ID ADA17_MOUSE Reviewed; 827 AA. AC Q9Z0F8; O88726; Q505A7; Q9R1U4; Q9Z0K3; DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 215. DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 17; DE Short=ADAM 17; DE EC=3.4.24.86 {ECO:0000250|UniProtKB:P78536}; DE AltName: Full=TNF-alpha convertase; DE AltName: Full=TNF-alpha-converting enzyme; DE AltName: CD_antigen=CD156b; DE Flags: Precursor; GN Name=Adam17; Synonyms=Tace; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS LONG AND SHORT). RX PubMed=10433800; DOI=10.1006/cyto.1998.0466; RA Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., RA Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.; RT "Characterization of the cDNA and gene for mouse tumour necrosis factor RT alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome RT 12 and human chromosome 2p25."; RL Cytokine 11:541-551(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND ACTIVITY REGULATION. RX PubMed=9755855; DOI=10.1016/s0014-5793(98)01031-x; RA Amour A., Slocombe P.M., Webster A., Butler M., Knight C.G., Smith B.J., RA Stephens P.E., Shelley C., Hutton M., Knauper V., Docherty A.J., Murphy G.; RT "TNF-alpha converting enzyme (TACE) is inhibited by TIMP-3."; RL FEBS Lett. 435:39-44(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RX PubMed=10375622; DOI=10.1016/s0378-1119(99)00155-9; RA Mizui Y., Yamazaki K., Sagane K., Tanaka I.; RT "cDNA cloning of mouse tumor necrosis factor-alpha converting enzyme (TACE) RT and partial analysis of its promoter."; RL Gene 233:67-74(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT). RA Cerretti D.P.; RT "Isolation of murine TNF-alpha converting enzyme."; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC STRAIN=C57BL/6J; TISSUE=Brain cortex; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC STRAIN=C57BL/6J; TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION IN PROCESSING OF GROWTH HORMONE RECEPTOR. RX PubMed=11108241; DOI=10.1210/endo.141.12.7858; RA Zhang Y., Jiang J., Black R.A., Baumann G., Frank S.J.; RT "Tumor necrosis factor-alpha converting enzyme (TACE) is a growth hormone RT binding protein (GHBP) sheddase: the metalloprotease TACE/ADAM-17 is RT critical for (PMA-induced) GH receptor proteolysis and GHBP generation."; RL Endocrinology 141:4342-4348(2000). RN [8] RP FUNCTION. RX PubMed=10799547; DOI=10.1074/jbc.275.19.14608; RA Reddy P., Slack J.L., Davis R., Cerretti D.P., Kozlosky C.J., Blanton R.A., RA Shows D., Peschon J.J., Black R.A.; RT "Functional analysis of the domain structure of tumor necrosis factor-alpha RT converting enzyme."; RL J. Biol. Chem. 275:14608-14614(2000). RN [9] RP FUNCTION. RX PubMed=10882063; DOI=10.1016/s1097-2765(00)80417-7; RA Brou C., Logeat F., Gupta N., Bessia C., LeBail O., Doedens J.R., RA Cumano A., Roux P., Black R.A., Israel A.; RT "A novel proteolytic cleavage involved in Notch signaling: the role of the RT disintegrin-metalloprotease TACE."; RL Mol. Cell 5:207-216(2000). RN [10] RP FUNCTION. RX PubMed=12907434; DOI=10.1182/blood-2003-04-1305; RA Bergmeier W., Burger P.C., Piffath C.L., Hoffmeister K.M., Hartwig J.H., RA Nieswandt B., Wagner D.D.; RT "Metalloproteinase inhibitors improve the recovery and hemostatic function RT of in vitro-aged or -injured mouse platelets."; RL Blood 102:4229-4235(2003). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=17245433; DOI=10.1038/sj.emboj.7601520; RA Li N., Wang Y., Forbes K., Vignali K.M., Heale B.S., Saftig P., RA Hartmann D., Black R.A., Rossi J.J., Blobel C.P., Dempsey P.J., RA Workman C.J., Vignali D.A.; RT "Metalloproteases regulate T-cell proliferation and effector function via RT LAG-3."; RL EMBO J. 26:494-504(2007). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-794, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006; RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M., RA Thibault P.; RT "The phagosomal proteome in interferon-gamma-activated macrophages."; RL Immunity 30:143-154(2009). