This gene encodes an adapter protein involved in adaptive and innate immunity. This protein includes a forkhead-associated (FHA) domain that specifically binds to phosphorylated serine and threonine residues. In response to bacterial infection, the encoded host cell protein undergoes an intermolecular interaction between the FHA domain and a phosphorylated threonine that leads ... See more...

Aliases for TIFA Gene

Aliases for TIFA Gene

  • TRAF Interacting Protein With Forkhead Associated Domain 2 3 5
  • T2BP 2 3 4
  • TRAF-Interacting Protein With FHA Domain-Containing Protein A 3 4
  • Putative NF-Kappa-B-Activating Protein 20 3 4
  • Putative MAPK-Activating Protein PM14 3 4
  • TRAF2 Binding Protein 2 3
  • TRAF6 Binding Protein 2 3
  • TIFAA 2 3
  • T6BP 2 3
  • TRAF-Interacting Protein With A Forkhead-Associated Domain 3
  • TRAF-Interacting Protein With Forkhead-Associated Domain 2
  • TRAF2-Binding Protein 4
  • MGC20791 2
  • TIFA 5

External Ids for TIFA Gene

Previous GeneCards Identifiers for TIFA Gene

  • GC04M113555
  • GC04M113416
  • GC04M113196
  • GC04M108928

Summaries for TIFA Gene

Entrez Gene Summary for TIFA Gene

  • This gene encodes an adapter protein involved in adaptive and innate immunity. This protein includes a forkhead-associated (FHA) domain that specifically binds to phosphorylated serine and threonine residues. In response to bacterial infection, the encoded host cell protein undergoes an intermolecular interaction between the FHA domain and a phosphorylated threonine that leads to protein oligomerization and stimulation of the NF-kappa B and other downstream signaling pathways. This protein exhibits reduced expression in hepatocellular carcinoma and may suppress hepatocellular carcinoma progression. This protein may also play a role in the DNA damage response. [provided by RefSeq, Jun 2018]

GeneCards Summary for TIFA Gene

TIFA (TRAF Interacting Protein With Forkhead Associated Domain) is a Protein Coding gene. Diseases associated with TIFA include Hepatocellular Carcinoma. Among its related pathways are Diseases associated with the TLR signaling cascade and Shigellosis. An important paralog of this gene is TIFAB.

UniProtKB/Swiss-Prot Summary for TIFA Gene

  • Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, PubMed:30111836). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PubMed:15492226, PubMed:26068852). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (PubMed:30111836).

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for TIFA Gene

Genomics for TIFA Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for TIFA Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around TIFA on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for TIFA

Top Transcription factor binding sites by QIAGEN in the TIFA gene promoter:
  • AP-2rep
  • Cdc5
  • FOXO3
  • FOXO3a
  • FOXO3b
  • HOXA3
  • Ik-3
  • IRF-7A
  • SRY
  • STAT3

Genomic Locations for TIFA Gene

Genomic Locations for TIFA Gene
chr4:112,274,537-112,285,904
(GRCh38/hg38)
Size:
11,368 bases
Orientation:
Minus strand
chr4:113,195,698-113,207,059
(GRCh37/hg19)
Size:
11,362 bases
Orientation:
Minus strand

Genomic View for TIFA Gene

Genes around TIFA on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TIFA Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TIFA Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TIFA Gene

Proteins for TIFA Gene

  • Protein details for TIFA Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96CG3-TIFA_HUMAN
    Recommended name:
    TRAF-interacting protein with FHA domain-containing protein A
    Protein Accession:
    Q96CG3

    Protein attributes for TIFA Gene

    Size:
    184 amino acids
    Molecular mass:
    21445 Da
    Quaternary structure:
    • Homooligomer; homooligomerizes following phosphorylation at Thr-9 (PubMed:12566447, PubMed:22566686, PubMed:26068852, PubMed:26389808). Interacts with IRAK1, TRAF2 and TRAF6 (PubMed:12566447). Interacts with TIFAB; binding to TIFAB inhibits TRAF6 activation, possibly by inducing a conformational change in TIFA (PubMed:15047173). Interacts with ZCCHC11; binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B (PubMed:16643855).

    Three dimensional structures from OCA and Proteopedia for TIFA Gene

neXtProt entry for TIFA Gene

Post-translational modifications for TIFA Gene

  • Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) by ALPK1 (PubMed:30111836). Phosphorylation at Thr-9 by ALPK1 leads to the formation of an intermolecular binding between the FHA domain and phosphorylated Thr-9, promoting TIFA oligomerization and TIFA-mediated NF-kappa-B activation (PubMed:22566686, PubMed:30111836, PubMed:26389808).
  • Ubiquitination at Lys48, Lys63, and Lys108
  • Modification sites at PhosphoSitePlus

Other Protein References for TIFA Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for TIFA Gene

Domains & Families for TIFA Gene

Gene Families for TIFA Gene

Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for TIFA Gene

InterPro:
Blocks:
  • Forkhead-associated (FHA)
ProtoNet:

Suggested Antigen Peptide Sequences for TIFA Gene

GenScript: Design optimal peptide antigens:
  • TRAF2-binding protein (TIFA_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96CG3

UniProtKB/Swiss-Prot:

TIFA_HUMAN :
  • The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B.
  • Belongs to the TIFA family.
Domain:
  • The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B.
Family:
  • Belongs to the TIFA family.
genes like me logo Genes that share domains with TIFA: view

Function for TIFA Gene

Molecular function for TIFA Gene

UniProtKB/Swiss-Prot Function:
Adapter molecule that plays a key role in the activation of proinflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, PubMed:30111836). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PubMed:15492226, PubMed:26068852). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of proinflammatory NF-kappa-B signaling (PubMed:30111836).

