Full text data of SNX6
SNX6
[Confidence: low (only semi-automatic identification from reviews)]
Sorting nexin-6 (TRAF4-associated factor 2; Sorting nexin-6, N-terminally processed)
Sorting nexin-6 (TRAF4-associated factor 2; Sorting nexin-6, N-terminally processed)
UniProt
Q9UNH7
ID SNX6_HUMAN Reviewed; 406 AA.
AC Q9UNH7; C0H5W9; Q9Y449;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Sorting nexin-6;
DE AltName: Full=TRAF4-associated factor 2;
DE Contains:
DE RecName: Full=Sorting nexin-6, N-terminally processed;
GN Name=SNX6;
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] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=11485546; DOI=10.1042/0264-6021:3580007;
RA Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.;
RT "A large family of endosome-localized proteins related to sorting
RT nexin 1.";
RL Biochem. J. 358:7-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Toji S., Yano M., Kobayasi A., Tamai K.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP CHARACTERIZATION, AND SUBUNIT.
RX PubMed=11279102; DOI=10.1074/jbc.M100606200;
RA Parks W.T., Frank D.B., Huff C., Haft C.R., Martin J., Meng X.,
RA de Caestecker M.P., McNally J.G., Reddi A., Taylor S.I., Roberts A.B.,
RA Wang T., Lechleider R.J.;
RT "Sorting nexin 6, a novel SNX, interacts with the transforming growth
RT factor-beta family of receptor serine-threonine kinases.";
RL J. Biol. Chem. 276:19332-19339(2001).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP FUNCTION, INTERACTION WITH DCTN1; SNX1 AND SNX2, MUTAGENESIS OF
RP ARG-68; GLN-69 AND ARG-97, AND SUBCELLULAR LOCATION.
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BACE1.
RX PubMed=20354142; DOI=10.1096/fj.09-146357;
RA Okada H., Zhang W., Peterhoff C., Hwang J.C., Nixon R.A., Ryu S.H.,
RA Kim T.W.;
RT "Proteomic identification of sorting nexin 6 as a negative regulator
RT of BACE1-mediated APP processing.";
RL FASEB J. 24:2783-2794(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRMS1.
RX PubMed=20830743; DOI=10.1002/jcb.22874;
RA Rivera J., Megias D., Bravo J.;
RT "Sorting nexin 6 interacts with breast cancer metastasis suppressor-1
RT and promotes transcriptional repression.";
RL J. Cell. Biochem. 111:1464-1472(2010).
RN [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, AND MASS
RP SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: May be involved in several stages of intracellular
CC trafficking. Promotes lysosomal degradation of CDKN1B (By
CC similarity). Plays a role in retrograde protein transport from
CC endosomes to the trans-Golgi network. May function as link between
CC transport vesicles and dynactin. Negatively regulates retrograde
CC transport of BACE1 from the cell surface to the trans-Golgi
CC network. May contribute to transcription regulation.
CC -!- SUBUNIT: Interacts with CDKN1B (By similarity). Interacts with
CC TGFB receptors. Interacts with dynactin subunit DCTN1. Interacts
CC with SNX1 and SNX2. Interacts with BACE1 and BRMS1.
CC -!- INTERACTION:
CC Q96CV9:OPTN; NbExp=2; IntAct=EBI-949294, EBI-748974;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Nucleus.
CC Note=Interaction with SNX1 or SNX2 promotes location at endosome
CC membranes. Only a minor proportion is seen in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UNH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNH7-2; Sequence=VSP_044824;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched
CC in phosphatidylinositol 3,4-bisphosphate and/or
CC phosphatidylinositol 4,5-bisphosphate (By similarity).
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD24202.1; Type=Erroneous initiation;
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DR EMBL; AF121856; AAD27829.1; -; mRNA.
DR EMBL; U83194; AAD24202.1; ALT_INIT; mRNA.
DR EMBL; AL445363; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65913.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65915.1; -; Genomic_DNA.
DR EMBL; BC001798; AAH01798.1; -; mRNA.
DR RefSeq; NP_067072.3; NM_021249.3.
DR RefSeq; NP_689419.2; NM_152233.2.
DR UniGene; Hs.356647; -.
DR ProteinModelPortal; Q9UNH7; -.
DR SMR; Q9UNH7; 21-175.
DR IntAct; Q9UNH7; 15.