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-735, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Kidney, Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). CC -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its CC mature soluble form. Responsible for the proteolytical release of CC soluble JAM3 from endothelial cells surface. Plays a role in the CC proteolytic processing of ACE2 (By similarity). Responsible for the CC proteolytic release of several other cell-surface proteins, including CC p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, CC transforming growth factor-alpha, L-selectin, growth hormone receptor, CC MUC1 and the amyloid precursor protein (PubMed:10799547, CC PubMed:11108241). Acts as an activator of Notch pathway by mediating CC cleavage of Notch, generating the membrane-associated intermediate CC fragment called notch extracellular truncation (NEXT) CC (PubMed:10882063). Plays a role in hemostasis through shedding of CC GP1BA, the platelet glycoprotein Ib alpha chain (PubMed:12907434). CC Mediates the proteolytic cleavage of LAG3, leading to release the CC secreted form of LAG3 (PubMed:17245433). Mediates the proteolytic CC cleavage of IL6R, leading to the release of secreted form of IL6R (By CC similarity). Mediates the proteolytic cleavage and shedding of FCGR3A CC upon NK cell stimulation, a mechanism that allows for increased NK cell CC motility and detachment from opsonized target cells. CC {ECO:0000250|UniProtKB:P78536, ECO:0000269|PubMed:10799547, CC ECO:0000269|PubMed:10882063, ECO:0000269|PubMed:11108241, CC ECO:0000269|PubMed:12907434, ECO:0000269|PubMed:17245433}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln- CC Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor CC necrosis factor alpha (TNFalpha). Similarly cleaves other membrane- CC anchored, cell-surface proteins to 'shed' the extracellular domains.; CC EC=3.4.24.86; Evidence={ECO:0000250|UniProtKB:P78536}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P78536}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P78536}; CC -!- ACTIVITY REGULATION: Inhibited by metalloproteinase inhibitor 3 (TIMP- CC 3), but not by TIMP-1, TIMP-2 and TIMP-4. {ECO:0000269|PubMed:9755855}. CC -!- SUBUNIT: Interacts with MAD2L1, MAPK14 and MUC1. Interacts with CC iRhom1/RHBDF1 and iRhom2/RHBDF2. Interacts with FRMD8 via its CC interaction with iRhom1/RHBDF1 and iRhom2/RHBDF2. CC {ECO:0000250|UniProtKB:P78536}. CC -!- INTERACTION: CC Q9Z0F8; Q80WQ6: Rhbdf2; NbExp=6; IntAct=EBI-7848498, EBI-647271; CC -!- SUBCELLULAR LOCATION: [Isoform Long]: Cell membrane; Single-pass type I CC membrane protein. CC -!- SUBCELLULAR LOCATION: [Isoform Short]: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q9Z0F8-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q9Z0F8-2; Sequence=VSP_005479, VSP_005480; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed at highest levels CC in heart, liver, skeletal muscle, kidney and testes. Expressed at lower CC levels in brain, spleen and lung. CC -!- DOMAIN: Must be membrane anchored to cleave the different substrates. CC The cytoplasmic domain is not required for the this activity. Only the CC catalytic domain is essential to shed TNF and p75 TNFR. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif CC binds the catalytic zinc ion, thus inhibiting the enzyme. The CC dissociation of the cysteine from the zinc ion upon the activation- CC peptide release activates the enzyme. CC -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}. CC -!