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Q9H0E2

- TOLIP_HUMAN

UniProt

Q9H0E2 - TOLIP_HUMAN

Protein

Toll-interacting protein

Gene

TOLLIP

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 Mar 2001)
      Previous versions | rss
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    Functioni

    Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Recruits IRAK1 to the IL-1 receptor complex. Inhibits IRAK1 phosphorylation and kinase activity (PubMed:11751856). Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (PubMed:25042851).2 Publications

    GO - Molecular functioni

    1. kinase binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. signal transducer activity Source: UniProtKB
    4. Toll-like receptor binding Source: UniProtKB

    GO - Biological processi

    1. cell-cell signaling Source: ProtInc
    2. epithelial cell differentiation Source: UniProt
    3. inflammatory response Source: UniProtKB
    4. innate immune response Source: UniProtKB-KW
    5. intracellular signal transduction Source: UniProtKB
    6. leukocyte activation Source: UniProtKB
    7. phosphorylation Source: UniProtKB
    8. positive regulation of protein sumoylation Source: Ensembl
    9. protein localization to endosome Source: UniProt
    10. signal transduction Source: UniProtKB

    Keywords - Biological processi

    Autophagy, Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_22442. Interleukin-1 signaling.
    SignaLinkiQ9H0E2.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Toll-interacting protein
    Gene namesi
    Name:TOLLIP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:16476. TOLLIP.

    Subcellular locationi

    Cytoplasm Curated

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. extracellular vesicular exosome Source: UniProt
    4. interleukin-18 receptor complex Source: UniProtKB
    5. interleukin-1 receptor complex Source: UniProtKB
    6. nuclear body Source: Ensembl
    7. perinuclear region of cytoplasm Source: Ensembl

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA134876213.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 274273Toll-interacting proteinPRO_0000072625Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication

    Post-translational modificationi

    Phosphorylated by IRAK1 upon stimulation by IL-1 or microbial products.

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiQ9H0E2.
    PaxDbiQ9H0E2.
    PRIDEiQ9H0E2.

    PTM databases

    PhosphoSiteiQ9H0E2.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9H0E2.
    BgeeiQ9H0E2.
    CleanExiHS_TOLLIP.
    GenevestigatoriQ9H0E2.

    Organism-specific databases

    HPAiHPA038621.
    HPA038622.

    Interactioni

    Subunit structurei

    Oligomerizes. Binds to TLR2 and the TLR4-MD2 complex via its C-terminus. Exists as complex with IRAK1 in unstimulated cells. Upon IL-1 signaling, Tollip binds to the activated IL-1 receptor complex containing IL-1RI, IL-1RacP and the adapter protein MyD88, where it interacts with the TIR domain of IL-1RacP. MyD88 then triggers IRAK1 autophosphorylation, which in turn leads to the dissociation of IRAK1 from Tollip and IL-1RAcP. Interacts with TOM1L2. Interacts with ATG8 family proteins (via AIM motifs), and ubiquitin (via CUE domain).3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CSTF1Q050482EBI-74615,EBI-1789619
    DAZAP2Q150383EBI-74615,EBI-724310
    DZIP3Q86Y132EBI-74615,EBI-948630
    EIF2AK2P195252EBI-74615,EBI-640775
    IRAK2O431872EBI-74615,EBI-447733
    PEG10Q86TG72EBI-74615,EBI-2858265
    TOM1L1O756743EBI-74615,EBI-712991
    WRNIP1Q96S552EBI-74615,EBI-2513471

    Protein-protein interaction databases

    BioGridi119978. 71 interactions.
    IntActiQ9H0E2. 43 interactions.
    MINTiMINT-4539075.
    STRINGi9606.ENSP00000314733.