DR MINT; MINT-2634416; -.
DR STRING; 9606.ENSP00000355217; -.
DR PhosphoSite; Q9UNH7; -.
DR DMDM; 10720285; -.
DR OGP; Q9UNH7; -.
DR REPRODUCTION-2DPAGE; IPI00298111; -.
DR PaxDb; Q9UNH7; -.
DR PRIDE; Q9UNH7; -.
DR DNASU; 58533; -.
DR Ensembl; ENST00000396526; ENSP00000379779; ENSG00000129515.
DR Ensembl; ENST00000396534; ENSP00000379785; ENSG00000129515.
DR GeneID; 58533; -.
DR KEGG; hsa:58533; -.
DR UCSC; uc001wse.1; human.
DR CTD; 58533; -.
DR GeneCards; GC14M035030; -.
DR H-InvDB; HIX0011592; -.
DR HGNC; HGNC:14970; SNX6.
DR HPA; HPA049374; -.
DR MIM; 606098; gene.
DR neXtProt; NX_Q9UNH7; -.
DR PharmGKB; PA37946; -.
DR eggNOG; NOG255198; -.
DR HOGENOM; HOG000231691; -.
DR HOVERGEN; HBG000716; -.
DR InParanoid; Q9UNH7; -.
DR OrthoDB; EOG7X0VH4; -.
DR SignaLink; Q9UNH7; -.
DR ChiTaRS; SNX6; human.
DR GenomeRNAi; 58533; -.
DR NextBio; 65116; -.
DR PRO; PR:Q9UNH7; -.
DR ArrayExpress; Q9UNH7; -.
DR Bgee; Q9UNH7; -.
DR CleanEx; HS_SNX6; -.
DR Genevestigator; Q9UNH7; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:HGNC.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR-dom.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR015404; Vps5_C.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Endosome; Lipid-binding; Membrane; Nucleus;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1 406 Sorting nexin-6.
FT /FTId=PRO_0000213846.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 406 Sorting nexin-6, N-terminally processed.
FT /FTId=PRO_0000423277.
FT DOMAIN 26 173 PX.
FT REGION 41 47 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT REGION 100 106 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT REGION 114 117 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylmethionine; in Sorting nexin-6,
FT N-terminally processed.
FT VAR_SEQ 1 116 Missing (in isoform 2).
FT /FTId=VSP_044824.
FT MUTAGEN 68 68 R->A: Reduces interaction with SNX1.
FT Abolishes location at endosome membranes.
FT MUTAGEN 69 69 Q->A: No effect on subcellular location.
FT MUTAGEN 97 97 R->A: No effect on subcellular location.
SQ SEQUENCE 406 AA; 46649 MW; E3659DB19C59E1BB CRC64;
MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDKVKFTV HTKSSLPNFK
QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF DASREKLQKL GEGEGSMTKE
EFTKMKQELE AEYLAIFKKT VAMHEVFLCR VAAHPILRRD 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
//
ID SNX6_HUMAN Reviewed; 406 AA.
AC Q9UNH7; C0H5W9; Q9Y449;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 118.
DE RecName: Full=Sorting nexin-6;
DE AltName: Full=TRAF4-associated factor 2;
DE Contains:
DE RecName: Full=Sorting nexin-6, N-terminally processed;
GN Name=SNX6;
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] (ISOFORM 1), AND SUBCELLULAR LOCATION.
RX PubMed=11485546; DOI=10.1042/0264-6021:3580007;
RA Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.;
RT "A large family of endosome-localized proteins related to sorting
RT nexin 1.";
RL Biochem. J. 358:7-16(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Toji S., Yano M., Kobayasi A., Tamai K.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP CHARACTERIZATION, AND SUBUNIT.
RX PubMed=11279102; DOI=10.1074/jbc.M100606200;
RA Parks W.T., Frank D.B., Huff C., Haft C.R., Martin J., Meng X.,
RA de Caestecker M.P., McNally J.G., Reddi A., Taylor S.I., Roberts A.B.,
RA Wang T., Lechleider R.J.;
RT "Sorting nexin 6, a novel SNX, interacts with the transforming growth
RT factor-beta family of receptor serine-threonine kinases.";
RL J. Biol. Chem. 276:19332-19339(2001).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, MASS
RP SPECTROMETRY, AND CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP FUNCTION, INTERACTION WITH DCTN1; SNX1 AND SNX2, MUTAGENESIS OF
RP ARG-68; GLN-69 AND ARG-97, AND SUBCELLULAR LOCATION.
