ADA17_HUMAN
ID ADA17_HUMAN Reviewed; 824 AA.
AC P78536; O60226;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 17;
DE Short=ADAM 17;
DE EC=3.4.24.86 {ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24227843};
DE AltName: Full=Snake venom-like protease;
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=CSVP, TACE;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), PARTIAL PROTEIN SEQUENCE, AND
RP FUNCTION.
RC TISSUE=Leukocyte, and Monocyte;
RX PubMed=9034191; DOI=10.1038/385733a0;
RA Moss M.L., Jin S.-L.C., Milla M.E., Burkhart W., Carter H.L., Chen W.-J.,
RA Clay W.C., Didsbury J.R., Hassler D., Hoffman C.R., Kost T.A.,
RA Lambert M.H., Leesnitzer M.A., McCauley P., McGeehan G., Mitchell J.,
RA Moyer M., Pahel G., Rocque W., Overton L.K., Schoenen F., Seaton T.,
RA Su J.-L., Warner J., Willard D., Becherer J.D.;
RT "Cloning of a disintegrin metalloproteinase that processes precursor
RT tumour-necrosis factor-alpha.";
RL Nature 385:733-736(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
RX PubMed=9034190; DOI=10.1038/385729a0;
RA Black R.A., Rauch C.T., Kozlosky C.J., Peschon J.J., Slack J.L.,
RA Wolfson M.F., Castner B.J., Stocking K.L., Reddy P., Srinivasan S.,
RA Nelson N., Bioani N., Schooley K.A., Gerhart M., Davis R., Fitzner J.N.,
RA Johnson R.S., Paxton R.J., March C.J., Cerretti D.P.;
RT "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha
RT from cells.";
RL Nature 385:729-733(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
RC TISSUE=Cartilage;
RX PubMed=9574564;
RA Patel I.R., Attur M.G., Patel R.N., Stuchin S.A., Abagyan R.A.,
RA Abramson S.B., Amin A.R.;
RT "TNF-alpha convertase enzyme from human arthritis-affected cartilage:
RT isolation of cDNA by differential display, expression of the active enzyme,
RT and regulation of TNF-alpha.";
RL J. Immunol. 160:4570-4579(1998).
RN [4]
RP PHOSPHORYLATION AT THR-735.
RX PubMed=12058067; DOI=10.1091/mbc.01-11-0561;
RA Diaz-Rodriguez E., Montero J.C., Esparis-Ogando A., Yuste L., Pandiella A.;
RT "Extracellular signal-regulated kinase phosphorylates tumor necrosis factor
RT alpha-converting enzyme at threonine 735: a potential role in regulated
RT shedding.";
RL Mol. Biol. Cell 13:2031-2044(2002).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH MUC1.
RX PubMed=12441351; DOI=10.1074/jbc.m208326200;
RA Thathiah A., Blobel C.P., Carson D.D.;
RT "Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1
RT shedding.";
RL J. Biol. Chem. 278:3386-3394(2003).
RN [6]
RP PHOSPHORYLATION AT SER-819.
RX PubMed=12621058; DOI=10.1074/jbc.m300331200;
RA Fan H., Turck C.W., Derynck R.;
RT "Characterization of growth factor-induced serine phosphorylation of tumor
RT necrosis factor-alpha converting enzyme and of an alternatively translated
RT polypeptide.";
RL J. Biol. Chem. 278:18617-18627(2003).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP ROLE IN PROTEOLYTICAL RELEASE OF JAM3.
RX PubMed=20592283; DOI=10.4049/jimmunol.1000556;
RA Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., Ruth J.H.,
RA Lesch C.A., Imhof B.A., Koch A.E.;
RT "Junctional adhesion molecule-C is a soluble mediator of angiogenesis.";
RL J. Immunol. 185:1777-1785(2010).
RN [10]
RP PHOSPHORYLATION AT THR-735, AND INTERACTION WITH MAPK14.
RX PubMed=20188673; DOI=10.1016/j.molcel.2010.01.034;
RA Xu P., Derynck R.;
RT "Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase
RT regulates EGF receptor-dependent cell proliferation.";
RL Mol. Cell 37:551-566(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [12]
RP INVOLVEMENT IN NISBD1.
RX PubMed=22010916; DOI=10.1056/nejmoa1100721;
RA Blaydon D.C., Biancheri P., Di W.L., Plagnol V., Cabral R.M., Brooke M.A.,
RA van Heel D.A., Ruschendorf F., Toynbee M., Walne A., O'Toole E.A.,
RA Martin J.E., Lindley K., Vulliamy T., Abrams D.J., MacDonald T.T.,
RA Harper J.I., Kelsell D.P.;
RT "Inflammatory skin and bowel disease linked to ADAM17 deletion.";
RL N. Engl. J. Med. 365:1502-1508(2011).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-761 AND SER-791, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP FUNCTION.
