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P58753

- TIRAP_HUMAN

UniProt

P58753 - TIRAP_HUMAN

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Protein

Toll/interleukin-1 receptor domain-containing adapter protein

Gene

TIRAP

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

Functioni

Adapter involved in TLR2 and TLR4 signaling pathways in the innate immune response. Acts via IRAK2 and TRAF-6, leading to the activation of NF-kappa-B, MAPK1, MAPK3 and JNK, and resulting in cytokine secretion and the inflammatory response. Positively regulates the production of TNF-alpha and interleukin-6.2 Publications

GO - Molecular functioni

  1. phosphatidylinositol-4,5-bisphosphate binding Source: BHF-UCL
  2. protein binding, bridging Source: BHF-UCL
  3. protein heterodimerization activity Source: BHF-UCL
  4. protein homodimerization activity Source: BHF-UCL
  5. protein kinase C binding Source: BHF-UCL
  6. Toll-like receptor 2 binding Source: BHF-UCL
  7. Toll-like receptor 4 binding Source: BHF-UCL

GO - Biological processi

  1. 3'-UTR-mediated mRNA stabilization Source: BHF-UCL
  2. cell surface receptor signaling pathway Source: BHF-UCL
  3. cellular response to bacterial lipopeptide Source: BHF-UCL
  4. cellular response to lipoteichoic acid Source: BHF-UCL
  5. defense response to Gram-positive bacterium Source: BHF-UCL
  6. I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  7. inflammatory response Source: UniProtKB-KW
  8. innate immune response Source: Reactome
  9. MyD88-dependent toll-like receptor signaling pathway Source: BHF-UCL
  10. myeloid cell differentiation Source: BHF-UCL
  11. negative regulation of growth of symbiont in host Source: BHF-UCL
  12. positive regulation of B cell proliferation Source: BHF-UCL
  13. positive regulation of chemokine (C-X-C motif) ligand 1 production Source: BHF-UCL
  14. positive regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  15. positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  16. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: BHF-UCL
  17. positive regulation of interleukin-12 production Source: BHF-UCL
  18. positive regulation of interleukin-15 production Source: BHF-UCL
  19. positive regulation of interleukin-6 biosynthetic process Source: BHF-UCL
  20. positive regulation of interleukin-8 production Source: BHF-UCL
  21. positive regulation of JNK cascade Source: BHF-UCL
  22. positive regulation of neutrophil chemotaxis Source: BHF-UCL
  23. positive regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  24. positive regulation of protein homodimerization activity Source: BHF-UCL
  25. positive regulation of toll-like receptor 2 signaling pathway Source: BHF-UCL
  26. positive regulation of toll-like receptor 3 signaling pathway Source: BHF-UCL
  27. positive regulation of toll-like receptor 4 signaling pathway Source: BHF-UCL
  28. positive regulation of tumor necrosis factor production Source: BHF-UCL
  29. regulation of innate immune response Source: BHF-UCL
  30. regulation of interferon-beta production Source: BHF-UCL
  31. response to lipopolysaccharide Source: BHF-UCL
  32. TIRAP-dependent toll-like receptor 4 signaling pathway Source: BHF-UCL
  33. toll-like receptor 2 signaling pathway Source: Reactome
  34. toll-like receptor 4 signaling pathway Source: Reactome
  35. toll-like receptor signaling pathway Source: Reactome
  36. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  37. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
SignaLinkiP58753.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll/interleukin-1 receptor domain-containing adapter protein
Short name:
TIR domain-containing adapter protein
Alternative name(s):
Adaptor protein Wyatt
MyD88 adapter-like protein
Short name:
MyD88-2
Gene namesi
Name:TIRAP
Synonyms:MAL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:17192. TIRAP.

Subcellular locationi

Cytoplasm 1 Publication. Cell membrane 1 Publication. Membrane 1 Publication
Note: Colocalizes with DAB2IP at the plasma membrane.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. endocytic vesicle Source: BHF-UCL
  4. plasma membrane Source: UniProtKB
  5. ruffle membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi125 – 1251P → H: Abolishes NF-kappa-B activation. 2 Publications

Organism-specific databases

MIMi607948. phenotype.
610799. phenotype.
611162. phenotype.
614382. phenotype.
PharmGKBiPA134972842.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 221221Toll/interleukin-1 receptor domain-containing adapter proteinPRO_0000072547Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi89 ↔ 1341 Publication
Disulfide bondi142 ↔ 1741 Publication

Post-translational modificationi

Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK.
Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.1 Publication

Keywords - PTMi

Disulfide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP58753.
PRIDEiP58753.

