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ENSG00000223952 Gene

protein-coding   GIFtS: 17
GCID: GC06Pm31619          (predicted)

ENSG00000223952


  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Cachectin3
TNF-a3
TNF-alpha3
TNFA3
TNFSF23
Tumor Necrosis Factor Ligand Superfamily Member 23

External Ids:    Ensembl: ENSG000002239527   UniProtKB: P013753   

Export aliases for ENSG00000223952 gene to outside databases


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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GeneCards Summary for ENSG00000223952 Gene:
ENSG00000223952 is a protein-coding gene. Diseases associated with ENSG00000223952 include hepatitis b virus infection, and psoriatic arthritis.

UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
Function: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can
induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by
stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions
it can stimulate cell proliferation and induce cell differentiation
Function: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells




(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Search for regulatory transcription factor binding sites for ENSG00000223952
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for ENSG00000223952

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ENSG00000223952


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_MCFp21.33   

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06Pm31619:       (about GC identifiers)

Start:
31,619,653 bp from start of contig ALT_REF_LOCI_5      End:
31,622,422 bp from start of contig ALT_REF_LOCI_5
Size:
2,770 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375 (See protein sequence)
Recommended Name: Tumor necrosis factor precursor  
Size: 233 amino acids; 25644 Da
Subunit: Homotrimer. Interacts with SPPL2B
Sequence caution: Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Sequence=CAA75070.1; Type=Erroneous
gene model prediction;
Selected PDB 3D structures from and Proteopedia for ENSG00000223952 (see all 14):
1A8M (3D)        1TNF (3D)        2AZ5 (3D)        2E7A (3D)        2TUN (3D)        2ZJC (3D)    
Secondary accessions: O43647 Q9P1Q2 Q9UIV3

Explore the universe of human proteins at neXtProt for ENSG00000223952: NX_P01375

Explore proteomics data for ENSG00000223952 at MOPED

Post-translational modifications: 

  • The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further
    proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF
    intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the
    extracellular space1
  • The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the
    membrane form occurs by binding to soluble TNFRSF1A/TNFR11
  • O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See ENSG00000223952 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB


    ENSEMBL proteins: 
     ENSP00000389490  
    Reactome Protein details: P01375

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    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 6):
     IPR008064 TNFalpha/TNFSF15
     IPR002959 TNF_alpha
     IPR006052 TNF_dom
     IPR006053 TNF
     IPR008983 Tumour_necrosis_fac-like_dom

    Graphical View of Domain Structure for InterPro Entry P01375

    ProtoNet protein and cluster: P01375

    3 Blocks protein domains:
    IPB002959 Tumour necrosis factor alpha (cachectin) signature
    IPB006052 Tumor Necrosis Factor
    IPB006053 Tumour necrosis factor family signature


    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
    Similarity: Belongs to the tumor necrosis factor family


    ENSG00000223952 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: TNFA_HUMAN, P01375
    Function: Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can
    induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by
    stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions
    it can stimulate cell proliferation and induce cell differentiation
    Function: The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells

         Gene Ontology (GO): Selected molecular function terms (see all 6):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002020protease binding ----
    GO:0005125cytokine activity ----
    GO:0005164tumor necrosis factor receptor binding ----
    GO:0005515protein binding ----
    GO:0042802identical protein binding ----
         
    ENSG00000223952 for ontologies           About GeneDecksing


    Animal Models:
       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ENSG00000223952
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    TNFA_HUMAN, P01375: Cell membrane; Single-pass type II membrane protein
    TNFA_HUMAN, P01375: Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein
    TNFA_HUMAN, P01375: Tumor necrosis factor, soluble form: Secreted
    TNFA_HUMAN, P01375: C-domain 1: Secreted
    TNFA_HUMAN, P01375: C-domain 2: Secreted

    Gene Ontology (GO): Selected cellular component terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001891phagocytic cup ----
    GO:0005576extracellular region ----
    GO:0005615extracellular space ----
    GO:0005886plasma membrane ----
    GO:0005887integral component of plasma membrane ----

    ENSG00000223952 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    Pathways by sourceSee SuperPaths
    Show all pathways


    2 Reactome Pathways for ENSG00000223952
        Transcriptional regulation of white adipocyte differentiation
    TNF signaling



    ENSG00000223952 for pathways           About GeneDecksing

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for ENSG00000223952
    Interactions:

        Search GeneGlobe Interaction Network for ENSG00000223952

    STRING Interaction Network Preview (showing 5 interactants - click image to see 9)