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 [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BACE1.
RX PubMed=20354142; DOI=10.1096/fj.09-146357;
RA Okada H., Zhang W., Peterhoff C., Hwang J.C., Nixon R.A., Ryu S.H.,
RA Kim T.W.;
RT "Proteomic identification of sorting nexin 6 as a negative regulator
RT of BACE1-mediated APP processing.";
RL FASEB J. 24:2783-2794(2010).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRMS1.
RX PubMed=20830743; DOI=10.1002/jcb.22874;
RA Rivera J., Megias D., Bravo J.;
RT "Sorting nexin 6 interacts with breast cancer metastasis suppressor-1
RT and promotes transcriptional repression.";
RL J. Cell. Biochem. 111:1464-1472(2010).
RN [11]
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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, AND MASS
RP SPECTROMETRY.
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
CC -!- FUNCTION: May be involved in several stages of intracellular
CC trafficking. Promotes lysosomal degradation of CDKN1B (By
CC similarity). Plays a role in retrograde protein transport from
CC endosomes to the trans-Golgi network. May function as link between
CC transport vesicles and dynactin. Negatively regulates retrograde
CC transport of BACE1 from the cell surface to the trans-Golgi
CC network. May contribute to transcription regulation.
CC -!- SUBUNIT: Interacts with CDKN1B (By similarity). Interacts with
CC TGFB receptors. Interacts with dynactin subunit DCTN1. Interacts
CC with SNX1 and SNX2. Interacts with BACE1 and BRMS1.
CC -!- INTERACTION:
CC Q96CV9:OPTN; NbExp=2; IntAct=EBI-949294, EBI-748974;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle membrane; Peripheral
CC membrane protein; Cytoplasmic side. Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Nucleus.
CC Note=Interaction with SNX1 or SNX2 promotes location at endosome
CC membranes. Only a minor proportion is seen in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UNH7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UNH7-2; Sequence=VSP_044824;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The PX domain mediates interaction with membranes enriched
CC in phosphatidylinositol 3,4-bisphosphate and/or
CC phosphatidylinositol 4,5-bisphosphate (By similarity).
CC -!- SIMILARITY: Belongs to the sorting nexin family.
CC -!- SIMILARITY: Contains 1 PX (phox homology) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD24202.1; Type=Erroneous initiation;
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DR EMBL; AF121856; AAD27829.1; -; mRNA.
DR EMBL; U83194; AAD24202.1; ALT_INIT; mRNA.
DR EMBL; AL445363; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65913.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65915.1; -; Genomic_DNA.
DR EMBL; BC001798; AAH01798.1; -; mRNA.
DR RefSeq; NP_067072.3; NM_021249.3.
DR RefSeq; NP_689419.2; NM_152233.2.
DR UniGene; Hs.356647; -.
DR ProteinModelPortal; Q9UNH7; -.
DR SMR; Q9UNH7; 21-175.
DR IntAct; Q9UNH7; 15.
DR MINT; MINT-2634416; -.
DR STRING; 9606.ENSP00000355217; -.
DR PhosphoSite; Q9UNH7; -.
DR DMDM; 10720285; -.
DR OGP; Q9UNH7; -.
DR REPRODUCTION-2DPAGE; IPI00298111; -.
DR PaxDb; Q9UNH7; -.
DR PRIDE; Q9UNH7; -.
DR DNASU; 58533; -.
DR Ensembl; ENST00000396526; ENSP00000379779; ENSG00000129515.
DR Ensembl; ENST00000396534; ENSP00000379785; ENSG00000129515.
DR GeneID; 58533; -.
DR KEGG; hsa:58533; -.
DR UCSC; uc001wse.1; human.
DR CTD; 58533; -.
DR GeneCards; GC14M035030; -.
DR H-InvDB; HIX0011592; -.
DR HGNC; HGNC:14970; SNX6.
DR HPA; HPA049374; -.
DR MIM; 606098; gene.
DR neXtProt; NX_Q9UNH7; -.
DR PharmGKB; PA37946; -.
DR eggNOG; NOG255198; -.
DR HOGENOM; HOG000231691; -.
DR HOVERGEN; HBG000716; -.
