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Protein

TRAF-interacting protein with FHA domain-containing protein A

Gene

TIFA

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

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 - Biological processi

Complete GO annotation...

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
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:19075. TIFA.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

Polymorphism and mutation databases

BioMutaiTIFA.
DMDMi74751795.

PTM / Processingi

Molecule processing

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

Proteomic databases

EPDiQ96CG3.
MaxQBiQ96CG3.
PaxDbiQ96CG3.
PRIDEiQ96CG3.

PTM databases

iPTMnetiQ96CG3.
PhosphoSiteiQ96CG3.

Expressioni

Gene expression databases

BgeeiQ96CG3.
CleanExiHS_TIFA.
GenevisibleiQ96CG3. HS.

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
AP1M1Q9BXS54EBI-740711,EBI-541426
ARHGEF39Q8N4T43EBI-740711,EBI-745468
GCD7P325023EBI-740711,EBI-6260From a different organism.
NXF1Q9UBU93EBI-740711,EBI-398874
RPL9P9P329693EBI-740711,EBI-358122
SDCBPO005603EBI-740711,EBI-727004
SDCBP2Q9H1904EBI-740711,EBI-742426
TNFAIP8O953793EBI-740711,EBI-1049336
TRAF2Q129336EBI-740711,EBI-355744
TXN2Q997573EBI-740711,EBI-2932492
ZCCHC11Q5TAX3-12EBI-740711,EBI-1606425

Protein-protein interaction databases

BioGridi124962. 19 interactions.
DIPiDIP-40185N.
IntActiQ96CG3. 16 interactions.
MINTiMINT-230795.
STRINGi9606.ENSP00000354911.

Structurei

Secondary structure

1
184
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni4 – 63Combined sources
Beta strandi14 – 218Combined sources
Helixi23 – 264Combined sources
Turni30 – 334Combined sources
Beta strandi37 – 426Combined sources
Beta strandi47 – 515Combined sources
Turni53 – 553Combined sources
Beta strandi57 – 593Combined sources
Beta strandi70 – 767Combined sources
Beta strandi81 – 899Combined sources
Beta strandi92 – 943Combined sources
Beta strandi96 – 983Combined sources
Beta strandi101 – 1033Combined sources
Beta strandi108 – 1103Combined sources
Beta strandi113 – 1197Combined sources
Beta strandi122 – 1298Combined sources
Beta strandi134 – 14310Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YM4X-ray3.12A10-150[»]
B1-12[»]
4ZGIX-ray2.70A10-149[»]
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

eggNOGiENOG410IYNH. Eukaryota.
ENOG4111T8W. LUCA.
GeneTreeiENSGT00510000048615.
HOGENOMiHOG000072694.
HOVERGENiHBG059530.
InParanoidiQ96CG3.
OMAiRNSNICH.
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

        10         20         30         40         50
MTSFEDADTE ETVTCLQMTV YHPGQLQCGI FQSISFNREK LPSSEVVKFG
60 70 80 90 100
RNSNICHYTF QDKQVSRVQF SLQLFKKFNS SVLSFEIKNM SKKTNLIVDS
110 120 130 140 150
RELGYLNKMD LPYRCMVRFG EYQFLMEKED GESLEFFETQ FILSPRSLLQ
160 170 180
ENNWPPHRPI PEYGTYSLCS SQSSSPTEMD ENES
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:
EMBLi
GenBanki
DDBJi
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.
XP_011530715.1. XM_011532413.1.
UniGeneiHs.310640.

Genome annotation databases

EnsembliENST00000361717; ENSP00000354911; ENSG00000145365.
ENST00000500655; ENSP00000424231; ENSG00000145365.
GeneIDi92610.
KEGGihsa:92610.
UCSCiuc003ial.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
XP_011530715.1. XM_011532413.1.
UniGeneiHs.310640.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4YM4X-ray3.12A10-150[»]
B1-12[»]
4ZGIX-ray2.70A10-149[»]
ProteinModelPortaliQ96CG3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124962. 19 interactions.
DIPiDIP-40185N.
IntActiQ96CG3. 16 interactions.
MINTiMINT-230795.
STRINGi9606.ENSP00000354911.

PTM databases

iPTMnetiQ96CG3.
PhosphoSiteiQ96CG3.

Polymorphism and mutation databases

BioMutaiTIFA.
DMDMi74751795.

Proteomic databases

EPDiQ96CG3.
MaxQBiQ96CG3.
PaxDbiQ96CG3.
PRIDEiQ96CG3.

Protocols and materials databases

DNASUi92610.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361717; ENSP00000354911; ENSG00000145365.
ENST00000500655; ENSP00000424231; ENSG00000145365.
GeneIDi92610.
KEGGihsa:92610.
UCSCiuc003ial.4. human.

Organism-specific databases

CTDi92610.
GeneCardsiTIFA.
HGNCiHGNC:19075. TIFA.
HPAiHPA045889.
MIMi609028. gene.
neXtProtiNX_Q96CG3.
PharmGKBiPA162405777.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYNH. Eukaryota.
ENOG4111T8W. LUCA.
GeneTreeiENSGT00510000048615.
HOGENOMiHOG000072694.
HOVERGENiHBG059530.
InParanoidiQ96CG3.
OMAiRNSNICH.
OrthoDBiEOG7C2R2H.
PhylomeDBiQ96CG3.
TreeFamiTF333218.

Enzyme and pathway databases

SignaLinkiQ96CG3.

Miscellaneous databases

GenomeRNAii92610.
NextBioi77823.
PROiQ96CG3.
SOURCEiSearch...

Gene expression databases

BgeeiQ96CG3.
CleanExiHS_TIFA.
GenevisibleiQ96CG3. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: April 13, 2016
This is version 113 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

3D-structure, 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.