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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ADAM17 Gene

protein-coding GIFtS: 71
GCID: GC02M009580

ADAM Metallopeptidase Domain 17

(Previous names: tumor necrosis factor, alpha, converting enzyme)
(Previous symbol: TACE)

Microbiology & Infectious Diseases Congress

71 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		CD156B²
TACE¹ ² ³ ⁵		NISBD²
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
ADAM18²		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

(According to Entrez Gene, 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 neonatal inflammatory skin and bowel disease, and vitamin b12 deficiency, and among its related super-pathways are Constitutive Signaling by NOTCH1 PEST Domain Mutants and Notch signaling pathway. GO annotations related to this gene include integrin binding and metalloendopeptidase activity. 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. Also involved in the activation of Notch pathway (By similarity)

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 73), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.2 NT_005334.16

Regulatory elements:

SABiosciences 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 SABiosciences Chromatin IP Primers for ADAM17

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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 GC02M009580: 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 UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MAXQB 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, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Ontologies according to Gene Ontology Consortium 01 Oct 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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

Subcellular location: Membrane; Single-pass type I membrane protein

6/23 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:

UniProtKB: The precursor is cleaved by a furin endopeptidase (By similarity)

UniProtKB: 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 shedding

View modification sites using PhosphoSitePlus

View neXtProt modification sites for NX_P78536

3 DME Specific Peptides for ADAM17 (P78536)

DGLAECA

CCKNCQF

LGLAYVGSPR

ADAM17 Protein expression data from MOPED¹, PaxDb² and MAXQB³ : About this image

REFSEQ proteins: NP_003174.3

ENSEMBL proteins:

ENSP00000309968 ENSP00000418728

Reactome Protein details: P78536
Human Recombinant Protein Products for ADAM17:

	EMD Millipore Purified and/or Recombinant ADAM17 Protein
	R&D Systems Recombinant & Natural Proteins for ADAM17 (TACE/ADAM17)
	Enzo Life Sciences proteins for ADAM17
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells Browse OriGene Protein Over-expression Lysates OriGene Custom MassSpec OriGene Custom Protein Services for ADAM17
	GenScript Custom Purified and Recombinant Proteins Services for ADAM17
	Novus Biologicals ADAM17 Proteins
	Sino Biological Recombinant Protein for ADAM17 Sino Biological Cell Lysate for ADAM17
	Browse ProSpec Recombinant Proteins
	Cloud-Clone Corp. Proteins for ADAM17

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

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

ADAM17 for ontologies About GeneDecksing

ADAM17 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of ADAM17
	R&D Systems Antibodies for ADAM17 (TACE/ADAM17)
	Cell Signaling Technology (CST) Antibodies for ADAM17 (TACE)
	OriGene Antibodies for ADAM17 OriGene Custom Antibody Services for ADAM17
	GenScript Custom Superior Antibodies Services for ADAM17
	Novus Biologicals ADAM17 Antibodies
	Abcam antibodies for ADAM17
	Cloud-Clone Corp. Antibodies for ADAM17
	ThermoFisher Antibody for ADAM17
	LSBio Antibodies in human, mouse, rat for ADAM17

Assay Products for ADAM17:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Assay Services for ADAM17
	R&D Systems ELISAs for ADAM17 (TACE/ADAM17) (see all)
	GenScript Custom Assay Services for ADAM17
	Enzo Life Sciences assays for ADAM17
	Cloud-Clone Corp. ELISAs for ADAM17 Cloud-Clone Corp. CLIAs for ADAM17

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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

ADAM17 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, Vector BioLabs, and Sirion Biotech, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Oct 2013 via Entrez Gene.)
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. Also involved in the activation of Notch pathway (By similarity)

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): 5/8 molecular function terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004222	metalloendopeptidase activity	TAS	--
GO:0005138	interleukin-6 receptor binding	IPI	16034137
GO:0005178	integrin binding	IPI	14970227
GO:0005515	protein binding	IPI	10527948
GO:0008237	metallopeptidase activity	TAS	--

ADAM17 for ontologies About GeneDecksing

Phenotypes:
2 GenomeRNAi human phenotypes for ADAM17:

Increased viability after born

Stronger migration

15/20 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	hematopoietic system	homeostasis/metabolism	immune system	integument
limbs/digits/tail	mortality/aging	muscle	nervous system	normal

ADAM17 for phenotypes About GeneDecksing

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

inGenious Targeting Laboratory - Custom generated mouse model solutions for ADAM17

inGenious Targeting Laboratory - Custom generated inducible mouse model solutions for ADAM17

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ADAM17

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ADAM17

miRNA Products:		miRTarBase miRNAs that target ADAM17: hsa-mir-122 (MIRT003112)

		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ADAM17
		8/17 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for ADAM17
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat ADAM17

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for ADAM17
			Sirion Biotech Customized adenovirus for overexpression of ADAM17

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		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
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ADAM17
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ADAM17
		Sirion Biotech Customized lentivirus for stable overexpression of ADAM17 Customized lentivirus expression plasmids for stable overexpression of ADAM17

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for ADAM17
		Search LifeMap BioReagents cell lines for ADAM17

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ADAM17

(Pathways according to EMD Millipore, 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 GeneDecks, Interaction Networks according to SABiosciences, 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 Oct 2013 via Entrez Gene).
About This Section

SuperPaths for ADAM17 About (see all 37)

See pathways by source

SuperPath

Selected contained pathways About (see all per SuperPath)

Signaling by NOTCH1 t(7 9)(NOTCH1:M1580 K2555) Translocation Mutant

Constitutive Signaling by NOTCH1 PEST Domain Mutants	0.89	Signaling by NOTCH1 in Cancer	0.79
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	0.89	Signaling by NOTCH1	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
Signaling by NOTCH1 PEST Domain Mutants in Cancer	0.79	Signaling by NOTCH	0.74

Notch signaling pathway

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

Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.

Alzheimer's disease

0.46

Alzheimers Disease

0.44

Regulation by c-FLIP

	Extrinsic Pathway for Apoptosis	0.93			TNF signaling	0.62
	Death Receptor Signalling	0.93

Signaling by FGFR

	Signaling by EGFR	0.84			Signalling by NGF	0.71
	Signaling by EGFR in Cancer	0.83

Pathways by source See SuperPaths
Show all pathways

4 EMD Millipore Pathways for ADAM17

	Development Growth hormone signaling via PI3K/AKT and MAPK cascades
	Development Notch Signaling Pathway
	Immune response IL-6 signaling pathway
	Development NOTCH1-mediated pathway for NF-KB activity modulation

2 R&D Systems Pathways for ADAM17

	A-beta Plaque Formation & APP Metabolism
	Notch Signaling Pathways

5/6 Downloadable PowerPoint Slides of QIAGEN 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

5/7 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

5/33 Reactome Pathways for ADAM17 (see all 33)

	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
	FBXW7 Mutants and NOTCH1 in Cancer
	Signaling by EGFR in Cancer
	Signaling by NOTCH1 in Cancer
	Death Receptor Signalling

3 Kegg Pathways (Kegg details for ADAM17):

	Notch signaling pathway
	Alzheimer's disease
	Epithelial cell signaling in Helicobacter pylori infection

ADAM17 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for ADAM17

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/43 Interacting proteins for ADAM17 (P78536^{1, 2, 3} ENSP00000309968⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 43)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
DLG1	Q12959²^,³, ENSP00000345731⁴	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): 5/40 biological process terms (GO ID links to tree view) (see all 40): 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

ADAM17 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

ADAM17 for compounds About GeneDecksing

EMD Millipore small molecules for ADAM17:
Small Molecule - inhibitor

Browse drugs & compounds from Enzo Life Sciences

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

10/37 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)

Search CenterWatch for drugs/clinical trials and news about ADAM17 / ADA17

(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,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Sirion Biotech, Primers from OriGene, SABiosciences, and/or QIAGEN )
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)

Congresses - knowledge worth sharing:
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

miRNA Products:		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ADAM17
		8/17 QIAGEN miScript miRNA 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:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene RNAi products in human, mouse, rat for ADAM17
		QIAGEN FlexiTube/FlexiPlate 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
		Sirion Biotech Customized lentivirus for stable overexpression of ADAM17 Customized lentivirus expression plasmids for stable overexpression of ADAM17

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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

24/88 AceView cDNA sequences (see all 88):

BM989580 AI075423 AI919444 BF059089 AW627690 AA933982 AI741293 AA827074

AA910834 BM827395 AI141532 AI141804 AI095477 BU734977 AI797833 CB159093

N27387 AW057613 AI911263 AY422721 NM_021832 BM705777 AA434423 AA377312

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 GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