    Structurei

    Secondary structure

    1
    274
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi231 – 24010
    Beta strandi242 – 2443
    Helixi246 – 2538
    Turni254 – 2585
    Helixi260 – 26910

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1WGLNMR-A229-274[»]
    ProteinModelPortaliQ9H0E2.
    SMRiQ9H0E2. Positions 48-174, 231-274.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9H0E2.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini40 – 13596C2Add
    BLAST
    Domaini229 – 27244CUEPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi133 – 1364AIM1
    Motifi151 – 1544AIM2

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi28 – 4417Gln-richAdd
    BLAST

    Domaini

    Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.1 Publication

    Sequence similaritiesi

    Belongs to the tollip family.Curated
    Contains 1 C2 domain.Curated
    Contains 1 CUE domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiNOG85357.
    HOGENOMiHOG000293427.
    HOVERGENiHBG054213.
    KOiK05402.
    OMAiHVTIPES.
    PhylomeDBiQ9H0E2.
    TreeFamiTF324180.

    Family and domain databases

    Gene3Di2.60.40.150. 1 hit.
    InterProiIPR000008. C2_dom.
    IPR003892. CUE.
    IPR009060. UBA-like.
    [Graphical view]
    PfamiPF00168. C2. 1 hit.
    PF02845. CUE. 1 hit.
    [Graphical view]
    SMARTiSM00239. C2. 1 hit.
    SM00546. CUE. 1 hit.
    [Graphical view]
    SUPFAMiSSF46934. SSF46934. 1 hit.
    SSF49562. SSF49562. 1 hit.
    PROSITEiPS51140. CUE. 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: Q9H0E2-1) [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

    MATTVSTQRG PVYIGELPQD FLRITPTQQQ RQVQLDAQAA QQLQYGGAVG    50
    TVGRLNITVV QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW 100
    NKVIHCTVPP GVDSFYLEIF DERAFSMDDR IAWTHITIPE SLRQGKVEDK 150
    WYSLSGRQGD DKEGMINLVM SYALLPAAMV MPPQPVVLMP TVYQQGVGYV 200
    PITGMPAVCS PGMVPVALPP AAVNAQPRCS EEDLKAIQDM FPNMDQEVIR 250
    SVLEAQRGNK DAAINSLLQM GEEP 274
    Length:274
    Mass (Da):30,282
    Last modified:March 1, 2001 - v1
    Checksum:i386E0F284D3837DA
    GO
    Isoform 2 (identifier: Q9H0E2-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-69: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:205
    Mass (Da):22,812
    Checksum:iDED391C6A30BAE56
    GO

    Sequence cautioni

    The sequence BAB14283.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti40 – 401Missing in CAB58118. (PubMed:10854325)Curated
    Sequence conflicti150 – 1501K → E in BAB14283. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti222 – 2221A → S.
    Corresponds to variant rs5744015 [ dbSNP | Ensembl ].
    VAR_034557

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6969Missing in isoform 2. 1 PublicationVSP_056301Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ242972 mRNA. Translation: CAB58118.1.
    AL136835 mRNA. Translation: CAB66769.1.
    AK022871 mRNA. Translation: BAB14283.1. Different initiation.
    AK127123 mRNA. Translation: BAG54438.1.
    AC136297 Genomic DNA. No translation available.
    BC004420 mRNA. Translation: AAH04420.1.
    BC012057 mRNA. Translation: AAH12057.1.
    BC018272 mRNA. Translation: AAH18272.1.
    CCDSiCCDS7723.1.
    RefSeqiNP_061882.2. NM_019009.3.
    UniGeneiHs.368527.

    Genome annotation databases

    EnsembliENST00000317204; ENSP00000314733; ENSG00000078902.
    ENST00000527886; ENSP00000434035; ENSG00000078902.
    GeneIDi54472.
    KEGGihsa:54472.
    UCSCiuc001ltd.3. human.

    Polymorphism databases

    DMDMi20140803.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AJ242972 mRNA. Translation: CAB58118.1 .
    AL136835 mRNA. Translation: CAB66769.1 .
    AK022871 mRNA. Translation: BAB14283.1 . Different initiation.
    AK127123 mRNA. Translation: BAG54438.1 .
    AC136297 Genomic DNA. No translation available.
    BC004420 mRNA. Translation: AAH04420.1 .
    BC012057 mRNA. Translation: AAH12057.1 .
    BC018272 mRNA. Translation: AAH18272.1 .
    CCDSi CCDS7723.1.
    RefSeqi NP_061882.2. NM_019009.3.
    UniGenei Hs.368527.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1WGL NMR - A 229-274 [» ]
    ProteinModelPortali Q9H0E2.
    SMRi Q9H0E2. Positions 48-174, 231-274.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 119978. 71 interactions.
    IntActi Q9H0E2. 43 interactions.
    MINTi MINT-4539075.
    STRINGi 9606.ENSP00000314733.

