorting nexin-1.
FT /FTId=PRO_0000213835.
FT DOMAIN 143 272 PX.
FT DOMAIN 302 522 BAR.
FT BINDING 186 186 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT BINDING 188 188 Phosphatidylinositol 3-phosphate; via
FT amide nitrogen and carbonyl oxygen (By
FT similarity).
FT BINDING 214 214 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT BINDING 238 238 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT MOD_RES 32 32 Phosphoserine.
FT MOD_RES 39 39 Phosphoserine.
FT MOD_RES 188 188 Phosphoserine.
FT MOD_RES 237 237 N6-acetyllysine.
FT VAR_SEQ 91 155 Missing (in isoform 1A).
FT /FTId=VSP_006189.
FT VAR_SEQ 507 522 LAKYWEAFLPEAKAIS -> AGEQLGIRSGILLTKKLPRYS
FT KFFSTVHKFCAAASLWKWGFFLSAYLSYLF (in
FT isoform 3).
FT /FTId=VSP_044823.
FT VARIANT 115 115 S -> Y (in dbSNP:rs1049501).
FT /FTId=VAR_052477.
FT VARIANT 466 466 D -> N (in dbSNP:rs1802376).
FT /FTId=VAR_034507.
FT MUTAGEN 214 214 K->A: Abolishes phosphatidylinositol
FT phosphate binding. Abolishes endosomal
FT location.
FT MUTAGEN 429 431 KKR->EEE: Loss of endosomal location.
FT CONFLICT 117 117 P -> S (in Ref. 2; AAC17182).
FT CONFLICT 211 211 P -> S (in Ref. 2; AAC17182/AAC17183).
FT CONFLICT 502 502 Y -> C (in Ref. 4; BAC87312).
FT STRAND 173 176
FT HELIX 187 199
FT STRAND 202 205
FT STRAND 210 213
FT STRAND 216 221
FT HELIX 234 251
FT HELIX 253 256
FT HELIX 259 262
FT TURN 263 266
FT HELIX 307 356
FT HELIX 361 385
FT HELIX 388 440
FT HELIX 443 483
FT TURN 484 487
FT HELIX 489 511
SQ SEQUENCE 522 AA; 59070 MW; 6AC8AA0A589513E3 CRC64;
MASGGGGCSA SERLPPPFPG LEPESEGAAG GSEPEAGDSD TEGEDIFTGA AVVSKHQSPK
ITTSLLPINN GSKENGIHEE QDQEPQDLFA DATVELSLDS TQNNQKKVLA KTLISLPPQE
ATNSSKPQPT YEELEEEEQE DQFDLTVGIT DPEKIGDGMN AYVAYKVTTQ TSLPLFRSKQ
FAVKRRFSDF LGLYEKLSEK HSQNGFIVPP PPEKSLIGMT KVKVGKEDSS SAEFLEKRRA
ALERYLQRIV NHPTMLQDPD VREFLEKEEL PRAVGTQTLS GAGLLKMFNK ATDAVSKMTI
KMNESDIWFE EKLQEVECEE QRLRKLHAVV ETLVNHRKEL ALNTAQFAKS LAMLGSSEDN
TALSRALSQL AEVEEKIEQL HQEQANNDFF LLAELLSDYI RLLAIVRAAF DQRMKTWQRW
QDAQATLQKK REAEARLLWA NKPDKLQQAK DEILEWESRV TQYERDFERI STVVRKEVIR
FEKEKSKDFK NHVIKYLETL LYSQQQLAKY WEAFLPEAKA IS
//
ID SNX1_HUMAN Reviewed; 522 AA.
AC Q13596; A6NM19; A8K6T7; H0Y2M5; O60750; O60751; Q6ZRJ8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 16-NOV-2001, sequence version 3.
DT 22-JAN-2014, entry version 127.
DE RecName: Full=Sorting nexin-1;
GN Name=SNX1;
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=8638121; DOI=10.1126/science.272.5264.1008;
RA Kurten R.C., Cadena D.L., Gill G.N.;
RT "Enhanced degradation of EGF receptors by a sorting nexin, SNX1.";
RL Science 272:1008-1010(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND INTERACTION WITH
RP VPS26A; VPS29; VPS35 AND SNX2.