RX PubMed=24226769; DOI=10.1038/nature12723;
RA Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H.,
RA Brueckner M., Khokha M.K.;
RT "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type
RT and laterality.";
RL Nature 504:456-459(2013).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=24337742; DOI=10.4049/jimmunol.1301024;
RA Lajoie L., Congy-Jolivet N., Bolzec A., Gouilleux-Gruart V., Sicard E.,
RA Sung H.C., Peiretti F., Moreau T., Vie H., Clemenceau B., Thibault G.;
RT "ADAM17-mediated shedding of FcgammaRIIIA on human NK cells: identification
RT of the cleavage site and relationship with activation.";
RL J. Immunol. 192:741-751(2014).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-791, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24227843; DOI=10.1128/jvi.02202-13;
RA Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O.,
RA Poehlmann S.;
RT "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by
RT TMPRSS2 augments entry driven by the severe acute respiratory syndrome
RT coronavirus spike protein.";
RL J. Virol. 88:1293-1307(2014).
RN [19]
RP FUNCTION.
RX PubMed=26876177; DOI=10.1016/j.celrep.2016.01.053;
RA Lokau J., Nitz R., Agthe M., Monhasery N., Aparicio-Siegmund S.,
RA Schumacher N., Wolf J., Moeller-Hackbarth K., Waetzig G.H., Groetzinger J.,
RA Mueller-Newen G., Rose-John S., Scheller J., Garbers C.;
RT "Proteolytic Cleavage Governs Interleukin-11 Trans-signaling.";
RL Cell Rep. 14:1761-1773(2016).
RN [20]
RP FUNCTION.
RX PubMed=28060820; DOI=10.1371/journal.pbio.2000080;
RA Riethmueller S., Somasundaram P., Ehlers J.C., Hung C.W., Flynn C.M.,
RA Lokau J., Agthe M., Duesterhoeft S., Zhu Y., Groetzinger J., Lorenzen I.,
RA Koudelka T., Yamamoto K., Pickhinke U., Wichert R., Becker-Pauly C.,
RA Raedisch M., Albrecht A., Hessefort M., Stahnke D., Unverzagt C.,
RA Rose-John S., Tholey A., Garbers C.;
RT "Proteolytic Origin of the Soluble Human IL-6R In Vivo and a Decisive Role
RT of N-Glycosylation.";
RL PLoS Biol. 15:e2000080-e2000080(2017).
RN [21]
RP INTERACTION WITH RHBDF1 AND RHBDF2.
RX PubMed=29897333; DOI=10.7554/elife.35032;
RA Oikonomidi I., Burbridge E., Cavadas M., Sullivan G., Collis B.,
RA Naegele H., Clancy D., Brezinova J., Hu T., Bileck A., Gerner C.,
RA Bolado A., von Kriegsheim A., Martin S.J., Steinberg F., Strisovsky K.,
RA Adrain C.;
RT "iTAP, a novel iRhom interactor, controls TNF secretion by policing the
RT stability of iRhom/TACE.";
RL Elife 7:0-0(2018).
RN [22]
RP INTERACTION WITH FRMD8; RHBDF1 AND RHBDF2.
RX PubMed=29897336; DOI=10.7554/elife.35012;
RA Kuenzel U., Grieve A.G., Meng Y., Sieber B., Cowley S.A., Freeman M.;
RT "FRMD8 promotes inflammatory and growth factor signalling by stabilising
RT the iRhom/ADAM17 sheddase complex.";
RL Elife 7:0-0(2018).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473 IN COMPLEX WITH ZINC,
RP COFACTOR, ACTIVE SITE, AND DISULFIDE BONDS.
RX PubMed=9520379; DOI=10.1073/pnas.95.7.3408;
RA Maskos K., Fernandez-Catalan C., Huber R., Bourenkov G.P., Bartunik H.,
RA Ellestad G.A., Reddy P., Wolfson M.F., Rauch C.T., Castner B.J., Davis R.,
RA Clarke H.R.G., Petersen M., Fitzner J.N., Cerretti D.P., March C.J.,
RA Paxton R.J., Black R.A., Bode W.;
RT "Crystal structure of the catalytic domain of human tumor necrosis factor-
RT alpha-converting enzyme.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:3408-3412(1998).
CC -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its
CC mature soluble form (PubMed:9034191). Responsible for the proteolytical
CC release of soluble JAM3 from endothelial cells surface
CC (PubMed:20592283). Responsible for the proteolytic release of several
CC other cell-surface proteins, including p75 TNF-receptor, interleukin 1
CC receptor type II, p55 TNF-receptor, transforming growth factor-alpha,
CC L-selectin, growth hormone receptor, MUC1 and the amyloid precursor
CC protein (PubMed:12441351). Acts as an activator of Notch pathway by
CC mediating cleavage of Notch, generating the membrane-associated
CC intermediate fragment called Notch extracellular truncation (NEXT)
CC (PubMed:24226769). Plays a role in the proteolytic processing of ACE2
CC (PubMed:24227843). Plays a role in hemostasis through shedding of
CC GP1BA, the platelet glycoprotein Ib alpha chain (By similarity).
CC Mediates the proteolytic cleavage of LAG3, leading to release the
CC secreted form of LAG3 (By similarity). Mediates the proteolytic
CC cleavage of IL6R, leading to the release of secreted form of IL6R
CC (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage
CC and shedding of FCGR3A upon NK cell stimulation, a mechanism that
CC allows for increased NK cell motility and detachment from opsonized
CC target cells. {ECO:0000250|UniProtKB:Q9Z0F8,
CC ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20592283,
CC ECO:0000269|PubMed:24226769, ECO:0000269|PubMed:24227843,
CC ECO:0000269|PubMed:24337742, ECO:0000269|PubMed:26876177,
CC ECO:0000269|PubMed:28060820, ECO:0000269|PubMed:9034191}.
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:0000269|PubMed:12441351,
CC ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:24227843};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:9520379};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:9520379};
CC -!- SUBUNIT: Interacts with MAD2L1, MAPK14 and MUC1 (PubMed:12441351,
CC PubMed:20188673). Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2
CC (PubMed:29897333). Interacts with FRMD8 via its interaction with
CC iRhom1/RHBDF1 and iRhom2/RHBDF2 (PubMed:29897333).
CC {ECO:0000269|PubMed:12441351, ECO:0000269|PubMed:20188673,
CC ECO:0000269|PubMed:29897333}.
CC -!- INTERACTION:
CC P78536; Q12959: DLG1; NbExp=7; IntAct=EBI-78188, EBI-357481;
CC P78536; P05556: ITGB1; NbExp=2; IntAct=EBI-78188, EBI-703066;
CC P78536; Q13257: MAD2L1; NbExp=3; IntAct=EBI-78188, EBI-78203;
CC P78536; Q80WQ6: Rhbdf2; Xeno; NbExp=2; IntAct=EBI-78188, EBI-647271;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=A;
CC IsoId=P78536-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P78536-2; Sequence=VSP_005478;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed at highest levels
CC in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus,
CC prostate, testes, ovary and small intestine, and in fetal brain, lung,
CC liver and kidney. Expressed in natural killer cells (at protein level)
CC (PubMed:24337742). {ECO:0000269|PubMed:24337742}.
CC -!- INDUCTION: In arthritis-affected cartilage.
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 (By similarity).
CC {ECO:0000250}.
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-819 but decreases
CC phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is
CC required for ADAM17-mediated ectodomain shedding.
CC {ECO:0000269|PubMed:12058067, ECO:0000269|PubMed:12621058,
CC ECO:0000269|PubMed:20188673}.
CC -!- DISEASE: Inflammatory skin and bowel disease, neonatal, 1 (NISBD1)
CC [MIM:614328]: A disorder characterized by inflammatory features with
CC neonatal onset, involving the skin, hair, and gut. The skin lesions
CC involve perioral and perianal erythema, psoriasiform erythroderma, with
CC flares of erythema, scaling, and widespread pustules. Gastrointestinal
CC symptoms include malabsorptive diarrhea that is exacerbated by
CC intercurrent gastrointestinal infections. The hair is short or broken,
CC and the eyelashes and eyebrows are wiry and disorganized.
CC {ECO:0000269|PubMed:22010916}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha-
CC converting enzyme entry;
CC URL="https://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/ADAM17ID572ch2p25.html";
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DR EMBL; U86755; AAB51586.1; -; mRNA.
DR EMBL; U69611; AAB51514.1; -; mRNA.
DR EMBL; U69612; AAB53014.1; -; mRNA.
DR EMBL; U92649; AAC39721.1; -; mRNA.
DR CCDS; CCDS1665.1; -. [P78536-1]
DR RefSeq; NP_003174.3; NM_003183.5. [P78536-1]
DR PDB; 1BKC; X-ray; 2.00 A; A/C/E/I=219-474.
DR PDB; 1ZXC; X-ray; 2.28 A; A/B=215-477.
DR PDB; 2A8H; X-ray; 2.30 A; A/B=215-477.
DR PDB; 2DDF; X-ray; 1.70 A; A/B=218-474.
DR PDB; 2FV5; X-ray; 2.10 A; A/B=216-475.
DR PDB; 2FV9; X-ray; 2.02 A; A/B=218-475.
DR PDB; 2I47; X-ray; 1.90 A; A/B/C/D=212-492.
DR PDB; 2M2F; NMR; -; A=581-642.
DR PDB; 2OI0; X-ray; 2.00 A; A=216-477.
DR PDB; 3B92; X-ray; 2.00 A; A=216-474.
DR PDB; 3CKI; X-ray; 2.30 A; A=219-474.
DR PDB; 3E8R; X-ray; 1.90 A; A/B=215-477.
DR PDB; 3EDZ; X-ray; 1.90 A; A/B=215-477.
DR PDB; 3EWJ; X-ray; 1.80 A; A/B=215-477.
DR PDB; 3G42; X-ray; 2.10 A; A/B/C/D=212-492.
DR PDB; 3KMC; X-ray; 1.80 A; A/B=215-476.
DR PDB; 3KME; X-ray; 1.85 A; A/B=215-476.
DR PDB; 3L0T; X-ray; 1.92 A; A/B=215-476.
DR PDB; 3L0V; X-ray; 1.75 A; A/B=215-476.
DR PDB; 3LE9; X-ray; 1.85 A; A/B=215-476.
DR PDB; 3LEA; X-ray; 2.00 A; A/B=215-476.
DR PDB; 3LGP; X-ray; 1.90 A; A/B=215-476.
DR PDB; 3O64; X-ray; 1.88 A; A/B=215-476.
DR PDBsum; 1BKC; -.
DR PDBsum; 1ZXC; -.
DR PDBsum; 2A8H; -.
DR PDBsum; 2DDF; -.
DR PDBsum; 2FV5; -.
DR PDBsum; 2FV9; -.
DR PDBsum; 2I47; -.
DR PDBsum; 2M2F; -.
DR PDBsum; 2OI0; -.
DR PDBsum; 3B92; -.
DR PDBsum; 3CKI; -.
DR PDBsum; 3E8R; -.
DR PDBsum; 3EDZ; -.
DR PDBsum; 3EWJ; -.
DR PDBsum; 3G42; -.
DR PDBsum; 3KMC; -.
DR PDBsum; 3KME; -.
DR PDBsum; 3L0T; -.
DR PDBsum; 3L0V; -.
DR PDBsum; 3LE9; -.
DR PDBsum; 3LEA; -.
DR PDBsum; 3LGP; -.
DR PDBsum; 3O64; -.
DR AlphaFoldDB; P78536; -.
DR BMRB; P78536; -.
DR SMR; P78536; -.
DR BioGRID; 112731; 73.
DR DIP; DIP-31044N; -.
DR IntAct; P78536; 33.
DR MINT; P78536; -.
DR STRING; 9606.ENSP00000309968; -.
DR BindingDB; P78536; -.
DR ChEMBL; CHEMBL3706; -.
DR DrugBank; DB07189; (1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acid.
DR DrugBank; DB07145; (2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE.
DR DrugBank; DB06943; (3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiol.
DR DrugBank; DB07964; (3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE.
DR DrugBank; DB07079; 3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol.
DR DrugBank; DB07121; 4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE.
DR DrugBank; DB07147; methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylate.
DR DrugBank; DB07233; N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan.
DR DrugCentral; P78536; -.
DR GuidetoPHARMACOLOGY; 1662; -.
DR MEROPS; M12.217; -.
DR TCDB; 8.A.77.1.2; the sheddase (sheddase) family.
DR GlyConnect; 1180; 18 N-Linked glycans (5 sites).
DR GlyGen; P78536; 10 sites, 20 N-linked glycans (5 sites).
DR iPTMnet; P78536; -.
DR PhosphoSitePlus; P78536; -.
DR SwissPalm; P78536; -.
DR BioMuta; ADAM17; -.
DR DMDM; 14423632; -.
DR CPTAC; CPTAC-1561; -.
DR EPD; P78536; -.
DR jPOST; P78536; -.
DR MassIVE; P78536; -.
DR MaxQB; P78536; -.
DR PaxDb; P78536; -.
DR PeptideAtlas; P78536; -.
DR PRIDE; P78536; -.