Phenotypes From GWAS Catalog for TIFA Gene

Gene Ontology (GO) - Molecular Function for TIFA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 11798190
genes like me logo Genes that share ontologies with TIFA: view
genes like me logo Genes that share phenotypes with TIFA: view

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIFA

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for TIFA Gene

Localization for TIFA Gene

Subcellular locations from UniProtKB/Swiss-Prot for TIFA Gene

Cytoplasm. Note=Colocalizes with lysosomal marker LAMP2 following homooligomerization and subsequent activation. {ECO:0000269 PubMed:26068852}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TIFA gene
Compartment Confidence
nucleus 3
cytosol 3
plasma membrane 1
extracellular 1
mitochondrion 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (2)
  • Nucleoli (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for TIFA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA,IDA 22566686
genes like me logo Genes that share ontologies with TIFA: view

Pathways & Interactions for TIFA Gene

genes like me logo Genes that share pathways with TIFA: view

Gene Ontology (GO) - Biological Process for TIFA Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002376 immune system process IEA --
GO:0002753 cytoplasmic pattern recognition receptor signaling pathway IDA 26068852
GO:0007249 I-kappaB kinase/NF-kappaB signaling IBA 21873635
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling IBA,IDA 26068852
GO:0045087 innate immune response IBA,IDA 26068852
genes like me logo Genes that share ontologies with TIFA: view

No data available for SIGNOR curated interactions for TIFA Gene

Drugs & Compounds for TIFA Gene

No Compound Related Data Available

Transcripts for TIFA Gene

mRNA/cDNA for TIFA Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for TIFA

Alternative Splicing Database (ASD) splice patterns (SP) for TIFA Gene

No ASD Table

Relevant External Links for TIFA Gene

GeneLoc Exon Structure for
TIFA

Expression for TIFA Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for TIFA Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TIFA Gene

This gene is overexpressed in Spleen (22.9), Blymphocyte (11.5), Fetal gut (10.1), Salivary gland (9.1), Skin (8.7), and Lymph node (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for TIFA Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for TIFA

SOURCE GeneReport for Unigene cluster for TIFA Gene:

Hs.310640

Evidence on tissue expression from TISSUES for TIFA Gene

  • Lung(4.2)
genes like me logo Genes that share expression patterns with TIFA: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for TIFA Gene

Orthologs for TIFA Gene

This gene was present in the common ancestor of chordates.

Orthologs for TIFA Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia TIFA 30 31
  • 99.46 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia TIFA 30 31
  • 87.8 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Tifa 30
  • 84.15 (n)
Cow
(Bos Taurus)
Mammalia TIFA 30 31
  • 82.51 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Tifa 30 17 31
  • 82.42 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia TIFA 31
  • 66 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 64 (a)
OneToMany
-- 31
  • 59 (a)
OneToMany
Chicken
(Gallus gallus)
Aves TIFA 30 31
  • 65.04 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia TIFA 31
  • 56 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia tifa 30
  • 54.12 (n)
Zebrafish
(Danio rerio)
Actinopterygii LOC560548 30
  • 50.12 (n)
TIFA 31
  • 31 (a)
OneToOne
Species where no ortholog for TIFA was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for TIFA Gene

ENSEMBL:
Gene Tree for TIFA (if available)
TreeFam:
Gene Tree for TIFA (if available)
Aminode:
Evolutionary constrained regions (ECRs) for TIFA: view image

Paralogs for TIFA Gene

Paralogs for TIFA Gene

genes like me logo Genes that share paralogs with TIFA: view

Variants for TIFA Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for TIFA Gene

SNP ID Clinical significance and condition Chr 04 pos Variation AA Info Type
rs6834237 - p.Thr19Met

Additional dbSNP identifiers (rs#s) for TIFA Gene

Variation tolerance for TIFA Gene

Residual Variation Intolerance Score: 75.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.30; 41.10% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TIFA Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
TIFA

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Structural Variations from Database of Genomic Variants (DGV) for TIFA Gene

Disorders for TIFA Gene

MalaCards: The human disease database

(1) MalaCards diseases for TIFA Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
hepatocellular carcinoma
  • hcc
- elite association - COSMIC cancer census association via MalaCards
Search TIFA in MalaCards View complete list of genes associated with diseases

Additional Disease Information for TIFA

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with TIFA: view

No data available for UniProtKB/Swiss-Prot and Genatlas for TIFA Gene

Publications for TIFA Gene

  1. TIFA activates IkappaB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6. (PMID: 15492226) Ea CK … Chen ZJ (Proceedings of the National Academy of Sciences of the United States of America 2004) 3 4 23
  2. Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose. (PMID: 30111836) Zhou P … Shao F (Nature 2018) 3 4
  3. ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria. (PMID: 28222186) Milivojevic M … Arrieumerlou C (PLoS pathogens 2017) 3 4
  4. ALPK1- and TIFA-Dependent Innate Immune Response Triggered by the Helicobacter pylori Type IV Secretion System. (PMID: 28877472) Zimmermann S … Meyer TF (Cell reports 2017) 3 4
  5. Uncovering the Mechanism of Forkhead-Associated Domain-Mediated TIFA Oligomerization That Plays a Central Role in Immune Responses. (PMID: 26389808) Weng JH … Tsai MD (Biochemistry 2015) 3 4

Products for TIFA Gene

Sources for TIFA Gene