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Q96CG3 (TIFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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:
TRAF-interacting protein with FHA domain-containing protein A
Alternative name(s):
Putative MAPK-activating protein PM14
Putative NF-kappa-B-activating protein 20
TRAF2-binding protein
Gene names
Name:TIFA
Synonyms:T2BP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length184 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adapter protein which mediates the IRAK1 and TRAF6 interaction following IL-1 stimulation, resulting in the downstream activation of NF-kappa-B and AP-1 pathways. Induces the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism. Ref.1 Ref.8

Subunit structure

Homotrimer. Interacts with IRAK1, TIFAB, ZCCHC11, TRAF2 and TRAF6. Binding to TIFAB inhibits TRAF6 activation possibly by inducing a conformational change in TIFA. Binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B. Ref.1 Ref.7 Ref.9 UniProtKB Q96CG3

Sequence similarities

Contains 1 FHA domain.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionprotein binding

Inferred from physical interaction Ref.9. Source: IntAct

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ZCCHC11Q5TAX3-12EBI-740711,EBI-1606425

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 184184TRAF-interacting protein with FHA domain-containing protein A
PRO_0000320689

Regions

Domain47 – 10357FHA

Natural variations

Natural variant191T → M.
Corresponds to variant rs6834237 [ dbSNP | Ensembl ].
VAR_051422

Experimental info

Mutagenesis501G → E: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with A-66. Ref.1
Mutagenesis661S → A: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with E-50. Ref.1
Mutagenesis1781E → A: Loss of binding to TRAF6 and activation of NF-kappa-B and JNK pathways. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q96CG3 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 2E7FE091A52415B0

FASTA18421,445
        10         20         30         40         50         60 
MTSFEDADTE ETVTCLQMTV YHPGQLQCGI FQSISFNREK LPSSEVVKFG RNSNICHYTF 

        70         80         90        100        110        120 
QDKQVSRVQF SLQLFKKFNS SVLSFEIKNM SKKTNLIVDS RELGYLNKMD LPYRCMVRFG 

       130        140        150        160        170        180 
EYQFLMEKED GESLEFFETQ FILSPRSLLQ ENNWPPHRPI PEYGTYSLCS SQSSSPTEMD 


ENES 

« Hide

References

« Hide 'large scale' references
[1]"Identification of TIFA as an adapter protein that links tumor necrosis factor receptor-associated factor 6 (TRAF6) to interleukin-1 (IL-1) receptor-associated kinase-1 (IRAK-1) in IL-1 receptor signaling."
Takatsuna H., Kato H., Gohda J., Akiyama T., Moriya A., Okamoto Y., Yamagata Y., Otsuka M., Umezawa K., Semba K., Inoue J.
J. Biol. Chem. 278:12144-12150(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TRIMERIZATION, INTERACTION WITH TRAF6 AND IRAK1, MUTAGENESIS OF GLY-50; SER-66 AND GLU-178.
Tissue: B-cell.
[2]"Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways."
Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S.
Oncogene 22:3307-3318(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[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. 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].
Tissue: Trachea.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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].
[6]"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: B-cell.
[7]"TIFAB inhibits TIFA, TRAF-interacting protein with a forkhead-associated domain."
Matsumura T., Semba K., Azuma S., Ikawa S., Gohda J., Akiyama T., Inoue J.
Biochem. Biophys. Res. Commun. 317:230-234(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TIFAB.
[8]"TIFA activates IkappaB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6."
Ea C.-K., Sun L., Inoue J., Chen Z.J.
Proc. Natl. Acad. Sci. U.S.A. 101:15318-15323(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"A novel Zinc finger protein, ZCCHC11, interacts with TIFA and modulates TLR signaling."
Minoda Y., Saeki K., Aki D., Takaki H., Sanada T., Koga K., Kobayashi T., Takaesu G., Yoshimura A.
Biochem. Biophys. Res. Commun. 344:1023-1030(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZCCHC11.
[10]"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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB062110 mRNA. Translation: BAB86902.1.
AB097011 mRNA. Translation: BAC77364.1.
AB097038 mRNA. Translation: BAC77391.1.
AK292900 mRNA. Translation: BAF85589.1.
AC109347 Genomic DNA. Translation: AAY40963.1.
CH471057 Genomic DNA. Translation: EAX06273.1.
BC014259 mRNA. Translation: AAH14259.1.
CCDSCCDS34051.1.
RefSeqNP_443096.1. NM_052864.2.
UniGeneHs.310640.

3D structure databases

ProteinModelPortalQ96CG3.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid124962. 13 interactions.
IntActQ96CG3. 9 interactions.
MINTMINT-230795.
STRING9606.ENSP00000354911.

PTM databases

PhosphoSiteQ96CG3.

Polymorphism databases

DMDM74751795.

Proteomic databases

MaxQBQ96CG3.
PaxDbQ96CG3.
PRIDEQ96CG3.

Protocols and materials databases

DNASU92610.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361717; ENSP00000354911; ENSG00000145365.
ENST00000500655; ENSP00000424231; ENSG00000145365.
GeneID92610.
KEGGhsa:92610.
UCSCuc003ial.3. human.

Organism-specific databases

CTD92610.
GeneCardsGC04M113196.
HGNCHGNC:19075. TIFA.
HPAHPA045889.
MIM609028. gene.
neXtProtNX_Q96CG3.
PharmGKBPA162405777.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46924.
HOGENOMHOG000072694.
HOVERGENHBG059530.
InParanoidQ96CG3.
OMAFGEYQFL.
OrthoDBEOG7C2R2H.
PhylomeDBQ96CG3.
TreeFamTF333218.

Enzyme and pathway databases

SignaLinkQ96CG3.

Gene expression databases

BgeeQ96CG3.
CleanExHS_TIFA.
GenevestigatorQ96CG3.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
InterProIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamPF00498. FHA. 1 hit.
[Graphical view]
SMARTSM00240. FHA. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
PROSITEPS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi92610.
NextBio77823.
PROQ96CG3.
SOURCESearch...

Entry information

Entry nameTIFA_HUMAN
AccessionPrimary (citable) accession number: Q96CG3
Entry history
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 99 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

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 4

Human chromosome 4: entries, gene names and cross-references to MIM