SNX6_MOUSE
ID SNX6_MOUSE Reviewed; 406 AA.
AC Q6P8X1; Q9CZ03;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Sorting nexin-6;
DE Contains:
DE RecName: Full=Sorting nexin-6, N-terminally processed;
GN Name=Snx6;
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;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP PROTEIN SEQUENCE OF 376-386, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [4]
RP FUNCTION, AND INTERACTION WITH GIT1.
RX PubMed=18523162; DOI=10.1096/fj.07-094086;
RA Cavet M.E., Pang J., Yin G., Berk B.C.;
RT "An epidermal growth factor (EGF) -dependent interaction between GIT1 and
RT sorting nexin 6 promotes degradation of the EGF receptor.";
RL FASEB J. 22:3607-3616(2008).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDKN1B.
RX PubMed=20228253; DOI=10.1096/fj.09-138255;
RA Fuster J.J., Gonzalez J.M., Edo M.D., Viana R., Boya P., Cervera J.,
RA Verges M., Rivera J., Andres V.;
RT "Tumor suppressor p27(Kip1) undergoes endolysosomal degradation through its
RT interaction with sorting nexin 6.";
RL FASEB J. 24:2998-3009(2010).
CC -!- FUNCTION: Involved in several stages of intracellular trafficking.
CC Interacts with membranes phosphatidylinositol 3,4-bisphosphate and/or
CC phosphatidylinositol 4,5-bisphosphate (Probable). Acts in part as
CC component of the retromer membrane-deforming SNX-BAR subcomplex. The
CC SNX-BAR retromer mediates retrograde transport of cargo proteins from
CC endosomes to the trans-Golgi network (TGN) and is involved in endosome-
CC to-plasma membrane transport for cargo protein recycling. The SNX-BAR
CC subcomplex functions to deform the donor membrane into a tubular
CC profile called endosome-to-TGN transport carrier (ETC). Does not have
CC in vitro vesicle-to-membrane remodeling activity (By similarity).
CC Involved in retrograde endosome-to-TGN transport of lysosomal enzyme
CC receptor IGF2R. May function as link between transport vesicles and
CC dynactin. Negatively regulates retrograde transport of BACE1 from the
CC cell surface to the trans-Golgi network. Involved in E-cadherin sorting
CC and degradation; inhibits PIP5K1C-mediated E-cadherin degradation (By
CC similarity). In association with GIT1 involved in EGFR degradation
CC (PubMed:18523162). Promotes lysosomal degradation of CDKN1B
CC (PubMed:20228253). May contribute to transcription regulation (By
CC similarity). {ECO:0000250|UniProtKB:Q9UNH7,
CC ECO:0000269|PubMed:18523162, ECO:0000269|PubMed:20228253}.
CC -!- SUBUNIT: Forms heterodimers with BAR domain-containing sorting nexins
CC SNX1 and SNX2. The heterodimers are proposed to self-assemble into
CC helical arrays on the membrane to stabilize and expand local membrane
CC curvature underlying endosomal tubule formation. Thought to be a
CC component of the originally described retromer complex (also called
CC SNX-BAR retromer) which is a pentamer containing the heterotrimeric
CC retromer cargo-selective complex (CSC), also described as vacuolar
CC protein sorting subcomplex (VPS), and a heterodimeric membrane-
CC deforming subcomplex formed between SNX1 or SNX2 and SNX5 or SNX6 (also
CC called SNX-BAR subcomplex); the respective CSC and SNX-BAR subcomplexes
CC associate with low affinity (By similarity). Interacts with SNX1, SNX2,
CC VPS26A, VPS29, VPS35, TGFB receptors, BACE1, BRMS1, PIP5K1C. Interacts
CC with DCTN1; the association with DCTN1 is involved in movement of
CC retromer-c ontaining vesicles toward the TGN. Interacts with PIM1;
CC translocating SNX6 to the nucleus (By similarity). Interacts with
CC CDKN1B and GIT1 (PubMed:18523162, PubMed:20228253).
CC {ECO:0000250|UniProtKB:Q9UNH7, ECO:0000269|PubMed:18523162,
CC ECO:0000269|PubMed:20228253}.
CC -!- SUBCELLULAR LOCATION: Early endosome membrane
CC {ECO:0000269|PubMed:20228253}; Peripheral membrane protein
CC {ECO:0000269|PubMed:20228253}; Cytoplasmic side
CC {ECO:0000269|PubMed:20228253}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:Q9UNH7}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9UNH7}. Nucleus {ECO:0000250|UniProtKB:Q9UNH7}.
CC Note=Interaction with SNX1 or SNX2 promotes location at endosome
CC membranes (By similarity). Only a minor proportion is seen in the
CC nucleus (By similarity). {ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched in
CC phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-
CC bisphosphate. {ECO:0000250}.
CC -!- DOMAIN: The BAR domain is able to sense membrane curvature upon
CC dimerization. Membrane remodeling seems to implicate insertion of an
CC amphipathic helix (AH) in the membrane (By similarity).
CC {ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- PTM: In vitro phosphorylated by PIM1; not affecting PIM1-dependent
CC nuclear translocation (By similarity). {ECO:0000250|UniProtKB:Q9UNH7}.
