P58753 (TIRAP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	TIRAP
Synonyms:	MAL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	221 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.13 Ref.14
Subunit structure	Homodimer. Also forms heterodimers with MyD88. Binds to TLR4 and IRAK2 via their respective TIR domains. Binds to BMX, PKR and TBK1. Does not interact with IRAK1, nor TLR9. Ref.11 Ref.13 Ref.14 Ref.16
Subcellular location	Cytoplasm By similarity.
Tissue specificity	Highly expressed in liver, kidney, spleen, skeletal muscle and heart. Also detected in peripheral blood leukocytes, lung, placenta, small intestine, thymus, colon and brain.
Post-translational modification	Phosphorylated by IRAK1 and IRAK4. Also phosphorylated by BTK. Ref.12 Ref.15 Polyubiquitinated. Polyubiquitination follows phosphorylation by BTK and leads to TIRAP degradation.
Polymorphism	Genetic variations in TIRAP may influence susceptibility or resistance to invasive pneumococcal disease [MIM:610799], malaria [MIM:611162], and tuberculosis [MIM:607948]. Genetic variations in TIRAP influence susceptibility or resistance to bacterial invasion of the blood and define the bacteremia susceptibility locus 1 (BACTS1) [MIM:614382].
Sequence similarities	Contains 1 TIR domain.
Caution	Variant Leu-180 has been reported to reduce TLR2 signal transduction (Ref.17). In contrast, Ref.14 reports that this variant is fully active and has no effect on signal transduction pathways and cytokine production.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
PTM	Disulfide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	3'-UTR-mediated mRNA stabilization Inferred from direct assay PubMed 15294994. Source: BHF-UCL I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara MyD88-dependent toll-like receptor signaling pathway Traceable author statement Ref.14. Source: BHF-UCL TIRAP-dependent toll-like receptor 4 signaling pathway Inferred from direct assay Ref.1. Source: BHF-UCL Toll signaling pathway Traceable author statement. Source: Reactome cellular response to bacterial lipopeptide Inferred from sequence or structural similarity. Source: BHF-UCL cellular response to lipoteichoic acid Inferred from sequence or structural similarity. Source: BHF-UCL defense response to Gram-positive bacterium Inferred from sequence or structural similarity. Source: BHF-UCL inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome myeloid cell differentiation Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of growth of symbiont in host Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of B cell proliferation Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.1. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.14. Source: BHF-UCL positive regulation of JNK cascade Inferred from mutant phenotype Ref.1. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from mutant phenotype Ref.14. Source: BHF-UCL positive regulation of chemokine (C-X-C motif) ligand 1 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of chemokine (C-X-C motif) ligand 2 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-12 production Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of interleukin-15 production Inferred from direct assay PubMed 18583567. Source: BHF-UCL positive regulation of interleukin-6 biosynthetic process Inferred from mutant phenotype PubMed 16301656. Source: BHF-UCL positive regulation of interleukin-8 production Inferred from mutant phenotype PubMed 16301656. Source: BHF-UCL positive regulation of neutrophil chemotaxis Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of protein homodimerization activity Inferred from direct assay PubMed 12062447. Source: BHF-UCL positive regulation of toll-like receptor 2 signaling pathway Inferred from mutant phenotype Ref.14. Source: BHF-UCL positive regulation of toll-like receptor 3 signaling pathway Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of toll-like receptor 4 signaling pathway Inferred from mutant phenotype Ref.14. Source: BHF-UCL positive regulation of tumor necrosis factor production Inferred from mutant phenotype PubMed 16301656Ref.14. Source: BHF-UCL regulation of interferon-beta production Inferred from sequence or structural similarity. Source: BHF-UCL response to lipopolysaccharide Inferred from direct assay Ref.1. Source: BHF-UCL toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome
Cellular_component	endocytic vesicle Inferred from sequence or structural similarity. Source: BHF-UCL ruffle membrane Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	phosphatidylinositol-4,5-bisphosphate binding Inferred from sequence or structural similarity. Source: BHF-UCL protein binding, bridging Non-traceable author statement Ref.14. Source: BHF-UCL protein heterodimerization activity Inferred from direct assay Ref.14. Source: BHF-UCL protein homodimerization activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ARAF	P10398	2	EBI-528644,EBI-365961
CCDC47	Q96A33	2	EBI-528644,EBI-720151
IRAK1	P51617	2	EBI-528644,EBI-358664
IRAK2	O43187	2	EBI-528644,EBI-447733
IRAK4	Q9NWZ3	2	EBI-528644,EBI-448378
LTN1	O94822	2	EBI-528644,EBI-1044684
MYD88	Q99836	4	EBI-528644,EBI-447677
SAMHD1	Q9Y3Z3	2	EBI-528644,EBI-1054601
TLR4	O00206	2	EBI-528644,EBI-528701

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P58753-1)

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.

