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ADAM17 Gene

protein-coding   GIFtS: 72
GCID: GC02M009628

ADAM Metallopeptidase Domain 17

(Previous names: tumor necrosis factor, alpha, converting enzyme)
(Previous symbol: TACE)
  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
ADAM Metallopeptidase Domain 171 2     ADAM182
TACE1 2 3 5     CD156B2
Tumor Necrosis Factor, Alpha, Converting Enzyme1 2     ADAM Metallopeptidase Domain 182
Snake Venom-Like Protease2 3     Disintegrin And Metalloproteinase Domain-Containing Protein 172
CSVP2 3     TNF-Alpha Converting Enzyme2
TNF-Alpha Convertase2 3     ADAM 173
EC 3.4.24.863 8     CD156b Antigen3
NISBD2 5     TNF-Alpha-Converting Enzyme3

External Ids:    HGNC: 1951   Entrez Gene: 68682   Ensembl: ENSG000001516947   OMIM: 6036395   UniProtKB: P785363   

Export aliases for ADAM17 gene to outside databases

Previous GC identifers: GC02M009412 GC02M009680 GC02M009651 GC02M009580


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ADAM17 Gene:
This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family
are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a
variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle
development, and neurogenesis. The protein encoded by this gene functions as a tumor necrosis factor-alpha
converting enzyme; binds mitotic arrest deficient 2 protein; and also plays a prominent role in the activation of
the Notch signaling pathway. (provided by RefSeq, Jul 2008)

GeneCards Summary for ADAM17 Gene:
ADAM17 (ADAM metallopeptidase domain 17) is a protein-coding gene. Diseases associated with ADAM17 include inflammatory skin and bowel disease, neonatal, and vitamin b12 deficiency. GO annotations related to this gene include integrin binding and SH3 domain binding. An important paralog of this gene is ADAM10.

UniProtKB/Swiss-Prot: ADA17_HUMAN, P78536
Function: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the
proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of
several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55
TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid
precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the
membrane-associated intermediate fragment called Notch extracellular truncation (NEXT)

Gene Wiki entry for ADAM17 Gene


(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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RefSeq DNA sequence:
NC_000002.12  NC_018913.2  NT_005334.17  
Regulatory elements:
   Regulatory transcription factor binding sites in the ADAM17 gene promoter:
         Bach1   Elk-1   AML1a   HOXA3   IRF-1   c-Ets-1   Nkx6-1   ATF   En-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidADAM17 promoter sequence
   Search Chromatin IP Primers for ADAM17

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ADAM17


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p25   Ensembl cytogenetic band:  2p25.1   HGNC cytogenetic band: 2p25

ADAM17 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ADAM17 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M009628:  view genomic region     (about GC identifiers)

Start:
9,628,615 bp from pter      End:
9,695,921 bp from pter
Size:
67,307 bases      Orientation:
minus 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, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: ADA17_HUMAN, P78536 (See protein sequence)
Recommended Name: Disintegrin and metalloproteinase domain-containing protein 17 precursor  
Size: 824 amino acids; 93021 Da
Cofactor: Binds 1 zinc ion per subunit
Subunit: Interacts with MAD2L1, MAPK14 and MUC1
Selected PDB 3D structures from and Proteopedia for ADAM17 (see all 23):
1BKC (3D)        1ZXC (3D)        2A8H (3D)        2DDF (3D)        2FV5 (3D)        2FV9 (3D)    
Secondary accessions: O60226
Alternative splicing: 2 isoforms:  P78536-1   P78536-2   (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ADAM17: NX_P78536

Explore proteomics data for ADAM17 at MOPED

Post-translational modifications: 

  • The precursor is cleaved by a furin endopeptidase (By similarity)1
  • Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819
    but decreases phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated
    ectodomain shedding1
  • Ubiquitination2 at Lys728
  • Glycosylation2 at Asn103, Asn157, Asn174, Asn264, Asn452, Asn498, Asn539, Asn551, Asn594
  • Modification sites at PhosphoSitePlus
  • 3 DME Specific Peptides for ADAM17 (P78536)
     DGLAECA  CCKNCQF  LGLAYVGSPR 