CC -!- SIMILARITY: Belongs to the sorting nexin family. {ECO:0000305}.
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DR EMBL; AK013158; BAB28684.1; -; mRNA.
DR EMBL; BC061028; AAH61028.1; -; mRNA.
DR CCDS; CCDS36447.1; -.
DR RefSeq; NP_081274.2; NM_026998.3.
DR AlphaFoldDB; Q6P8X1; -.
DR SMR; Q6P8X1; -.
DR BioGRID; 215205; 26.
DR IntAct; Q6P8X1; 4.
DR MINT; Q6P8X1; -.
DR STRING; 10090.ENSMUSP00000005798; -.
DR iPTMnet; Q6P8X1; -.
DR PhosphoSitePlus; Q6P8X1; -.
DR REPRODUCTION-2DPAGE; Q6P8X1; -.
DR EPD; Q6P8X1; -.
DR jPOST; Q6P8X1; -.
DR MaxQB; Q6P8X1; -.
DR PaxDb; Q6P8X1; -.
DR PeptideAtlas; Q6P8X1; -.
DR PRIDE; Q6P8X1; -.
DR ProteomicsDB; 261305; -.
DR Antibodypedia; 23146; 312 antibodies from 28 providers.
DR DNASU; 72183; -.
DR Ensembl; ENSMUST00000005798; ENSMUSP00000005798; ENSMUSG00000005656.
DR GeneID; 72183; -.
DR KEGG; mmu:72183; -.
DR UCSC; uc007nnv.1; mouse.
DR CTD; 58533; -.
DR MGI; MGI:1919433; Snx6.
DR VEuPathDB; HostDB:ENSMUSG00000005656; -.
DR eggNOG; KOG1660; Eukaryota.
DR GeneTree; ENSGT00940000154940; -.
DR HOGENOM; CLU_040966_0_0_1; -.
DR InParanoid; Q6P8X1; -.
DR OMA; FLKMKHD; -.
DR OrthoDB; 1009572at2759; -.
DR PhylomeDB; Q6P8X1; -.
DR TreeFam; TF313698; -.
DR BioGRID-ORCS; 72183; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Snx6; mouse.
DR PRO; PR:Q6P8X1; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q6P8X1; protein.
DR Bgee; ENSMUSG00000005656; Expressed in epithelium of stomach and 265 other tissues.
DR ExpressionAtlas; Q6P8X1; baseline and differential.
DR Genevisible; Q6P8X1; 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; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0030904; C:retromer complex; ISS:UniProtKB.
DR GO; GO:0097422; C:tubular endosome; ISS:UniProtKB.
DR GO; GO:0034452; F:dynactin binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0034713; F:type I transforming growth factor beta receptor binding; IPI:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0071364; P:cellular response to epidermal growth factor stimulus; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; ISS:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; ISS:UniProtKB.
DR CDD; cd07292; PX_SNX6; 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; IPR042136; PX_SNX6.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR028657; SNX6.
DR InterPro; IPR015404; Vps5_C.
DR PANTHER; PTHR45850:SF4; PTHR45850:SF4; 1.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing;
KW Endosome; Lipid-binding; Membrane; Nucleus; Phosphoprotein;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1..406
FT /note="Sorting nexin-6"
FT /id="PRO_0000423278"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT CHAIN 2..406
FT /note="Sorting nexin-6, N-terminally processed"
FT /id="PRO_0000236198"
FT DOMAIN 26..173
FT /note="PX"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00147"
FT DOMAIN 203..406
FT /note="BAR"
FT /evidence="ECO:0000305"
FT REGION 2..179
FT /note="Interaction with PIM1"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT REGION 182..199
FT /note="Membrane-binding amphipathic helix"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT BINDING 41..47
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 100..106
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT BINDING 114..117
FT /ligand="phosphatidylinositol bisphosphate"
FT /ligand_id="ChEBI:CHEBI:83191"
FT /evidence="ECO:0000250|UniProtKB:B1H267"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 2
FT /note="N-acetylmethionine; in Sorting nexin-6, N-terminally
FT processed"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 116
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT MOD_RES 194
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UNH7"
FT CONFLICT 47
FT /note="K -> N (in Ref. 2; AAH61028)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 406 AA; 46649 MW; 7B33A7325B814DAF CRC64;
MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDRVKFTV HTKSSLPNFK
QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF DASREKLQKL GEGEGSMTKE
EFTKMKQELE AEYLAIFKKT VAMHEVFLCR VAAHPILRKD LNFHVFLEYN QDLSVRGKNK
KEKLEDFFKN MVKSADGVIV SGVKDVDDFF EHERTFLLEY HNRVKDASAK SDRMTRSHKS
AADDYNRIGS SLYALGTQDS TDICKFFLKV SELFDKTRKI EARVSADEDL KLSDLLKYYL
RESQAAKDLL YRRSRSLVDY ENANKALDKA RAKNKDVLQA ETSQQLCCQK FEKISESAKQ
ELIDFKTRRV AAFRKNLVEL AELELKHAKG NLQLLQNCLA VLNGDT