RX PubMed=9819414;
RA Haft C.R., de la Luz Sierra M., Barr V.A., Haft D.H., Taylor S.I.;
RT "Identification of a family of sorting nexin molecules and
RT characterization of their association with receptors.";
RL Mol. Cell. Biol. 18:7278-7287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [8]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-214, AND
RP INTERACTION WITH PHOSPHATIDYLINOSITIDES.
RX PubMed=12198132; DOI=10.1074/jbc.M206986200;
RA Cozier G.E., Carlton J., McGregor A.H., Gleeson P.A., Teasdale R.D.,
RA Mellor H., Cullen P.J.;
RT "The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated
RT association of sorting nexin-1 with an early sorting endosomal
RT compartment is required for its ability to regulate epidermal growth
RT factor receptor degradation.";
RL J. Biol. Chem. 277:48730-48736(2002).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SNX2.
RX PubMed=11997453; DOI=10.1073/pnas.092142699;
RA Zhong Q., Lazar C.S., Tronchere H., Sato T., Meerloo T., Yeo M.,
RA Songyang Z., Emr S.D., Gill G.N.;
RT "Endosomal localization and function of sorting nexin 1.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:6767-6772(2002).
RN [10]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-214
RP AND 429-LYS--ARG-431.
RX PubMed=15498486; DOI=10.1016/j.cub.2004.09.077;
RA Carlton J., Bujny M., Peter B.J., Oorschot V.M., Rutherford A.,
RA Mellor H., Klumperman J., McMahon H.T., Cullen P.J.;
RT "Sorting nexin-1 mediates tubular endosome-to-TGN transport through
RT coincidence sensing of high- curvature membranes and 3-
RT phosphoinositides.";
RL Curr. Biol. 14:1791-1800(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=17101778; DOI=10.1128/MCB.00156-06;
RA Rojas R., Kametaka S., Haft C.R., Bonifacino J.S.;
RT "Interchangeable but essential functions of SNX1 and SNX2 in the
RT association of retromer with endosomes and the trafficking of mannose
RT 6-phosphate receptors.";
RL Mol. Cell. Biol. 27:1112-1124(2007).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-32; SER-39 AND SER-188,
RP AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP INTERACTION WITH SNX6.
RX PubMed=19935774; DOI=10.1038/cr.2009.130;
RA Hong Z., Yang Y., Zhang C., Niu Y., Li K., Zhao X., Liu J.J.;
RT "The retromer component SNX6 interacts with dynactin p150(Glued) and
RT mediates endosome-to-TGN transport.";
RL Cell Res. 19:1334-1349(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-237, 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 [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
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 [19]
RP STRUCTURE BY NMR OF 142-269, AND SUBCELLULAR LOCATION.
RX PubMed=15673616; DOI=10.1091/mbc.E04-06-0504;
RA Zhong Q., Watson M.J., Lazar C.S., Hounslow A.M., Waltho J.P.,
RA Gill G.N.;
RT "Determinants of the endosomal localization of sorting nexin 1.";
RL Mol. Biol. Cell 16:2049-2057(2005).
CC -!- FUNCTION: May be involved in several stages of intracellular
CC trafficking. Plays a role in targeting ligand-activated EGFR to
CC the lysosomes for degradation after endocytosis from the cell
CC surface and release from the Golgi. Component of the retromer
CC complex, a complex required to retrieve lysosomal enzyme receptors
CC (IGF2R and M6PR) from endosomes to the trans-Golgi network.
CC Interacts with membranes containing phosphatidylinositol 3-
CC phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate
CC (PtdIns(3,5)P2).
CC -!- SUBUNIT: Homodimer. Self-assembles into a complex of approximately
CC 300 kDa (By similarity). Interacts with HGS (By similarity).
CC Component of the retromer complex composed of VPS26 (VPS26A or
CC VPS26B), VPS29, VPS35, SNX1 and SNX2. Interacts with SNX6.
