Adam17 a disintegrin and metallopeptidase domain 17 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Adam17provided by MGI
Official Full Name: a disintegrin and metallopeptidase domain 17provided by MGI
Primary source: MGI:MGI:1096335
See related: Ensembl:ENSMUSG00000052593 AllianceGenome:MGI:1096335
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Tace; CD156b
Summary: This gene encodes a member of a disintegrin and metalloprotease (ADAM) family of endoproteases that play important roles in various biological processes including cell signaling, adhesion and migration. The encoded preproprotein undergoes proteolytic processing to generate a mature enzyme that is involved in the proteolytic release of membrane-bound proteins in a process called ectodomain shedding. Mice lacking the encoded protein die in utero or fail to survive beyond one week of age. Alternative splicing results in multiple transcript variants encoding different isoforms, some of which may undergo similar processing. [provided by RefSeq, May 2016]
Expression: Ubiquitous expression in placenta adult (RPKM 12.8), CNS E11.5 (RPKM 9.9) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 12 A1.3; 12 8.3 cM

Exon count:: 20

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	12	NC_000078.7 (21373510..21423633, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	12	NC_000078.6 (21323509..21373632, complement)

Chromosome 12 - NC_000078.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.
Title: Downregulation of the metalloproteinases ADAM10 or ADAM17 promotes osteoclast differentiation.
GRWD1 Over-Expression Promotes Gastric Cancer Progression by Activating Notch Signaling Pathway via Up-Regulation of ADAM17.
Title: GRWD1 Over-Expression Promotes Gastric Cancer Progression by Activating Notch Signaling Pathway via Up-Regulation of ADAM17.
Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.
Title: Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.
Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis.
Title: Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis.
ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17 : ARPC5 serves as an oncogene in prostate cancer.
Title: ARPC5 is transcriptionally activated by KLF4, and promotes cell migration and invasion in prostate cancer via up-regulating ADAM17 : ARPC5 serves as an oncogene in prostate cancer.
P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction.
Title: P38 MAPK activated ADAM17 mediates ACE2 shedding and promotes cardiac remodeling and heart failure after myocardial infarction.
The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.
Title: The ADAM17 sheddase complex regulator iTAP/Frmd8 modulates inflammation and tumor growth.
Blockade of the protease ADAM17 ameliorates experimental pancreatitis.
Title: Blockade of the protease ADAM17 ameliorates experimental pancreatitis.
Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.
Title: Cardiomyocyte-specific knockout of ADAM17 ameliorates left ventricular remodeling and function in diabetic cardiomyopathy of mice.

Submit: New GeneRIF Correction See all GeneRIFs (240)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1) 1 citation
Endonuclease-mediated (7) 1 citation
Gene trapped (1)
Spontaneous (1) 1 citation
Targeted (13) 1 citation

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

Gene Ontology Provided by MGI

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

Process	Evidence Code	Pubs
involved_in B cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in Notch receptor processing	ISO Inferred from Sequence Orthology more info
involved_in Notch receptor processing	ISS Inferred from Sequence or Structural Similarity more info
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in Notch signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in T cell differentiation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in amyloid precursor protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in cell adhesion	ISO Inferred from Sequence Orthology more info
involved_in cell adhesion mediated by integrin	ISO Inferred from Sequence Orthology more info
involved_in cell motility	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to high density lipoprotein particle stimulus	ISO Inferred from Sequence Orthology more info
involved_in commissural neuron axon guidance	ISO Inferred from Sequence Orthology more info
involved_in defense response to Gram-positive bacterium	ISO Inferred from Sequence Orthology more info
involved_in germinal center formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein ectodomain proteolysis	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
involved_in membrane protein ectodomain proteolysis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within membrane protein ectodomain proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein ectodomain proteolysis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in membrane protein ectodomain proteolysis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cold-induced thermogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of neuron projection development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of ERK1 and ERK2 cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of T cell chemotaxis	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of blood vessel endothelial cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell migration	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chemokine production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cyclin-dependent protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of positive regulation of epidermal growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epidermal growth factor receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of epidermal growth factor-activated receptor activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of neuron projection development	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of tumor necrosis factor production	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of vascular endothelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in production of molecular mediator involved in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	ISO Inferred from Sequence Orthology more info
involved_in proteolysis	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within regulation of axon regeneration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of mast cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of neuron migration	IGI Inferred from Genetic Interaction more info	PubMed
involved_in response to hypoxia	ISO Inferred from Sequence Orthology more info
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in response to xenobiotic stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal release	ISO Inferred from Sequence Orthology more info
involved_in signaling receptor ligand precursor processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signaling receptor ligand precursor processing	ISO Inferred from Sequence Orthology more info	PubMed
involved_in spleen development	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in actin cytoskeleton	ISO Inferred from Sequence Orthology more info
located_in apical part of cell	ISO Inferred from Sequence Orthology more info
located_in apical plasma membrane	ISO Inferred from Sequence Orthology more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
colocalizes_with cell-cell junction	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in extracellular region	TAS Traceable Author Statement more info
colocalizes_with focal adhesion	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info
colocalizes_with ruffle membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: disintegrin and metalloproteinase domain-containing protein 17

