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

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; AllianceGenome:HGNC:195
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, and 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. Additionally, this protease may play a role in viral infection through its cleavage of ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for COVID-19 treatment.
Expression: Ubiquitous expression in testis (RPKM 11.1), placenta (RPKM 10.9) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p25.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (9488486..9555830, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (9513510..9580869, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (9628615..9695959, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17 axis.
Title: Mesenchymal stem cell-derived extracellular vesicles ameliorate renal interstitial fibrosis via the miR-13474/ADAM17 axis.
TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis.
Title: TACE inhibition: a promising therapeutic intervention against AATF-mediated steatohepatitis to hepatocarcinogenesis.
Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.
Title: Ectodomain shedding of PLA2R1 is mediated by the metalloproteases ADAM10 and ADAM17.
Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.
Title: Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.
Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.
Title: Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals.
Regulation of Mertk Surface Expression via ADAM17 and gamma-Secretase Proteolytic Processing.
Title: Regulation of Mertk Surface Expression via ADAM17 and γ-Secretase Proteolytic Processing.
The Important Role of Phosphatidylserine, ADAM17, TNF-Alpha, and Soluble MER on Efferocytosis Activity in Central Obesity.
Title: The Important Role of Phosphatidylserine, ADAM17, TNF-Alpha, and Soluble MER on Efferocytosis Activity in Central Obesity.
MiR-145 Alleviates Sepsis-Induced Inflammatory Responses and Organ Injury by Targeting ADAM17.
Title: MiR-145 Alleviates Sepsis-Induced Inflammatory Responses and Organ Injury by Targeting ADAM17.
Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer.
Title: Tumor-derived exosomal ADAM17 promotes pre-metastatic niche formation by enhancing vascular permeability in colorectal cancer.
Expression of ADAM17 and its clinical value for patients with pernicious placenta previa: A retrospective study of 148 PPP patients underwent cesarean section.
Title: Expression of ADAM17 and its clinical value for patients with pernicious placenta previa: A retrospective study of 148 PPP patients underwent cesarean section.

Submit: New GeneRIF Correction See all GeneRIFs (448)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

EBI GWAS Catalog

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

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70698 (e-PCR)
- UniSTS:62215

Adam17 (e-PCR), detects polymorphism
- UniSTS:471064

D15S981 (e-PCR), detects polymorphism
- UniSTS:17093

ADAM17_1239 (e-PCR)
- UniSTS:276963

SHGC-145828 (e-PCR)
- UniSTS:174820

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Notch binding	IDA Inferred from Direct Assay more info	PubMed
enables PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables cytokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables endopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables interleukin-6 receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metalloendopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables metalloendopeptidase activity	TAS Traceable Author Statement more info
enables metalloendopeptidase activity involved in amyloid precursor protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
enables metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metallopeptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables peptidase activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables tumor necrosis factor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in Notch receptor processing	IDA Inferred from Direct Assay more info	PubMed
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell differentiation in thymus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in amyloid precursor protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in cell adhesion mediated by integrin	IDA Inferred from Direct Assay more info	PubMed
involved_in cell motility	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in cellular response to high density lipoprotein particle stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in commissural neuron axon guidance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to Gram-positive bacterium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in germinal center formation	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in membrane protein ectodomain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein ectodomain proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neutrophil mediated immunity	IC Inferred by Curator more info	PubMed
involved_in positive regulation of G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of T cell chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of blood vessel endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cyclin-dependent protein serine/threonine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epidermal growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of epidermal growth factor receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of epidermal growth factor-activated receptor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of leukocyte chemotaxis	IC Inferred by Curator more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of mast cell apoptotic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
involved_in response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in signal release	IDA Inferred from Direct Assay more info	PubMed
involved_in spleen development	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in wound healing, spreading of epidermal cells	IEP Inferred from Expression Pattern more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
located_in actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
colocalizes_with focal adhesion	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	HDA more info	PubMed
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
colocalizes_with ruffle membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: disintegrin and metalloproteinase domain-containing protein 17

Names: ADAM metallopeptidase domain 18; TNF-alpha convertase; TNF-alpha convertase enzyme; TNF-alpha converting enzyme; a disintegrin and metalloproteinase 17; cartilage snake venom-like protease; snake venom-like protease; tumor necrosis factor, alpha, converting enzyme

NP_001369706.1

EC 3.4.24.86

NP_001369707.1

EC 3.4.24.86

NP_003174.3

EC 3.4.24.86

XP_047301566.1

EC 3.4.24.86

XP_047301567.1

EC 3.4.24.86

XP_047301568.1

EC 3.4.24.86

XP_054199547.1

EC 3.4.24.86

XP_054199548.1

EC 3.4.24.86

NCBI Reference Sequences (RefSeq)

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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

NG_029873.1 RefSeqGene

Range

4959..72303

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1203

mRNA and Protein(s)

NM_001382777.1 → NP_001369706.1 disintegrin and metalloproteinase domain-containing protein 17 isoform 2

Status: REVIEWED

Source sequence(s)

AC073195, AC080162, AC092206

UniProtKB/TrEMBL

Q53RS1

Related

ENST00000648548.1

Conserved Domains (3) summary

smart00050
Location:264 → 340

DISIN; Homologues of snake disintegrins

cd04270
Location:3 → 257

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.

pfam16698
Location:361 → 422

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
NM_001382778.1 → NP_001369707.1 disintegrin and metalloproteinase domain-containing protein 17 isoform 3

Status: REVIEWED

Source sequence(s)

AC073195, AC080162, AC092206

UniProtKB/TrEMBL

Q53RS1

Conserved Domains (3) summary

smart00050
Location:185 → 261

DISIN; Homologues of snake disintegrins

pfam16698
Location:282 → 343

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17

cl00064
Location:3 → 178

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

O60226, P78536

UniProtKB/TrEMBL

A0A8V8TN27, B2RNB2

Related

ENSP00000309968.3, ENST00000310823.8

Conserved Domains (4) summary

smart00050
Location:484 → 560

DISIN; Homologues of snake disintegrins

cd04270
Location:223 → 477

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:56 → 152

Pep_M12B_propep; Reprolysin family propeptide

pfam16698
Location:581 → 641

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

9488486..9555830 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047445610.1 → XP_047301566.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X1
XM_047445611.1 → XP_047301567.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X2
XM_047445612.1 → XP_047301568.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X2

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

9513510..9580869 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054343572.1 → XP_054199547.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X1
XM_054343573.1 → XP_054199548.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X2

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_021832.1: Suppressed sequence

Description

NM_021832.1: This RefSeq was removed because currently there is insufficient support for the transcript and the protein.