    See ADAM17 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_003174.3  
    ENSEMBL proteins: 
     ENSP00000309968   ENSP00000418728  
    Reactome Protein details: P78536

    ADAM17 Human Recombinant Protein Products:

    Browse Purified and Recombinant Proteins at EMD Millipore
    R&D Systems Recombinant & Natural Proteins for ADAM17 (TACE/ADAM17)
    Enzo Life Sciences proteins for ADAM17
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    Browse OriGene Protein Over-expression Lysates
    OriGene Custom MassSpec
    OriGene Custom Protein Services for ADAM17
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    Novus Biologicals ADAM17 Proteins
    Sino Biological Recombinant Protein for ADAM17
    Sino Biological Cell Lysate for ADAM17
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for ADAM17

    ADAM17 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of ADAM17
    R&D Systems Antibodies for ADAM17 (TACE/ADAM17)
    Cell Signaling Technology (CST) Antibodies for ADAM17  (TACE)
    OriGene Antibodies for ADAM17
    OriGene Custom Antibody Services for ADAM17
    Novus Biologicals ADAM17 Antibodies
    Abcam antibodies for ADAM17
    Cloud-Clone Corp. Antibodies for ADAM17
    ThermoFisher Antibody for ADAM17
    LSBio Antibodies in human, mouse, rat for ADAM17

    ADAM17 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for ADAM17
    R&D Systems ELISAs for ADAM17 (TACE/ADAM17)         (see all)
    GenScript Custom Assay Services for ADAM17
    Enzo Life Sciences assays for ADAM17
    Cloud-Clone Corp. ELISAs for ADAM17
    Cloud-Clone Corp. CLIAs for ADAM17


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CD: CD molecules
    ADAM: ADAM metallopeptidase domain containing

    IUPHAR Guide to PHARMACOLOGY protein family classification: ADAM17
    ADAM

    4 InterPro protein domains:
     IPR024079 MetalloPept_cat_dom
     IPR001762 Blood-coag_inhib_Disintegrin
     IPR001590 Peptidase_M12B
     IPR002870 Peptidase_M12B_N

    Graphical View of Domain Structure for InterPro Entry P78536

    ProtoNet protein and cluster: P78536

    2 Blocks protein domains:
    IPB001368 TNFR/CD27/30/40/95 cysteine-rich region
    IPB001762 Disintegrin


    UniProtKB/Swiss-Prot: ADA17_HUMAN, P78536
    Domain: Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for
    the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity)
    Domain: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting
    the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the
    enzyme
    Similarity: Contains 1 disintegrin domain
    Similarity: Contains 1 peptidase M12B domain


    ADAM17 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: ADA17_HUMAN, P78536
    Function: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the
    proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of
    several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55
    TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid
    precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the
    membrane-associated intermediate fragment called Notch extracellular truncation (NEXT)
    Catalytic activity: Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala- -Val-Arg-Ser-Ser-Ser in the
    membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other
    membrane-anchored, cell-surface proteins to 'shed' the extracellular domains
    Induction: In arthritis-affected cartilage

         Genatlas biochemistry entry for ADAM17:
    a disintegrin and metalloprotease (active) domain 17,membrane anchored cell surface adhesion protein,expressed in
    somatic tissues,releasing TNFA from its membrane bound precursor,also reported to cleave APP

         Enzyme Number (IUBMB): EC 3.4.24.861 2

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004222metalloendopeptidase activity TAS--
    GO:0005112Notch binding IDA--
    GO:0005138interleukin-6 receptor binding IPI16034137
    GO:0005178integrin binding IPI14970227
    GO:0005515protein binding IPI10527948
         
    ADAM17 for ontologies           About GeneDecksing


    Phenotypes:
         2 GenomeRNAi human phenotypes for ADAM17:
     Increased viability after born  Stronger migration 

