ADA17_MOUSE
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 03-AUG-2022, entry version 206.
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}.
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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; 3.
DR DIP; DIP-41747N; -.
DR IntAct; Q9Z0F8; 3.
DR MINT; Q9Z0F8; -.
DR STRING; 10090.ENSMUSP00000067953; -.
DR BindingDB; Q9Z0F8; -.
DR ChEMBL; CHEMBL4379; -.
DR MEROPS; M12.217; -.
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; Q9Z0F8; -.
DR PeptideAtlas; Q9Z0F8; -.
DR PRIDE; Q9Z0F8; -.
DR ProteomicsDB; 285546; -. [Q9Z0F8-1]
DR ProteomicsDB; 285547; -. [Q9Z0F8-2]
DR ABCD; Q9Z0F8; 2 sequenced antibodies.
DR Antibodypedia; 2540; 932 antibodies from 49 providers.
DR DNASU; 11491; -.
DR Ensembl; ENSMUST00000064536; ENSMUSP00000067953; ENSMUSG00000052593. [Q9Z0F8-1]
DR Ensembl; ENSMUST00000145118; ENSMUSP00000136407; ENSMUSG00000052593. [Q9Z0F8-2]
DR GeneID; 11491; -.
DR KEGG; mmu:11491; -.
DR UCSC; uc007ndu.2; mouse. [Q9Z0F8-1]
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; FYHGRVF; -.
DR OrthoDB; 162519at2759; -.
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; 4 hits in 71 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 227 other tissues.
DR ExpressionAtlas; Q9Z0F8; baseline and differential.
DR Genevisible; Q9Z0F8; MM.
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:0005911; C:cell-cell junction; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
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:0032587; C:ruffle membrane; ISO: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: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:0050830; P:defense response to Gram-positive bacterium; ISO:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; 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:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; ISO:MGI.
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:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; ISO:MGI.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; IMP:BHF-UCL.
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:0035624; P:receptor transactivation; ISO:MGI.
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; 3.40.390.10; -; 1.
DR Gene3D; 4.10.70.10; -; 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 InterPro; IPR002870; Peptidase_M12B_N.
DR Pfam; PF16698; ADAM17_MPD; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
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; AAD09627/
FT 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
