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Q9UNH7

- SNX6_HUMAN

UniProt

Q9UNH7 - SNX6_HUMAN

Protein

Sorting nexin-6

Gene

SNX6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 125 (01 Oct 2014)
      Sequence version 1 (01 May 2000)
      Previous versions | rss
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    Functioni

    May be involved in several stages of intracellular trafficking. Promotes lysosomal degradation of CDKN1B By similarity. Plays a role in retrograde protein transport from endosomes to the trans-Golgi network. May function as link between transport vesicles and dynactin. Negatively regulates retrograde transport of BACE1 from the cell surface to the trans-Golgi network. May contribute to transcription regulation.By similarity3 Publications

    GO - Molecular functioni

    1. phosphatidylinositol binding Source: RefGenome
    2. protein binding Source: UniProtKB
    3. protein homodimerization activity Source: HGNC

    GO - Biological processi

    1. intracellular protein transport Source: UniProtKB
    2. negative regulation of epidermal growth factor-activated receptor activity Source: UniProtKB
    3. negative regulation of transcription, DNA-templated Source: UniProtKB
    4. negative regulation of transforming growth factor beta receptor signaling pathway Source: HGNC
    5. retrograde transport, endosome to Golgi Source: UniProtKB

    Keywords - Biological processi

    Protein transport, Transport

    Keywords - Ligandi

    Lipid-binding

    Enzyme and pathway databases

    SignaLinkiQ9UNH7.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sorting nexin-6
    Alternative name(s):
    TRAF4-associated factor 2
    Cleaved into the following chain:
    Gene namesi
    Name:SNX6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:14970. SNX6.

    Subcellular locationi

    Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Nucleus
    Note: Interaction with SNX1 or SNX2 promotes location at endosome membranes. Only a minor proportion is seen in the nucleus.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytoplasmic vesicle membrane Source: UniProtKB-SubCell
    3. early endosome membrane Source: UniProtKB
    4. intracellular Source: UniProtKB
    5. nucleus Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi68 – 681R → A: Reduces interaction with SNX1. Abolishes location at endosome membranes. 1 Publication
    Mutagenesisi69 – 691Q → A: No effect on subcellular location. 1 Publication
    Mutagenesisi97 – 971R → A: No effect on subcellular location. 1 Publication

    Organism-specific databases

    PharmGKBiPA37946.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 406406Sorting nexin-6PRO_0000423277Add
    BLAST
    Initiator methioninei1 – 11Removed; alternate1 Publication
    Chaini2 – 406405Sorting nexin-6, N-terminally processedPRO_0000213846Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine2 Publications
    Modified residuei2 – 21N-acetylmethionine; in Sorting nexin-6, N-terminally processed2 Publications

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiQ9UNH7.
    PaxDbiQ9UNH7.
    PRIDEiQ9UNH7.

    2D gel databases

    OGPiQ9UNH7.
    REPRODUCTION-2DPAGEIPI00298111.

    PTM databases

    PhosphoSiteiQ9UNH7.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9UNH7.
    BgeeiQ9UNH7.
    CleanExiHS_SNX6.
    GenevestigatoriQ9UNH7.

    Organism-specific databases

    HPAiHPA049374.

    Interactioni

    Subunit structurei

    Interacts with CDKN1B By similarity. Interacts with TGFB receptors. Interacts with dynactin subunit DCTN1. Interacts with SNX1 and SNX2. Interacts with BACE1 and BRMS1.By similarity4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    OPTNQ96CV92EBI-949294,EBI-748974

    Protein-protein interaction databases

    BioGridi121852. 40 interactions.
    DIPiDIP-37549N.
    IntActiQ9UNH7. 15 interactions.
    MINTiMINT-2634416.
    STRINGi9606.ENSP00000355217.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9UNH7.
    SMRiQ9UNH7. Positions 21-175.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini26 – 173148PXPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni41 – 477Phosphatidylinositol bisphosphate bindingBy similarity
    Regioni100 – 1067Phosphatidylinositol bisphosphate bindingBy similarity
    Regioni114 – 1174Phosphatidylinositol bisphosphate bindingBy similarity

    Domaini

    The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3,4-bisphosphate and/or phosphatidylinositol 4,5-bisphosphate.By similarity

    Sequence similaritiesi

    Belongs to the sorting nexin family.Curated
    Contains 1 PX (phox homology) domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG255198.
    HOGENOMiHOG000231691.
    HOVERGENiHBG000716.
    InParanoidiQ9UNH7.
    KOiK17920.
    OrthoDBiEOG7X0VH4.
    PhylomeDBiQ9UNH7.
    TreeFamiTF313698.

