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Conserved domains on  [gi|239915999|ref|NP_001155218|]
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tumor necrosis factor receptor superfamily member 12A isoform 2 [Mus musculus]

Protein Classification

tumor necrosis factor receptor family protein( domain architecture ID 366323)

tumor necrosis factor receptor (TNFR) family protein may interact with TNF superfamily (TNFSF) ligands (TNFL) to control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth; similar to Rattus norvegicus tumor necrosis factor receptor superfamily member 8

CATH:  2.10.50.10
Gene Ontology:  GO:0005515
PubMed:  7917108

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TNFRSF super family cl22855
Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) ...
 1-94 7.36e-33

Tumor necrosis factor receptor superfamily (TNFRSF); Members of TNFR superfamily (TNFRSF) interactions with TNF superfamily (TNFSF) ligands (TNFL) control key cellular processes such as differentiation, proliferation, apoptosis, and cell growth. Dysregulation of these pathways has been shown to result in a wide range of pathological conditions, including autoimmune diseases, inflammation, cancer, and viral infection. There are 29 very diverse family members of TNFRSF reported in humans: 22 are type I transmembrane receptors (single pass with the N terminus on extracellular side of the cell membrane) and have a clear signal peptide; the remaining 7 members are either type III transmembrane receptors (single pass with the N terminus on extracellular side of the membrane but no signal sequence; TNFR13B, TNFR13C, TNFR17, and XEDAR), or attached to the membrane via a glycosylphosphatidylinositol (GPI) linker (TNFR10C), or secreted as soluble receptors (TNFR11B and TNFR6B). All TNFRs contain relatively short cysteine-rich domains (CRDs) in the ectodomain, and are involved in interaction with the TNF homology domain (THD) of their ligands. TNFRs often have multiple CRDs (between one and six), with the most frequent configurations of three or four copies; most CRDs possess three disulfide bridges, but could have between one and four. Localized or genome-wide duplication and evolution of the TNFRSF members appear to have paralleled the emergence of the adaptive immune system; teleosts (i.e. ray-finned, bony fish), which possess an immune system with B and T cells, possess primary and secondary lymphoid organs, and are capable of adaptive responses to pathogens also display several characteristics that are different from the mammalian immune system, making teleost TNFSF orthologs and paralogs of interest to better understand immune system evolution and the immunological pathways elicited to pathogens.


The actual alignment was detected with superfamily member pfam12191:

Pssm-ID: 473981  Cd Length: 129  Bit Score: 110.47  E-value: 7.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 239915999    1 MASAWPRSLPQILVLGFGLVLMRAAAGEQAPG-----------------------------------AAAPPAHFRLLWP 45
Cdd:pfam12191   1 MAPGPLRPLLRLLVLGLGLALLHAAAGEQAPGnapcsrgsswsadldkcmdcascparphsdfclgcAAAPPAHFRLLWP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 239915999   46 ILGGALSLVLVLALVSSFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 94
Cdd:pfam12191  81 ILGGALSLALVLGLLSGFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 129
 
Name Accession Description Interval E-value
stn_TNFRSF12A pfam12191
Tumour necrosis factor receptor stn_TNFRSF12A_TNFR domain; This family of proteins is found in ...
 1-94 7.36e-33

Tumour necrosis factor receptor stn_TNFRSF12A_TNFR domain; This family of proteins is found in eukaryotes. Proteins in this family are typically between 129 and 184 amino acids in length. This is the stn_TNFRSF12A_TNFR domain from the tumour necrosis factor receptor. The function of this domain is unknown.


Pssm-ID: 403424  Cd Length: 129  Bit Score: 110.47  E-value: 7.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 239915999    1 MASAWPRSLPQILVLGFGLVLMRAAAGEQAPG-----------------------------------AAAPPAHFRLLWP 45
Cdd:pfam12191   1 MAPGPLRPLLRLLVLGLGLALLHAAAGEQAPGnapcsrgsswsadldkcmdcascparphsdfclgcAAAPPAHFRLLWP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 239915999   46 ILGGALSLVLVLALVSSFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 94
Cdd:pfam12191  81 ILGGALSLALVLGLLSGFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 129
TNFRSF12A cd13413
Tumor necrosis factor receptor superfamily member 12A (TNFRSFA), also known as receptor ...
 9-91 4.22e-20

Tumor necrosis factor receptor superfamily member 12A (TNFRSFA), also known as receptor fibroblast growth factor inducible 14 (FN14); TNFRSF12A (also known as receptor fibroblast growth factor inducible 14, FN14, CD266, TWEAKR) is induced by a large variety of growth factors including Fibroblast Growth Factor 1 (FGF1), FGF2, Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF) and Vascular Endothelial Growth Factor (VEGF), as well as cytokines such as tumor necrosis factor alpha (TNFalpha), Interleukin-1beta (IL-1beta), Interferon gamma (IFNgamma), and transforming growth factor-beta (TGF-beta). FN14 is expressed on a wide variety of different cell types and binds the ligand TWEAK (tumor necrosis factor-like weak inducer of apoptosis) to activate several signaling cascades through activation of NF-kappaB signaling mediated by adaptor TRAF proteins. The FN14/TWEAK pathway controls a range of cellular activities such as proliferation, differentiation, and apoptosis, and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with cardiovascular diseases (CVDs). The complex is a positive regulator of cardiac hypertrophy and it has been shown that deletion of FN14 receptor protects from right heart fibrosis and dysfunction; the TWEAK/Fn14 axis could be a potential new therapeutic target for achieving cardiac protection in patients with CVDs. FN14 expression is also stimulated under specific atrophic conditions, such as denervation, immobilization, and starvation, leading to activation of TWEAK/Fn14 signaling and eventually skeletal muscle atrophy. FN14 is also a factor that promotes prostate cancer bone metastasis.


