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Q96CG3

- TIFA_HUMAN

UniProt

Q96CG3 - TIFA_HUMAN

Protein

TRAF-interacting protein with FHA domain-containing protein A

Gene

TIFA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 100 (01 Oct 2014)
      Sequence version 1 (01 Dec 2001)
      Previous versions | rss
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    Functioni

    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.2 Publications

    GO - Molecular functioni

    1. protein binding Source: IntAct

    GO - Biological processi

    1. I-kappaB kinase/NF-kappaB signaling Source: Ensembl

    Enzyme and pathway databases

    SignaLinkiQ96CG3.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:TIFA
    Synonyms:T2BP
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:19075. TIFA.

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi50 – 501G → E: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with A-66. 1 Publication
    Mutagenesisi66 – 661S → A: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with E-50. 1 Publication
    Mutagenesisi178 – 1781E → A: Loss of binding to TRAF6 and activation of NF-kappa-B and JNK pathways. 1 Publication

    Organism-specific databases

    PharmGKBiPA162405777.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 184184TRAF-interacting protein with FHA domain-containing protein APRO_0000320689Add
    BLAST

    Proteomic databases

    MaxQBiQ96CG3.
    PaxDbiQ96CG3.
    PRIDEiQ96CG3.

    PTM databases

    PhosphoSiteiQ96CG3.

    Expressioni

    Gene expression databases

    BgeeiQ96CG3.
    CleanExiHS_TIFA.
    GenevestigatoriQ96CG3.

    Organism-specific databases

    HPAiHPA045889.

    Interactioni

    Subunit structurei

    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.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ZCCHC11Q5TAX3-12EBI-740711,EBI-1606425

    Protein-protein interaction databases

    BioGridi124962. 13 interactions.
    IntActiQ96CG3. 9 interactions.
    MINTiMINT-230795.
    STRINGi9606.ENSP00000354911.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96CG3.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini47 – 10357FHAPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Contains 1 FHA domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG46924.
    HOGENOMiHOG000072694.
    HOVERGENiHBG059530.
    InParanoidiQ96CG3.
    OMAiFGEYQFL.
    OrthoDBiEOG7C2R2H.
    PhylomeDBiQ96CG3.
    TreeFamiTF333218.

    Family and domain databases

    Gene3Di2.60.200.20. 1 hit.
    InterProiIPR000253. FHA_dom.
    IPR008984. SMAD_FHA_domain.
    [Graphical view]
    PfamiPF00498. FHA. 1 hit.
    [Graphical view]
    SMARTiSM00240. FHA. 1 hit.
    [Graphical view]
    SUPFAMiSSF49879. SSF49879. 1 hit.
    PROSITEiPS50006. FHA_DOMAIN. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q96CG3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MTSFEDADTE ETVTCLQMTV YHPGQLQCGI FQSISFNREK LPSSEVVKFG    50
    RNSNICHYTF QDKQVSRVQF SLQLFKKFNS SVLSFEIKNM SKKTNLIVDS 100
    RELGYLNKMD LPYRCMVRFG EYQFLMEKED GESLEFFETQ FILSPRSLLQ 150
    ENNWPPHRPI PEYGTYSLCS SQSSSPTEMD ENES 184
    Length:184
    Mass (Da):21,445
    Last modified:December 1, 2001 - v1
    Checksum:i2E7FE091A52415B0
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti19 – 191T → M.
    Corresponds to variant rs6834237 [ dbSNP | Ensembl ].
    VAR_051422

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS34051.1.
    RefSeqiNP_443096.1. NM_052864.2.
    UniGeneiHs.310640.

    Genome annotation databases

    EnsembliENST00000361717; ENSP00000354911; ENSG00000145365.
    ENST00000500655; ENSP00000424231; ENSG00000145365.
    GeneIDi92610.
    KEGGihsa:92610.
    UCSCiuc003ial.3. human.

    Polymorphism databases

    DMDMi74751795.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS34051.1.
    RefSeqi NP_443096.1. NM_052864.2.
    UniGenei Hs.310640.

    3D structure databases

    ProteinModelPortali Q96CG3.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 124962. 13 interactions.
    IntActi Q96CG3. 9 interactions.
    MINTi MINT-230795.
    STRINGi 9606.ENSP00000354911.

    PTM databases

    PhosphoSitei Q96CG3.

    Polymorphism databases

    DMDMi 74751795.

    Proteomic databases

    MaxQBi Q96CG3.
    PaxDbi Q96CG3.
    PRIDEi Q96CG3.

    Protocols and materials databases

    DNASUi 92610.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000361717 ; ENSP00000354911 ; ENSG00000145365 .
    ENST00000500655 ; ENSP00000424231 ; ENSG00000145365 .
    GeneIDi 92610.
    KEGGi hsa:92610.
    UCSCi uc003ial.3. human.

    Organism-specific databases

    CTDi 92610.
    GeneCardsi GC04M113196.
    HGNCi HGNC:19075. TIFA.
    HPAi HPA045889.
    MIMi 609028. gene.
    neXtProti NX_Q96CG3.
    PharmGKBi PA162405777.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46924.
    HOGENOMi HOG000072694.
    HOVERGENi HBG059530.
    InParanoidi Q96CG3.
    OMAi FGEYQFL.
    OrthoDBi EOG7C2R2H.
    PhylomeDBi Q96CG3.
    TreeFami TF333218.

    Enzyme and pathway databases

    SignaLinki Q96CG3.

    Miscellaneous databases

    GenomeRNAii 92610.
    NextBioi 77823.
    PROi Q96CG3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q96CG3.
    CleanExi HS_TIFA.
    Genevestigatori Q96CG3.

    Family and domain databases

    Gene3Di 2.60.200.20. 1 hit.
    InterProi IPR000253. FHA_dom.
    IPR008984. SMAD_FHA_domain.
    [Graphical view ]
    Pfami PF00498. FHA. 1 hit.
    [Graphical view ]
    SMARTi SM00240. FHA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    PROSITEi PS50006. FHA_DOMAIN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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-cell1 Publication.
    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: LungImported.
    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.
      , 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: TracheaImported.
    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.
      , 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. 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-cellImported.
    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiTIFA_HUMAN
    AccessioniPrimary (citable) accession number: Q96CG3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 26, 2008
    Last sequence update: December 1, 2001
    Last modified: October 1, 2014
    This is version 100 of the entry and version 1 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3