CC -!- SUBCELLULAR LOCATION: Endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side. Golgi apparatus, trans-Golgi network
CC membrane; Peripheral membrane protein; Cytoplasmic side
CC (Potential). Early endosome membrane; Peripheral membrane protein;
CC Cytoplasmic side. Note=Enriched on tubular elements of the early
CC endosome membrane. Binds preferentially to highly curved membranes
CC enriched in phosphatidylinositol 3-phosphate (PtdIns(3P)) or
CC phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q13596-1; Sequence=Displayed;
CC Name=1A;
CC IsoId=Q13596-2; Sequence=VSP_006189;
CC Name=3;
CC IsoId=Q13596-3; Sequence=VSP_044823;
CC Note=No experimental confirmation available;
CC -!- MISCELLANEOUS: Binds phosphatidylinositol 3-phosphate (PtdIns-
CC (3)P) and phosphatidylinositol 3,5-bisphosphate (PtdIns-(3,5)P2)
CC in liposome-based assays. Can bind PtdIns(3,4,5)P3 in
CC protein:lipid overlay assays, but not in liposome-based assays.
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 BAR domain.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
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DR EMBL; U53225; AAA98672.1; -; mRNA.
DR EMBL; AF065483; AAC17182.1; -; mRNA.
DR EMBL; AF065484; AAC17183.1; -; mRNA.
DR EMBL; BT006983; AAP35629.1; -; mRNA.
DR EMBL; AK128179; BAC87312.1; -; mRNA.
DR EMBL; AK291752; BAF84441.1; -; mRNA.
DR EMBL; AC021541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC100840; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77663.1; -; Genomic_DNA.
DR EMBL; CH471082; EAW77665.1; -; Genomic_DNA.
DR EMBL; BC000357; AAH00357.1; -; mRNA.
DR PIR; G02522; G02522.
DR RefSeq; NP_001229862.1; NM_001242933.1.
DR RefSeq; NP_003090.2; NM_003099.4.
DR RefSeq; NP_683758.1; NM_148955.3.
DR UniGene; Hs.188634; -.
DR PDB; 2I4K; NMR; -; A=142-269.
DR PDB; 4FZS; X-ray; 2.80 A; A/B=301-522.
DR PDBsum; 2I4K; -.
DR PDBsum; 4FZS; -.
DR ProteinModelPortal; Q13596; -.
DR SMR; Q13596; 142-269.
DR DIP; DIP-398N; -.
DR IntAct; Q13596; 10.
DR MINT; MINT-4135098; -.
DR STRING; 9606.ENSP00000369638; -.
DR PhosphoSite; Q13596; -.
DR DMDM; 17380569; -.
DR PaxDb; Q13596; -.
DR PRIDE; Q13596; -.
DR DNASU; 6642; -.
DR Ensembl; ENST00000261889; ENSP00000261889; ENSG00000028528.
DR Ensembl; ENST00000559844; ENSP00000453785; ENSG00000028528.
DR Ensembl; ENST00000561026; ENSP00000453567; ENSG00000028528.
DR GeneID; 6642; -.
DR KEGG; hsa:6642; -.
DR UCSC; uc010uio.2; human.
DR CTD; 6642; -.
DR GeneCards; GC15P064875; -.
DR HGNC; HGNC:11172; SNX1.
DR HPA; HPA047373; -.
DR MIM; 601272; gene.
DR neXtProt; NX_Q13596; -.
DR PharmGKB; PA36011; -.
DR eggNOG; COG5391; -.
DR HOVERGEN; HBG000618; -.
DR InParanoid; Q13596; -.
DR OMA; PQPTYEE; -.
DR OrthoDB; EOG7HHWSB; -.
DR ChiTaRS; SNX1; human.
DR EvolutionaryTrace; Q13596; -.
DR GeneWiki; SNX1; -.
DR GenomeRNAi; 6642; -.
DR NextBio; 25881; -.
DR PRO; PR:Q13596; -.
DR ArrayExpress; Q13596; -.
DR Bgee; Q13596; -.
DR CleanEx; HS_SNX1; -.
DR Genevestigator; Q13596; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0008565; F:protein transporter activity; IEA:InterPro.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0034498; P:early endosome to Golgi transport; IMP:UniProtKB.
DR GO; GO:0006897; P:endocytosis; TAS:ProtInc.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IEA:Ensembl.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR005329; Sorting_nexin_N.
DR InterPro; IPR015404; Vps5_C.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF03700; Sorting_nexin; 1.
DR Pfam; PF09325; Vps5; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS51021; BAR; FALSE_NEG.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Endosome; Golgi apparatus; Lipid-binding; Membrane; Phosphoprotein;
KW Polymorphism; Protein transport; Reference proteome; Transport.
FT CHAIN 1 522 Sorting nexin-1.
FT /FTId=PRO_0000213835.
FT DOMAIN 143 272 PX.
FT DOMAIN 302 522 BAR.
FT BINDING 186 186 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT BINDING 188 188 Phosphatidylinositol 3-phosphate; via
FT amide nitrogen and carbonyl oxygen (By
FT similarity).
FT BINDING 214 214 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT BINDING 238 238 Phosphatidylinositol 3-phosphate (By
FT similarity).
FT MOD_RES 32 32 Phosphoserine.
FT MOD_RES 39 39 Phosphoserine.
FT MOD_RES 188 188 Phosphoserine.
FT MOD_RES 237 237 N6-acetyllysine.
FT VAR_SEQ 91 155 Missing (in isoform 1A).
FT /FTId=VSP_006189.
FT VAR_SEQ 507 522 LAKYWEAFLPEAKAIS -> AGEQLGIRSGILLTKKLPRYS
FT KFFSTVHKFCAAASLWKWGFFLSAYLSYLF (in
FT isoform 3).
FT /FTId=VSP_044823.
FT VARIANT 115 115 S -> Y (in dbSNP:rs1049501).
FT /FTId=VAR_052477.
FT VARIANT 466 466 D -> N (in dbSNP:rs1802376).
FT /FTId=VAR_034507.
FT MUTAGEN 214 214 K->A: Abolishes phosphatidylinositol
FT phosphate binding. Abolishes endosomal
FT location.
FT MUTAGEN 429 431 KKR->EEE: Loss of endosomal location.
FT CONFLICT 117 117 P -> S (in Ref. 2; AAC17182).
FT CONFLICT 211 211 P -> S (in Ref. 2; AAC17182/AAC17183).
FT CONFLICT 502 502 Y -> C (in Ref. 4; BAC87312).
FT STRAND 173 176
FT HELIX 187 199
FT STRAND 202 205
FT STRAND 210 213
FT STRAND 216 221
FT HELIX 234 251
FT HELIX 253 256
FT HELIX 259 262
FT TURN 263 266
FT HELIX 307 356
FT HELIX 361 385
FT HELIX 388 440
FT HELIX 443 483
FT TURN 484 487
FT HELIX 489 511
SQ SEQUENCE 522 AA; 59070 MW; 6AC8AA0A589513E3 CRC64;
MASGGGGCSA SERLPPPFPG LEPESEGAAG GSEPEAGDSD TEGEDIFTGA AVVSKHQSPK
ITTSLLPINN GSKENGIHEE QDQEPQDLFA DATVELSLDS TQNNQKKVLA KTLISLPPQE
ATNSSKPQPT YEELEEEEQE DQFDLTVGIT DPEKIGDGMN AYVAYKVTTQ TSLPLFRSKQ
FAVKRRFSDF LGLYEKLSEK HSQNGFIVPP PPEKSLIGMT KVKVGKEDSS SAEFLEKRRA
ALERYLQRIV NHPTMLQDPD VREFLEKEEL PRAVGTQTLS GAGLLKMFNK ATDAVSKMTI
KMNESDIWFE EKLQEVECEE QRLRKLHAVV ETLVNHRKEL ALNTAQFAKS LAMLGSSEDN
TALSRALSQL AEVEEKIEQL HQEQANNDFF LLAELLSDYI RLLAIVRAAF DQRMKTWQRW
QDAQATLQKK REAEARLLWA NKPDKLQQAK DEILEWESRV TQYERDFERI STVVRKEVIR
FEKEKSKDFK NHVIKYLETL LYSQQQLAKY WEAFLPEAKA IS
//
MIM
601272
*RECORD*
*FIELD* NO
601272
*FIELD* TI
*601272 SORTING NEXIN 1; SNX1
SORTING NEXIN 1A, INCLUDED; SNX1A, INCLUDED
*FIELD* TX
read more
DESCRIPTION
SNX1 is a member of the sorting nexin family of molecules that contain
an approximately 100-amino acid region termed the phox homology (PX)
domain (Haft et al., 1998).
