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ADAM17 ADAM metallopeptidase domain 17 [ Homo sapiens (human) ]

Gene ID: 6868, updated on 5-Apr-2020

Summary

Official Symbol
ADAM17provided by HGNC
Official Full Name
ADAM metallopeptidase domain 17provided by HGNC
Primary source
HGNC:HGNC:195
See related
Ensembl:ENSG00000151694 MIM:603639
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CSVP; TACE; NISBD; ADAM18; CD156B; NISBD1
Summary
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 encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands. The encoded protein also plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. [provided by RefSeq, Feb 2016]
Expression
Ubiquitous expression in testis (RPKM 11.1), placenta (RPKM 10.9) and 25 other tissues See more
Orthologs

Genomic context

See ADAM17 in Genome Data Viewer
Location:
2p25.1
Exon count:
20
Annotation release Status Assembly Chr Location
109.20200228 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (9488486..9555830, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (9629392..9695917, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 Neighboring gene Sharpr-MPRA regulatory region 10317 Neighboring gene integrin subunit beta 1 binding protein 1 Neighboring gene cleavage and polyadenylation specific factor 3 Neighboring gene uncharacterized LOC107985850 Neighboring gene isoamyl acetate hydrolyzing esterase 1 (putative) Neighboring gene uncharacterized LOC101929643 Neighboring gene tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Inflammatory skin and bowel disease, neonatal 1
MedGen: C3280501 OMIM: 614328 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study on dimethylarginines reveals novel AGXT2 variants associated with heart rate variability but not with overall mortality.
NHGRI GWA Catalog
Genome-wide survival analysis of age at onset of alcohol dependence in extended high-risk COGA families.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 infected clinical samples have plasma extracellular vesicles that contain elevated ADAM10, ADAM17, and TNF when compared to healthy donors PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with ADAM17; predicted interaction to be relevant to viral egress at plasma membrane/extracellular matrix PubMed
Nef nef HIV-1 Nef incorporates ADAM17 into exosomes from infected U1 cells PubMed
nef HIV-1 Nef-mediated activation of TACE cleaves pro-TNF alpha in endosomal compartments PubMed
nef ADAM17 is involved in both activation and HIV-1 replication in primary quiescent CD4+ T lymphocytes treated with exosomes from cells infected by HIV-1, but not by delta-Nef HIV-1 or Nef (62EEEE/AAAA65) HIV-1 strains PubMed
nef The Nef/hnRNPK/PKC-delta/Hck protein complex activates Pak2 activity but inhibits Pak1 activity, which induces paxillin phosphorylation on Ser272/274 and regulates paxillin/TACE association and secretion PubMed
nef The Nef/hnRNPK/PKC-delta/Hck protein complex increases paxillin phosphorylation at Y118 and activates and secretes TACE through Erk1/2 activation PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC71942

Gene Ontology Provided by GOA

Function Evidence Code Pubs
Notch binding IDA
Inferred from Direct Assay
more info
PubMed 
PDZ domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
SH3 domain binding IEA
Inferred from Electronic Annotation
more info
 
endopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
integrin binding IPI
Inferred from Physical Interaction
more info
PubMed 
interleukin-6 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
metalloendopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
metalloendopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
metalloendopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
metalloendopeptidase activity TAS
Traceable Author Statement
more info
 
metallopeptidase activity IDA
Inferred from Direct Assay
more info
PubMed 
metallopeptidase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
peptidase activity TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
B cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
Notch receptor processing IDA
Inferred from Direct Assay
more info
PubMed 
Notch signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
PMA-inducible membrane protein ectodomain proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
PMA-inducible membrane protein ectodomain proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
PMA-inducible membrane protein ectodomain proteolysis IMP
Inferred from Mutant Phenotype
more info
PubMed 
T cell differentiation in thymus ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cell adhesion IDA
Inferred from Direct Assay
more info
PubMed 
cell adhesion mediated by integrin IDA
Inferred from Direct Assay
more info
PubMed 
cell motility ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
cellular response to high density lipoprotein particle stimulus IDA
Inferred from Direct Assay
more info
PubMed 
defense response to Gram-positive bacterium IMP
Inferred from Mutant Phenotype
more info
PubMed 
epidermal growth factor receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
germinal center formation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
membrane protein ectodomain proteolysis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
membrane protein ectodomain proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
membrane protein ectodomain proteolysis IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane protein intracellular domain proteolysis TAS
Traceable Author Statement
more info
 
negative regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
negative regulation of transforming growth factor beta receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
neutrophil mediated immunity IC
Inferred by Curator
more info
PubMed 
positive regulation of G1/S transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of T cell chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of blood vessel endothelial cell migration IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cellular component movement ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of chemokine production IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cyclin-dependent protein serine/threonine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of epidermal growth factor-activated receptor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of epidermal growth factor-activated receptor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of leukocyte chemotaxis IC
Inferred by Curator
more info
PubMed 
positive regulation of protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transforming growth factor beta receptor signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
positive regulation of tumor necrosis factor-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of vascular endothelial cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis IDA
Inferred from Direct Assay
more info
PubMed 
receptor transactivation IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of mast cell apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
response to drug ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
response to hypoxia IDA
Inferred from Direct Assay
more info
PubMed 
response to lipopolysaccharide IDA
Inferred from Direct Assay
more info
PubMed 
spleen development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
tumor necrosis factor-mediated signaling pathway TAS
Traceable Author Statement
more info
 