         Selected MGI mutant phenotypes (inferred from 13 alleles(MGI details for Adam17) (see all 20):
     cardiovascular system  cellular  digestive/alimentary  embryogenesis  endocrine/exocrine gland 
     growth/size/body  hematopoietic system  homeostasis/metabolism  immune system  integument 
     limbs/digits/tail  mortality/aging  muscle  nervous system  normal 

    ADAM17 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for ADAM17: Adam17tm1.1Bbl Adam17tm1Imx Adam17tm1.2Rain

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ADAM17
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ADAM17

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ADAM17
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ADAM17

    miRNA
    Products:
        
    miRTarBase miRNAs that target ADAM17:
    hsa-mir-145-5p (MIRT007275), hsa-mir-122-5p (MIRT003112)

    Block miRNA regulation of human, mouse, rat ADAM17 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate ADAM17 (see all 17):
    hsa-miR-140-3p hsa-miR-224 hsa-miR-148b hsa-miR-520d-5p hsa-miR-634 hsa-miR-767-5p hsa-miR-512-3p hsa-miR-507
    SwitchGear 3'UTR luciferase reporter plasmidADAM17 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ADAM17
    Predesigned siRNA for gene silencing in human, mouse, rat ADAM17

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ADAM17

    Clone
    Products:
         
    OriGene clones in human, mouse for ADAM17 (see all 6)
    OriGene ORF clones in mouse, rat for ADAM17
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ADAM17 (NM_003183)
    Sino Biological Human cDNA Clone for ADAM17
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ADAM17
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ADAM17

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for ADAM17
    Browse ESI BIO Cell Lines and PureStem Progenitors for ADAM17 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ADAM17


    (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
    ADA17_HUMAN, P78536: Membrane; Single-pass type I membrane protein
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytoskeleton4
    plasma membrane4
    cytosol2
    extracellular2
    endoplasmic reticulum1
    nucleus1
    peroxisome1

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

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm IDA--
    GO:0005886plasma membrane TAS--
    GO:0005887integral component of plasma membrane IDA17786981
    GO:0005911colocalizes with cell-cell junction IDA14970227
    GO:0005925colocalizes with focal adhesion IDA14970227

    ADAM17 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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    SuperPaths for ADAM17 About   (see all 33)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Notch signaling pathway (KEGG)
    Notch signaling pathway0.84
    Delta-Notch Signaling Pathway0.33
    Notch Signaling Pathway0.84
    Notch Signaling0.30
    2Alzheimer's disease
    Alzheimers Disease0.44
    Alzheimer's disease0.44
    3Signaling by NOTCH1 PEST Domain Mutants in Cancer
    Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants0.79
    Signaling by NOTCH1 HD Domain Mutants in Cancer0.79
    Signaling by NOTCH1 PEST Domain Mutants in Cancer0.79
    Constitutive Signaling by NOTCH1 PEST Domain Mutants0.79
    Signaling by NOTCH1 in Cancer0.79
    Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant0.79
    Signaling by NOTCH10.79
    FBXW7 Mutants and NOTCH1 in Cancer0.79
    4Signaling by FGFR
    Signaling by EGFR0.83
    Signalling by NGF0.71
    Signaling by EGFR in Cancer0.82
    5Death Receptor Signalling
    Death Receptor Signalling0.71
    Extrinsic Pathway for Apoptosis0.00
    TNF signaling0.00

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    2 R&D Systems Pathways for ADAM17
        A-beta Plaque Formation & APP Metabolism
    Notch Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ADAM17 (see all 6)
        Notch Signaling
    Inhibition of Matrix Metalloproteinases
    Molecular Mechanisms of Cancer
    Alzheimers Disease Pathway
    Presenilin-Mediated Signaling

    2 Cell Signaling Technology (CST) Pathways for ADAM17
        Wnt / Hedgehog / Notch
    Neuroscience

    5 GeneGo (Thomson Reuters) Pathways for ADAM17
        Immune response IL-6 signaling pathway
    Development NOTCH1-mediated pathway for NF-KB activity modulation
    Development Growth hormone signaling via PI3K/AKT and MAPK cascades
    Development Notch Signaling Pathway
    Development MAG-dependent inhibition of neurite outgrowth

