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Q9H0E2

- TOLIP_HUMAN

UniProt

Q9H0E2 - TOLIP_HUMAN

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Protein

Toll-interacting protein

Gene

TOLLIP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

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. signal transducer activity Source: UniProtKB
  3. Toll-like receptor binding Source: UniProtKB

GO - Biological processi

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

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: UniProtKB
  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
Complete GO annotation...

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

BgeeiQ9H0E2.
CleanExiHS_TOLLIP.
ExpressionAtlasiQ9H0E2. baseline and differential.
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. 75 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.
GeneTreeiENSGT00390000013104.
HOGENOMiHOG000293427.
HOVERGENiHBG054213.
InParanoidiQ9H0E2.
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

        10         20         30         40         50
MATTVSTQRG PVYIGELPQD FLRITPTQQQ RQVQLDAQAA QQLQYGGAVG
60 70 80 90 100
TVGRLNITVV QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW
110 120 130 140 150
NKVIHCTVPP GVDSFYLEIF DERAFSMDDR IAWTHITIPE SLRQGKVEDK
160 170 180 190 200
WYSLSGRQGD DKEGMINLVM SYALLPAAMV MPPQPVVLMP TVYQQGVGYV
210 220 230 240 250
PITGMPAVCS PGMVPVALPP AAVNAQPRCS EEDLKAIQDM FPNMDQEVIR
260 270
SVLEAQRGNK DAAINSLLQM GEEP
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. [Q9H0E2-1]
RefSeqiNP_061882.2. NM_019009.3.
UniGeneiHs.368527.

Genome annotation databases

EnsembliENST00000317204; ENSP00000314733; ENSG00000078902. [Q9H0E2-1]
ENST00000527886; ENSP00000434035; ENSG00000078902. [Q9H0E2-2]
GeneIDi54472.
KEGGihsa:54472.
UCSCiuc001ltd.3. human. [Q9H0E2-1]

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. [Q9H0E2-1 ]
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. 75 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 . [Q9H0E2-1 ]
ENST00000527886 ; ENSP00000434035 ; ENSG00000078902 . [Q9H0E2-2 ]
GeneIDi 54472.
KEGGi hsa:54472.
UCSCi uc001ltd.3. human. [Q9H0E2-1 ]

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.
GeneTreei ENSGT00390000013104.
HOGENOMi HOG000293427.
HOVERGENi HBG054213.
InParanoidi Q9H0E2.
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 35470571.
PROi Q9H0E2.
SOURCEi Search...

Gene expression databases

Bgeei Q9H0E2.
CleanExi HS_TOLLIP.
ExpressionAtlasi Q9H0E2. baseline and differential.
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

« Hide 'large scale' publications
  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 158:549-563(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 29, 2014
This is version 126 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