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TACE (human)

Overview TACE a type I membrane protein with disintegrin and metalloprotease activity. An ubiquitously expressed ectoenzyme of peptidase family M12B. Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Possesses a 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) to its mature soluble form. 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, and the amyloid precursor protein. Also involved in the activation of Notch pathway. Binds 1 zinc ion per subunit. Two splice variant isoforms have been described. Note: This description may include information from UniProtKB. Protein type: Protease; Membrane protein, integral; EC 3.4.24.86; Motility/polarity/chemotaxis Cellular Component: focal adhesion; cell surface; integral to plasma membrane; cytoplasm; apical plasma membrane; plasma membrane; intercellular junction; actin cytoskeleton; lipid raft Molecular Function: integrin binding; protein binding; interleukin-6 receptor binding; zinc ion binding; metallopeptidase activity; metalloendopeptidase activity; SH3 domain binding; PDZ domain binding Biological Process: nerve growth factor receptor signaling pathway; cell motility involved in cell locomotion; neutrophil mediated immunity; T cell differentiation in the thymus; response to lipopolysaccharide; positive regulation of leukocyte chemotaxis; G1/S-specific positive regulation of cyclin-dependent protein kinase activity; positive regulation of epidermal growth factor receptor activity; positive regulation of cell proliferation; negative regulation of interleukin-8 production; germinal center formation; cell adhesion; response to drug; spleen development; epidermal growth factor receptor signaling pathway; Notch signaling pathway; membrane protein intracellular domain proteolysis; response to high density lipoprotein stimulus; membrane protein ectodomain proteolysis; positive regulation of transforming growth factor beta receptor signaling pathway; positive regulation of cell motility; positive regulation of cell growth; positive regulation of chemokine production; regulation of mast cell apoptosis; PMA-inducible membrane protein ectodomain proteolysis; B cell differentiation; response to hypoxia; cell adhesion mediated by integrin; positive regulation of protein amino acid phosphorylation; wound healing, spreading of epidermal cells; positive regulation of cell migration Reference #:  P78536 (UniProtKB) Alt. Names/Synonyms: ADA17; ADAM 17; ADAM metallopeptidase domain 17; ADAM metallopeptidase domain 18; ADAM17; ADAM18; CD156B; CSVP; Disintegrin and metalloproteinase domain-containing protein 17; MGC71942; Snake venom-like protease; TACE; TNF-alpha convertase; TNF-alpha converting enzyme; TNF-alpha-converting enzyme; tumor necrosis factor, alpha, converting enzyme Gene Symbols: ADAM17 Molecular weight: 93,021 Da Basal Isoelectric point: 5.5  Predict pI for various phosphorylation states CST Pathways:  Alzheimer's Disease  |  ErbB/HER Signaling  |  Notch Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below TACE 1BKC - A/C/E/I=219-474 (human) 1ZXC - A/B=215-477 (human) 2A8H - A/B=215-477 (human) 2DDF - A/B=218-474 (human) 2FV5 - A/B=216-475 (human) 2FV9 - A/B=218-475 (human) 2I47 - A/B/C/D=212-492 (human) 2M2F - A=581-642 (human) 2OI0 - A=216-477 (human) 3B92 - A=216-474 (human) 3CKI - A=219-474 (human) 3E8R - A/B=215-477 (human) 3EDZ - A/B=215-477 (human) 3EWJ - A/B=215-477 (human) 3G42 - A/D/C/B=212-492 (human) 3KMC - A/B=215-476 (human) 3KME - A/B=215-476 (human) 3L0T - A/B=215-476 (human) 3L0V - A/B=215-476 (human) 3LE9 - A/B=215-476 (human) 3LEA - A/B=215-476 (human) 3LGP - A/B=215-476 (human) 3O64 - A/B=215-476 (human)

