Q9H0E2 (TOLIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Toll-interacting protein

Gene names

Name:

TOLLIP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	274 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.8
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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell-cell signaling Traceable author statement. Source: ProtInc 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. Source: UniProtKB phosphorylation Inferred from direct assay. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: Reactome interleukin-1 receptor complex Non-traceable author statement Ref.1. Source: UniProtKB interleukin-18 receptor complex Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	Toll-like receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB kinase binding Inferred from physical interaction Ref.1. Source: UniProtKB signal transducer activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAZAP2	Q15038	3	EBI-74615,EBI-724310

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 274

273

Toll-interacting protein

PRO_0000072625

Regions

Domain

40 – 135

96

C2

Domain

229 – 272

44

CUE

Compositional bias

28 – 44

17

Gln-rich

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.7

Modified residue

83

1

Phosphotyrosine Ref.8

Natural variations

Natural variant

222

1

A → S.
Corresponds to variant rs5744015 [ dbSNP | Ensembl ].

VAR_034557

Experimental info

Sequence conflict

40

1

Missing in CAB58118. Ref.1

Sequence conflict

150

1

K → E in BAB14283. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

274

Helix Strand Turn

Details...

Helix

231 – 240

10

Beta strand

242 – 244

3

Helix

246 – 253

8

Turn

254 – 258

5

Helix

260 – 269

10

Sequences

	Sequence		Length	Mass (Da)
	Q9H0E2 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 386E0F284D3837DA	FASTA	274	30,282
	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

References

	« Hide 'large scale' referencesShow '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: 10854325] [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. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [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: 15489334] [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. , 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: 14702039] [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: 11751856] [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: 16412388] [Abstract] Cited for: INTERACTION WITH TOM1L2.
[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: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-83, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[9]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"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.

IPI

IPI00100154.

RefSeq

NP_061882.2. NM_019009.3.

UniGene

Hs.368527.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WGL	NMR	-	A	229-274	[»]

ProteinModelPortal

Q9H0E2.

SMR

Q9H0E2. Positions 13-173, 231-274.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H0E2. 22 interactions.

STRING

Q9H0E2.

PTM databases

PhosphoSite

Q9H0E2.

Polymorphism databases

DMDM

20140803.

Proteomic databases

PRIDE

Q9H0E2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000317204; ENSP00000314733; ENSG00000078902.

GeneID

54472.

KEGG

hsa:54472.

UCSC

uc001lte.1. human.

Organism-specific databases

CTD

54472.

GeneCards

GC11M001295.

H-InvDB

HIX0009360.

HGNC

HGNC:16476. TOLLIP.

HPA

HPA038621.
HPA038622.

MIM

606277. gene.

neXtProt

NX_Q9H0E2.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00390000013104.

HOVERGEN

HBG054213.

OrthoDB

EOG4PK28P.

PhylomeDB

Q9H0E2.

Enzyme and pathway databases

Pathway_Interaction_DB

il1pathway. IL1-mediated signaling events.

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

Q9H0E2.

Bgee

Q9H0E2.

CleanEx

HS_TOLLIP.

Genevestigator

Q9H0E2.

GermOnline

ENSG00000078902. Homo sapiens.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR003892. CUE.
IPR009060. UBA-like.
[Graphical view]

KO

K05402.

Pfam

PF00168. C2. 1 hit.
PF02845. CUE. 1 hit.
[Graphical view]

SMART

SM00239. C2. 1 hit.
SM00546. CUE. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF46934. UBA_like. 1 hit.

PROSITE

PS50004. C2. False negative.
PS51140. CUE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

56772.

SOURCE

Search...

Entry information

Entry name

TOLIP_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.