CLONING
Kurten et al. (1996) described a protein, designated sorting nexin-1,
that plays a role in targeting ligand-activated EGFR (131550) to the
lysosomes for degradation after endocytosis from the cell surface and
release from the Golgi. Kurten et al. (1996) isolated a cDNA encoding
the COOH-terminal 58 amino acids of SNX1 from a HeLa cDNA library in a
yeast 2-hybrid system, using the core tyrosine kinase domain of EGFR. A
1,974-bp SNX1 cDNA was then assembled from full-length and partial cDNA
clones from a HeLa cell cDNA library. They identified a human EST that
was 70% identical to SNX1, suggesting that SNX1 defines a family of
molecules.
By EST database searching with the human SNX1 sequence, Haft et al.
(1998) isolated a putative splice variant isoform of SNX1, which they
designated SNX1A. The major difference between SNX1 and SNX1A is a
deletion of 195 nucleotides that results in an in-frame deletion of 65
amino acids; thus, SNX1A cDNA is predicted to encode a 457-amino acid
hydrophilic protein. By PCR, the authors confirmed the presence of both
SNX1 and SNX1A mRNAs in multiple tissues. Northern blot analysis showed
that human SNX1/1A mRNAs are ubiquitously expressed, with highest levels
in the medulla oblongata, prostate, spinal cord, spleen, pancreas, and
pituitary gland.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX1
gene to chromosome 15 (TMAP stSG27380).
GENE FUNCTION
Kurten et al. (1996) demonstrated that overexpression of SNX1
downregulated endogenous EGFR in CV-1 cells that were stably transfected
with SNX1. They also demonstrated that the turnover of cell surface
receptors in these SNX1 overexpressing cells was enhanced by EGF
(131530) treatment and required an active kinase.
By Western blot analysis, Haft et al. (1998) showed that SNX1, SNX1A,
SNX2 (605929), and SNX4 (605931) are associated predominantly with
membranes, whereas SNX3 (605930) is found mainly in the cytosol. SNX2
forms heteromeric complexes with SNX1, SNX1A, and SNX4, but not with
SNX3. When expressed in COS-7 cells, epitope-tagged SNX1, SNX1A, SNX2,
and SNX4 coimmunoprecipitated with receptor tyrosine kinases for EGF,
platelet-derived growth factor (see 173490), and insulin (147670). They
also associated with the long isoform of the leptin receptor (601007)
but not with the short and medium isoforms. Only SNX1 and SNX1A
coimmunoprecipitated with endogenous transferrin receptors (see 190010).
Based on the functions of their yeast homologs, Haft et al. (1998)
suggested that mammalian sorting nexins function in intracellular
trafficking of proteins to various organelles.
Zhong et al. (2002) demonstrated that SNX1 and SNX2 are colocalized to
tubulovesicular endosomal membranes and that this localization depends
on PI3K (see 171834). Point mutations in the PX domain that abolish
recognition of phosphorylated phosphatidylinositol in vitro abolished
vesicle localization in vivo, indicating that lipid binding by the PX
domain is necessary for localization to vesicle membranes.
The cell surface receptor CED1 (107770) mediates apoptotic cell
recognition by phagocytic cells, enabling cell corpse clearance in C.
elegans. Chen et al. (2010) found that the C. elegans intracellular
protein sorting complex, retromer, was required for cell corpse
clearance by mediating the recycling of CED1. The mammalian retromer
complex contains sorting nexins 1 and 2 (C. elegans homolog snx1) and
5/6 (605937, 606098) (C. elegans homolog snx6). Retromer was recruited
to the surfaces of phagosomes containing cell corpses, and its loss of
function caused defective cell corpse removal. The retromer probably
acted through direct interaction with CED1 in the cell corpse
recognition pathway. In the absence of retromer function, CED1
associated with lysosomes and failed to recycle from phagosomes and
cytosol to the plasma membrane. Thus, Chen et al. (2010) concluded that
retromer is an essential mediator of apoptotic cell clearance by
regulating phagocytic receptor(s) during cell corpse engulfment.
