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FLASH GENE
Symbol ADAM17 contributors: mct/shn - updated : 27-03-2016
HGNC name ADAM metallopeptidase domain 17
HGNC id 195
Location 2p25.1      Physical location : 9.629.412 - 9.695.917
Synonym name
  • ADAM metallopeptidase domain 18
  • snake venom-like protease
  • tumor necrosis factor-alpha converting enzyme
  • tumor necrosis factor, alpha, converting enzyme
  • CD156b antigen
  • TNF-alpha converting enzyme
  • TNF-alpha convertase
  • disintegrin and metalloproteinase domain 17
  • disintegrin and metalloproteinase domain-containing protein 17
  • CD156b antigen
  • Synonym symbol(s) TACE, cSVP, CD156B, MGC71942, ADAM18, NISBD
    EC.number 3.4.24.86
    DNA
    TYPE functioning gene
    STRUCTURE 66.51 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map pter - D2S287 - D2S2207 - ADAM17 - D2S2169 - D2S423 - cen
    Authors Hirohata (98)
    Physical map
    LOC129607 2p25.2 hypothetical protein LOC129607 cig5 2p25.2 viperin RNF144 2p25 ring finger protein 144 LOC129614 2p25.2 similar to acidic integral membrane protein LOC391350 2 similar to ENSANGP00000014942 ID2 2p25 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein KIDINS220 2p24 likely homolog of rat kinase D-interacting substance of 220 kDa LOC129642 2p25.2 hypothetical protein BC016005 DDEF2 2p24 development and differentiation enhancing factor 2 ITGB1BP1 2p25.2 integrin beta 1 binding protein 1 CPSF3 2pter-p25 cleavage and polyadenylation specific factor 3, 73kDa LOC285148 2p25.2 hypothetical protein LOC285148 ADAM17 2p25 a disintegrin and metalloproteinase domain 17 (tumor necrosis factor, alpha, converting enzyme) YWHAQ 2p25 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide TAF1B 2p25 TATA box binding protein (TBP)-associated factor, RNA polymerase I, B, 63kDa TFCP2L2 2p25.1 transcription factor CP2-like 2 TIEG2 2p25 TGFB inducible early growth response 2 RRM2 2p24 ribonucleotide reductase M2 polypeptide FLJ25102 2p25.1 hypothetical protein FLJ25102 HPCAL1 2p25.1 hippocalcin-like 1 ODC1 2p25 ornithine decarboxylase 1 LOC130063 2p25.1 hypothetical gene LOC130063 FLJ14075 2p25.1 hypothetical protein FLJ14075 ATP6V1C2 2p25.1 ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C isoform 2 P5 2p25.1 protein disulfide isomerase-related protein LOC388924 2 LOC388924 KCNF1 2p25 potassium voltage-gated channel, subfamily F, member 1 FLJ33534 2p25.1 hypothetical protein FLJ33534 LOC391351 2 similar to RPL6 protein FLJ25143 2p25.1 hypothetical protein FLJ25143 MGC33602 ROCK2 2p24 Rho-associated, coiled-coil containing protein kinase 2 LOC391352 2 similar to peptidyl-Pro cis trans isomerase E2F6 22q11.2 E2F transcription factor 6 GREB1 2p25.1 E2F transcription factor 6 NTSR2 2p25.1 neurotensin receptor 2 LPIN1 2p25.1 lipin 1 FAM10A3 2p25.1 family with sequence similarity 10, member A3
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    19 - 3572 70 824 - - 9034191
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly Homo sapiens
    Digestiveintestinesmall intestine  moderately Homo sapiens
     liver   lowly Homo sapiens
    Endocrinepancreas   specific Homo sapiens
    Lymphoid/Immunespleen   moderately Homo sapiens
     thymus   moderately Homo sapiens
    Nervousbrain   lowly Homo sapiens
    Reproductivefemale systemovary  highly Homo sapiens
     female systemplacenta  highly Homo sapiens
     male systemprostate  moderately Homo sapiens
     male systemtestis  highly Homo sapiens
    Respiratorylung   lowly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal, growth/childhood
    Text brain, lung, liver, kidney (
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an unknown prodomain, a cysteine switch, a catalytic domain, a zinc binding region, a disintegrin region, an EGF-like domain, a transmembrane domain, and a unique cytoplasmic region (
  • conjugated GlycoP , MetalloP
    isoforms Precursor TNFalpha induces the conversion from the proform of ADAM-17 to its mature form
    HOMOLOGY