PTM databases

PhosphoSiteiP58753.

Expressioni

Tissue specificityi

Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.

Gene expression databases

BgeeiP58753.
CleanExiHS_MAL.
HS_TIRAP.
ExpressionAtlasiP58753. baseline and differential.
GenevestigatoriP58753.

Organism-specific databases

HPAiHPA054431.

Interactioni

Subunit structurei

Homodimer. Also forms heterodimers with MYD88. May interact with PIK3AP1 (By similarity). Interacts with TLR4 and IRAK2 via their respective TIR domains. Interacts with BMX and TBK1. Interacts with EIF2AK2. Does not interact with IRAK1, nor TLR9.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARAFP103982EBI-528644,EBI-365961
CCDC47Q96A332EBI-528644,EBI-720151
IRAK1P516172EBI-528644,EBI-358664
IRAK2O431872EBI-528644,EBI-447733
IRAK4Q9NWZ32EBI-528644,EBI-448378
LTN1O948222EBI-528644,EBI-1044684
MYD88Q998366EBI-528644,EBI-447677
PIK3R1P279863EBI-528644,EBI-79464
SAMHD1Q9Y3Z32EBI-528644,EBI-1054601
TLR4O002062EBI-528644,EBI-528701

Protein-protein interaction databases

BioGridi125325. 42 interactions.
DIPiDIP-33489N.
IntActiP58753. 31 interactions.
MINTiMINT-4950450.
STRINGi9606.ENSP00000376445.

Structurei

Secondary structure

1
221
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi83 – 919Combined sources
Helixi94 – 963Combined sources
Helixi97 – 10812Combined sources
Beta strandi131 – 1333Combined sources
Beta strandi140 – 1478Combined sources
Helixi149 – 1535Combined sources
Helixi155 – 16612Combined sources
Beta strandi168 – 17912Combined sources
Helixi184 – 1863Combined sources
Helixi189 – 1935Combined sources
Helixi202 – 2054Combined sources
Helixi206 – 21712Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Y92X-ray3.01A79-221[»]
3UB2X-ray2.40A78-221[»]
3UB3X-ray2.75A78-221[»]
3UB4X-ray3.10A78-221[»]
4FZ5X-ray3.60A/B72-221[»]
4LQDX-ray2.45A81-221[»]
ProteinModelPortaliP58753.
SMRiP58753. Positions 79-221.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini84 – 221138TIRPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 TIR domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG80263.
GeneTreeiENSGT00510000048428.
HOGENOMiHOG000068972.
HOVERGENiHBG054203.
InParanoidiP58753.
KOiK05403.
OMAiFRQVKEA.
PhylomeDBiP58753.
TreeFamiTF330734.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000157. TIR_dom.
IPR017279. Tol-interleuk_rcpt_adapt_Tirap.
[Graphical view]
PANTHERiPTHR22662. PTHR22662. 1 hit.
PfamiPF13676. TIR_2. 1 hit.
[Graphical view]
PIRSFiPIRSF037750. TIR_Tirap. 1 hit.
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P58753-1) [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
MASSTSLPAP GSRPKKPLGK MADWFRQTLL KKPKKRPNSP ESTSSDASQP
60 70 80 90 100
TSQDSPLPPS LSSVTSPSLP PTHASDSGSS RWSKDYDVCV CHSEEDLVAA
110 120 130 140 150
QDLVSYLEGS TASLRCFLQL RDATPGGAIV SELCQALSSS HCRVLLITPG
160 170 180 190 200
FLQDPWCKYQ MLQALTEAPG AEGCTIPLLS GLSRAAYPPE LRFMYYVDGR
210 220
GPDGGFRQVK EAVMRYLQTL S
Length:221
Mass (Da):23,883
Last modified:July 19, 2004 - v2
Checksum:i44A8454D04704540
GO
Isoform 2 (identifier: P58753-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     216-221: YLQTLS → CKLLQEGEGERDSATVSDLL