DR InParanoid; Q9UNH7; -.
DR OrthoDB; EOG7X0VH4; -.
DR SignaLink; Q9UNH7; -.
DR ChiTaRS; SNX6; human.
DR GenomeRNAi; 58533; -.
DR NextBio; 65116; -.
DR PRO; PR:Q9UNH7; -.
DR ArrayExpress; Q9UNH7; -.
DR Bgee; Q9UNH7; -.
DR CleanEx; HS_SNX6; -.
DR Genevestigator; Q9UNH7; -.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0006886; P:intracellular protein transport; IMP:UniProtKB.
DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; NAS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:HGNC.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR Gene3D; 1.20.1270.60; -; 1.
DR Gene3D; 3.30.1520.10; -; 1.
DR InterPro; IPR027267; AH/BAR-dom.
DR InterPro; IPR001683; Phox.
DR InterPro; IPR014637; SNX5/SNX6/SNX32.
DR InterPro; IPR015404; Vps5_C.
DR Pfam; PF00787; PX; 1.
DR Pfam; PF09325; Vps5; 1.
DR PIRSF; PIRSF036924; Snx5_Snx6; 1.
DR SUPFAM; SSF64268; SSF64268; 1.
DR PROSITE; PS50195; PX; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm;
KW Cytoplasmic vesicle; Endosome; Lipid-binding; Membrane; Nucleus;
KW Protein transport; Reference proteome; Transport.
FT CHAIN 1 406 Sorting nexin-6.
FT /FTId=PRO_0000213846.
FT INIT_MET 1 1 Removed; alternate.
FT CHAIN 2 406 Sorting nexin-6, N-terminally processed.
FT /FTId=PRO_0000423277.
FT DOMAIN 26 173 PX.
FT REGION 41 47 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT REGION 100 106 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT REGION 114 117 Phosphatidylinositol bisphosphate binding
FT (By similarity).
FT MOD_RES 1 1 N-acetylmethionine.
FT MOD_RES 2 2 N-acetylmethionine; in Sorting nexin-6,
FT N-terminally processed.
FT VAR_SEQ 1 116 Missing (in isoform 2).
FT /FTId=VSP_044824.
FT MUTAGEN 68 68 R->A: Reduces interaction with SNX1.
FT Abolishes location at endosome membranes.
FT MUTAGEN 69 69 Q->A: No effect on subcellular location.
FT MUTAGEN 97 97 R->A: No effect on subcellular location.
SQ SEQUENCE 406 AA; 46649 MW; E3659DB19C59E1BB CRC64;
MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDKVKFTV HTKSSLPNFK
QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF DASREKLQKL GEGEGSMTKE
EFTKMKQELE AEYLAIFKKT VAMHEVFLCR VAAHPILRRD 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
//
MIM
606098
*RECORD*
*FIELD* NO
606098
*FIELD* TI
*606098 SORTING NEXIN 6; SNX6
*FIELD* TX
DESCRIPTION
SNX6 if a member of the sorting nexin family of molecules that contain a
read morephox homology (PX) domain and share homology with several yeast proteins
involved in protein trafficking (Parks et al., 2001).
CLONING
Using a yeast 2-hybrid screen with SMAD1 (601595) as bait, Parks et al.
(2001) identified sorting nexin-6 and cloned a full-length cDNA from a
human heart cDNA library. The deduced 406-amino acid protein shares 66%
sequence identity with the SNX5 (605937) protein. Northern blot analysis
detected wide expression of major 2.2-kb and minor 3.0-kb transcripts,
with highest levels in heart, skeletal muscle, and placenta and low
levels in lung and liver.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX6
gene to chromosome 14 (TMAP WI-6202).
GENE FUNCTION
Parks et al. (2001) found that the interaction of SNX6 with Smad1 was
very weak, but immunoprecipitation studies showed that SNX6 interacts
strongly through its PX domain with members of the transforming growth
factor-beta family of receptor serine-threonine kinases, including
ActRIIB (602730), TGFBR1 (see 190181), and TGFBR2 (see 190182). Parks et
al. (2001) found that SNXs 1-4 (see 601272) also interacted with the
TGFB receptor family, showing different receptor preferences.
