Linked Life Data

P78536

Source:http://identifiers.org/uniprot/P78536

Statements in which the resource exists.
SubjectPredicateObjectContext
http://identifiers.org/unip...rdf:typebiopax3:ProteinReferencelld:biopax3
http://identifiers.org/unip...biopax3:commentFUNCTION: 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. COFACTOR: Binds 1 zinc ion per subunit. SUBUNIT: Interacts with MAD2L1, MAPK14 and MUC1. SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=A; IsoId=P78536-1; Sequence=Displayed; Name=B; IsoId=P78536-2; Sequence=VSP_005478; Note=No experimental confirmation available; 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. INDUCTION: In arthritis-affected cartilage. 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. PTM: The precursor is cleaved by a furin endopeptidase (By similarity). PTM: 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. DISEASE: Defects in ADAM17 are a cause of neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]. NISBD is 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. SIMILARITY: Contains 1 disintegrin domain. SIMILARITY: Contains 1 peptidase M12B domain. WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha- converting enzyme entry; URL="http://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme"; GENE SYNONYMS:ADAM17 CSVP TACE. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:biopax3
http://identifiers.org/unip...biopax3:commentSEQUENCE 824 AA; 93021 MW; 5B1032F6B88A837F CRC64;lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:RelationshipXref...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
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http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:displayNameADA17_HUMANlld:biopax3
http://identifiers.org/unip...biopax3:nameADAM17lld:biopax3
http://identifiers.org/unip...biopax3:nameTNF-alpha convertaselld:biopax3
http://identifiers.org/unip...biopax3:nameADAM 17lld:biopax3
http://identifiers.org/unip...biopax3:name3.4.24.86lld:biopax3
http://identifiers.org/unip...biopax3:nameTNF-alpha-converting enzymelld:biopax3
http://identifiers.org/unip...biopax3:nameCD156blld:biopax3
http://identifiers.org/unip...biopax3:nameSnake venom-like proteaselld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:organismhttp://identifiers.org/taxo...lld:biopax3
http://identifiers.org/unip...biopax3:sequenceMRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEClld:biopax3
http://identifiers.org/unip...biopax3:standardNameDisintegrin and metalloproteinase domain-containing protein 17lld:biopax3
http://www.reactome.org/bio...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://pid.nci.nih.gov/biop...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://pid.nci.nih.gov/biop...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
HTTP://PATHWAYCOMMONS.ORG/P...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://pid.nci.nih.gov/biop...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.reactome.org/bio...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.pantherdb.org/pa...biopax3:memberEntityReferen...http://identifiers.org/unip...lld:biopax3