Q96CG3 (TIFA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	TIFA
Synonyms:	T2BP

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	184 AA.
Sequence status	Complete.
Protein existence	Evidence 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 diversity	Polymorphism
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	I-kappaB kinase/NF-kappaB cascade Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ZCCHC11	Q5TAX3-1	2	EBI-740711,EBI-1606425

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 184	184	TRAF-interacting protein with FHA domain-containing protein A		PRO_0000320689
Regions
	Domain	47 – 103	57	FHA
Natural variations
	Natural variant	19	1	T → M. Corresponds to variant rs6834237 [ dbSNP | Ensembl ].		VAR_051422
Experimental info
	Mutagenesis	50	1	G → E: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with A-66. Ref.1
	Mutagenesis	66	1	S → A: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with E-50. Ref.1
	Mutagenesis	178	1	E → A: Loss of binding to TRAF6 and activation of NF-kappa-B and JNK pathways. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q96CG3 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 2E7FE091A52415B0	FASTA	184	21,445
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
IPI	IPI00060419.
RefSeq	NP_443096.1. NM_052864.2.
UniGene	Hs.310640.
3D structure databases
ProteinModelPortal	Q96CG3.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q96CG3. 9 interactions.
MINT	MINT-230795.
STRING	9606.ENSP00000354911.
PTM databases
PhosphoSite	Q96CG3.
Polymorphism databases
DMDM	74751795.
Proteomic databases
PaxDb	Q96CG3.
PRIDE	Q96CG3.
Protocols and materials databases
DNASU	92610.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000361717; ENSP00000354911; ENSG00000145365. ENST00000500655; ENSP00000424231; ENSG00000145365.
GeneID	92610.
KEGG	hsa:92610.
UCSC	uc003ial.3. human.
Organism-specific databases
CTD	92610.
GeneCards	GC04M113196.
HGNC	HGNC:19075. TIFA.
HPA	HPA045889.
MIM	609028. gene.
neXtProt	NX_Q96CG3.
PharmGKB	PA162405777.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG46924.
HOGENOM	HOG000072694.
HOVERGEN	HBG059530.
InParanoid	Q96CG3.
OMA	FGEYQFL.
OrthoDB	EOG466VNB.
PhylomeDB	Q96CG3.
Gene expression databases
Bgee	Q96CG3.
CleanEx	HS_TIFA.
Genevestigator	Q96CG3.
Family and domain databases
Gene3D	2.60.200.20. 1 hit.
InterPro	IPR000253. FHA_dom. [Graphical view]
Pfam	PF00498. FHA. 1 hit. [Graphical view]
SMART	SM00240. FHA. 1 hit. [Graphical view]
PROSITE	PS50006. FHA_DOMAIN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	92610.
NextBio	77823.
SOURCE	Search...

Entry information

Entry name

TIFA_HUMAN

Accession

Primary (citable) accession number: Q96CG3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	December 1, 2001
Last modified:	April 3, 2013
This is version 91 of the entry and version 1 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.