ADAM17 expression in normal human tissues (normalized intensities) ADAM17 embryonic expression: see
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

5/4 selected tissues (see all 4) fully expand


Blood (Respiratory System) fully expand to see all 4 entries
bone marrow cd34+

Lung (Respiratory System) fully expand to see all 2 entries
bronchoalveolar lavage cells

Hair (Integumentary System)
Bulge Stem Cells Bulge

Umbilical Cord (Extraembryonic Tissues)
stem cells (umbilical cord cd34+)

See ADAM17 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for ADAM17

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

SABiosciences Expression via Pathway-Focused PCR Arrays including ADAM17:

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Multiple Sclerosis in human mouse rat

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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 14 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_009615.5¹ NP_033745.4¹ 21323509⁵
rat (Rattus norvegicus)	Mammalia	Adam17¹	ADAM metallopeptidase domain 17	88.03(n) 92.48(a)		57027 NM_020306.1 NP_064702.1
cow (Bos taurus)	Mammalia	ADAM17¹	ADAM metallopeptidase domain 17	88.28(n) 92.94(a)		517541 XM_002691486.2 XP_002691532.1
dog (Canis familiaris)	Mammalia	ADAM17¹	ADAM metallopeptidase domain 17	89.71(n) 95.21(a)		475662 XM_532870.4 XP_532870.4
oppossum (Monodelphis domestica)	Mammalia	ADAM17⁶	ADAM metallopeptidase domain 17	85(a)	1 ↔ 1	1(530249276-530308357)
platypus (Ornithorhynchus anatinus)	Mammalia	-- ox_plat1_134721⁶ (see all 3)	Uncharacterized protein (see all 3)	91(a) 88(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	74.25(n) 77.51(a)		421931 NM_001008682.1 NP_001008682.1
lizard (Anolis carolinensis)	Reptilia	ADAM17⁶	Uncharacterized protein	73(a)	1 ↔ 1	1(148417544-148444228)
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 CG7908-PA¹	41(a)³ 51.25(n)¹ 44.87(a)¹		99D1³ 43558¹ NM_170455.2¹ NP_733334.1¹
mosquito (Anopheles gambiae)	Insecta	AgaP_AGAP002381¹	AGAP002381-PA	51.21(n) 47.8(a)		1273579 XM_312572.4 XP_312572.4
worm (Caenorhabditis elegans)	Secernentea	adm-4^{1 , 3}	metalloprotease³ Protein ADM-4¹	34(a)³ 48.39(n)¹ 37.3(a)¹		X(7830565-7833527)³ 181041¹ NM_076917.2¹ 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)
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

ADAM17 for paralogs About GeneDecksing

(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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

OMIM gene information: 603639 OMIM disorders: --

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

20/71 diseases for ADAM17 (see all 71): About MalaCards

neonatal inflammatory skin and bowel disease vitamin b12 deficiency renal osteodystrophy chorioamnionitis

differentiating neuroblastoma severe acute respiratory syndrome interstitial lung disease acute myocardial infarction

toxic shock syndrome congestive heart failure dilated cardiomyopathy gastrointestinal stromal tumor

pulmonary tuberculosis myocarditis abdominal aortic aneurysm rabies

osteoarthritis pancreatic ductal adenocarcinoma aortic aneurysm cleft lip

ADAM17 for disorders About GeneDecksing

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

10/27 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 9 sources (see all 488):
(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. (1998)
A metalloproteinase disintegrin that releases tumour-necrosis factor- alpha from cells. (PubMed id 9034190)^{1, 2, 3} Black R.A.... Cerretti D.P. (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. (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. (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. (1997)
Direct activation of TACE-mediated ectodomain sheddin g by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. (PubMed id 20188673)^{1, 2, 9} Xu P. and Derynck R. (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. (1998)
Inflammatory skin and bowel disease linked to ADAM17 deletion. (PubMed id 22010916)^{1, 2} Blaydon D.C....Kelsell D.P. (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. (2010)
Polymorphisms spanning the TNFR2 and TACE genes do no t contribute towards variable anti-TNF treatment response. (PubMed id 20300049)^{1, 4} Potter C....Barton A. (2010)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		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, and/or UniProtKB/TrEMBL,
Wikipedia and/or 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:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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ADAM17 Gene

ADAM Metallopeptidase Domain 17

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ADAM17 Gene

ADAM Metallopeptidase Domain 17

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