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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

BioCyciZFISH:ENSG00000145365-MONOMER.
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)DescriptionActionsGraphical viewLength
Mutagenesisi50G → E: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with A-66. 1 Publication1
Mutagenesisi66S → A: Loss of trimerization and activation of NF-kappa-B and JNK pathways; when associated with E-50. 1 Publication1
Mutagenesisi178E → A: Loss of binding to TRAF6 and activation of NF-kappa-B and JNK pathways. 1 Publication1

Organism-specific databases

DisGeNETi92610.
OpenTargetsiENSG00000145365.
PharmGKBiPA162405777.

Polymorphism and mutation databases

BioMutaiTIFA.
DMDMi74751795.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003206891 – 184TRAF-interacting protein with FHA domain-containing protein AAdd BLAST184

Proteomic databases

EPDiQ96CG3.
MaxQBiQ96CG3.
PaxDbiQ96CG3.
PeptideAtlasiQ96CG3.
PRIDEiQ96CG3.

PTM databases

iPTMnetiQ96CG3.
PhosphoSitePlusiQ96CG3.

Expressioni

Gene expression databases

BgeeiENSG00000145365.
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
AP1M1Q9BXS56EBI-740711,EBI-541426
ARHGEF39Q8N4T43EBI-740711,EBI-745468
DVL2O146413EBI-740711,EBI-740850
LNX1Q8TBB13EBI-740711,EBI-739832
NXF1Q9UBU93EBI-740711,EBI-398874
RPL9P9P329695EBI-740711,EBI-358122
SDCBPO005607EBI-740711,EBI-727004
SDCBP2Q9H1906EBI-740711,EBI-742426
TNFAIP8O953793EBI-740711,EBI-1049336
TRAF2Q129337EBI-740711,EBI-355744
TXN2Q997573EBI-740711,EBI-2932492
ZCCHC11Q5TAX3-12EBI-740711,EBI-1606425

Protein-protein interaction databases

BioGridi124962. 19 interactors.
DIPiDIP-40185N.
IntActiQ96CG3. 23 interactors.
MINTiMINT-230795.
STRINGi9606.ENSP00000354911.

Structurei

Secondary structure

1184
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 6Combined sources3
Beta strandi14 – 21Combined sources8
Helixi23 – 26Combined sources4
Turni30 – 33Combined sources4
Beta strandi37 – 42Combined sources6
Beta strandi47 – 51Combined sources5
Turni53 – 55Combined sources3
Beta strandi57 – 59Combined sources3
Beta strandi70 – 76Combined sources7
Beta strandi81 – 89Combined sources9
Beta strandi92 – 94Combined sources3
Beta strandi96 – 98Combined sources3
Beta strandi101 – 103Combined sources3
Beta strandi108 – 110Combined sources3
Beta strandi113 – 119Combined sources7
Beta strandi122 – 129Combined sources8
Beta strandi134 – 143Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YM4X-ray3.12A10-150[»]
B1-12[»]
4ZGIX-ray2.70A10-149[»]
ProteinModelPortaliQ96CG3.
SMRiQ96CG3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini47 – 103FHAPROSITE-ProRule annotationAdd BLAST57

Sequence similaritiesi

Contains 1 FHA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IYNH. Eukaryota.
ENOG4111T8W. LUCA.
GeneTreeiENSGT00510000048615.
HOGENOMiHOG000072694.
HOVERGENiHBG059530.
InParanoidiQ96CG3.
OMAiRNSNICH.
OrthoDBiEOG091G0KR0.
PhylomeDBiQ96CG3.
TreeFamiTF333218.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
InterProiIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR033621. TIFA.
[Graphical view]
PANTHERiPTHR31266. PTHR31266. 1 hit.
PfamiPF00498. 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_05142219T → M.Corresponds to variant rs6834237dbSNPEnsembl.1

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.
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.
UniGeneiHs.310640.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4YM4X-ray3.12A10-150[»]
B1-12[»]
4ZGIX-ray2.70A10-149[»]
ProteinModelPortaliQ96CG3.
SMRiQ96CG3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124962. 19 interactors.
DIPiDIP-40185N.
IntActiQ96CG3. 23 interactors.
MINTiMINT-230795.
STRINGi9606.ENSP00000354911.

PTM databases

iPTMnetiQ96CG3.
PhosphoSitePlusiQ96CG3.

Polymorphism and mutation databases

BioMutaiTIFA.
DMDMi74751795.

Proteomic databases

EPDiQ96CG3.
MaxQBiQ96CG3.
PaxDbiQ96CG3.
PeptideAtlasiQ96CG3.
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.
DisGeNETi92610.
GeneCardsiTIFA.
HGNCiHGNC:19075. TIFA.
HPAiHPA045889.
MIMi609028. gene.
neXtProtiNX_Q96CG3.
OpenTargetsiENSG00000145365.
PharmGKBiPA162405777.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IYNH. Eukaryota.
ENOG4111T8W. LUCA.
GeneTreeiENSGT00510000048615.
HOGENOMiHOG000072694.
HOVERGENiHBG059530.
InParanoidiQ96CG3.
OMAiRNSNICH.
OrthoDBiEOG091G0KR0.
PhylomeDBiQ96CG3.
TreeFamiTF333218.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000145365-MONOMER.
SignaLinkiQ96CG3.

Miscellaneous databases

GenomeRNAii92610.
PROiQ96CG3.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145365.
CleanExiHS_TIFA.
GenevisibleiQ96CG3. HS.

Family and domain databases

Gene3Di2.60.200.20. 1 hit.
InterProiIPR000253. FHA_dom.
IPR008984. SMAD_FHA_domain.
IPR033621. TIFA.
[Graphical view]
PANTHERiPTHR31266. PTHR31266. 1 hit.
PfamiPF00498. FHA. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS50006. FHA_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 120 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.