SNX2_HUMAN
ID SNX2_HUMAN Reviewed; 519 AA.
AC O60749; B3KN44; B4DEK4; B7Z408; O43650; P82862; Q53XK8; Q597H6; Q9BTS8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Sorting nexin-2;
DE AltName: Full=Transformation-related gene 9 protein;
DE Short=TRG-9;
GN Name=SNX2; ORFNames=TRG9;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RA Kurten R.C., Leychkis Y., Wiley H.S., Gill G.N.;
RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBUNIT.
RX PubMed=9819414; DOI=10.1128/mcb.18.12.7278;
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 characterization
RT of their association with receptors.";
RL Mol. Cell. Biol. 18:7278-7287(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kim J.W.;
RT "Identification of a human transforming gene.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Cerebellum, Colon, and Placenta;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP SUBUNIT.
RX PubMed=11102511; DOI=10.1091/mbc.11.12.4105;
RA Renfrew Haft C., de la Luz Sierra M., Bafford R., Lesniak M.A., Barr V.A.,
RA Taylor S.I.;
RT "Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and
RT 35: assembly into multimeric complexes.";
RL Mol. Biol. Cell 11:4105-4116(2000).
RN [10]
RP INTERACTION WITH FNBP1.
RX PubMed=11438682; DOI=10.1073/pnas.121433898;
RA Fuchs U., Rehkamp G.F., Haas O.A., Slany R., Koenig M., Bojesen S.,
RA Bohle R.M., Damm-Welk C., Ludwig W.-D., Harbott J., Borkhardt A.;
RT "The human formin-binding protein 17 (FBP17) interacts with sorting nexin,
RT SNX2, and is an MLL-fusion partner in acute myelogeneous leukemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:8756-8761(2001).
RN [11]
RP INTERACTION WITH FNBP1.
RX PubMed=14596906; DOI=10.1016/s0014-5793(03)01063-9;
RA Fuchs U., Rehkamp G.F., Slany R., Follo M., Borkhardt A.;
RT "The formin-binding protein 17, FBP17, binds via a TNKS binding motif to
RT tankyrase, a protein involved in telomere maintenance.";
RL FEBS Lett. 554:10-16(2003).
RN [12]
RP FUNCTION, MUTAGENESIS OF LYS-211, AND SUBCELLULAR LOCATION.
RX PubMed=16179610; DOI=10.1242/jcs.02568;
RA Carlton J.G., Bujny M.V., Peter B.J., Oorschot V.M., Rutherford A.,
RA Arkell R.S., Klumperman J., McMahon H.T., Cullen P.J.;
RT "Sorting nexin-2 is associated with tubular elements of the early endosome,
RT but is not essential for retromer-mediated endosome-to-TGN transport.";
RL J. Cell Sci. 118:4527-4539(2005).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
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 6-
RT phosphate receptors.";
RL Mol. Cell. Biol. 27:1112-1124(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119 AND SER-185, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [16]
RP SUBCELLULAR LOCATION.
RX PubMed=18088323; DOI=10.1111/j.1600-0854.2007.00686.x;
RA Mari M., Bujny M.V., Zeuschner D., Geerts W.J., Griffith J., Petersen C.M.,
RA Cullen P.J., Klumperman J., Geuze H.J.;
RT "SNX1 defines an early endosomal recycling exit for sortilin and mannose 6-
RT phosphate receptors.";
RL Traffic 9:380-393(2008).
RN [17]
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 [18]
RP INTERACTION WITH SNX5; SNX6; VPS26A; VPS29 AND VPS35.
RX PubMed=19619496; DOI=10.1016/j.devcel.2009.04.016;
RA Wassmer T., Attar N., Harterink M., van Weering J.R., Traer C.J.,
RA Oakley J., Goud B., Stephens D.J., Verkade P., Korswagen H.C., Cullen P.J.;
RT "The retromer coat complex coordinates endosomal sorting and dynein-
RT mediated transport, with carrier recognition by the trans-Golgi network.";
RL Dev. Cell 17:110-122(2009).
RN [19]
RP DOMAIN.