- PTM: Phosphorylated. Stimulation by growth factor or phorbol 12- CC myristate 13-acetate induces phosphorylation of Ser-822 but decreases CC phosphorylation of Ser-794. Phosphorylation at Thr-735 by MAPK14 is CC required for ADAM17-mediated ectodomain shedding (By similarity). CC {ECO:0000250|UniProtKB:P78536}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF056359; AAC62934.1; -; Genomic_DNA. DR EMBL; AF056345; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056346; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056347; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056348; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056349; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056350; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056351; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056352; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056353; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056354; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056355; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056356; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056357; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AF056358; AAC62934.1; JOINED; Genomic_DNA. DR EMBL; AJ007365; CAA07480.1; -; mRNA. DR EMBL; AB021709; BAA78578.1; -; mRNA. DR EMBL; U69613; AAD09627.1; -; mRNA. DR EMBL; U69614; AAD09628.1; -; mRNA. DR EMBL; AK139471; BAE24023.1; -; mRNA. DR EMBL; BC094655; AAH94655.1; -; mRNA. DR CCDS; CCDS25836.1; -. [Q9Z0F8-1] DR RefSeq; NP_001264195.1; NM_001277266.1. DR RefSeq; NP_001278800.1; NM_001291871.1. DR RefSeq; NP_033745.4; NM_009615.6. [Q9Z0F8-1] DR AlphaFoldDB; Q9Z0F8; -. DR SMR; Q9Z0F8; -. DR BioGRID; 197964; 4. DR DIP; DIP-41747N; -. DR IntAct; Q9Z0F8; 3. DR MINT; Q9Z0F8; -. DR STRING; 10090.ENSMUSP00000099087; -. DR BindingDB; Q9Z0F8; -. DR ChEMBL; CHEMBL4379; -. DR MEROPS; M12.217; -. DR GlyCosmos; Q9Z0F8; 7 sites, No reported glycans. DR GlyGen; Q9Z0F8; 7 sites. DR iPTMnet; Q9Z0F8; -. DR PhosphoSitePlus; Q9Z0F8; -. DR SwissPalm; Q9Z0F8; -. DR EPD; Q9Z0F8; -. DR jPOST; Q9Z0F8; -. DR MaxQB; Q9Z0F8; -. DR PaxDb; 10090-ENSMUSP00000067953; -. DR PeptideAtlas; Q9Z0F8; -. DR ProteomicsDB; 285546; -. [Q9Z0F8-1] DR ProteomicsDB; 285547; -. [Q9Z0F8-2] DR Pumba; Q9Z0F8; -. DR ABCD; Q9Z0F8; 2 sequenced antibodies. DR Antibodypedia; 2540; 1034 antibodies from 49 providers. DR DNASU; 11491; -. DR Ensembl; ENSMUST00000064536.13; ENSMUSP00000067953.7; ENSMUSG00000052593.17. [Q9Z0F8-1] DR Ensembl; ENSMUST00000145118.8; ENSMUSP00000136407.2; ENSMUSG00000052593.17. [Q9Z0F8-2] DR GeneID; 11491; -. DR KEGG; mmu:11491; -. DR UCSC; uc007ndu.2; mouse. [Q9Z0F8-1] DR AGR; MGI:1096335; -. DR CTD; 6868; -. DR MGI; MGI:1096335; Adam17. DR VEuPathDB; HostDB:ENSMUSG00000052593; -. DR eggNOG; KOG3658; Eukaryota. DR GeneTree; ENSGT00940000155443; -. DR HOGENOM; CLU_004602_2_1_1; -. DR InParanoid; Q9Z0F8; -. DR OMA; NINKVMR; -. DR OrthoDB; 5395001at2759; -. DR TreeFam; TF314733; -. DR BRENDA; 3.4.24.86; 3474. DR Reactome; R-MMU-193692; Regulated proteolysis of p75NTR. DR Reactome; R-MMU-75893; TNF signaling. DR BioGRID-ORCS; 11491; 5 hits in 76 CRISPR screens. DR ChiTaRS; Adam17; mouse. DR PRO; PR:Q9Z0F8; -. DR Proteomes; UP000000589; Chromosome 12. DR RNAct; Q9Z0F8; Protein. DR Bgee; ENSMUSG00000052593; Expressed in ear vesicle and 230 other cell types or tissues. DR ExpressionAtlas; Q9Z0F8; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; ISO:MGI. DR GO; GO:0045177; C:apical part of cell; ISO:MGI. DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI. DR GO; GO:0009986; C:cell surface; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0045121; C:membrane raft; ISO:MGI. DR GO; GO:0005886; C:plasma membrane; IMP:MGI. DR GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB. DR GO; GO:0005178; F:integrin binding; ISO:MGI. DR GO; GO:0005138; F:interleukin-6 receptor binding; ISO:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0070573; F:metallodipeptidase activity; IMP:MGI. DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:MGI. DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; ISO:MGI. DR GO; GO:0008237; F:metallopeptidase activity; IDA:BHF-UCL. DR GO; GO:0005112; F:Notch binding; ISS:UniProtKB. DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI. DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0043120; F:tumor necrosis factor binding; ISO:MGI. DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:MGI. DR GO; GO:0030183; P:B cell differentiation; IMP:BHF-UCL. DR GO; GO:0007155; P:cell adhesion; ISO:MGI. DR GO; GO:0033627; P:cell adhesion mediated by integrin; ISO:MGI. DR GO; GO:0048870; P:cell motility; IMP:BHF-UCL. DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; ISO:MGI. DR GO; GO:0071679; P:commissural neuron axon guidance; ISO:MGI. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:MGI. DR GO; GO:0002467; P:germinal center formation; IMP:BHF-UCL. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI. DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab. DR GO; GO:0010977; P:negative regulation of neuron projection development; IGI:MGI. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:MGI. DR GO; GO:0007220; P:Notch receptor processing; ISS:UniProtKB. DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI. DR GO; GO:0030307; P:positive regulation of cell growth; ISO:MGI. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI. DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI. DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISO:MGI. DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI. DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:MGI. DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; ISO:MGI. DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; ISO:MGI. DR GO; GO:0002532; P:production of molecular mediator involved in inflammatory response; IDA:CACAO. DR GO; GO:0016485; P:protein processing; ISO:MGI. DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB. DR GO; GO:0048679; P:regulation of axon regeneration; IGI:MGI. DR GO; GO:0033025; P:regulation of mast cell apoptotic process; IMP:BHF-UCL. DR GO; GO:2001222; P:regulation of neuron migration; IGI:MGI. DR GO; GO:0001666; P:response to hypoxia; ISO:MGI. DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI. DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:BHF-UCL. DR GO; GO:0140448; P:signaling receptor ligand precursor processing; IMP:MGI. DR GO; GO:0048536; P:spleen development; IMP:BHF-UCL. DR GO; GO:0033077; P:T cell differentiation in thymus; IMP:BHF-UCL. DR CDD; cd14246; ADAM17_MPD; 1. DR CDD; cd04270; ZnMc_TACE_like; 1. DR Gene3D; 4.10.70.30; -; 1. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 4.10.70.10; Disintegrin domain; 1. DR InterPro; IPR034025; ADAM10_ADAM17. DR InterPro; IPR032029; ADAM17_MPD. DR InterPro; IPR001762; Disintegrin_dom. DR InterPro; IPR036436; Disintegrin_dom_sf. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR001590; Peptidase_M12B. DR PANTHER; PTHR45702; ADAM10/ADAM17 METALLOPEPTIDASE FAMILY MEMBER; 1. DR PANTHER; PTHR45702:SF6; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 17; 1. DR Pfam; PF16698; ADAM17_MPD; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF13574; Reprolysin_2; 1. DR SMART; SM00050; DISIN; 1. DR SUPFAM; SSF57552; Blood coagulation inhibitor (disintegrin); 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS50215; ADAM_MEPRO; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; Q9Z0F8; MM. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues; KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding; KW Metalloprotease; Notch signaling pathway; Phosphoprotein; Protease; KW Reference proteome; Secreted; SH3-binding; Signal; Transmembrane; KW Transmembrane helix; Zinc; Zymogen. FT SIGNAL 1..17 FT /evidence="ECO:0000250|UniProtKB:Q9Z1K9" FT PROPEP 18..214 FT /evidence="ECO:0000250|UniProtKB:P78536" FT /id="PRO_0000029090" FT CHAIN 215..827 FT /note="Disintegrin and metalloproteinase domain-containing FT protein 17" FT /id="PRO_0000029091" FT TOPO_DOM 215..671 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 672..692 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 693..827 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 223..474 FT /note="Peptidase M12B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276" FT