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Conserved domains on  [gi|568983257|ref|XP_006517267|]
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TRAF-interacting protein with FHA domain-containing protein B isoform X1 [Mus musculus]

Protein Classification

FHA domain-containing protein( domain architecture ID 1702)

FHA (forkhead-associated) domain-containing protein participates in signal transduction pathways via protein-protein interactions involving recognition of pThr and pTyr phosphopeptides

Gene Ontology:  GO:0051219
PubMed:  10518219|11069759
SCOP:  4002605

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FHA super family cl00062
forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small ...
 5-133 2.23e-66

forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function.


The actual alignment was detected with superfamily member cd22715:

Pssm-ID: 469597  Cd Length: 129  Bit Score: 197.77  E-value: 2.23e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257   5 LTVLQVSLYHPTQGPVAFAHVPQQLQHDASRLLVGRGQNTHLQLQLPQLSRYHLSLEPYLEKGSSLLAFCLKVLTRKSCV 84
Cdd:cd22715    1 LTKLDISLYHPEGQNGIFQDVPKKLQCDTQNLSIGRGPKAHLQLNLPFISRRHLSLEPYLEKGNPYLCFCLKNLSRKGIV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568983257  85 WVNGLPLRYLEQVPLGTINRISFSGIQMLVRKEGGASLETFVCYFHLSP 133
Cdd:cd22715   81 WVNGLTLEYLEQVPLHAVNTVLFSGFQMLVTVDQGVSWDGFVCEIHVSD 129
 
Name Accession Description Interval E-value
FHA_TIFAB cd22715
forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing ...
 5-133 2.23e-66

forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing protein B (TIFAB); TIFAB, also called TIFA-like protein, inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA. It regulates USP15-mediated p53 signaling during stressed and malignant hematopoiesis. It contains an FHA domain, which is a small phosphopeptide recognition module.


Pssm-ID: 438767  Cd Length: 129  Bit Score: 197.77  E-value: 2.23e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257   5 LTVLQVSLYHPTQGPVAFAHVPQQLQHDASRLLVGRGQNTHLQLQLPQLSRYHLSLEPYLEKGSSLLAFCLKVLTRKSCV 84
Cdd:cd22715    1 LTKLDISLYHPEGQNGIFQDVPKKLQCDTQNLSIGRGPKAHLQLNLPFISRRHLSLEPYLEKGNPYLCFCLKNLSRKGIV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568983257  85 WVNGLPLRYLEQVPLGTINRISFSGIQMLVRKEGGASLETFVCYFHLSP 133
Cdd:cd22715   81 WVNGLTLEYLEQVPLHAVNTVLFSGFQMLVTVDQGVSWDGFVCEIHVSD 129
FHA pfam00498
FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.
 37-107 1.54e-05

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.


Pssm-ID: 459831 [Multi-domain]  Cd Length: 66  Bit Score: 40.64  E-value: 1.54e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568983257   37 LVGRGQNTHLQLQLPQLSRYHLSLEpYLEKGSsllaFCLKVLTRKSCVWVNGLPLRYlEQVPLGTINRISF 107
Cdd:pfam00498   2 TIGRSPDCDIVLDDPSVSRRHAEIR-YDGGGR----FYLEDLGSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66
 
Name Accession Description Interval E-value
FHA_TIFAB cd22715
forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing ...
 5-133 2.23e-66

forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing protein B (TIFAB); TIFAB, also called TIFA-like protein, inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA. It regulates USP15-mediated p53 signaling during stressed and malignant hematopoiesis. It contains an FHA domain, which is a small phosphopeptide recognition module.


Pssm-ID: 438767  Cd Length: 129  Bit Score: 197.77  E-value: 2.23e-66
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257   5 LTVLQVSLYHPTQGPVAFAHVPQQLQHDASRLLVGRGQNTHLQLQLPQLSRYHLSLEPYLEKGSSLLAFCLKVLTRKSCV 84
Cdd:cd22715    1 LTKLDISLYHPEGQNGIFQDVPKKLQCDTQNLSIGRGPKAHLQLNLPFISRRHLSLEPYLEKGNPYLCFCLKNLSRKGIV 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 568983257  85 WVNGLPLRYLEQVPLGTINRISFSGIQMLVRKEGGASLETFVCYFHLSP 133
Cdd:cd22715   81 WVNGLTLEYLEQVPLHAVNTVLFSGFQMLVTVDQGVSWDGFVCEIHVSD 129
FHA_TIFA-like cd22664
forkhead associated (FHA) domain found in the family of TRAF-interacting protein with FHA ...
 5-133 8.39e-51

forkhead associated (FHA) domain found in the family of TRAF-interacting protein with FHA domain-containing protein A (TIFA); The TIFA family includes TIFA and TIFA-like protein, TIFAB. TIFA, also called putative MAPK-activating protein PM14, putative NF-kappa-B-activating protein 20, or TRAF2-binding protein (T2BP), is an 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). It 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. 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. TIFAB, also called TIFA-like protein, inhibits TIFA-mediated TRAF6 activation possibly by inducing a conformational change in TIFA. It regulates USP15-mediated p53 signaling during stressed and malignant hematopoiesis. Both TIFA and TIFAB harbor a conserved FHA domain, which is a small phosphopeptide recognition module.