    Selected BioSystems Pathways for ADAM17 (see all 7)
        Notch Signaling Pathway
    BDNF signaling pathway
    Delta-Notch Signaling Pathway
    Alzheimers Disease
    ErbB4 signaling events

    1 Sino Biological Pathway for ADAM17
        Notch Signaling Pathway

    Selected Reactome Pathways for ADAM17 (see all 11)
        Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
    Regulated proteolysis of p75NTR
    Collagen degradation
    TNF signaling
    Constitutive Signaling by NOTCH1 t(7 9)(NOTCH1:M1580_K2555) Translocation Mutant


    3 Kegg Pathways  (Kegg details for ADAM17):
        Notch signaling pathway
    Alzheimer's disease
    Epithelial cell signaling in Helicobacter pylori infection


    ADAM17 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ADAM17: 
              Endothelial Cell Biology in human mouse rat
              Multiple Sclerosis in human mouse rat
              Liver Cancer in human mouse rat
              Notch Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ADAM17

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

    Selected Interacting proteins for ADAM17 (P785361, 2, 3 ENSP000003099684) via UniProtKB, MINT, STRING, and/or I2D (see all 44)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    DLG1Q129591, 2, 3, ENSP000003457314EBI-78188,EBI-357481 MINT-1901891 MINT-1901801 MINT-1901824 MINT-1901856 MINT-1901710 MINT-1901743 MINT-1901775 I2D: score=4 STRING: ENSP00000345731
    PTPN3P260452, 3, ENSP000002625394MINT-58311 MINT-58317 I2D: score=3 STRING: ENSP00000262539
    PDIA3P301012, 3MINT-4301309 I2D: score=1 
    TNFP013753, ENSP000003986984I2D: score=2 STRING: ENSP00000398698
    ENSG00000204490P013753I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 41):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001666response to hypoxia IDA18276953
    GO:0001934positive regulation of protein phosphorylation IMP18625725
    GO:0002446neutrophil mediated immunity IC16034137
    GO:0002467germinal center formation ISS10433800
    GO:0002690positive regulation of leukocyte chemotaxis IC16034137

    ADAM17 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 compounds at ApexBio 

    Browse Tocris compounds for ADAM17 (ADA17)

    8 DrugBank Compounds for ADAM17    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    (1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acid-- --target--10592235
    (2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE-- --target--10592235
    (3S)-1-{[4-(BUT-2-YN-1-YLOXY)PHENYL]SULFONYL}PYRROLIDINE-3-THIOL-- --target--10592235
    (3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE-- --target--10592235
    3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol-- --target--10592235
    4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE-- --target--10592235
    N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan-- --target--10592235
    methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylate-- --target--10592235