    interspecies ortholog to Adam17, Mus musculus
    ortholog to Adam17, Rattus norvegicus
    ortholog to ADAM17, Pan troglodytes
    Homologene
    FAMILY
  • ADAM (a disintegrin and metalloprotease domain) family
  • CATEGORY adhesion , enzyme
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane
    text membrane bound processed to a secreted form, (membrane type 1 protein)
    basic FUNCTION
  • a functional paracrine/autocrine role in osteoarthritis -affected cartilage (
  • role in the processing of cell surface proteins TNF receptor, the L-selectin adhesion molecule, and transforming growth factor-alpha (
  • an essential role mammalian development (
  • role in the regulated shedding of EGFR ligands (
  • acts as alpha-secretases in A172 cells (
  • functions as an effector of GPCR-mediated signalling and represents a key element of the cellular receptor cross-talk network (
  • mediating the cleavage and shedding of fraktalkine (CX3CL1)
  • releasing TNFA from its membrane bound precursor, also reported to cleave APP
  • contributing to heart development
  • growth hormone binding protein sheddase (see GHR)
  • metalloprotease disintegrin cleaving a variety of membrane proteins, releasing ("shedding") their extracellular domains from cells
  • playing a role in the regulation of platelet glycoprotein V
  • may be having a role in both the induction and down-regulation of neutrophil activity
  • involved in invasion of oral squamous cell carcinoma, probably through CD44 cleavage
  • being responsible with ADAM10 for the cytokine-induced shedding of CXCL16
  • involved in the tumor-associated proteolytic release of soluble MICA facilitating tumor immune escape (
  • important regulator of several key steps during angiogenesis
  • involved in the conversion of MMP2 from the latent form to the intermediate-sized form and plays a particularly key role in the conversion of the intermediate-sized form to the fully activated form
  • may regulate angiogenesis via its effects on endothelial cells proliferation, network formation, invasion and MMP2 activation
  • involved in the cleavage of NOTCH1
  • is required for NOTCH1 signaling independent of ligands
  • mediates inflammation-induced shedding of SDC1 and SDC4 by lung epithelial cells
  • responsible for cleaving the membrane-proximal extracellular domain of L-selectin, which reduces the efficiency of leucocyte recruitment to sites of inflammation
  • shedding JAG1 in a lipid-raft-independent manner, and the cytosolic domain of the former protein is not a pre-requisite for either constitutive or regulated shedding
  • through the cleavage of VASN, the metalloprotease controls TGFB-mediated epithelial-to-mesenchymal transition
  • cleaves neuregulin-1 type III in the epidermal growth factor domain and negatively regulates peripheral nervous system myelination (
  • a modulator of NRG1 type III activity and is a negative regulator of myelination in the peripheral nervous system (
  • its induction during apoptosis may rapidly diminish neutrophil sensitivity to the inflammatory environment, complementing other anti-inflammatory activities by these cells during inflammation resolution
  • may play a broad role in the homeostatic maintenance of various substrates in the blood
  • is a novel UPR-regulated gene in response to severe hypoxia and ER stress, which is actively involved in the release of TNFRSF1A under these conditions
  • potential functional link between ADAM17 and ICOSLG in controlling adaptive immune responses
  • ADAM10 and ADAM17 have opposite effects on sprouting angiogenesis that may be unrelated to Notch signalling and involves differentially expressed anti-angiogenic proteins such as TSP1
  • both ADAM10 and ADAM17 are associated with FASLG-containing secretory lysosomes
  • ADAM17 has a prominent role in ANCA-associated vasculitis (AAV) and might account for the vascular complications associated with this disease
  • ADAM12 and ADAM17 are essential molecules for hypoxia-induced impairment of neural vascular barrier function