Show »
Length:235
Mass (Da):25,323
Checksum:i383386AA03B70F32
GO
Isoform 3 (identifier: P58753-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     221-221: S → WHLLYHGTPEIGVKLETENPCRASDSHKCDKRYRE

Show »
Length:255
Mass (Da):27,948
Checksum:i97287F7E2A010915
GO

Polymorphismi

Genetic variations in TIRAP may influence susceptibility or resistance to invasive pneumococcal disease [MIMi:610799], malaria [MIMi:611162], and tuberculosis [MIMi:607948].
Genetic variations in TIRAP influence susceptibility or resistance to bacterial invasion of the blood and define the bacteremia susceptibility locus 1 (BACTS1) [MIMi:614382].

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91A → P Does not affect NF-kappa-B activation and TNF-alpha production. 1 Publication
Corresponds to variant rs8177369 [ dbSNP | Ensembl ].
VAR_019143
Natural varianti13 – 131R → W Does not affect NF-kappa-B activation and TNF-alpha production. 1 Publication
Corresponds to variant rs8177399 [ dbSNP | Ensembl ].
VAR_019144
Natural varianti55 – 551S → N Does not affect NF-kappa-B activation and TNF-alpha production. 2 Publications
Corresponds to variant rs3802813 [ dbSNP | Ensembl ].
VAR_036691
Natural varianti96 – 961D → N Hypomorphic variant resulting in impaired NF-kappa-B activation and TNF-alpha production; cannot bind MYD88. 2 Publications
Corresponds to variant rs8177400 [ dbSNP | Ensembl ].
VAR_019145
Natural varianti180 – 1801S → L At heterozygosity it protects against invasive pneumococcal disease, malaria, bacteremia and tuberculosis; does not affect NF-kappa-B activation and TNF-alpha production; attenuates TLR2 signal transduction. 3 Publications
Corresponds to variant rs8177374 [ dbSNP | Ensembl ].
VAR_019146
Natural varianti197 – 1971V → I Does not affect NF-kappa-B activation and TNF-alpha production.
Corresponds to variant rs7932976 [ dbSNP | Ensembl ].
VAR_061713

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei216 – 2216YLQTLS → CKLLQEGEGERDSATVSDLL in isoform 2. 4 PublicationsVSP_010765
Alternative sequencei221 – 2211S → WHLLYHGTPEIGVKLETENP CRASDSHKCDKRYRE in isoform 3. 1 PublicationVSP_017239

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF406652 mRNA. Translation: AAL01160.1.
AF378129 mRNA. Translation: AAL05627.1.
AF410783 mRNA. Translation: AAL05036.1.
AY576785 mRNA. Translation: AAT90417.1.
AY576786 mRNA. Translation: AAT90418.1.
AY576787 mRNA. Translation: AAT90419.1.
AB446477 mRNA. Translation: BAG55254.1.
AK124298 mRNA. Translation: BAG54027.1.
AK313147 mRNA. Translation: BAG35965.1.
AY282416 Genomic DNA. Translation: AAP31973.1.
AP001318 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67687.1.
CH471065 Genomic DNA. Translation: EAW67689.1.
BC032474 mRNA. Translation: AAH32474.1.
CCDSiCCDS41731.1. [P58753-2]
CCDS8472.1. [P58753-1]
RefSeqiNP_001034750.1. NM_001039661.1. [P58753-1]
NP_683708.1. NM_148910.2. [P58753-2]
UniGeneiHs.537126.