RX PubMed=19816406; DOI=10.1038/emboj.2009.261;
RA Bhatia V.K., Madsen K.L., Bolinger P.Y., Kunding A., Hedegaard P.,
RA Gether U., Stamou D.;
RT "Amphipathic motifs in BAR domains are essential for membrane curvature
RT sensing.";
RL EMBO J. 28:3303-3314(2009).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-469, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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 [22]
RP FUNCTION.
RX PubMed=20138391; DOI=10.1016/j.ejcb.2009.10.021;
RA Lieu Z.Z., Gleeson P.A.;
RT "Identification of different itineraries and retromer components for
RT endosome-to-Golgi transport of TGN38 and Shiga toxin.";
RL Eur. J. Cell Biol. 89:379-393(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-277, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [24]
RP FUNCTION, INTERACTION WITH KALRN AND RHOG, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 182-ARG--PHE-184; LYS-426 AND ARG-428.
RX PubMed=20604901; DOI=10.1111/j.1600-0854.2010.01100.x;
RA Prosser D.C., Tran D., Schooley A., Wendland B., Ngsee J.K.;
RT "A novel, retromer-independent role for sorting nexins 1 and 2 in RhoG-
RT dependent membrane remodeling.";
RL Traffic 11:1347-1362(2010).
RN [25]
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., Buerckstuemmer T.,
RA 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 [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP FUNCTION, INTERACTION WITH SNX5; SNX6 AND SNX32, SELF-ASSOCIATION, AND
RP DOMAIN.
RX PubMed=23085988; DOI=10.1038/emboj.2012.283;
RA van Weering J.R., Sessions R.B., Traer C.J., Kloer D.P., Bhatia V.K.,
RA Stamou D., Carlsson S.R., Hurley J.H., Cullen P.J.;
RT "Molecular basis for SNX-BAR-mediated assembly of distinct endosomal
RT sorting tubules.";
RL EMBO J. 31:4466-4480(2012).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-119; SER-185 AND
RP SER-277, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-101; THR-104; SER-185 AND
RP SER-277, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes containing phosphatidylinositol 3-phosphate
CC (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)
CC (PubMed:16179610). Acts in part as component of the retromer membrane-
CC deforming SNX-BAR subcomplex (PubMed:17101778). The SNX-BAR retromer
CC mediates retrograde transport of cargo proteins from endosomes to the
CC trans-Golgi network (TGN) and is involved in endosome-to-plasma
CC membrane transport for cargo protein recycling. The SNX-BAR subcomplex
CC functions to deform the donor membrane into a tubular profile called
CC endosome-to-TGN transport carrier (ETC) (Probable). Can sense membrane
CC curvature and has in vitro vesicle-to-membrane remodeling activity
CC (PubMed:23085988). Required for retrograde endosome-to-TGN transport of
CC TGN38 (PubMed:20138391). Promotes KALRN- and RHOG-dependent but
CC retromer-independent membrane remodeling such as lamellipodium
CC formation; the function is dependent on GEF activity of KALRN
CC (PubMed:20604901). {ECO:0000269|PubMed:16179610,
CC ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:20138391,
CC ECO:0000269|PubMed:20604901, ECO:0000269|PubMed:23085988,
CC ECO:0000303|PubMed:16179610}.
CC -!- SUBUNIT: Predominantly forms heterodimers with BAR domain-containing
CC sorting nexins SNX5, SNX6 and SNX32; can self-associate to form
CC homodimers (PubMed:23085988). The heterodimers are proposed to self-
CC assemble into helical arrays on the membrane to stabilize and expand
CC local membrane curvature underlying endosomal tubule formation. Thought
CC to be a component of the originally described retromer complex (also
CC called SNX-BAR retromer) which is a pentamer containing the
CC heterotrimeric retromer cargo-selective complex (CSC), also described
CC as vacuolar protein sorting subcomplex (VPS), and a heterodimeric
CC membrane-deforming subcomplex formed between SNX1 or SNX2 and SNX5 or
CC SNX6 (also called SNX-BAR subcomplex); the respective CSC and SNX-BAR
CC subcomplexes associate with low affinity (Probable). Interacts with
CC SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35, FNBP1, KALRN, RHOG (GDP-bound
CC form) (PubMed:11438682, PubMed:14596906, PubMed:17101778,
CC PubMed:19935774., PubMed:19619496, PubMed:20604901, PubMed:23085988).