    Family and domain databases

    Gene3Di1.20.1270.60. 1 hit.
    3.30.1520.10. 1 hit.
    InterProiIPR027267. AH/BAR-dom.
    IPR001683. Phox.
    IPR014637. SNX5/SNX6/SNX32.
    IPR028657. SNX6.
    IPR015404. Vps5_C.
    [Graphical view]
    PANTHERiPTHR10555:SF120. PTHR10555:SF120. 1 hit.
    PfamiPF00787. PX. 1 hit.
    PF09325. Vps5. 1 hit.
    [Graphical view]
    PIRSFiPIRSF036924. Snx5_Snx6. 1 hit.
    SUPFAMiSSF64268. SSF64268. 1 hit.
    PROSITEiPS50195. PX. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9UNH7-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MMEGLDDGPD FLSEEDRGLK AINVDLQSDA ALQVDISDAL SERDKVKFTV    50
    HTKSSLPNFK QNEFSVVRQH EEFIWLHDSF VENEDYAGYI IPPAPPRPDF 100
    DASREKLQKL GEGEGSMTKE EFTKMKQELE AEYLAIFKKT VAMHEVFLCR 150
    VAAHPILRRD LNFHVFLEYN QDLSVRGKNK KEKLEDFFKN MVKSADGVIV 200
    SGVKDVDDFF EHERTFLLEY HNRVKDASAK SDRMTRSHKS AADDYNRIGS 250
    SLYALGTQDS TDICKFFLKV SELFDKTRKI EARVSADEDL KLSDLLKYYL 300
    RESQAAKDLL YRRSRSLVDY ENANKALDKA RAKNKDVLQA ETSQQLCCQK 350
    FEKISESAKQ ELIDFKTRRV AAFRKNLVEL AELELKHAKG NLQLLQNCLA 400
    VLNGDT 406
    Length:406
    Mass (Da):46,649
    Last modified:May 1, 2000 - v1
    Checksum:iE3659DB19C59E1BB
    GO
    Isoform 2 (identifier: Q9UNH7-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-116: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:290
    Mass (Da):33,570
    Checksum:iC12EC83110C71CA8
    GO

    Sequence cautioni

    The sequence AAD24202.1 differs from that shown. Reason: Erroneous initiation.

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 116116Missing in isoform 2. 1 PublicationVSP_044824Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF121856 mRNA. Translation: AAD27829.1.
    U83194 mRNA. Translation: AAD24202.1. Different initiation.
    AL445363 Genomic DNA. No translation available.
    AL445883 Genomic DNA. No translation available.
    CH471078 Genomic DNA. Translation: EAW65913.1.
    CH471078 Genomic DNA. Translation: EAW65915.1.
    BC001798 mRNA. Translation: AAH01798.1.
    CCDSiCCDS9648.1. [Q9UNH7-2]
    RefSeqiNP_067072.3. NM_021249.3. [Q9UNH7-2]
    NP_689419.2. NM_152233.2.
    UniGeneiHs.356647.

    Genome annotation databases

    EnsembliENST00000396526; ENSP00000379779; ENSG00000129515. [Q9UNH7-2]
    GeneIDi58533.
    KEGGihsa:58533.
    UCSCiuc001wse.1. human. [Q9UNH7-1]

    Polymorphism databases

    DMDMi10720285.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF121856 mRNA. Translation: AAD27829.1 .
    U83194 mRNA. Translation: AAD24202.1 . Different initiation.
    AL445363 Genomic DNA. No translation available.
    AL445883 Genomic DNA. No translation available.
    CH471078 Genomic DNA. Translation: EAW65913.1 .
    CH471078 Genomic DNA. Translation: EAW65915.1 .
    BC001798 mRNA. Translation: AAH01798.1 .
    CCDSi CCDS9648.1. [Q9UNH7-2 ]
    RefSeqi NP_067072.3. NM_021249.3. [Q9UNH7-2 ]
    NP_689419.2. NM_152233.2.
    UniGenei Hs.356647.

