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Q9H0E2 (TOLIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Toll-interacting protein
Gene names
Name:TOLLIP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length274 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5

Subunit structure

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. Ref.5 Ref.6

Subcellular location

Cytoplasm Probable.

Post-translational modification

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

Sequence similarities

Belongs to the tollip family.

Contains 1 C2 domain.

Contains 1 CUE domain.

Sequence caution

The sequence BAB14283.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell-cell signaling

Traceable author statement Ref.1. Source: ProtInc

epithelial cell differentiation

Inferred from expression pattern PubMed 21492153. Source: UniProt

inflammatory response

Non-traceable author statement Ref.1. Source: UniProtKB

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Non-traceable author statement Ref.1. Source: UniProtKB

leukocyte activation

Non-traceable author statement PubMed 11441107. Source: UniProtKB

phosphorylation

Inferred from direct assay PubMed 1085432. Source: UniProtKB

positive regulation of protein sumoylation

Inferred from electronic annotation. Source: Ensembl

protein localization to endosome

Inferred from direct assay Ref.6. Source: UniProt

signal transduction

Inferred from physical interaction PubMed 11441107. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred by curator PubMed 11441107. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

interleukin-1 receptor complex

Non-traceable author statement Ref.1. Source: UniProtKB

interleukin-18 receptor complex

Non-traceable author statement Ref.1. Source: UniProtKB

nuclear body

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionToll-like receptor binding

Inferred from physical interaction Ref.1PubMed 11441107. Source: UniProtKB

kinase binding

Inferred from physical interaction Ref.1. Source: UniProtKB

signal transducer activity

Non-traceable author statement PubMed 11441107. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.8
Chain2 – 274273Toll-interacting protein
PRO_0000072625

Regions

Domain40 – 13596C2
Domain229 – 27244CUE
Compositional bias28 – 4417Gln-rich

Amino acid modifications

Modified residue21N-acetylalanine Ref.8

Natural variations

Natural variant2221A → S.
Corresponds to variant rs5744015 [ dbSNP | Ensembl ].
VAR_034557

Experimental info

Sequence conflict401Missing in CAB58118. Ref.1
Sequence conflict1501K → E in BAB14283. Ref.3

Secondary structure

.......... 274
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9H0E2 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 386E0F284D3837DA

FASTA27430,282
        10         20         30         40         50         60 
MATTVSTQRG PVYIGELPQD FLRITPTQQQ RQVQLDAQAA QQLQYGGAVG TVGRLNITVV 

        70         80         90        100        110        120 
QAKLAKNYGM TRMDPYCRLR LGYAVYETPT AHNGAKNPRW NKVIHCTVPP GVDSFYLEIF 

       130        140        150        160        170        180 
DERAFSMDDR IAWTHITIPE SLRQGKVEDK WYSLSGRQGD DKEGMINLVM SYALLPAAMV 

       190        200        210        220        230        240 
MPPQPVVLMP TVYQQGVGYV PITGMPAVCS PGMVPVALPP AAVNAQPRCS EEDLKAIQDM 

       250        260        270 
FPNMDQEVIR SVLEAQRGNK DAAINSLLQM GEEP 

« Hide

References

« Hide 'large scale' references
[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].
[2]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"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].
Tissue: Eye and Placenta.
[4]"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. expand/collapse author list , 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] OF 34-274.
[5]"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.
[6]"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.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[9]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ242972 mRNA. Translation: CAB58118.1.
AL136835 mRNA. Translation: CAB66769.1.
BC004420 mRNA. Translation: AAH04420.1.
BC012057 mRNA. Translation: AAH12057.1.
BC018272 mRNA. Translation: AAH18272.1.
AK022871 mRNA. Translation: BAB14283.1. Different initiation.
RefSeqNP_061882.2. NM_019009.3.
UniGeneHs.368527.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WGLNMR-A229-274[»]
ProteinModelPortalQ9H0E2.
SMRQ9H0E2. Positions 13-173, 231-274.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid119978. 71 interactions.
IntActQ9H0E2. 43 interactions.
MINTMINT-4539075.
STRING9606.ENSP00000314733.

PTM databases

PhosphoSiteQ9H0E2.

Polymorphism databases

DMDM20140803.

Proteomic databases

PaxDbQ9H0E2.
PRIDEQ9H0E2.

Protocols and materials databases

DNASU54472.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000317204; ENSP00000314733; ENSG00000078902.
GeneID54472.
KEGGhsa:54472.
UCSCuc001ltd.3. human.

Organism-specific databases

CTD54472.
GeneCardsGC11M001295.
HGNCHGNC:16476. TOLLIP.
HPAHPA038621.
HPA038622.
MIM606277. gene.
neXtProtNX_Q9H0E2.
PharmGKBPA134876213.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG85357.
HOGENOMHOG000293427.
HOVERGENHBG054213.
KOK05402.
OMAHVTIPES.
PhylomeDBQ9H0E2.
TreeFamTF324180.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkQ9H0E2.

Gene expression databases

ArrayExpressQ9H0E2.
BgeeQ9H0E2.
CleanExHS_TOLLIP.
GenevestigatorQ9H0E2.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR003892. CUE.
IPR009060. UBA-like.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF02845. CUE. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00546. CUE. 1 hit.
[Graphical view]
SUPFAMSSF46934. SSF46934. 1 hit.
SSF49562. SSF49562. 1 hit.
PROSITEPS51140. CUE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9H0E2.
GeneWikiTOLLIP.
GenomeRNAi54472.
NextBio56772.
PROQ9H0E2.
SOURCESearch...

Entry information

Entry nameTOLIP_HUMAN
AccessionPrimary (citable) accession number: Q9H0E2
Secondary accession number(s): Q9H9E6, Q9UJ69
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: March 1, 2001
Last modified: April 16, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM