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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 ADAM17-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
About This Section

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)
About This Section

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, 1, and heterotaxy. 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)
About This Section

RefSeq DNA sequence at NCBI GenBank:

NC_000002.11 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 plasmid: ADAM17 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, Cloud-Clone Corp., eBioscience, antibodies-online, and/or GeneTex,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
About This Section

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:

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	Search GeneTex for Proteins for ADAM17
	antibodies-online proteins for ADAM17 (10 products)
	antibodies-online peptides for ADAM17

ADAM17 Antibody Products:

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	antibodies-online antibodies for ADAM17 (173 products)

ADAM17 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	antibodies-online kits for ADAM17 (22 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GenesLikeMe)
About This Section

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

Find genes that share domains with ADAM17 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, 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, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene, Sets of similar genes according to GenesLikeMe)
About This Section

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 ID	Qualified GO term	Evidence	PubMed IDs
GO:0004222	metalloendopeptidase activity	TAS	--
GO:0005112	Notch binding	IDA	--
GO:0005138	interleukin-6 receptor binding	IPI	16034137
GO:0005178	integrin binding	IPI	14970227
GO:0005515	protein binding	IPI	10527948

Find genes that share ontologies with ADAM17 About GenesLikeMe

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

Find genes that share phenotypes with ADAM17 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for ADAM17: Adam17^tm1.1Bbl Adam17^tm1Imx Adam17^tm1.2Rain

genOway: Develop your customized and physiologically relevant rodent model for ADAM17

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		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 plasmid: ADAM17 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
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ADAM17
		Addgene plasmids for 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, Sets of similar genes according to GenesLikeMe)
About This Section

Subcellular locations from UniProtKB/Swiss-Prot

ADA17_HUMAN, P78536: Membrane; Single-pass type I membrane protein

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytoskeleton	4
plasma membrane	4
cytosol	2
extracellular	2
endoplasmic reticulum	1
nucleus	1
peroxisome	1

About this image

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	IDA	--
GO:0005886	plasma membrane	TAS	--
GO:0005887	integral component of plasma membrane	IDA	17786981
GO:0005911	colocalizes with cell-cell junction	IDA	14970227
GO:0005925	colocalizes with focal adhesion	IDA	14970227

Find genes that share ontologies with ADAM17 About GenesLikeMe

(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 GenesLikeMe, 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, Sets of similar genes according to GenesLikeMe)
About This Section

SuperPaths for ADAM17 About (see all 34)

See pathways by source

Powered
by

SuperPath

Selected contained pathways About (see all per SuperPath)

Notch signaling pathway (KEGG)

	Notch signaling pathway	0.84			Delta-Notch Signaling Pathway	0.33
	Notch Signaling Pathway	0.84			Notch Signaling	0.30

Alzheimer's disease

Alzheimers Disease

0.44

Alzheimer's disease

0.44

Signaling by NOTCH1 PEST Domain Mutants in Cancer

Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	0.79	Constitutive Signaling by NOTCH1 PEST Domain Mutants	0.79
Signaling by NOTCH1 PEST Domain Mutants in Cancer	0.79	Signaling by NOTCH1 in Cancer	0.79
Signaling by NOTCH1 HD Domain Mutants in Cancer	0.79	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	0.79
Signaling by NOTCH1 t(7;9)(NOTCH1-M1580 K2555) Translocation Mutant	0.79	FBXW7 Mutants and NOTCH1 in Cancer	0.79

Signaling by FGFR

	Signaling by EGFR	0.83			Signalling by NGF	0.71
	Signaling by EGFR in Cancer	0.82

Death Receptor Signalling

	Death Receptor Signalling	0.71			Extrinsic Pathway for Apoptosis	0.00
	TNF signaling	0.00

Find genes that share SuperPaths with ADAM17 About GenesLikeMe

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

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 (P78536^{1, 2, 3} ENSP00000309968⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 44)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
DLG1	Q12959¹^,²^,³, ENSP00000345731⁴	EBI-78188,EBI-357481 MINT-1901891 MINT-1901801 MINT-1901824 MINT-1901856 MINT-1901710 MINT-1901743 MINT-1901775 I2D: score=4 STRING: ENSP00000345731
PTPN3	P26045²^,³, ENSP00000262539⁴	MINT-58311 MINT-58317 I2D: score=3 STRING: ENSP00000262539
PDIA3	P30101²^,³	MINT-4301309 I2D: score=1
TNF	P01375³, ENSP00000398698⁴	I2D: score=2 STRING: ENSP00000398698
ENSG00000204490	P01375³	I2D: score=2

About this table

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

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	IDA	18276953
GO:0001934	positive regulation of protein phosphorylation	IMP	18625725
GO:0002446	neutrophil mediated immunity	IC	16034137
GO:0002467	germinal center formation	ISS	10433800
GO:0002690	positive regulation of leukocyte chemotaxis	IC	16034137

Find genes that share ontologies with ADAM17 About GenesLikeMe

(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, Sets of similar genes according to GenesLikeMe)
About This Section

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for ADAM17 (ADA17)

8 DrugBank Compounds for ADAM17 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed 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

Selected Novoseek inferred chemical compound relationships for ADAM17 gene (see all 37) 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)

Find genes that share compounds with ADAM17 About GenesLikeMe

(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, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
About This Section

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 Products:		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 plasmid: ADAM17 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

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)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ADAM17
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ADAM17
		Addgene plasmids for ADAM17

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for ADAM17
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ADAM17
		QuantiTect SYBR Green Assays in human, mouse, rat ADAM17
		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 GenesLikeMe, 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)
About This Section

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

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:

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

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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)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for ADAM17 gene from 15 species (see representative species ) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chimpanzee (Pan troglodytes)	Mammalia	ADAM17¹	ADAM metallopeptidase domain 17	99.6(n) 100(a)		459018 XM_515293.4 XP_515293.2
mouse (Mus musculus)	Mammalia	Adam17^{1 , 5}	a disintegrin and metallopeptidase domain 17^{1, 5}	88.07(n)¹ 92.11(a)¹		12 (8.30 cM)⁵ 11491¹ NM_009615.6¹ NP_033745.4¹ 21323509⁵
rat (Rattus norvegicus)	Mammalia	Adam17¹	ADAM metallopeptidase domain 17	88.03(n) 92.48(a)		57027 NM_020306.2 NP_064702.1
cow (Bos taurus)	Mammalia	ADAM17¹	ADAM metallopeptidase domain 17	88.28(n) 92.94(a)		517541 XM_002691486.3 XP_002691532.1
dog (Canis familiaris)	Mammalia	ADAM17¹	ADAM metallopeptidase domain 17	89.59(n) 94.63(a)		475662 XM_005630109.1 XP_005630166.1
oppossum (Monodelphis domestica)	Mammalia	ADAM17⁶	ADAM metallopeptidase domain 17	83(a)	1 ↔ 1	1(530249276-530308357)
platypus (Ornithorhynchus anatinus)	Mammalia	-- -- (see all 3)	--	90(a) 83(a) (see all 3)	1 ↔ many 1 ↔ many (see all 3)	Contig5134(2725-23644) Contig10465(491-10001)
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
sea squirt (Ciona savignyi)	Ascidiacea	--	Uncharacterized protein	36(a)	1 ↔ 1	reftig_17(463970-472793)
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
mosquito (Anopheles gambiae)	Insecta	AgaP_AGAP002381¹	AgaP_AGAP002381	50.05(n) 46.06(a)		1273579 XM_312572.5 XP_312572.5
worm (Caenorhabditis elegans)	Secernentea	adm-4^{1 , 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

Species with no ortholog for ADAM17

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,Sets of similar genes according to GenesLikeMe)
About This Section

Paralogs for ADAM17 gene

ADAM10²

1 SIMAP similar gene for ADAM17 using alignment to 8 protein entries: ADA17_HUMAN (see all proteins):

ADAM22

Find genes that share paralogs with ADAM17 About GenesLikeMe

(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)
About This Section

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs138626956^1,2		--	9601091(+)	`TAATTC/TAAATA`	1	--	ds500¹		0	--	--	--	--
rs141699199^1,2		--	9601136(+)	`TATCAA/CGTCTT`	1	--	ds500¹		0	--	--	--	--
rs146246797^1,2		--	9601153(+)	`ACAGCC/TCCCAA`	1	--	ds500¹		0	--	--	--	--
rs184520738^1,2		--	9601183(+)	`TCTATA/CTCCTG`	1	--	ds500¹		0	--	--	--	--
rs201449226^1,2		--	9601221(+)	`TTTTT-/TTGTTTGT`	1	--	cds¹		0	--	--	--	--
rs138788849^1,2	C	--	9601234(+)	`TGTTG-/TTCTTGTT`	1	--	cds¹		0	--	--	--	--
rs187433589^1,2		--	9601234(+)	`TTGTTC/GTTGTT`	1	--	ds500¹		0	--	--	--	--
rs59317355^1,2	C	--	9601236(+)	`TTGTT-/CTTGTTAA`	1	--	cds¹		0	--	--	--	--
rs138095350^1,2		--	9601248(+)	`AAATAC/TCTCAC`	1	--	ds500¹		0	--	--	--	--
rs141799282^1,2	C	--	9601263(+)	`TTATTC/TAATAG`	1	--	ds500¹		0	--	--	--	--

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, Sets of similar genes according to GenesLikeMe)
About This Section

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

3 diseases for ADAM17:
About MalaCards

inflammatory skin and bowel disease, neonatal, 1 heterotaxy dilated cardiomyopathy

Find genes that share disorders with ADAM17 About GenesLikeMe

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)
About This Section

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

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)
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)
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)
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)
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)
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)
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)
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)
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)
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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		AND	OR
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)
About This Section

Entrez Gene: 6868	HGNC: 195	AceView: ADAM17	Ensembl:ENSG00000151694	euGenes: HUgn6868
ECgene: ADAM17	Kegg: 6868	H-InvDB: ADAM17

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
About This Section

Name	Description
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

Intellectual Property for ADAM17 gene
(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:
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ADAM17 Gene

ADAM Metallopeptidase Domain 17

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ADAM17 Gene

ADAM Metallopeptidase Domain 17

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