    37 Novoseek inferred chemical compound relationships for ADAM17 gene (see top 10)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    adamalysin 84.6 3 12621058 (1), 10419777 (1)
    tapi 78.5 4 11106509 (1), 11156944 (1)
    hydroxamate 76.3 10 17368021 (1), 15284022 (1), 12723945 (1), 15128827 (1) (see all 7)
    (4-aminophenyl)mercuric acetate 70.7 2 18239612 (1), 15182369 (1)
    batimastat 70.4 4 15319441 (1), 9684866 (1), 10971741 (1), 12226103 (1)
    marimastat 58.1 4 10579851 (3), 12384559 (1)
    phorbol 50.3 3 10799547 (1), 15142990 (1), 19535569 (1)
    ag 1478 46.3 1 15319441 (1)
    phorbol-12-myristate 45.5 3 17942404 (1)
    zinc 40.1 24 15102849 (4), 15100227 (3), 10521439 (1), 17368021 (1) (see all 12)
    adalimumab 39.4 5 19854762 (2), 19949420 (2)
    etanercept 35.3 1 19796498 (1)
    serine 24.1 9 17464354 (2), 17545155 (1), 19386603 (1), 19292764 (1) (see all 6)
    sulfonamide 23.7 2 10579851 (1), 12789686 (1)
    hyaluronic acid 22.3 2 17180679 (1), 15197174 (1)
    nadph 20 2 15640347 (1), 17220369 (1)
    ionomycin 19.7 3 15556048 (1), 19411314 (1)
    1,10-phenanthroline 18.1 3 14659806 (1), 16002728 (1), 12226103 (1)
    cysteine 14.5 14 15100227 (4), 12530549 (1), 15581423 (1), 15749738 (1) (see all 8)
    leucine 5.7 4 17464354 (2), 15713681 (1), 15308656 (1)
    p002 5.07 1 10385500 (1)
    oxygen 4.93 12 16148149 (1), 17600314 (1), 17884817 (1), 18276953 (1) (see all 8)
    cholesterol 0 9 17786981 (4), 15034047 (2), 17010968 (1)
    ethanol 0 3 10857859 (1), 18822146 (1), 12488495 (1)
    atp 0 2 19386603 (2)
    lipid 0 18 17010968 (5), 19633828 (2), 17786981 (2), 15034047 (2) (see all 5)
    calcium 0 3 16229685 (1), 15641051 (1)
    threonine 0 5 19386603 (1), 20087163 (1), 12621058 (1)
    glyceraldehyde 3-phosphate 0 2 12605594 (1), 15888146 (1)
    tyrosine 0 1 12621058 (1)
    phosphatidylinositol 0 2 16641105 (1)
    methionine 0 4 15492278 (1), 17464354 (1)
    5-hydroxytryptamine 0 4 16737974 (3)
    glutamate 0 2 12224947 (1), 14715932 (1)
    histamine 0 3 10818238 (2)
    heparin 0 3 16737974 (2)
    h2o2 0 12 11156944 (4), 19386603 (2), 19482949 (1)



    ADAM17 for compounds           About GeneDecksing



    (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,
    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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    REFSEQ mRNAs for ADAM17 gene: 
    NM_003183.4  

    Unigene Cluster for ADAM17:

    ADAM metallopeptidase domain 17
    Hs.404914  [show with all ESTs]
    Unigene Representative Sequence: NM_003183
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000310823(uc002qzu.3 uc010ewy.3 uc010ewz.3) ENST00000497134(uc010exa.3 uc010exb.1)
    ENST00000478059(uc002qzv.3)
    miRNA
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      QuantiFast Probe-based Assays in human, mouse, rat ADAM17

    Additional mRNA sequence: 

    AK289829.1 AY422721.1 BC062687.1 BC136783.1 BC146658.1 GQ402545.1 U69611.1 U69612.1 
    U86755.1 U92649.1 

    11 DOTS entries:

    DT.97840889  DT.101978379  DT.75154588  DT.91723298  DT.100737460  DT.91868817  DT.86857558  DT.100671075 
    DT.121006903  DT.121006944  DT.95089565 

    Selected AceView cDNA sequences (see all 88):

    AI141532 AI741293 AI919444 AI797833 AW057613 BF059089 AA827074 BU734977 
    AI141804 AA933982 AI075423 BM989580 AA910834 AW627690 AI095477 AI911263 
    N27387 CB159093 BM827395 NM_003183 CB068513 AY422721 BE645266 CA439922 

    GeneLoc Exon Structure

    4 Alternative Splicing Database (ASD) splice patterns (SP) for ADAM17    About this scheme

    ExUns: 1 ^ 2a · 2b ^ 3 ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18 ^ 19
    SP1:                                      -                                                                                                         
    SP2:                                                                                      -                                                         
    SP3:                                                                                                                                                
    SP4:                                                                                                                                                


    ECgene alternative splicing isoforms for ADAM17

    (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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    ADAM17 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    ADAM17 Expression
    About this image


    ADAM17 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 8) fully expand
     
     Brain (Nervous System)    fully expand to see all 3 entries
             Cerebral Cortex
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Testis (Reproductive System)
             Leydig Cells Testis Interstitium
     
     Ovary (Reproductive System)
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
    ADAM17 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ADAM17 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.404914

    UniProtKB/Swiss-Prot: ADA17_HUMAN, P78536
    Tissue specificity: Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle,
    pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ADAM17: 
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              Liver Cancer in human mouse rat
              Notch Signaling Pathway in human mouse rat

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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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    This gene was present in the common ancestor of animals.