Genome annotation databases

EnsembliENST00000392678; ENSP00000376445; ENSG00000150455. [P58753-2]
ENST00000392679; ENSP00000376446; ENSG00000150455. [P58753-1]
ENST00000392680; ENSP00000376447; ENSG00000150455. [P58753-1]
ENST00000479770; ENSP00000436967; ENSG00000150455. [P58753-1]
GeneIDi114609.
KEGGihsa:114609.
UCSCiuc001qdl.1. human. [P58753-2]
uc001qdm.1. human. [P58753-1]

Polymorphism databases

DMDMi50403750.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF406652 mRNA. Translation: AAL01160.1 .
AF378129 mRNA. Translation: AAL05627.1 .
AF410783 mRNA. Translation: AAL05036.1 .
AY576785 mRNA. Translation: AAT90417.1 .
AY576786 mRNA. Translation: AAT90418.1 .
AY576787 mRNA. Translation: AAT90419.1 .
AB446477 mRNA. Translation: BAG55254.1 .
AK124298 mRNA. Translation: BAG54027.1 .
AK313147 mRNA. Translation: BAG35965.1 .
AY282416 Genomic DNA. Translation: AAP31973.1 .
AP001318 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67687.1 .
CH471065 Genomic DNA. Translation: EAW67689.1 .
BC032474 mRNA. Translation: AAH32474.1 .
CCDSi CCDS41731.1. [P58753-2 ]
CCDS8472.1. [P58753-1 ]
RefSeqi NP_001034750.1. NM_001039661.1. [P58753-1 ]
NP_683708.1. NM_148910.2. [P58753-2 ]
UniGenei Hs.537126.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2Y92 X-ray 3.01 A 79-221 [» ]
3UB2 X-ray 2.40 A 78-221 [» ]
3UB3 X-ray 2.75 A 78-221 [» ]
3UB4 X-ray 3.10 A 78-221 [» ]
4FZ5 X-ray 3.60 A/B 72-221 [» ]
4LQD X-ray 2.45 A 81-221 [» ]
ProteinModelPortali P58753.
SMRi P58753. Positions 79-221.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 125325. 42 interactions.
DIPi DIP-33489N.
IntActi P58753. 31 interactions.
MINTi MINT-4950450.
STRINGi 9606.ENSP00000376445.

PTM databases

PhosphoSitei P58753.

Polymorphism databases

DMDMi 50403750.

Proteomic databases

PaxDbi P58753.
PRIDEi P58753.

Protocols and materials databases

DNASUi 114609.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000392678 ; ENSP00000376445 ; ENSG00000150455 . [P58753-2 ]
ENST00000392679 ; ENSP00000376446 ; ENSG00000150455 . [P58753-1 ]
ENST00000392680 ; ENSP00000376447 ; ENSG00000150455 . [P58753-1 ]
ENST00000479770 ; ENSP00000436967 ; ENSG00000150455 . [P58753-1 ]
GeneIDi 114609.
KEGGi hsa:114609.
UCSCi uc001qdl.1. human. [P58753-2 ]
uc001qdm.1. human. [P58753-1 ]

Organism-specific databases

CTDi 114609.
GeneCardsi GC11P126153.
HGNCi HGNC:17192. TIRAP.
HPAi HPA054431.
MIMi 606252. gene.
607948. phenotype.
610799. phenotype.
611162. phenotype.
614382. phenotype.
neXtProti NX_P58753.
PharmGKBi PA134972842.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG80263.
GeneTreei ENSGT00510000048428.
HOGENOMi HOG000068972.
HOVERGENi HBG054203.
InParanoidi P58753.
KOi K05403.
OMAi FRQVKEA.
PhylomeDBi P58753.
TreeFami TF330734.

Enzyme and pathway databases

Reactomei REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
SignaLinki P58753.

Miscellaneous databases

GenomeRNAii 114609.
NextBioi 79099.
PROi P58753.
SOURCEi Search...

Gene expression databases

Bgeei P58753.
CleanExi HS_MAL.
HS_TIRAP.
ExpressionAtlasi P58753. baseline and differential.
Genevestigatori P58753.