wound healing, spreading of epidermal cells IEP
Inferred from Expression Pattern
more info
PubMed 
Component Evidence Code Pubs
actin cytoskeleton IDA
Inferred from Direct Assay
more info
PubMed 
apical plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
cell surface IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with cell-cell junction IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
colocalizes_with focal adhesion IDA
Inferred from Direct Assay
more info
PubMed 
integral component of plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
membrane HDA PubMed 
membrane raft IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
colocalizes_with ruffle membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
disintegrin and metalloproteinase domain-containing protein 17
Names
ADAM metallopeptidase domain 18
TNF-alpha convertase
TNF-alpha converting enzyme
snake venom-like protease
tumor necrosis factor, alpha, converting enzyme
NP_003174.3
XP_011508677.1
XP_011508678.1
XP_016860274.1
XP_016860275.1
XP_024308824.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029873.1 RefSeqGene

    Range
    4959..72303
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1203

mRNA and Protein(s)

  1. NM_003183.6NP_003174.3  disintegrin and metalloproteinase domain-containing protein 17 preproprotein

    See identical proteins and their annotated locations for NP_003174.3

    Status: REVIEWED

    Source sequence(s)
    AC073195, AC080162, GQ402545
    Consensus CDS
    CCDS1665.1
    UniProtKB/Swiss-Prot
    P78536
    UniProtKB/TrEMBL
    B2RNB2
    Related
    ENSP00000309968.3, ENST00000310823.8
    Conserved Domains (4) summary
    smart00050
    Location:484560
    DISIN; Homologues of snake disintegrins
    cd04270
    Location:223477
    ZnMc_TACE_like; Zinc-dependent metalloprotease; TACE_like subfamily. TACE, the tumor-necrosis factor-alpha converting enzyme, releases soluble TNF-alpha from transmembrane pro-TNF-alpha.
    pfam01562
    Location:56152
    Pep_M12B_propep; Reprolysin family propeptide
    pfam16698
    Location:581641
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

    Range
    9488486..9555830 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011510376.3XP_011508678.1  disintegrin and metalloproteinase domain-containing protein 17 isoform X2

    Conserved Domains (4) summary
    smart00050
    Location:264340
    DISIN; Homologues of snake disintegrins
    cd04270
    Location:3257
    ZnMc_TACE_like; Zinc-dependent metalloprotease; TACE_like subfamily. TACE, the tumor-necrosis factor-alpha converting enzyme, releases soluble TNF-alpha from transmembrane pro-TNF-alpha.
    pfam13574
    Location:27240
    Reprolysin_2; Metallo-peptidase family M12B Reprolysin-like
    pfam16698
    Location:361421
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
  2. XM_011510375.3XP_011508677.1  disintegrin and metalloproteinase domain-containing protein 17 isoform X1

    Conserved Domains (5) summary
    smart00050
    Location:453529
    DISIN; Homologues of snake disintegrins
    cd04270
    Location:192446
    ZnMc_TACE_like; Zinc-dependent metalloprotease; TACE_like subfamily. TACE, the tumor-necrosis factor-alpha converting enzyme, releases soluble TNF-alpha from transmembrane pro-TNF-alpha.
    pfam01562
    Location:25135
    Pep_M12B_propep; Reprolysin family propeptide
    pfam13574
    Location:216429
    Reprolysin_2; Metallo-peptidase family M12B Reprolysin-like
    pfam16698
    Location:550610
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
  3. XM_017004785.2XP_016860274.1  disintegrin and metalloproteinase domain-containing protein 17 isoform X3

    Conserved Domains (3) summary
    smart00050
    Location:185261
    DISIN; Homologues of snake disintegrins
    pfam16698
    Location:282342
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
    cl00064
    Location:3178
    ZnMc; Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which ...
  4. XM_024453056.1XP_024308824.1  disintegrin and metalloproteinase domain-containing protein 17 isoform X3

    Conserved Domains (3) summary
    smart00050
    Location:185261
    DISIN; Homologues of snake disintegrins
    pfam16698
    Location:282342
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
    cl00064
    Location:3178
    ZnMc; Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which ...
  5. XM_017004786.2XP_016860275.1  disintegrin and metalloproteinase domain-containing protein 17 isoform X3

    Related
    ENST00000648548.1
    Conserved Domains (3) summary
    smart00050
    Location:185261
    DISIN; Homologues of snake disintegrins
    pfam16698
    Location:282342
    ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
    cl00064
    Location:3178
    ZnMc; Zinc-dependent metalloprotease. This super-family of metalloproteases contains two major branches, the astacin-like proteases and the adamalysin/reprolysin-like proteases. Both branches have wide phylogenetic distribution, and contain sub-families, which ...
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