    Orthologs for ADAM17 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Adam171 , 5 a disintegrin and metallopeptidase domain 171, 5 88.07(n)1
    92.11(a)1
      12 (8.30 cM)5
    114911  NM_009615.61  NP_033745.41 
     213235095 
    chicken
    (Gallus gallus)
    Aves ADAM171 ADAM metallopeptidase domain 17 74.16(n)
    77.38(a)
      421931  NM_001008682.1  NP_001008682.1 
    lizard
    (Anolis carolinensis)
    Reptilia ADAM176
    ADAM metallopeptidase domain 17
    73(a)
    1 ↔ 1
    1(148417544-148444228)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia adam171 ADAM metallopeptidase domain 17 68.62(n)
    70.57(a)
      100492947  NM_001195230.1  NP_001182159.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufc20b012 wufc20b01 75.1(n)   324142  BC057410.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta CG79083
    Tace1
    proteolysis and peptidolysis
    metalloendopeptidase3
    Tace1
    41(a)3
    51.35(n)1
    45.02(a)1
      99D13
    435581  NM_170455.31  NP_733334.11 
    worm
    (Caenorhabditis elegans)
    Secernentea adm-41 , 3 metalloprotease3
    adm-41
    34(a)3
    47.65(n)1
    36.01(a)1
      X(7830565-7833527)3
    1810411  NM_076917.31  NP_509318.11 


    ENSEMBL Gene Tree for ADAM17 (if available)
    TreeFam Gene Tree for ADAM17 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ADAM17 gene
    ADAM102  
    1 SIMAP similar gene for ADAM17 using alignment to 8 protein entries:     ADA17_HUMAN (see all proteins):
    ADAM22

    ADAM17 for paralogs           About GeneDecksing



    (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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    Selected SNPs for ADAM17 (see all 1397)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1386269561,2
    --9601091(+) TAATTC/TAAATA 1 -- ds50010--------
    rs1416991991,2
    --9601136(+) TATCAA/CGTCTT 1 -- ds50010--------
    rs1462467971,2
    --9601153(+) ACAGCC/TCCCAA 1 -- ds50010--------
    rs1845207381,2
    --9601183(+) TCTATA/CTCCTG 1 -- ds50010--------
    rs2014492261,2
    --9601221(+) TTTTT-/TTGTTTGT 1 -- cds10--------
    rs1387888491,2
    C--9601234(+) TGTTG-/TTCTTGTT 1 -- cds10--------
    rs1874335891,2
    --9601234(+) TTGTTC/GTTGTT 1 -- ds50010--------
    rs593173551,2
    C--9601236(+) TTGTT-/CTTGTTAA 1 -- cds10--------
    rs1380953501,2
    --9601248(+) AAATAC/TCTCAC 1 -- ds50010--------
    rs1417992821,2
    C--9601263(+) TTATTC/TAATAG 1 -- ds50010--------

    HapMap Linkage Disequilibrium report for ADAM17 (9628615 - 9695921 bp)

    Structural Variations
          Database of Genomic Variants (DGV) variations for ADAM17: --
    Human Gene Mutation Database (HGMD): ADAM17
    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing ADAM17
    DNA2.0 Custom Variant and Variant Library Synthesis for ADAM17

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 603639   
    OMIM disorders: 614328  
    UniProtKB/Swiss-Prot: ADA17_HUMAN, P78536
  • Neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]: A disorder characterized by
    inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral
    and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules.
    Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal
    infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized. Note=The
    disease is caused by mutations affecting the gene represented in this entry