Conversely, SNX6 behaved similarly to the other SNX proteins in its
interactions with receptor tyrosine kinases, including epidermal growth
factor (131550), platelet-derived growth factor (see 173490), insulin
(147670), and the long form of the leptin receptor (601007). Strong
heteromeric interactions were seen among SNX1 (601272), SNX2 (605929),
SNX4 (605931) and SNX6, suggesting the formation in vivo of oligomeric
complexes. Both the PX domain and the coiled-coil regions of the
molecules may contribute to the heterooligomerization. Indirect
immunofluorescence studies demonstrated that SNX6 colocalizes with other
SNXs specifically in the cell cytoplasm.
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 (601272, 605929) (C. elegans
homolog snx1) and 5 and 6 (605937) (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. Parks, W. T.; Frank, D. B.; Huff, C.; Haft, C. R.; Martin, J.;
Meng, X.; de Caestecker, M. P.; McNally, J. G.; Reddi, A.; Taylor,
S. I.; Roberts, A. B.; Wang, T.; Lechleider, R. J.: Sorting nexin
6, a novel SNX, interacts with the transforming growth factor-beta
family of receptor serine-threonine kinases. J. Biol. Chem. 276:
19332-19339, 2001.
*FIELD* CN
Ada Hamosh - updated: 4/22/2010
*FIELD* CD
Carol A. Bocchini: 7/10/2001
*FIELD* ED
alopez: 04/26/2010
terry: 4/22/2010
carol: 10/19/2009
cwells: 7/11/2001
carol: 7/11/2001
*RECORD*
*FIELD* NO
606098
*FIELD* TI
*606098 SORTING NEXIN 6; SNX6
*FIELD* TX
DESCRIPTION
SNX6 if a member of the sorting nexin family of molecules that contain a
read morephox homology (PX) domain and share homology with several yeast proteins
involved in protein trafficking (Parks et al., 2001).
CLONING
Using a yeast 2-hybrid screen with SMAD1 (601595) as bait, Parks et al.
(2001) identified sorting nexin-6 and cloned a full-length cDNA from a
human heart cDNA library. The deduced 406-amino acid protein shares 66%
sequence identity with the SNX5 (605937) protein. Northern blot analysis
detected wide expression of major 2.2-kb and minor 3.0-kb transcripts,
with highest levels in heart, skeletal muscle, and placenta and low
levels in lung and liver.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the SNX6
gene to chromosome 14 (TMAP WI-6202).
GENE FUNCTION
Parks et al. (2001) found that the interaction of SNX6 with Smad1 was
very weak, but immunoprecipitation studies showed that SNX6 interacts
strongly through its PX domain with members of the transforming growth
factor-beta family of receptor serine-threonine kinases, including
ActRIIB (602730), TGFBR1 (see 190181), and TGFBR2 (see 190182). Parks et
al. (2001) found that SNXs 1-4 (see 601272) also interacted with the
TGFB receptor family, showing different receptor preferences.
Conversely, SNX6 behaved similarly to the other SNX proteins in its
interactions with receptor tyrosine kinases, including epidermal growth
factor (131550), platelet-derived growth factor (see 173490), insulin
(147670), and the long form of the leptin receptor (601007). Strong
heteromeric interactions were seen among SNX1 (601272), SNX2 (605929),
SNX4 (605931) and SNX6, suggesting the formation in vivo of oligomeric
complexes. Both the PX domain and the coiled-coil regions of the
molecules may contribute to the heterooligomerization. Indirect
immunofluorescence studies demonstrated that SNX6 colocalizes with other
SNXs specifically in the cell cytoplasm.
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 (601272, 605929) (C. elegans
homolog snx1) and 5 and 6 (605937) (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. Parks, W. T.; Frank, D. B.; Huff, C.; Haft, C. R.; Martin, J.;
Meng, X.; de Caestecker, M. P.; McNally, J. G.; Reddi, A.; Taylor,
S. I.; Roberts, A. B.; Wang, T.; Lechleider, R. J.: Sorting nexin
6, a novel SNX, interacts with the transforming growth factor-beta
family of receptor serine-threonine kinases. J. Biol. Chem. 276:
19332-19339, 2001.
*FIELD* CN
Ada Hamosh - updated: 4/22/2010
*FIELD* CD
Carol A. Bocchini: 7/10/2001
*FIELD* ED
alopez: 04/26/2010
terry: 4/22/2010
carol: 10/19/2009
cwells: 7/11/2001
carol: 7/11/2001