    3D structure databases

    ProteinModelPortali Q9UNH7.
    SMRi Q9UNH7. Positions 21-175.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 121852. 40 interactions.
    DIPi DIP-37549N.
    IntActi Q9UNH7. 15 interactions.
    MINTi MINT-2634416.
    STRINGi 9606.ENSP00000355217.

    PTM databases

    PhosphoSitei Q9UNH7.

    Polymorphism databases

    DMDMi 10720285.

    2D gel databases

    OGPi Q9UNH7.
    REPRODUCTION-2DPAGE IPI00298111.

    Proteomic databases

    MaxQBi Q9UNH7.
    PaxDbi Q9UNH7.
    PRIDEi Q9UNH7.

    Protocols and materials databases

    DNASUi 58533.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000396526 ; ENSP00000379779 ; ENSG00000129515 . [Q9UNH7-2 ]
    GeneIDi 58533.
    KEGGi hsa:58533.
    UCSCi uc001wse.1. human. [Q9UNH7-1 ]

    Organism-specific databases

    CTDi 58533.
    GeneCardsi GC14M035030.
    H-InvDB HIX0011592.
    HGNCi HGNC:14970. SNX6.
    HPAi HPA049374.
    MIMi 606098. gene.
    neXtProti NX_Q9UNH7.
    PharmGKBi PA37946.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG255198.
    HOGENOMi HOG000231691.
    HOVERGENi HBG000716.
    InParanoidi Q9UNH7.
    KOi K17920.
    OrthoDBi EOG7X0VH4.
    PhylomeDBi Q9UNH7.
    TreeFami TF313698.

    Enzyme and pathway databases

    SignaLinki Q9UNH7.

    Miscellaneous databases

    ChiTaRSi SNX6. human.
    GenomeRNAii 58533.
    NextBioi 65116.
    PROi Q9UNH7.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UNH7.
    Bgeei Q9UNH7.
    CleanExi HS_SNX6.
    Genevestigatori Q9UNH7.

    Family and domain databases

    Gene3Di 1.20.1270.60. 1 hit.
    3.30.1520.10. 1 hit.
    InterProi IPR027267. AH/BAR-dom.
    IPR001683. Phox.
    IPR014637. SNX5/SNX6/SNX32.
    IPR028657. SNX6.
    IPR015404. Vps5_C.
    [Graphical view ]
    PANTHERi PTHR10555:SF120. PTHR10555:SF120. 1 hit.
    Pfami PF00787. PX. 1 hit.
    PF09325. Vps5. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF036924. Snx5_Snx6. 1 hit.
    SUPFAMi SSF64268. SSF64268. 1 hit.
    PROSITEi PS50195. PX. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A large family of endosome-localized proteins related to sorting nexin 1."
      Teasdale R.D., Loci D., Houghton F., Karlsson L., Gleeson P.A.
      Biochem. J. 358:7-16(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION.
    2. Toji S., Yano M., Kobayasi A., Tamai K.
      Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Eye.
    6. "Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases."
      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.
      J. Biol. Chem. 276:19332-19339(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION, SUBUNIT.
    7. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    8. "The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport."
      Hong Z., Yang Y., Zhang C., Niu Y., Li K., Zhao X., Liu J.J.
      Cell Res. 19:1334-1349(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH DCTN1; SNX1 AND SNX2, MUTAGENESIS OF ARG-68; GLN-69 AND ARG-97, SUBCELLULAR LOCATION.
    9. "Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing."
      Okada H., Zhang W., Peterhoff C., Hwang J.C., Nixon R.A., Ryu S.H., Kim T.W.
      FASEB J. 24:2783-2794(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BACE1.
    10. "Sorting nexin 6 interacts with breast cancer metastasis suppressor-1 and promotes transcriptional repression."
      Rivera J., Megias D., Bravo J.
      J. Cell. Biochem. 111:1464-1472(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH BRMS1.
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    12. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND MET-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiSNX6_HUMAN
    AccessioniPrimary (citable) accession number: Q9UNH7
    Secondary accession number(s): C0H5W9, Q9Y449
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 1, 2000
    Last sequence update: May 1, 2000
    Last modified: October 1, 2014
    This is version 125 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3