  • Selected diseases for ADAM17 (see all 74):    
    About MalaCards
    inflammatory skin and bowel disease, neonatal    vitamin b12 deficiency    renal osteodystrophy    differentiating neuroblastoma
    chorioamnionitis    toxic shock syndrome    acute myocardial infarction    severe acute respiratory syndrome
    interstitial lung disease    dilated cardiomyopathy    congestive heart failure    gastrointestinal stromal tumor
    osteoarthritis    pulmonary tuberculosis    myocarditis    rabies
    abdominal aortic aneurysm    periodontal disease    aortic aneurysm    pancreatic ductal adenocarcinoma


    ADAM17 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for ADAM17 gene (see all 27)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    necrosis 79.5 222 15206946 (4), 10521439 (2), 15075334 (2), 16737974 (2) (see all 99)
    tumors 63.1 208 15206946 (3), 17822026 (3), 17227756 (3), 10521439 (2) (see all 99)
    rheumatoid arthritis 43.1 8 14579524 (1), 14718605 (1), 12670535 (1), 20303413 (1) (see all 7)
    inflammation 34.7 14 12973924 (1), 19581416 (1), 20331435 (1), 17822026 (1) (see all 9)
    alzheimers disease 28.3 8 19234765 (3), 11032903 (2)
    arthritis 24.9 5 18471442 (1), 12463167 (1), 15859325 (1), 17376651 (1) (see all 5)
    senile plaques 23.4 1 11536196 (1)
    multiple sclerosis 15.9 5 16511637 (2), 19324423 (1), 12474981 (1), 15859325 (1)
    cancer 11.6 32 19843672 (5), 19408347 (2), 15309730 (1), 15197174 (1) (see all 10)
    osteoarthritis 5.26 6 9574564 (1), 14579524 (1), 10419777 (1), 11508576 (1)

    Genetic Association Database (GAD): ADAM17
    Human Genome Epidemiology (HuGE) Navigator: ADAM17 (16 documents)

    Export disorders for ADAM17 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 ADAM17 gene, integrated from 10 sources (see all 507):
    (articles sorted by number of sources associating them with ADAM17)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by differential display, expression of the active enzyme, and regulation of TNF-alpha. (PubMed id 9574564)1, 2, 3, 9 Patel I.R.... Amin A.R. (J. Immunol. 1998)
    2. A metalloproteinase disintegrin that releases tumour-necrosis factor- alpha from cells. (PubMed id 9034190)1, 2, 3 Black R.A.... Cerretti D.P. (Nature 1997)
    3. Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study. (PubMed id 18600307)1, 4, 9 Morange P.E....Tiret L. (J. Mol. Med. 2008)
    4. Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide. (PubMed id 12621058)1, 2, 9 Fan H.... Derynck R. (J. Biol. Chem. 2003)
    5. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. (PubMed id 9034191)1, 2, 9 Moss M.L.... Becherer J.D. (Nature 1997)
    6. Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. (PubMed id 20188673)1, 2, 9 Xu P. and Derynck R. (Mol. Cell 2010)
    7. Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme. (PubMed id 9520379)1, 2, 9 Maskos K.... Bode W. (Proc. Natl. Acad. Sci. U.S.A. 1998)
    8. Inflammatory skin and bowel disease linked to ADAM17 deletion. (PubMed id 22010916)1, 2 Blaydon D.C.... Kelsell D.P. (N. Engl. J. Med. 2011)
    9. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PubMed id 20379614)1, 4 Rose J.E....Uhl G.R. (Mol. Med. 2010)
    10. Polymorphisms spanning the TNFR2 and TACE genes do not contribute towards variable anti-TNF treatment response. (PubMed id 20300049)1, 4 Potter C....Barton A. (Pharmacogenet. Genomics 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    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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    Entrez Gene: 6868 HGNC: 195 AceView: ADAM17 Ensembl:ENSG00000151694 euGenes: HUgn6868
    ECgene: ADAM17 Kegg: 6868 H-InvDB: ADAM17

    (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
    PharmGKB entry for ADAM17 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ADAM17 Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia http://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ADAM17 gene:
    Search GeneIP for patents involving ADAM17

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



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