CC {ECO:0000269|PubMed:11438682, ECO:0000269|PubMed:14596906,
CC ECO:0000269|PubMed:17101778, ECO:0000269|PubMed:19619496,
CC ECO:0000269|PubMed:19935774, ECO:0000269|PubMed:20604901,
CC ECO:0000269|PubMed:23085988, ECO:0000303|PubMed:11102511,
CC ECO:0000303|PubMed:19619496, ECO:0000303|PubMed:9819414}.
CC -!- INTERACTION:
CC O60749; P05067: APP; NbExp=3; IntAct=EBI-1046690, EBI-77613;
CC O60749; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-1046690, EBI-714543;
CC O60749; Q7L2Z9: CENPQ; NbExp=3; IntAct=EBI-1046690, EBI-2350265;
CC O60749; P50570-2: DNM2; NbExp=3; IntAct=EBI-1046690, EBI-10968534;
CC O60749; Q96RU3: FNBP1; NbExp=4; IntAct=EBI-1046690, EBI-1111248;
CC O60749; Q8TB36: GDAP1; NbExp=3; IntAct=EBI-1046690, EBI-11110431;
CC O60749; P42858: HTT; NbExp=6; IntAct=EBI-1046690, EBI-466029;
CC O60749; Q9H2K0: MTIF3; NbExp=3; IntAct=EBI-1046690, EBI-3923617;
CC O60749; O60664: PLIN3; NbExp=3; IntAct=EBI-1046690, EBI-725795;
CC O60749; Q96T60: PNKP; NbExp=3; IntAct=EBI-1046690, EBI-1045072;
CC O60749; Q16637: SMN2; NbExp=3; IntAct=EBI-1046690, EBI-395421;
CC O60749; Q13596: SNX1; NbExp=3; IntAct=EBI-1046690, EBI-2822329;
CC O60749; Q86XE0: SNX32; NbExp=4; IntAct=EBI-1046690, EBI-8099743;
CC O60749; Q9UNH7: SNX6; NbExp=7; IntAct=EBI-1046690, EBI-949294;
CC O60749; Q8WW34-2: TMEM239; NbExp=3; IntAct=EBI-1046690, EBI-11528917;
CC O60749; O95070: YIF1A; NbExp=3; IntAct=EBI-1046690, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000269|PubMed:16179610, ECO:0000269|PubMed:17101778}; Peripheral
CC membrane protein {ECO:0000269|PubMed:16179610,
CC ECO:0000269|PubMed:17101778}; Cytoplasmic side
CC {ECO:0000269|PubMed:16179610, ECO:0000269|PubMed:17101778}. Cell
CC projection, lamellipodium {ECO:0000269|PubMed:20604901}.
CC Note=Colocalized with SORT1 to tubular endosomal membrane structures
CC called endosome-to-TGN transport carriers (ETCs) which are budding from
CC early endosome vacuoles just before maturing into late endosome
CC vacuoles (PubMed:18088323). Colocalized with F-actin at the leading
CC edge of lamellipodia in cells in a KALRN-dependent manner
CC (PubMed:20604901). {ECO:0000269|PubMed:18088323,
CC ECO:0000269|PubMed:20604901}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O60749-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O60749-2; Sequence=VSP_054785;
CC -!- DOMAIN: The BAR domain is able to sense membrane curvature upon
CC dimerization. Membrane remodeling seems to implicate insertion of a N-
CC terminal amphipathic helix (AH) in the membrane (Probable).
CC {ECO:0000303|PubMed:19816406, ECO:0000303|PubMed:23085988}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AF065482; AAC17181.1; -; mRNA.
DR EMBL; AF043453; AAB99852.1; -; mRNA.
DR EMBL; AY272044; AAQ02693.1; -; mRNA.