Pssm-ID: 276918  Cd Length: 117  Bit Score: 77.51  E-value: 4.22e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 239915999   9 LPQILVLGFGLVLMRAAAGEQAPGA----------------------------------AAPPAHFRLLWPILGGALSLV 54
Cdd:cd13413    1 LPRLLVLGFVLVLLRSAAGQAAATSpcpggsswspdldkcmdcsscparpksdfclgcgAAPPPPFPLLWPILGGALGLV 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 239915999  55 LVLALVSSFLVWRRCRRREKFTTPIEETGGEGCPGVA 91
Cdd:cd13413   81 LLLALLSGTLVWRRCRRREKFTTPIEETGGEGCPGVA 117
 
Name Accession Description Interval E-value
stn_TNFRSF12A pfam12191
Tumour necrosis factor receptor stn_TNFRSF12A_TNFR domain; This family of proteins is found in ...
 1-94 7.36e-33

Tumour necrosis factor receptor stn_TNFRSF12A_TNFR domain; This family of proteins is found in eukaryotes. Proteins in this family are typically between 129 and 184 amino acids in length. This is the stn_TNFRSF12A_TNFR domain from the tumour necrosis factor receptor. The function of this domain is unknown.


Pssm-ID: 403424  Cd Length: 129  Bit Score: 110.47  E-value: 7.36e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 239915999    1 MASAWPRSLPQILVLGFGLVLMRAAAGEQAPG-----------------------------------AAAPPAHFRLLWP 45
Cdd:pfam12191   1 MAPGPLRPLLRLLVLGLGLALLHAAAGEQAPGnapcsrgsswsadldkcmdcascparphsdfclgcAAAPPAHFRLLWP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 239915999   46 ILGGALSLVLVLALVSSFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 94
Cdd:pfam12191  81 ILGGALSLALVLGLLSGFLVWRRCRRREKFTTPIEETGGEGCPGVALIQ 129
TNFRSF12A cd13413
Tumor necrosis factor receptor superfamily member 12A (TNFRSFA), also known as receptor ...
 9-91 4.22e-20

Tumor necrosis factor receptor superfamily member 12A (TNFRSFA), also known as receptor fibroblast growth factor inducible 14 (FN14); TNFRSF12A (also known as receptor fibroblast growth factor inducible 14, FN14, CD266, TWEAKR) is induced by a large variety of growth factors including Fibroblast Growth Factor 1 (FGF1), FGF2, Platelet-Derived Growth Factor (PDGF), Epidermal Growth Factor (EGF) and Vascular Endothelial Growth Factor (VEGF), as well as cytokines such as tumor necrosis factor alpha (TNFalpha), Interleukin-1beta (IL-1beta), Interferon gamma (IFNgamma), and transforming growth factor-beta (TGF-beta). FN14 is expressed on a wide variety of different cell types and binds the ligand TWEAK (tumor necrosis factor-like weak inducer of apoptosis) to activate several signaling cascades through activation of NF-kappaB signaling mediated by adaptor TRAF proteins. The FN14/TWEAK pathway controls a range of cellular activities such as proliferation, differentiation, and apoptosis, and has diverse biological functions in pathological mechanisms like inflammation and fibrosis that are associated with cardiovascular diseases (CVDs). The complex is a positive regulator of cardiac hypertrophy and it has been shown that deletion of FN14 receptor protects from right heart fibrosis and dysfunction; the TWEAK/Fn14 axis could be a potential new therapeutic target for achieving cardiac protection in patients with CVDs. FN14 expression is also stimulated under specific atrophic conditions, such as denervation, immobilization, and starvation, leading to activation of TWEAK/Fn14 signaling and eventually skeletal muscle atrophy. FN14 is also a factor that promotes prostate cancer bone metastasis.


Pssm-ID: 276918  Cd Length: 117  Bit Score: 77.51  E-value: 4.22e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 239915999   9 LPQILVLGFGLVLMRAAAGEQAPGA----------------------------------AAPPAHFRLLWPILGGALSLV 54
Cdd:cd13413    1 LPRLLVLGFVLVLLRSAAGQAAATSpcpggsswspdldkcmdcsscparpksdfclgcgAAPPPPFPLLWPILGGALGLV 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 239915999  55 LVLALVSSFLVWRRCRRREKFTTPIEETGGEGCPGVA 91
Cdd:cd13413   81 LLLALLSGTLVWRRCRRREKFTTPIEETGGEGCPGVA 117
 
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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