Isoform 2 (identifier: P58753-2)

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

Isoform 3 (identifier: P58753-3)

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 221

221

Toll/interleukin-1 receptor domain-containing adapter protein

PRO_0000072547

Regions

Domain

84 – 221

138

TIR

Amino acid modifications

Disulfide bond

89 ↔ 134

Ref.16

Disulfide bond

142 ↔ 174

Ref.16

Natural variations

Alternative sequence

216 – 221

6

YLQTLS → CKLLQEGEGERDSATVSDLL in isoform 2.

VSP_010765

Alternative sequence

221

1

S → WHLLYHGTPEIGVKLETENP CRASDSHKCDKRYRE in isoform 3.

VSP_017239

Natural variant

9

1

A → P Does not affect NF-kappa-B activation and TNF-alpha production. Ref.7 Ref.14
Corresponds to variant rs8177369 [ dbSNP | Ensembl ].

VAR_019143

Natural variant

13

1

R → W Does not affect NF-kappa-B activation and TNF-alpha production. Ref.7 Ref.14
Corresponds to variant rs8177399 [ dbSNP | Ensembl ].

VAR_019144

Natural variant

55

1

S → N Does not affect NF-kappa-B activation and TNF-alpha production. Ref.1 Ref.6
Corresponds to variant rs3802813 [ dbSNP | Ensembl ].

VAR_036691

Natural variant

96

1

D → N Hypomorphic variant resulting in impaired NF-kappa-B activation and TNF-alpha production; cannot bind MYD88. Ref.7 Ref.14
Corresponds to variant rs8177400 [ dbSNP | Ensembl ].

VAR_019145

Natural variant

180

1

S → 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. Ref.7 Ref.14 Ref.17 Ref.18
Corresponds to variant rs8177374 [ dbSNP | Ensembl ].

VAR_019146

Natural variant

197

1

V → I Does not affect NF-kappa-B activation and TNF-alpha production. Ref.14
Corresponds to variant rs7932976 [ dbSNP | Ensembl ].

VAR_061713

Experimental info

Mutagenesis

125

1

P → H: Abolishes NF-kappa-B activation. Ref.1 Ref.2

Secondary structure

1

.

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221

Helix Strand Turn

Details...