*FIELD* RF
1. Chen, D.; Xiao, H.; Zhang, K.; Wang, B.; Gao, Z.; Jian, Y.; Qi,
X.; Sun, J.; Miao, L.; Yang, C.: Retromer is required for apoptotic
cell clearance by phagocytic receptor recycling. Science 327: 1261-1264,
2010.
2. Haft, C. R.; de la Luz Sierra, M.; Barr, V. A.; Haft, D. H.; Taylor,
S. I.: Identification of a family of sorting nexin molecules and
characterization of their association with receptors. Molec. Cell.
Biol. 18: 7278-7287, 1998.
3. Kurten, R. C.; Cadena, D. L.; Gill, G. N.: Enhanced degradation
of EGF receptors by a sorting nexin, SNX1. Science 272: 1008-1010,
1996.
4. Zhong, Q.; Lazar, C. S.; Tronchere, H.; Sato, T.; Meerloo, T.;
Yeo, M.; Songyang, Z.; Emr, S. D.; Gill, G. N.: Endosomal localization
and function of sorting nexin 1. Proc. Nat. Acad. Sci. 99: 6767-6772,
2002.
*FIELD* CN
Ada Hamosh - updated: 4/22/2010
Victor A. McKusick - updated: 6/14/2002
Carol A. Bocchini - updated: 5/16/2001
*FIELD* CD
Moyra Smith: 5/21/1996
*FIELD* ED
alopez: 04/26/2010
terry: 4/22/2010
carol: 10/19/2009
cwells: 6/27/2002
terry: 6/14/2002
mcapotos: 5/16/2001
carol: 5/15/2001
carol: 9/9/1998
dkim: 9/9/1998
carol: 7/17/1996
mark: 5/28/1996
carol: 5/22/1996
*RECORD*
*FIELD* NO
601272
*FIELD* TI
*601272 SORTING NEXIN 1; SNX1
SORTING NEXIN 1A, INCLUDED; SNX1A, INCLUDED
*FIELD* TX
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DESCRIPTION
SNX1 is a member of the sorting nexin family of molecules that contain
an approximately 100-amino acid region termed the phox homology (PX)
domain (Haft et al., 1998).
CLONING
Kurten et al. (1996) described a protein, designated sorting nexin-1,
that plays a role in targeting ligand-activated EGFR (131550) to the
lysosomes for degradation after endocytosis from the cell surface and
release from the Golgi. Kurten et al. (1996) isolated a cDNA encoding
the COOH-terminal 58 amino acids of SNX1 from a HeLa cDNA library in a
yeast 2-hybrid system, using the core tyrosine kinase domain of EGFR. A
1,974-bp SNX1 cDNA was then assembled from full-length and partial cDNA
clones from a HeLa cell cDNA library. They identified a human EST that
was 70% identical to SNX1, suggesting that SNX1 defines a family of
molecules.
By EST database searching with the human SNX1 sequence, Haft et al.
(1998) isolated a putative splice variant isoform of SNX1, which they
designated SNX1A. The major difference between SNX1 and SNX1A is a
deletion of 195 nucleotides that results in an in-frame deletion of 65
amino acids; thus, SNX1A cDNA is predicted to encode a 457-amino acid
hydrophilic protein. By PCR, the authors confirmed the presence of both
SNX1 and SNX1A mRNAs in multiple tissues. Northern blot analysis showed
that human SNX1/1A mRNAs are ubiquitously expressed, with highest levels
in the medulla oblongata, prostate, spinal cord, spleen, pancreas, and
pituitary gland.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX1
gene to chromosome 15 (TMAP stSG27380).
GENE FUNCTION
Kurten et al. (1996) demonstrated that overexpression of SNX1
downregulated endogenous EGFR in CV-1 cells that were stably transfected
with SNX1. They also demonstrated that the turnover of cell surface
receptors in these SNX1 overexpressing cells was enhanced by EGF
(131530) treatment and required an active kinase.