DR EMBL; BT009841; AAP88843.1; -; mRNA.
DR EMBL; AK023581; BAG51206.1; -; mRNA.
DR EMBL; AK293671; BAG57115.1; -; mRNA.
DR EMBL; AK296596; BAH12394.1; -; mRNA.
DR EMBL; AC008669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471086; EAW48884.1; -; Genomic_DNA.
DR EMBL; BC003382; AAH03382.1; -; mRNA.
DR CCDS; CCDS34217.1; -. [O60749-1]
DR CCDS; CCDS64234.1; -. [O60749-2]
DR RefSeq; NP_001265128.1; NM_001278199.1. [O60749-2]
DR RefSeq; NP_003091.2; NM_003100.3. [O60749-1]
DR AlphaFoldDB; O60749; -.
DR SMR; O60749; -.
DR BioGRID; 112526; 184.
DR CORUM; O60749; -.
DR IntAct; O60749; 59.
DR MINT; O60749; -.
DR STRING; 9606.ENSP00000368831; -.
DR GlyGen; O60749; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O60749; -.
DR MetOSite; O60749; -.
DR PhosphoSitePlus; O60749; -.
DR SwissPalm; O60749; -.
DR BioMuta; SNX2; -.
DR EPD; O60749; -.
DR jPOST; O60749; -.
DR MassIVE; O60749; -.
DR MaxQB; O60749; -.
DR PaxDb; O60749; -.
DR PeptideAtlas; O60749; -.
DR PRIDE; O60749; -.
DR ProteomicsDB; 3966; -.
DR ProteomicsDB; 49584; -. [O60749-1]
DR Antibodypedia; 25631; 180 antibodies from 25 providers.
DR DNASU; 6643; -.
DR Ensembl; ENST00000379516.7; ENSP00000368831.2; ENSG00000205302.7. [O60749-1]
DR Ensembl; ENST00000514949.1; ENSP00000421663.1; ENSG00000205302.7. [O60749-2]
DR GeneID; 6643; -.
DR KEGG; hsa:6643; -.
DR MANE-Select; ENST00000379516.7; ENSP00000368831.2; NM_003100.4; NP_003091.2.
DR UCSC; uc003kte.5; human. [O60749-1]
DR CTD; 6643; -.
DR DisGeNET; 6643; -.
DR GeneCards; SNX2; -.
DR HGNC; HGNC:11173; SNX2.
DR HPA; ENSG00000205302; Low tissue specificity.
DR MIM; 605929; gene.
DR neXtProt; NX_O60749; -.
DR OpenTargets; ENSG00000205302; -.
DR PharmGKB; PA36012; -.
DR VEuPathDB; HostDB:ENSG00000205302; -.
DR eggNOG; KOG2273; Eukaryota.
DR GeneTree; ENSGT00940000155798; -.
DR HOGENOM; CLU_022783_2_1_1; -.
DR InParanoid; O60749; -.
DR OMA; TWLESAI; -.
DR OrthoDB; 947320at2759; -.
DR PhylomeDB; O60749; -.
DR TreeFam; TF313698; -.
DR PathwayCommons; O60749; -.
DR Reactome; R-HSA-432722; Golgi Associated Vesicle Biogenesis.
DR SignaLink; O60749; -.
DR BioGRID-ORCS; 6643; 7 hits in 1080 CRISPR screens.
DR ChiTaRS; SNX2; human.
DR GeneWiki; SNX2; -.
DR GenomeRNAi; 6643; -.
DR Pharos; O60749; Tbio.
DR PRO; PR:O60749; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O60749; protein.
DR Bgee; ENSG00000205302; Expressed in monocyte and 203 other tissues.
DR ExpressionAtlas; O60749; baseline and differential.
DR Genevisible; O60749; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:HPA.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:HPA.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0030904; C:retromer complex; IDA:UniProtKB.
DR GO; GO:0030905; C:retromer, tubulation complex; IPI:ParkinsonsUK-UCL.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; IDA:UniProtKB.
DR GO; GO:1990460; F:leptin receptor binding; IDA:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:ParkinsonsUK-UCL.