Beta strand

83 – 91

9

Helix

94 – 96

3

Helix

97 – 108

12

Beta strand

131 – 133

3

Beta strand

140 – 147

8

Helix

149 – 153

5

Helix

155 – 166

12

Beta strand

168 – 179

12

Helix

184 – 186

3

Helix

189 – 193

5

Helix

202 – 205

4

Helix

206 – 217

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: 44A8454D04704540	FASTA	221	23,883
	10 20 30 40 50 60 MASSTSLPAP GSRPKKPLGK MADWFRQTLL KKPKKRPNSP ESTSSDASQP TSQDSPLPPS 70 80 90 100 110 120 LSSVTSPSLP PTHASDSGSS RWSKDYDVCV CHSEEDLVAA QDLVSYLEGS TASLRCFLQL 130 140 150 160 170 180 RDATPGGAIV SELCQALSSS HCRVLLITPG FLQDPWCKYQ MLQALTEAPG AEGCTIPLLS 190 200 210 220 GLSRAAYPPE LRFMYYVDGR GPDGGFRQVK EAVMRYLQTL S
	Isoform 2 [UniParc]. Checksum: 383386AA03B70F32	FASTA	235	25,323
	10 20 30 40 50 60 MASSTSLPAP GSRPKKPLGK MADWFRQTLL KKPKKRPNSP ESTSSDASQP TSQDSPLPPS 70 80 90 100 110 120 LSSVTSPSLP PTHASDSGSS RWSKDYDVCV CHSEEDLVAA QDLVSYLEGS TASLRCFLQL 130 140 150 160 170 180 RDATPGGAIV SELCQALSSS HCRVLLITPG FLQDPWCKYQ MLQALTEAPG AEGCTIPLLS 190 200 210 220 230 GLSRAAYPPE LRFMYYVDGR GPDGGFRQVK EAVMRCKLLQ EGEGERDSAT VSDLL
	Isoform 3 [UniParc]. Checksum: 97287F7E2A010915	FASTA	255	27,948
	10 20 30 40 50 60 MASSTSLPAP GSRPKKPLGK MADWFRQTLL KKPKKRPNSP ESTSSDASQP TSQDSPLPPS 70 80 90 100 110 120 LSSVTSPSLP PTHASDSGSS RWSKDYDVCV CHSEEDLVAA QDLVSYLEGS TASLRCFLQL 130 140 150 160 170 180 RDATPGGAIV SELCQALSSS HCRVLLITPG FLQDPWCKYQ MLQALTEAPG AEGCTIPLLS 190 200 210 220 230 240 GLSRAAYPPE LRFMYYVDGR GPDGGFRQVK EAVMRYLQTL WHLLYHGTPE IGVKLETENP 250 CRASDSHKCD KRYRE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction." Fitzgerald K.A., Palsson-McDermott E.M., Bowie A.G., Jefferies C.A., Mansell A.S., Brady G., Brint E., Dunne A., Gray P., Harte M.T., McMurray D., Smith D.E., Sims J.E., Bird T.A., O'Neill L.A.J. Nature 413:78-83(2001) [PubMed] [Europe PMC] [Abstract] 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.
[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]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases 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]	"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.
[16]	"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.
[17]	"A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis." Khor C.C., Chapman S.J., Vannberg F.O., Dunne A., Murphy C., Ling E.Y., Frodsham A.J., Walley A.J., Kyrieleis O., Khan A., Aucan C., Segal S., Moore C.E., Knox K., Campbell S.J., Lienhardt C., Scott A., Aaby P. , Sow O.Y., Grignani R.T., Sillah J., Sirugo G., Peshu N., Williams T.N., Maitland K., Davies R.J.O., Kwiatkowski D.P., Day N.P., Yala D., Crook D.W., Marsh K., Berkley J.A., O'Neill L.A.J., Hill A.V.S. Nat. Genet. 39:523-528(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-180, POSSIBLE INVOLVEMENT IN PROTECTION AGAINST INVASIVE PNEUMOCOCCAL DISEASE; BACTEREMIA; MALARIA AND TUBERCULOSIS.
[18]	"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.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00104143.
IPI00171090.
IPI00718966.

RefSeq

NP_001034750.1. NM_001039661.1.
NP_683708.1. NM_148910.2.

UniGene

Hs.537126.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P58753.

ModBase

Search...

Protein-protein interaction databases

IntAct

P58753. 24 interactions.

MINT

MINT-4950450.

STRING

9606.ENSP00000376445.

PTM databases

PhosphoSite

P58753.

Polymorphism databases

DMDM

50403750.

Proteomic databases

PaxDb

P58753.

PRIDE

P58753.

Protocols and materials databases

DNASU

114609.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000392678; ENSP00000376445; ENSG00000150455.
ENST00000392679; ENSP00000376446; ENSG00000150455.
ENST00000392680; ENSP00000376447; ENSG00000150455.
ENST00000479770; ENSP00000436967; ENSG00000150455.

GeneID

114609.

KEGG

hsa:114609.

UCSC

uc001qdm.1. human.

Organism-specific databases

CTD

114609.

GeneCards

GC11P126153.

HGNC

HGNC:17192. TIRAP.

HPA

HPA054431.

MIM

606252. gene.
607948. phenotype.
610799. phenotype.
611162. phenotype.
614382. phenotype.

neXtProt

NX_P58753.

PharmGKB

PA134972842.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG80263.

HOGENOM

HOG000068972.

HOVERGEN

HBG054203.

KO

K05403.

OrthoDB

EOG4W3SP0.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P58753.

Bgee

P58753.

CleanEx

HS_MAL.
HS_TIRAP.

Genevestigator

P58753.

GermOnline

ENSG00000150455. Homo sapiens.

Family and domain databases

InterPro

IPR000157. TIR_dom.
IPR017279. Tol-interleuk_rcpt_adapt_Tirap.
[Graphical view]

PANTHER

PTHR22662. PTHR22662. 1 hit.

Pfam

PF13676. TIR_2. 1 hit.
[Graphical view]

PIRSF

PIRSF037750. TIR_Tirap. 1 hit.

SUPFAM

SSF52200. TIR. 1 hit.

PROSITE

PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

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Other

GenomeRNAi

114609.

NextBio

79099.

SOURCE

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Entry information

Entry name

TIRAP_HUMAN

Accession

Primary (citable) accession number: P58753
Secondary accession number(s): B3KW65 , Q56UH9, Q56UI0, Q8N5E5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 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.