By Western blot analysis, Haft et al. (1998) showed that SNX1, SNX1A,
SNX2 (605929), and SNX4 (605931) are associated predominantly with
membranes, whereas SNX3 (605930) is found mainly in the cytosol. SNX2
forms heteromeric complexes with SNX1, SNX1A, and SNX4, but not with
SNX3. When expressed in COS-7 cells, epitope-tagged SNX1, SNX1A, SNX2,
and SNX4 coimmunoprecipitated with receptor tyrosine kinases for EGF,
platelet-derived growth factor (see 173490), and insulin (147670). They
also associated with the long isoform of the leptin receptor (601007)
but not with the short and medium isoforms. Only SNX1 and SNX1A
coimmunoprecipitated with endogenous transferrin receptors (see 190010).
Based on the functions of their yeast homologs, Haft et al. (1998)
suggested that mammalian sorting nexins function in intracellular
trafficking of proteins to various organelles.
Zhong et al. (2002) demonstrated that SNX1 and SNX2 are colocalized to
tubulovesicular endosomal membranes and that this localization depends
on PI3K (see 171834). Point mutations in the PX domain that abolish
recognition of phosphorylated phosphatidylinositol in vitro abolished
vesicle localization in vivo, indicating that lipid binding by the PX
domain is necessary for localization to vesicle membranes.
The cell surface receptor CED1 (107770) mediates apoptotic cell
recognition by phagocytic cells, enabling cell corpse clearance in C.
elegans. Chen et al. (2010) found that the C. elegans intracellular
protein sorting complex, retromer, was required for cell corpse
clearance by mediating the recycling of CED1. The mammalian retromer
complex contains sorting nexins 1 and 2 (C. elegans homolog snx1) and
5/6 (605937, 606098) (C. elegans homolog snx6). Retromer was recruited
to the surfaces of phagosomes containing cell corpses, and its loss of
function caused defective cell corpse removal. The retromer probably
acted through direct interaction with CED1 in the cell corpse
recognition pathway. In the absence of retromer function, CED1
associated with lysosomes and failed to recycle from phagosomes and
cytosol to the plasma membrane. Thus, Chen et al. (2010) concluded that
retromer is an essential mediator of apoptotic cell clearance by
regulating phagocytic receptor(s) during cell corpse engulfment.
*FIELD* RF
1. Chen, D.; Xiao, H.; Zhang, K.; Wang, B.; Gao, Z.; Jian, Y.; Qi,
X.; Sun, J.; Miao, L.; Yang, C.: Retromer is required for apoptotic
cell clearance by phagocytic receptor recycling. Science 327: 1261-1264,
2010.
2. Haft, C. R.; de la Luz Sierra, M.; Barr, V. A.; Haft, D. H.; Taylor,
S. I.: Identification of a family of sorting nexin molecules and
characterization of their association with receptors. Molec. Cell.
Biol. 18: 7278-7287, 1998.
3. Kurten, R. C.; Cadena, D. L.; Gill, G. N.: Enhanced degradation
of EGF receptors by a sorting nexin, SNX1. Science 272: 1008-1010,
1996.
4. Zhong, Q.; Lazar, C. S.; Tronchere, H.; Sato, T.; Meerloo, T.;
Yeo, M.; Songyang, Z.; Emr, S. D.; Gill, G. N.: Endosomal localization
and function of sorting nexin 1. Proc. Nat. Acad. Sci. 99: 6767-6772,
2002.
*FIELD* CN
Ada Hamosh - updated: 4/22/2010
Victor A. McKusick - updated: 6/14/2002
Carol A. Bocchini - updated: 5/16/2001
*FIELD* CD
Moyra Smith: 5/21/1996
*FIELD* ED
alopez: 04/26/2010
terry: 4/22/2010
carol: 10/19/2009
cwells: 6/27/2002
terry: 6/14/2002
mcapotos: 5/16/2001
carol: 5/15/2001
carol: 9/9/1998
dkim: 9/9/1998
carol: 7/17/1996
mark: 5/28/1996
carol: 5/22/1996