Family and domain databases

Gene3Di 3.40.50.10140. 1 hit.
InterProi IPR000157. TIR_dom.
IPR017279. Tol-interleuk_rcpt_adapt_Tirap.
[Graphical view ]
PANTHERi PTHR22662. PTHR22662. 1 hit.
Pfami PF13676. TIR_2. 1 hit.
[Graphical view ]
PIRSFi PIRSF037750. TIR_Tirap. 1 hit.
SUPFAMi SSF52200. SSF52200. 1 hit.
PROSITEi PS50104. TIR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), MUTAGENESIS OF PRO-125, VARIANT ASN-55.
    Tissue: Dendritic cell.
  2. "TIRAP: an adapter molecule in the Toll signaling pathway."
    Horng T., Barton G.M., Medzhitov R.
    Nat. Immunol. 2:835-841(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), MUTAGENESIS OF PRO-125, INTERACTION WITH EIF2AK2.
  3. "Characterization and structural analysis of TIR domain-containing adaptor protein Wyatt."
    Kirk P.B., Pereira J.P., Bazan J.F.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "Two isoforms of MAL, generated by alternative splicing, are found in humans but not mice."
    Hardy M.P., O'Neill L.A.J.
    Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
  5. "Natural selection in the TLR-related genes in the course of primate evolution."
    Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
    Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  6. "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] (ISOFORMS 1 AND 2), VARIANT ASN-55.
    Tissue: Brain and Trachea.
  7. SeattleSNPs variation discovery resource
    Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-9; TRP-13; ASN-96 AND LEU-180.
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "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 3).
    Tissue: Blood.
  11. "Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like receptor signaling."
    Sato S., Sugiyama M., Yamamoto M., Watanabe Y., Kawai T., Takeda K., Akira S.
    J. Immunol. 171:4304-4310(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TBK1.
  12. "Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation."
    Mansell A., Smith R., Doyle S.L., Gray P., Fenner J.E., Crack P.J., Nicholson S.E., Hilton D.J., O'Neill L.A., Hertzog P.J.
    Nat. Immunol. 7:148-155(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY BTK, UBIQUITINATION.
  13. "Etk/BMX, a Btk family tyrosine kinase, and Mal contribute to the cross-talk between MyD88 and FAK pathways."
    Semaan N., Alsaleh G., Gottenberg J.E., Wachsmann D., Sibilia J.
    J. Immunol. 180:3485-3491(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH BMX.
  14. "A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling."
    Nagpal K., Plantinga T.S., Wong J., Monks B.G., Gay N.J., Netea M.G., Fitzgerald K.A., Golenbock D.T.
    J. Biol. Chem. 284:25742-25748(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MYD88, VARIANT ASN-96, CHARACTERIZATION OF VARIANTS PRO-9; TRP-13; ASN-96; LEU-180 AND ILE-197.
  15. "AIP1 functions as Arf6-GAP to negatively regulate TLR4 signaling."
    Wan T., Liu T., Zhang H., Tang S., Min W.
    J. Biol. Chem. 285:3750-3757(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MYD88, SUBCELLULAR LOCATION.
  16. "IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal)."
    Dunne A., Carpenter S., Brikos C., Gray P., Strelow A., Wesche H., Morrice N., O'Neill L.A.
    J. Biol. Chem. 285:18276-18282(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY IRAK1 AND IRAK4.
  17. "Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection."
    Valkov E., Stamp A., Dimaio F., Baker D., Verstak B., Roversi P., Kellie S., Sweet M.J., Mansell A., Gay N.J., Martin J.L., Kobe B.
    Proc. Natl. Acad. Sci. U.S.A. 108:14879-14884(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 79-221, SUBUNIT, DISULFIDE BONDS.
  18. Cited for: VARIANT LEU-180, POSSIBLE INVOLVEMENT IN PROTECTION AGAINST INVASIVE PNEUMOCOCCAL DISEASE; BACTEREMIA; MALARIA AND TUBERCULOSIS.
  19. "Low frequency of the TIRAP S180L polymorphism in Africa, and its potential role in malaria, sepsis, and leprosy."
    Hamann L., Kumpf O., Schuring R.P., Alpsoy E., Bedu-Addo G., Bienzle U., Oskam L., Mockenhaupt F.P., Schumann R.R.
    BMC Med. Genet. 10:65-65(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LEU-180.

Entry informationi

Entry nameiTIRAP_HUMAN
AccessioniPrimary (citable) accession number: P58753
Secondary accession number(s): B3KW65
, Q56UH9, Q56UI0, Q8N5E5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: July 19, 2004
Last modified: October 29, 2014
This is version 125 of the entry and version 2 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

Caution

Variant Leu-180 has been reported to reduce TLR2 signal transduction (PubMed:17322885). In contrast, PubMed:19509286 reports that this variant is fully active and has no effect on signal transduction pathways and cytokine production.1 Publication

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