SNX2_MOUSE
ID SNX2_MOUSE Reviewed; 519 AA.
AC Q9CWK8; Q3UKW3; Q9CQV0;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Sorting nexin-2;
GN Name=Snx2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell, Kidney, and Placenta;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=12388759; DOI=10.1091/mbc.e02-03-0145;
RA Schwarz D.G., Griffin C.T., Schneider E.A., Yee D., Magnuson T.;
RT "Genetic analysis of sorting nexins 1 and 2 reveals a redundant and
RT essential function in mice.";
RL Mol. Biol. Cell 13:3588-3600(2002).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-119, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97; THR-101; THR-104; SER-119
RP AND SER-185, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 Acts in part as component of the retromer membrane-deforming SNX-BAR
CC subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo
CC proteins from endosomes to the trans-Golgi network (TGN) and is
CC involved in endosome-to-plasma membrane transport for cargo protein
CC recycling. The SNX-BAR subcomplex functions to deform the donor
CC membrane into a tubular profile called endosome-to-TGN transport
CC carrier (ETC). Can sense membrane curvature and has in vitro vesicle-
CC to-membrane remodeling activity. Required for retrograde endosome-to-
CC TGN transport of TGN38. 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 (By
CC similarity). {ECO:0000250|UniProtKB:O60749}.
CC -!- SUBUNIT: Predominantly forms heterodimers with BAR domain-containing
CC sorting nexins SNX5, SNX6 and SNX32; can self-associate to form
CC homodimers. The heterodimers are proposed to self-assemble into helical
CC arrays on the membrane to stabilize and expand local membrane curvature
CC underlying endosomal tubule formation. Thought to be a component of the
CC originally described retromer complex (also called SNX-BAR retromer)
CC which is a pentamer containing the heterotrimeric retromer cargo-
CC selective complex (CSC), also described as vacuolar protein sorting
CC subcomplex (VPS), and a heterodimeric membrane-deforming subcomplex
CC formed between SNX1 or SNX2 and SNX5 or SNX6 (also called SNX-BAR
CC subcomplex); the respective CSC and SNX-BAR subcomplexes associate with
CC low affinity. Interacts with SNX5, SNX6, SNX32, VPS26A, VPS29, VPS35,
CC FNBP1, KALRN, RHOG (GDP-bound form) (By similarity).
CC {ECO:0000250|UniProtKB:O60749}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane; Peripheral membrane
CC protein; Cytoplasmic side {ECO:0000250|UniProtKB:O60749}. Cell
CC projection, lamellipodium. Note=Colocalized with SORT1 to tubular
CC endosomal membrane structures called endosome-to-TGN transport carriers
CC (ETCs) which are budding from early endosome vacuoles just before
CC maturing into late endosome vacuoles. Colocalized with F-actin at the
CC leading edge of lamellipodia in cells in a KALRN-dependent manner (By
CC similarity). {ECO:0000250|UniProtKB:O60749}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:O60749}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are born at the
CC expected Mendelian ratio and are fertile. Mice lacking both Snx1 and
CC Snx2 die during embryonic development, around 9.5 and 11.5 dpc.
CC {ECO:0000269|PubMed:12388759}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AK002692; BAB22287.1; -; mRNA.
DR EMBL; AK005470; BAB24060.1; -; mRNA.
DR EMBL; AK010572; BAB27035.1; -; mRNA.
DR EMBL; AK075929; BAC36060.1; -; mRNA.
DR EMBL; AK145840; BAE26688.1; -; mRNA.
DR CCDS; CCDS37821.1; -.
DR RefSeq; NP_080662.1; NM_026386.1.
DR AlphaFoldDB; Q9CWK8; -.
DR SMR; Q9CWK8; -.
DR BioGRID; 212452; 24.
DR STRING; 10090.ENSMUSP00000039243; -.
DR iPTMnet; Q9CWK8; -.
DR PhosphoSitePlus; Q9CWK8; -.
DR EPD; Q9CWK8; -.