  • is regarded as a first line of defense against injury and infection, by releasing tumor necrosis factor alpha (TNF) to promote inflammation and epidermal growth factor (EGF) receptor ligands to maintain epidermal barrier function
  • PDIA6 regulation of ADAM17 shedding activity and EGFR-mediated migration and invasion of glioblastoma cells
  • CELLULAR PROCESS protein, post translation
    protein, degradation
    PHYSIOLOGICAL PROCESS development
    text
  • major sheddase for ectodomain shedding of TNF-alpha (
  • PATHWAY
    metabolism
    signaling
  • part of a novel pro-angiogenic pathway leading to MMP2 activation and vessel formation
  • critical role of the ADAM17-EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier
  • a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Zn2+
  • protein
  • mitotic arrest deficient 2, MAD2 and metalloprotease-disintegrin MDC9 (
  • protein-tyrosine phosphatase PTPH1 (
  • SAP97 (
  • Integrin alpha5beta1 (
  • Four and Half LIM domain 2 protein, FHL2 (
  • ALCAM
  • ADAM17 mediates ectodomain shedding of the scavenger receptor CD163
  • VASN
  • participates at least in part in the shedding of LMAN2
  • SIGMAR1 overexpression diminished ADAM17- and ADAM10-dependent shedding
  • ANXA2, ANXA8, ANXA9, play an essential role in the ADAM17-mediated ectodomain shedding of EGFR ligands
  • ADAM17 is likely the PTK7 sheddase
  • ALCAM directly associates with the tetraspanin CD9 on the leukocyte surface in protein complexes that also include the metalloproteinase ADAM17/TACE
  • role of ADAM17 during embryonic eyelid closure is to transactivate EGFR signaling
  • over-activation of ADAM17 in NK cells may be detrimental to their effector functions by down-regulating surface expression of FCGR3A and SELL
  • PROCR can be shed from the cell surface, and this is mediated by tumor necrosis factor-alpha-converting enzyme (ADAM17)
  • in hepatocytes, CAV1 is required for TGFB1-mediated activation of the metalloprotease ADAM17 that is responsible for shedding of EGFR ligands and activation of the EGFR pathway, which counteracts the TGFB1 pro-apoptotic effects
  • FCGR3A cleavage by ADAM17, but non-cleavable version of FCGR3A can be expressed in engineered NK cells (
  • PACS2 is a regulator of ADAM17 trafficking and ErbB signalling
  • HSPA5 protects ADAM17 against PDIAA6 catalyzed inactivation
  • cell & other
    REGULATION
    activated by in response to cellular stimulation
    HDLs (
    induced by and redistributed in AGT-damaged kidneys
    inhibited by TIMP3
    Phosphorylated by Erk at threonine 735 (
    Other regulated by IL10 (regulates ADAM17, involving a TIMP3 dependent and independent mechanism)
    negatively regulated by protein-tyrosine phosphatase PTPH1 (
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in arthritis affected cartilage
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • participating in signaling intrinsic to NOTCH1 mutations associated with leukemia
  • Marker
    Therapy target
  • therapeutic strategy for preventing progression of chronic renal diseases (inhibitor of ADAM17)
  • a principal target for the treatment of TNF-dependent pathologies (
  • may serve as a novel therapeutic target for diseases in which the inhibition or stimulation of angiogenesis could be beneficial
  • ANIMAL & CELL MODELS
  • inactivation of Adam17 gene in mouse cells caused a marked decrease in soluble TNF-alpha production (
  • TACE inactivation in mouse myeloid cells or temporal inactivation at 6 wk offers strong protection from endotoxin shock lethality in mice by preventing increased TNF serum levels (
  • perinatal and postnatal defects in mice lacking TACE were associated with numerous epithelial anomalies (
  • Lentivirus-mediated knockdown of ADAM17 in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination (
  • motor neurons of conditional knockout mice lacking ADAM17 are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated (