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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

ENSG00000228321 Gene

protein-coding   GIFtS: 17
GCID: GC06Pl31582          (predicted)

ENSG00000228321


  Search for ENSG00000228321
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
About This Section

Aliases
Cachectin3
TNF-a3
TNF-alpha3
TNFA3
TNFSF23
Tumor Necrosis Factor Ligand Superfamily Member 23

External Ids:    Ensembl: ENSG000002283217   UniProtKB: P013753   

Export aliases for ENSG00000228321 gene to outside databases


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

GeneCards Summary for ENSG00000228321 Gene: 
ENSG00000228321 is a protein-coding gene.

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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
Regulatory elements:
   Search SABiosciences Regulatory transcription factor binding sites for ENSG00000228321
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search SABiosciences Chromatin IP Primers for ENSG00000228321

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ENSG00000228321


Genomic Location:
Chromosome:6   

Ensembl cytogenetic band:  HSCHR6_MHC_MANNp22.1   

GeneLoc information about chromosome 6         GeneLoc Exon Structure

GeneLoc location for GC06Pl31582:       (about GC identifiers)

Start:
31,582,831 bp from pter      End:
31,585,600 bp from pter
Size:
2,770 bases      Orientation:
plus strand

(According to UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MAXQB 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., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, 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
Subcellular location: Cell membrane; Single-pass type II membrane protein
Subcellular location: Tumor necrosis factor, membrane form: Membrane; Single-pass type II membrane protein
Subcellular location: Tumor necrosis factor, soluble form: Secreted
Subcellular location: C-domain 1: Secreted
Subcellular location: C-domain 2: Secreted
Sequence caution: Sequence=AAF71992.1; Type=Frameshift; Positions=91, 157; Sequence=CAA75070.1; Type=Erroneous
gene model prediction;
6/13 PDB 3D structures from and Proteopedia for ENSG00000228321 (see all 13):
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 ENSG00000228321: NX_P01375

Explore proteomics data for ENSG00000228321 at MOPED 

Post-translational modifications:

  • UniProtKB: 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 space
  • UniProtKB: The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the
    membrane form occurs by binding to soluble TNFRSF1A/TNFR1
  • UniProtKB: O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid
  • View modification sites using PhosphoSitePlus
  • View neXtProt modification sites for NX_P01375

  • ENSG00000228321 Protein expression data from MOPED1, PaxDb2 and MAXQB3 :    About this image 

    ENSG00000228321 Protein Expression

    ENSEMBL proteins: 
     ENSP00000392858  
    Reactome Protein details: P01375
    Human Recombinant Protein Products for ENSG00000228321: 
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    Browse Sino Biological Cell Lysates 
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    Browse Proteins at Cloud-Clone Corp. 

    Gene Ontology (GO): 5/11 cellular component terms (GO ID links to tree view) (see all 11):    About this table

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

    ENSG00000228321 for ontologies           About GeneDecksing



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    Browse ELISAs at Cloud-Clone Corp. 
    Browse CLIAs at Cloud-Clone Corp.


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    5 InterPro protein domains:
     IPR002959 TNF_alpha
     IPR006052 TNF
     IPR006053 TNF_a/b/c
     IPR008983 Tumour_necrosis_fac-like_dom
     IPR021184 TNF_CS

    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


    ENSG00000228321 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,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
    About This Section

    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): 5/6 molecular function terms (GO ID links to tree view) (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 ----
         
    ENSG00000228321 for ontologies           About GeneDecksing


    Animal Models:
       inGenious Targeting Laboratory - Custom generated mouse model solutions for ENSG00000228321 
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    (Pathways according to EMD Millipore, 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 SABiosciences, 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 Oct 2013 via Entrez Gene).
    About This Section

    Pathways by sourceSee SuperPaths
    Show all pathways


    4        Reactome Pathways for ENSG00000228321
        Death Receptor Signalling
    TNF signaling
    Extrinsic Pathway for Apoptosis
    Apoptosis



    ENSG00000228321 for pathways           About GeneDecksing

    Interactions:

        Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for ENSG00000228321

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    5/112 Interacting proteins for ENSG00000228321 (P013751, 2, 3 ENSP000003928584) via UniProtKB, MINT, STRING, and/or I2D (see all 112)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    RBCK1Q9BYM82, 3, ENSP000003486324MINT-8410390 I2D: score=1 STRING: ENSP00000348632
    RNF31Q96EP02, 3, ENSP000003151124MINT-8410390 I2D: score=1 STRING: ENSP00000315112
    ENSG00000096150P622693I2D: score=1 
    ENSG00000223367P622693I2D: score=1 
    ENSG00000226225P622693I2D: score=1 
    About this table

    Gene Ontology (GO): 5/115 biological process terms (GO ID links to tree view) (see all 115):    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 ----

    ENSG00000228321 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section
    EMD Millipore small molecules for ENSG00000228321:
    Small Molecule - inhibitor
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for ENSG00000228321 (TNFA)

    Search CenterWatch for drugs/clinical trials and news about ENSG00000228321 / 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000412275(uc011gyk.2 uc011gyl.2)
    miRNA
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      Search QIAGEN QuantiFast Probe-based Assays in human, mouse, rat ENSG00000228321

    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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section
    See probesets specificity/sensitivity at GeneAnnot
    CGAP TAG: --


    See ENSG00000228321 Protein Expression from SPIRE MOPED and PaxDB    SABiosciences Custom PCR Arrays for ENSG00000228321
    Primer
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    In Situ
    Assay Products:
     

     
    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for ENSG00000228321

    (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)
    About This Section
      --

    ENSEMBL Gene Tree for ENSG00000228321 (if available)
    TreeFam Gene Tree for ENSG00000228321 (if available)

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

    (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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    UniProtKB/Swiss-Prot: TNFA_HUMAN, P01375
    Polymorphism: Genetic variations in TNF influence susceptibility to hepatitis B virus (HBV) infection [MIM:610424]
    Polymorphism: Genetic variations in TNF are involved in susceptibility to malaria [MIM:611162]

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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.)
    About This Section

    ENSG00000228321 for disorders           About MalaCards
    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


  • ENSG00000228321 for disorders           About GeneDecksing


    Export disorders for ENSG00000228321 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)
    About This Section

    PubMed articles for ENSG00000228321 gene, integrated from 9 sources (see all 26):
    (articles sorted by number of sources associating them with ENSG00000228321)
        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. (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. (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. (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. (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. (2003)
    6. Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity. (PubMed id 12746914)2 Balding J.... FitzGerald O. (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. (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. (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. (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. (1998)

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     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)
    About This Section
    Ensembl:ENSG00000228321

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    ATLAS Chromosomes in Cancer entry for ENSG00000228321 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.)
    About This Section
    Patent Information for ENSG00000228321 gene:
    Search GeneIP for patents involving ENSG00000228321

    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, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0 and Sirion Biotech, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Sirion Biotech, Cell lines from GenScript, and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
    About This Section

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    GeneCards Homepage - Last full update: 23 Oct 2013 - Incrementals: 3 Nov 2013 , 7 Nov 2013 , 23 Jan 2014

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    Category
    (GIFtS: 73)
    transforming growth factor, beta 1
    GIFtS Group
    The GeneCards human gene database gene index: 1 3 5 6 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z 


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