    PTM databases

    PhosphoSitei Q9H0E2.

    Polymorphism databases

    DMDMi 20140803.

    Proteomic databases

    MaxQBi Q9H0E2.
    PaxDbi Q9H0E2.
    PRIDEi Q9H0E2.

    Protocols and materials databases

    DNASUi 54472.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000317204 ; ENSP00000314733 ; ENSG00000078902 .
    ENST00000527886 ; ENSP00000434035 ; ENSG00000078902 .
    GeneIDi 54472.
    KEGGi hsa:54472.
    UCSCi uc001ltd.3. human.

    Organism-specific databases

    CTDi 54472.
    GeneCardsi GC11M001295.
    HGNCi HGNC:16476. TOLLIP.
    HPAi HPA038621.
    HPA038622.
    MIMi 606277. gene.
    neXtProti NX_Q9H0E2.
    PharmGKBi PA134876213.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG85357.
    HOGENOMi HOG000293427.
    HOVERGENi HBG054213.
    KOi K05402.
    OMAi HVTIPES.
    PhylomeDBi Q9H0E2.
    TreeFami TF324180.

    Enzyme and pathway databases

    Reactomei REACT_22442. Interleukin-1 signaling.
    SignaLinki Q9H0E2.

    Miscellaneous databases

    EvolutionaryTracei Q9H0E2.
    GeneWikii TOLLIP.
    GenomeRNAii 54472.
    NextBioi 56772.
    PROi Q9H0E2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9H0E2.
    Bgeei Q9H0E2.
    CleanExi HS_TOLLIP.
    Genevestigatori Q9H0E2.

    Family and domain databases

    Gene3Di 2.60.40.150. 1 hit.
    InterProi IPR000008. C2_dom.
    IPR003892. CUE.
    IPR009060. UBA-like.
    [Graphical view ]
    Pfami PF00168. C2. 1 hit.
    PF02845. CUE. 1 hit.
    [Graphical view ]
    SMARTi SM00239. C2. 1 hit.
    SM00546. CUE. 1 hit.
    [Graphical view ]
    SUPFAMi SSF46934. SSF46934. 1 hit.
    SSF49562. SSF49562. 1 hit.
    PROSITEi PS51140. CUE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Tollip, a new component of the IL-1R1 pathway, links IRAK to the IL-1 receptor."
      Burns K., Clatworthy J., Martin L., Martinon F., Plumpton C., Maschera B., Lewis A., Ray K., Tschopp J., Volpe F.
      Nat. Cell Biol. 2:346-351(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Testis.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 34-274 (ISOFORM 1).
    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 1).
      Tissue: Eye and Placenta.
    6. "Negative regulation of Toll-like receptor-mediated signaling by Tollip."
      Zhang G., Ghosh S.
      J. Biol. Chem. 277:7059-7065(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TLR2 AND TLR4, FUNCTION.
    7. "Recruitment of clathrin onto endosomes by the Tom1-Tollip complex."
      Katoh Y., Imakagura H., Futatsumori M., Nakayama K.
      Biochem. Biophys. Res. Commun. 341:143-149(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TOM1L2.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    9. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    10. "Autophagic clearance of PolyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family."
      Lu K., Psakhye I., Jentsch S.
      Cell 158:0-0(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ATG8 FAMILY PROTEINS AND UBIQUITIN, DOMAIN, FUNCTION.
    11. "Solution structure of CUE domain in the C-terminal of human Toll-interacting protein (TOLLIP)."
      RIKEN structural genomics initiative (RSGI)
      Submitted (NOV-2004) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 229-274.

    Entry informationi

    Entry nameiTOLIP_HUMAN
    AccessioniPrimary (citable) accession number: Q9H0E2
    Secondary accession number(s): B3KXC6, Q9H9E6, Q9UJ69
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 27, 2002
    Last sequence update: March 1, 2001
    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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3