DR GO; GO:1990459; F:transferrin receptor binding; IDA:UniProtKB.
DR GO; GO:0034498; P:early endosome to Golgi transport; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0072673; P:lamellipodium morphogenesis; IDA:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR CDD; cd07282; PX_SNX2; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR001683; PX_dom.
DR InterPro; IPR036871; PX_dom_sf.
DR InterPro; IPR028653; SNX2.
DR InterPro; IPR037918; SNX2_PX.
DR InterPro; IPR005329; Sorting_nexin_N.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR10555:SF31; PTHR10555:SF31; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF03700; Sorting_nexin; 1.
DR Pfam; PF09325; Vps5; 1.
DR SMART; SM00312; PX; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cell projection; Endosome;
KW Lipid-binding; Membrane; Phosphoprotein; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..519
FT /note="Sorting nexin-2"
FT /id="PRO_0000213838"
FT DOMAIN 140..269
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 299..519
FT /note="BAR"
FT /evidence="ECO:0000250|UniProtKB:Q13596"
FT REGION 1..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..519
FT /note="Interaction with RhoG"
FT /evidence="ECO:0000269|PubMed:20604901"
FT REGION 278..295
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000303|PubMed:19816406"
FT COMPBIAS 27..60
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 183
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 185
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 211
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT BINDING 235
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3-phosphate)"
FT /ligand_id="ChEBI:CHEBI:58088"
FT /evidence="ECO:0000250|UniProtKB:Q96L94"
FT MOD_RES 97
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9CWK8"
FT MOD_RES 101
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 104
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..117
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054785"
FT MUTAGEN 182..184
FT /note="RRF->AAA: Decreases KALRN-dependent lamellipodium
FT formation; no effect on interaction with KALRN."
FT /evidence="ECO:0000269|PubMed:20604901"
FT MUTAGEN 211
FT /note="K->A: Abolishes phosphatidylinositol phosphate
FT binding. Abolishes endosomal location."
FT /evidence="ECO:0000269|PubMed:16179610"
FT MUTAGEN 426
FT /note="K->A: Decreases KALRN-dependent lamellipodium
FT formation; no effect on interaction with KALRN; when
FT associated with A-428."
FT /evidence="ECO:0000269|PubMed:20604901"
FT MUTAGEN 428
FT /note="R->A: Decreases KALRN-dependent lamellipodium
FT formation; no effect on interaction with KALRN; when
FT associated with A-426."
FT /evidence="ECO:0000269|PubMed:20604901"
FT CONFLICT 87
FT /note="E -> A (in Ref. 3; AAQ02693)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="V -> I (in Ref. 5; BAH12394)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="V -> F (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 384
FT /note="A -> S (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 58471 MW; 7DC07DFA523312B5 CRC64;
MAAEREPPPL GDGKPTDFED LEDGEDLFTS TVSTLESSPS SPEPASLPAE DISANSNGPK
PTEVVLDDDR EDLFAEATEE VSLDSPEREP ILSSEPSPAV TPVTPTTLIA PRIESKSMSA
PVIFDRSREE IEEEANGDIF DIEIGVSDPE KVGDGMNAYM AYRVTTKTSL SMFSKSEFSV
KRRFSDFLGL HSKLASKYLH VGYIVPPAPE KSIVGMTKVK VGKEDSSSTE FVEKRRAALE
RYLQRTVKHP TLLQDPDLRQ FLESSELPRA VNTQALSGAG ILRMVNKAAD AVNKMTIKMN
ESDAWFEEKQ QQFENLDQQL RKLHVSVEAL VCHRKELSAN TAAFAKSAAM LGNSEDHTAL
SRALSQLAEV EEKIDQLHQE QAFADFYMFS ELLSDYIRLI AAVKGVFDHR MKCWQKWEDA
QITLLKKREA EAKMMVANKP DKIQQAKNEI REWEAKVQQG ERDFEQISKT IRKEVGRFEK
ERVKDFKTVI IKYLESLVQT QQQLIKYWEA FLPEAKAIA