DR jPOST; Q9CWK8; -.
DR MaxQB; Q9CWK8; -.
DR PaxDb; Q9CWK8; -.
DR PeptideAtlas; Q9CWK8; -.
DR PRIDE; Q9CWK8; -.
DR ProteomicsDB; 261543; -.
DR Antibodypedia; 25631; 180 antibodies from 25 providers.
DR DNASU; 67804; -.
DR Ensembl; ENSMUST00000037850; ENSMUSP00000039243; ENSMUSG00000034484.
DR GeneID; 67804; -.
DR KEGG; mmu:67804; -.
DR UCSC; uc008exr.1; mouse.
DR CTD; 6643; -.
DR MGI; MGI:1915054; Snx2.
DR VEuPathDB; HostDB:ENSMUSG00000034484; -.
DR eggNOG; KOG2273; Eukaryota.
DR GeneTree; ENSGT00940000155798; -.
DR HOGENOM; CLU_022783_2_1_1; -.
DR InParanoid; Q9CWK8; -.
DR OMA; TWLESAI; -.
DR OrthoDB; 947320at2759; -.
DR PhylomeDB; Q9CWK8; -.
DR TreeFam; TF313698; -.
DR Reactome; R-MMU-432722; Golgi Associated Vesicle Biogenesis.
DR BioGRID-ORCS; 67804; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Snx2; mouse.
DR PRO; PR:Q9CWK8; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q9CWK8; protein.
DR Bgee; ENSMUSG00000034484; Expressed in blastocyst and 137 other tissues.
DR ExpressionAtlas; Q9CWK8; baseline and differential.
DR Genevisible; Q9CWK8; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030904; C:retromer complex; ISO:MGI.
DR GO; GO:0030905; C:retromer, tubulation complex; ISO:MGI.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:1990460; F:leptin receptor binding; ISO:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:1990459; F:transferrin receptor binding; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS: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; Cell projection; Endosome; Lipid-binding; Membrane;
KW Phosphoprotein; Protein transport; Reference proteome; Transport.
FT CHAIN 1..519
FT /note="Sorting nexin-2"
FT /id="PRO_0000213839"
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 30..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..519
FT /note="Interaction with RhoG"
FT /evidence="ECO:0000250|UniProtKB:O60749"
FT REGION 278..295
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:O60749"
FT COMPBIAS 30..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:0007744|PubMed:21183079"
FT MOD_RES 101
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 104
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60749"
FT MOD_RES 119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O60749"
FT MOD_RES 469
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O60749"
FT CONFLICT 245
FT /note="R -> I (in Ref. 1; BAB27035)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="R -> P (in Ref. 1; BAB27035)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 58471 MW; 55DD0BB74E82CD82 CRC64;
MAAEREPPPL GDVKPTDFEE LEDGEDLFTS TVSTLESSPS SPEPASLPAE DISANSNGSK
PVEVVLDDDR EDLFAEATEE VSLDSPEREL ILSSEPSPAV TPVTPTTLIA PRIESKSISA
PVIFDRSRDE IEEEANGDIF DIEIGVSDPE KVGDGMNAYM AYRVTTKTSL SMFSKSEFSV
KRRFSDFLGL HSKLASKYLH VGYIVPPAPE KSIVGMTKVK VGKEDSSSTE FVEKRRAALE
RYLQRTVKHP TLLQDPDLRQ FLESSELPRA VNTQALSGAG ILRMVNKAAD AVNKMTIKMN
ESDAWFEEKQ QQFENLDQQL RKLHASVEAL VCHRKELSAN TAAFAKSAAM LGNSEDHTAL
SRALSQLAEV EEKIDQLHQE QAFADFYMFS ELLSDYIRLI AAVKGVFDHR MKCWQKWEDA
QITLLKKRET EAKMMVANKP DKIQQAKNEI REWEAKVQQG ERDFEQISKT IRKEVGRFEK
ERVKDFKAVI IKYLESLVQT QQQLIKYWEA FLPEAKAIA