Names: TNF-alpha convertase; TNF-alpha converting enzyme

NP_001264195.1

EC 3.4.24.86

NP_001278800.1

EC 3.4.24.86

NP_033745.4

EC 3.4.24.86

XP_030102390.1

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.

mRNA and Protein(s)

NM_001277266.1 → NP_001264195.1 disintegrin and metalloproteinase domain-containing protein 17 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate in-frame exon compared to variant 1. The resulting isoform (2) contains an alternate internal 19 aa segment compared to isoform 1. This isoform (2) may undergo processing similar to isoform 1.

Source sequence(s)

AC140457, AC156032, BC094655

Consensus CDS

CCDS70376.1

UniProtKB/TrEMBL

E9PXU2, Q3UNK7

Related

ENSMUSP00000099087.4, ENSMUST00000101551.10

Conserved Domains (4) summary

smart00050
Location:503 → 578

DISIN; Homologues of snake disintegrins

cd04270
Location:223 → 496

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:49 → 167

Pep_M12B_propep; Reprolysin family propeptide

pfam16698
Location:600 → 660

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
NM_001291871.1 → NP_001278800.1 disintegrin and metalloproteinase domain-containing protein 17 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate 5' splice site, lacks a portion of the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded protein (isoform 4) has a shorter N-terminus than isoform 1.

Source sequence(s)

AC140457, AC156032, AK142441, BC094655, BM248808

UniProtKB/Swiss-Prot

Q9Z0F8

Conserved Domains (4) summary

smart00050
Location:246 → 321

DISIN; Homologues of snake disintegrins

cd04270
Location:1 → 239

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:9 → 222

Reprolysin_2; Metallo-peptidase family M12B Reprolysin-like

pfam16698
Location:343 → 403

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17
NM_009615.6 → NP_033745.4 disintegrin and metalloproteinase domain-containing protein 17 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_033745.4

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the predominant isoform (1).

Source sequence(s)

AC140457, AC156032, BC094655

Consensus CDS

CCDS25836.1

UniProtKB/Swiss-Prot

O88726, Q505A7, Q9R1U4, Q9Z0F8, Q9Z0K3

UniProtKB/TrEMBL

Q3UV09

Related

ENSMUSP00000067953.7, ENSMUST00000064536.13

Conserved Domains (5) summary

smart00050
Location:484 → 559

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 → 166

Pep_M12B_propep; Reprolysin family propeptide

pfam13574
Location:247 → 460

Reprolysin_2; Metallo-peptidase family M12B Reprolysin-like

pfam16698
Location:581 → 641

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17

RNA

NR_102380.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks three alternate exons compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC140457, AC156032, BC094655
NR_120376.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate 3' splice site, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC140457, AC156032, AK137693, AK142441, AK149614, BC094655, BM248808

Related

ENSMUST00000145118.8

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000078.7 Reference GRCm39 C57BL/6J

Range

21373510..21423633 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_030246530.2 → XP_030102390.1 disintegrin and metalloproteinase domain-containing protein 17 isoform X1

UniProtKB/TrEMBL

B7ZNJ0

Conserved Domains (3) summary

smart00050
Location:321 → 396

DISIN; Homologues of snake disintegrins

cd04270
Location:60 → 314

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:418 → 478

ADAM17_MPD; Membrane-proximal domain, switch, for ADAM17