DOMAIN 475..563 FT /note="Disintegrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068" FT REGION 603..671 FT /note="Crambin-like" FT REGION 766..827 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 182..189 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT MOTIF 731..738 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 766..783 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 798..827 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 406 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276, FT ECO:0000255|PROSITE-ProRule:PRU10095" FT BINDING 184 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000250" FT BINDING 405 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P78536" FT BINDING 409 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P78536" FT BINDING 415 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P78536" FT MOD_RES 735 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 764 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P78536" FT MOD_RES 770 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z1K9" FT MOD_RES 794 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19144319" FT MOD_RES 822 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P78536" FT CARBOHYD 157 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 264 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 452 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 498 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 539 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 551 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 606 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 225..333 FT /evidence="ECO:0000250|UniProtKB:P78536" FT DISULFID 365..469 FT /evidence="ECO:0000250|UniProtKB:P78536" FT DISULFID 423..453 FT /evidence="ECO:0000250|UniProtKB:P78536" FT DISULFID 534..555 FT /evidence="ECO:0000250" FT DISULFID 573..582 FT /evidence="ECO:0000250" FT DISULFID 578..591 FT /evidence="ECO:0000250" FT DISULFID 593..600 FT /evidence="ECO:0000250" FT VAR_SEQ 639..655 FT /note="GKCEKRVQDVIERFWDF -> CDFFSPYRANVRNEYRT (in isoform FT Short)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_005479" FT VAR_SEQ 656..827 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|Ref.4" FT /id="VSP_005480" FT CONFLICT 3..4 FT /note="RR -> QS (in Ref. 2; CAA07480)" FT /evidence="ECO:0000305" FT CONFLICT 7 FT /note="I -> F (in Ref. 2; CAA07480)" FT /evidence="ECO:0000305" FT CONFLICT 28 FT /note="S -> A (in Ref. 2; CAA07480 and 3; BAA78578)" FT /evidence="ECO:0000305" FT CONFLICT 113 FT /note="N -> D (in Ref. 1; AAC62934, 2; CAA07480, 3; FT BAA78578 and 4; AAD09627/AAD09628)" FT /evidence="ECO:0000305" FT CONFLICT 149 FT /note="V -> I (in Ref. 2; CAA07480 and 3; BAA78578)" FT /evidence="ECO:0000305" FT CONFLICT 594 FT /note="V -> I (in Ref. 1; AAC62934 and 4; FT AAD09627/AAD09628)" FT /evidence="ECO:0000305" FT CONFLICT 752 FT /note="P -> S (in Ref. 2; CAA07480 and 3; BAA78578)" FT /evidence="ECO:0000305" FT CONFLICT 775 FT /note="A -> V (in Ref. 2; CAA07480 and 3; BAA78578)" FT /evidence="ECO:0000305" SQ SEQUENCE 827 AA; 93056 MW; 6B434F80878197F5 CRC64; MRRRLLILTT LVPFVLAPRP PEEAGSGSHP RLEKLDSLLS DYDILSLANI QQHSIRKRDL QSATHLETLL TFSALKRHFK LYLTSSTERF SQNLRVVVVD GKEESEYSVK WQNFFSGHVV GEPDSRVLAH IGDDDVTVRI NTDGAEYNVE PLWRFVNDTK DKRMLVYKSE DIKDFSRLQS PKVCGYLNAD SEELLPKGLI DREPSEEFVR RVKRRAEPNP LKNTCKLLVV ADHRFYKYMG RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGVQIE QIRILKSPQE VKPGERHFNM AKSFPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS HGGVCPKAYY NPTVKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT CCNSDCTLKP GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG NSSECPPPGD AEDDTVCLDL GKCKAGKCIP FCKREQELES CACVDTDNSC KVCCRNLSGP CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHH SNIEMLSSMD SASVRIIKPF PAPQTPGRLQ ALQPAAMMPP VPAAPKLDHQ RMDTIQEDPS TDSHADDDGF EKDPFPNSST AAKSFEDLTD HPVTRSEKAA SFKLQRQSRV DSKETEC //