STRING  |  Scansite  |  Phospho.ELM  |  NetworKIN  |  Pfam  |  RCSB PDB 1BKC 1ZXC 2A8H 2DDF 2FV5 2FV9 2I47 2M2F 2OI0 3B92 3CKI 3E8R 3EDZ 3EWJ 3G42 3KMC 3KME 3L0T 3L0V 3LE9 3LEA 3LGP 3O64  |  ENZYME  |  Phospho3D  |  DISEASE  |  Source  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene

	Sites Implicated In
cell cycle regulation: T735‑p enzymatic activity, induced: T735‑p, S819‑p intracellular localization: T735‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human
0	1		F26	RPPDDPGFGPHQRLE
0	1		P28	PDDPGFGPHQRLEKL
0	1		Y82-p	LKRHFKLyLTSSTER
0	1		K168-u	DKRMLVYkSEDIKNV
0	1		K182-u	VSRLQSPkVCGYLKV
0	1		Y275	DNAGFKGYGIQIEQI
0	1		K302-u	EKHYNMAkSYPNEEK
0	1		Y379-p	PVGKKNIyLNSGLTS
0	1		Y433-p	NEDQGGKyVMyPIAV
0	1		Y436-p	QGGKyVMyPIAVSGD
0	1		S706-p	DKQYESLsLFHPSNV
0	3		K728-u	SASVRIIkPFPAPQt
10	4		T735-p	kPFPAPQtPGRLQPA
0	9		T761-p	LDHQRMDtIQEDPST
0	1		S767	DtIQEDPSTDsHMDE
0	1		T768	tIQEDPSTDsHMDED
0	2		S770-p	QEDPSTDsHMDEDGF
0	1		K779-u	MDEDGFEkDPFPNSS
0	1		K790-u	PNSSTAAksFEDLtD
2	16		S791-p	NSSTAAksFEDLtDH
0	1		T796-p	AksFEDLtDHPVTRS
2	1		S819-p	QRQNRVDsKETEC__

	mouse
S26-p	RPPEEAGsGsHPRLE
S28-p	PEEAGsGsHPRLEKL
Y82	LKRHFKLYLTSSTER
K168	DKRMLVYKSEDIKDF
K182	FSRLQSPKVCGYLNA
Y275	DNAGFKGYGVQIEQI
K302	ERHFNMAKSFPNEEK
Y379	PTVKKNIYLNSGLTS
Y433	NEDQGGKYVMYPIAV
Y436	QGGKYVMYPIAVSGD
S706	DKQYESLSLFHHSNI
K728-u	SASVRIIkPFPAPQt
T735-p	kPFPAPQtPGRLQAL
T764-p	LDHQRMDtIQEDPst
S770-p	DtIQEDPstDsHADD
T771-p	tIQEDPstDsHADDD
S773-p	QEDPstDsHADDDGF
K782	ADDDGFEKDPFPNSS
K793	PNSSTAAKsFEDLTD
S794-p	NSSTAAKsFEDLTDH
T799	AKsFEDLTDHPVTRS
S822-p	QRQSRVDsKETEC__

	rat
S26	RPPEEPGSGSHLRLE
S28	PEEPGSGSHLRLEKL
Y82	LKRHFKLYLTSSTER
K168	DKRMLVYKSEDIKDF
K182	FSRLQSPKVCGYLNA
Y275-p	DNAGFKGyGVQIEQI
K302	ERHFNMAKSFPNEEK
Y379	PGVKKNIYLNSGLTS
Y433	NEDQGGKYVMYPIAV
Y436	QGGKYVMYPIAVSGD
S706	DKQYESLSLFHHSNI
K728	SASVRIIKPFPAPQt
T735-p	KPFPAPQtPGRLQAL
T764	LDHQRMDTIQEDPST
S770	DTIQEDPSTDSHVDD
T771	TIQEDPSTDSHVDDD
S773	QEDPSTDSHVDDDGF
K782	VDDDGFEKDPFPNSS
K793	PNSSAAAKSFEDLTD
S794	NSSAAAKSFEDLTDH
T799	AKSFEDLTDHPVTRS
S822	QRQSRVDSKETEC__

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