    Selected Interacting proteins for ENSG00000223952 (P013751, 2, 3 ENSP000003894904) via UniProtKB, MINT, STRING, and/or I2D (see all 115)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    TNFRSF1AP194381, 2, 3EBI-359977,EBI-299451 MINT-48045 MINT-49295 I2D: score=12 
    TNFRSF1BP203331, 2, 3EBI-359977,EBI-358983 MINT-48048 MINT-49370 I2D: score=10 
    IKBKGQ9Y6K91, 2, 3EBI-359977,EBI-81279 MINT-8410390 I2D: score=1 
    RBCK1Q9BYM82, 3MINT-8410390 I2D: score=1 
    RNF31Q96EP02, 3MINT-8410390 I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 112):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000060protein import into nucleus, translocation ----
    GO:0000122negative regulation of transcription from RNA polymerase II promoter ----
    GO:0000165MAPK cascade ----
    GO:0000185activation of MAPKKK activity ----
    GO:0000187activation of MAPK activity ----

    ENSG00000223952 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for ENSG00000223952 (TNFA)



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000448781(uc011hra.2 uc011hrb.2)
    miRNA
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    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --

    ENSG00000223952 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ENSG00000223952 Protein Expression
        Custom PCR Arrays for ENSG00000223952
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    In Situ
    Assay Products:
     

     
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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      --

    ENSEMBL Gene Tree for ENSG00000223952 (if available)
    TreeFam Gene Tree for ENSG00000223952 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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      --

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    TNFA_HUMAN, P01375: Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]
    TNFA_HUMAN, P01375: Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162]

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
  • Psoriatic arthritis (PSORAS) [MIM:607507]: An inflammatory, seronegative arthritis associated with
    psoriasis. It is a heterogeneous disorder ranging from a mild, non-destructive disease to a severe, progressive,
    erosive arthropathy. Five types of psoriatic arthritis have been defined: asymmetrical oligoarthritis
    characterized by primary involvement of the small joints of the fingers or toes; asymmetrical arthritis which
    involves the joints of the extremities; symmetrical polyarthritis characterized by a rheumatoid like pattern that
    can involve hands, wrists, ankles, and feet; arthritis mutilans, which is a rare but deforming and destructive
    condition; arthritis of the sacroiliac joints and spine (psoriatic spondylitis). Note=Disease susceptibility is
    associated with variations affecting the gene represented in this entry

  • 10 diseases for ENSG00000223952:    
    About MalaCards
    hepatitis b virus infection    psoriatic arthritis    malaria    hepatitis b
    hypoxia    arthritis    multiple myeloma    myeloma
    hepatitis    neuronitis


    ENSG00000223952 for disorders           About GeneDecksing


    Export disorders for ENSG00000223952 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ENSG00000223952 gene, integrated from 10 sources (see all 26):
    (articles sorted by number of sources associating them with ENSG00000223952)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A gamma-secretase-like intramembrane cleavage of TNFalpha by the GxGD aspartyl protease SPPL2b. (PubMed id 16829951)2 Fluhrer R....Haass C. (Nat. Cell Biol. 2006)
    2. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFalpha in activated dendritic cells to trigger IL-12 production. (PubMed id 16829952)2 Friedmann E.... Martoglio B. (Nat. Cell Biol. 2006)
    3. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)2 Gerhard D.S.... Malek J. (Genome Res. 2004)
    4. Association of TNF-alpha promoter polymorphisms with the clearance of hepatitis B virus infection. (PubMed id 12915457)2 Kim Y.J.... Shin H.D. (Hum. Mol. Genet. 2003)
    5. Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. (PubMed id 14656967)2 Xie T.... Hood L. (Genome Res. 2003)
    6. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. (PubMed id 12746914)2 Balding J.... FitzGerald O. (Arthritis Rheum. 2003)
    7. A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. (PubMed id 10205166)2 Watts A.D.... Chaudhri G. (EMBO J. 1999)
    8. A new member of the Ig superfamily and a V-ATPase G subunit are among the predicted products of novel genes close to the TNF locus in the human MHC. (PubMed id 10202016)2 Neville M.J. and Campbell R.D. (J. Immunol. 1999)
    9. A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria. (PubMed id 10369255)2 Knight J.C.... Kwiatkowski D. (Nat. Genet. 1999)
    10. High resolution crystal structure of a human tumor necrosis factor- alpha mutant with low systemic toxicity. (PubMed id 9442056)2 Cha S.S.... Oh B.H. (J. Biol. Chem. 1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Ensembl:ENSG00000223952

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    ATLAS Chromosomes in Cancer entry for ENSG00000223952 Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha
    NIEHS-SNPshttp://egp.gs.washington.edu/data/tnf/
    SeattleSNPshttp://pga.gs.washington.edu/data/tnf/
    SHMPDhttp://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=TNF

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ENSG00000223952 gene:
    Search GeneIP for patents involving ENSG00000223952

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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