Pssm-ID: 438716  Cd Length: 133  Bit Score: 158.26  E-value: 8.39e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257   5 LTVLQVSLYHPTQGPV----AFAHVPQQLQHDASrLLVGRGQNT-HLQLQLPQLSRYHLSLEPYLEKGSSLLAFCLKVLT 79
Cdd:cd22664    1 LTCLQITLYHPGQQDKgfqsIFFDKKEKLQSDEV-LKFGRDSNCcHYTLQDKRVSRIQFSLQPFKEFNSSVLCFEIKNLS 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568983257  80 RKSCVWVNGLPLRYLEQVPLGTINRISFSGIQMLVRKEGGASLETFVCYFHLSP 133
Cdd:cd22664   80 KKTKLWVNGLELGYLNKVELPAKCTVRFGEFQFLLEKEDGESLEKFETQFHLSP 133
FHA_TIFA cd22714
forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing ...
 5-133 7.16e-15

forkhead associated (FHA) domain found in TRAF-interacting protein with FHA domain-containing protein A (TIFA) and similar proteins; TIFA, also called putative MAPK-activating protein PM14, putative NF-kappa-B-activating protein 20, or TRAF2-binding protein (T2BP), is an 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). It 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. 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. TIFA contains an FHA domain, which is a small phosphopeptide recognition module.


Pssm-ID: 438766  Cd Length: 135  Bit Score: 66.68  E-value: 7.16e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257   5 LTVLQVSLYHPTQG-PVAFA--HVPQQLQHDASRLL-VGRGQNT-HLQLQLPQLSRYHLSLEPYLEKGSSLLAFCLKVLT 79
Cdd:cd22714    1 VTCLQMTVYHPGQEqKGVFQsiNFSKKEKFPSDEVVkFGRDSNIcHYTLQDKRVSRIQFSLQAFKKFNSSVLCFEIKNLS 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 568983257  80 RKSCVWVNGLPLRYLEQVPLGTINRISFSGIQMLVRKEGGASLETFVCYFHLSP 133
Cdd:cd22714   81 KKTKLYVDNTELGYLNKVELPYKCMLRFGEYQFLLEKEDGESLEKFETQFILSP 134
FHA pfam00498
FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.
 37-107 1.54e-05

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.


Pssm-ID: 459831 [Multi-domain]  Cd Length: 66  Bit Score: 40.64  E-value: 1.54e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 568983257   37 LVGRGQNTHLQLQLPQLSRYHLSLEpYLEKGSsllaFCLKVLTRKSCVWVNGLPLRYlEQVPLGTINRISF 107
Cdd:pfam00498   2 TIGRSPDCDIVLDDPSVSRRHAEIR-YDGGGR----FYLEDLGSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66
FHA_PS1-like cd22691
forkhead associated (FHA) domain found in Arabidopsis thaliana Protein PARALLEL SPINDLE 1 (PS1) ...
 22-91 2.48e-04

forkhead associated (FHA) domain found in Arabidopsis thaliana Protein PARALLEL SPINDLE 1 (PS1) and similar proteins; PS1 is an FHA domain-containing protein required for normal spindle orientation at male meiosis II and normal formation of tetrad of microspores. It is not involved in female meiosis. Mutations in PS1 lead to the production of diploid pollen grains. The FHA domain is a small phosphopeptide recognition module.


Pssm-ID: 438743 [Multi-domain]  Cd Length: 113  Bit Score: 38.17  E-value: 2.48e-04
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257  22 FAHVPQQLQHDASRLLVGRGQNTHLQLQLPQLSRYHLSlepyLEKGSSLLAFCLKVLTRKSCVWVNGLPL 91
Cdd:cd22691   17 FLHGKFSKSEEEDILVVGRHPDCDIVLDHPSISRFHLE----IRIIPSRRKITLTDLSSVHGTWVNGQRI 82
FHA cd00060
forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small ...
 32-115 8.88e-04

forkhead associated (FHA) domain superfamily; Forkhead-associated (FHA) domains are small phosphopeptide recognition modules mostly found in eubacteria and eukaryotes. It is about 95-120 residues long that fold into an 11-stranded beta-sandwich. FHA domains can mediate the recognition of phosphorylated and non-phosphorylated substrates, as well as protein oligomerization. They specifically recognize threonine phosphorylation (pThr) accompanying activation of protein serine/threonine kinases. FHA domains show diverse ligand specificity. They may recognize the pTXXD motif, the pTXXI/L motif, and TQ clusters (singly and multiply phosphorylated). In eukaryotes, FHA superfamily members include forkhead-type transcription factors, as well as other signaling proteins, such as many regulatory proteins, kinases, phosphatases, motor proteins called kinesins, and metabolic enzymes. Many of them localize to the nucleus, where they participate in establishing or maintaining cell cycle checkpoints, DNA repair, or transcriptional regulation. FHA domains play important roles in human diseases, particularly in relation to DNA damage responses and cancers. In bacteria, FHA domain-containing proteins may participate in injection of viral proteins into host cells, transmembrane transporters, and cell division. FHA domain-containing proteins rarely include more than one copy of the domain. The only exception in eukaryotes is the checkpoint kinase Rad53 from Saccharomyces cerevisiae, which harbors two FHA domains (FHA1 and FHA2) flanking a central kinase domain. The two FHA domains recognize different phosphorylated targets and function independently from one another. In contrast, Mycobacterium tuberculosis ABC transporter Rv1747 contains two FHA domains but only one of them is essential for protein function.


Pssm-ID: 438714 [Multi-domain]  Cd Length: 92  Bit Score: 36.48  E-value: 8.88e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568983257  32 DASRLLVGRGQNTHLQLQLPQLSRYHLSLepYLEKGSsllaFCLKVLTRKSCVWVNGLPLRYLEQVPLGTinRISFSGIQ 111
Cdd:cd00060   17 TKGVVTIGRSPDCDIVLDDPSVSRRHARI--EVDGGG----VYLEDLGSTNGTFVNGKRITPPVPLQDGD--VIRLGDTT 88


                 ....
gi 568983257 112 MLVR 115
Cdd:cd00060   89 FRFE 92
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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