DR ProteomicsDB; 57637; -. [P78536-1]
DR ProteomicsDB; 57638; -. [P78536-2]
DR ABCD; P78536; 34 sequenced antibodies.
DR Antibodypedia; 2540; 932 antibodies from 49 providers.
DR DNASU; 6868; -.
DR Ensembl; ENST00000310823.8; ENSP00000309968.3; ENSG00000151694.14. [P78536-1]
DR GeneID; 6868; -.
DR KEGG; hsa:6868; -.
DR MANE-Select; ENST00000310823.8; ENSP00000309968.3; NM_003183.6; NP_003174.3.
DR UCSC; uc002qzu.5; human. [P78536-1]
DR CTD; 6868; -.
DR DisGeNET; 6868; -.
DR GeneCards; ADAM17; -.
DR HGNC; HGNC:195; ADAM17.
DR HPA; ENSG00000151694; Low tissue specificity.
DR MalaCards; ADAM17; -.
DR MIM; 603639; gene.
DR MIM; 614328; phenotype.
DR neXtProt; NX_P78536; -.
DR OpenTargets; ENSG00000151694; -.
DR Orphanet; 294023; Neonatal inflammatory skin and bowel disease.
DR PharmGKB; PA24512; -.
DR VEuPathDB; HostDB:ENSG00000151694; -.
DR eggNOG; KOG3658; Eukaryota.
DR GeneTree; ENSGT00940000155443; -.
DR HOGENOM; CLU_004602_2_0_1; -.
DR InParanoid; P78536; -.
DR OMA; FYHGRVF; -.
DR PhylomeDB; P78536; -.
DR TreeFam; TF314733; -.
DR BRENDA; 3.4.24.86; 2681.
DR PathwayCommons; P78536; -.
DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-177929; Signaling by EGFR.
DR Reactome; R-HSA-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2660826; Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
DR Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-5362798; Release of Hh-Np from the secreting cell.
DR Reactome; R-HSA-75893; TNF signaling.
DR Reactome; R-HSA-9662834; CD163 mediating an anti-inflammatory response.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SignaLink; P78536; -.
DR SIGNOR; P78536; -.
DR BioGRID-ORCS; 6868; 12 hits in 1088 CRISPR screens.
DR ChiTaRS; ADAM17; human.
DR EvolutionaryTrace; P78536; -.
DR GeneWiki; ADAM17; -.
DR GenomeRNAi; 6868; -.
DR Pharos; P78536; Tchem.
DR PRO; PR:P78536; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P78536; protein.
DR Bgee; ENSG00000151694; Expressed in oocyte and 207 other tissues.
DR ExpressionAtlas; P78536; baseline and differential.
DR Genevisible; P78536; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; IMP:UniProtKB.
DR GO; GO:0005178; F:integrin binding; IPI:BHF-UCL.
DR GO; GO:0005138; F:interleukin-6 receptor binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IDA:ARUK-UCL.
DR GO; GO:0008237; F:metallopeptidase activity; IDA:BHF-UCL.
DR GO; GO:0005112; F:Notch binding; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0008233; F:peptidase activity; TAS:ARUK-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IDA:ARUK-UCL.
DR GO; GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IDA:BHF-UCL.
DR GO; GO:0033627; P:cell adhesion mediated by integrin; IDA:BHF-UCL.
DR GO; GO:0048870; P:cell motility; ISS:BHF-UCL.
DR GO; GO:0071403; P:cellular response to high density lipoprotein particle stimulus; IDA:BHF-UCL.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:BHF-UCL.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0002467; P:germinal center formation; ISS:BHF-UCL.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0002446; P:neutrophil mediated immunity; IC:BHF-UCL.
DR GO; GO:0007220; P:Notch receptor processing; IDA:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:ARUK-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:BHF-UCL.
DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IMP:BHF-UCL.
DR GO; GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:BHF-UCL.
DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; IC:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL.
DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:1903265; P:positive regulation of tumor necrosis factor-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:1905564; P:positive regulation of vascular endothelial cell proliferation; IDA:BHF-UCL.
DR GO; GO:0016485; P:protein processing; IDA:ARUK-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0035624; P:receptor transactivation; IMP:BHF-UCL.
DR GO; GO:0033025; P:regulation of mast cell apoptotic process; ISS:BHF-UCL.
DR GO; GO:0001666; P:response to hypoxia; IDA:BHF-UCL.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISS:BHF-UCL.
DR GO; GO:0048536; P:spleen development; ISS:BHF-UCL.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:BHF-UCL.
DR GO; GO:0035313; P:wound healing, spreading of epidermal cells; IEP: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 3D-structure; Alternative splicing; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Notch signaling pathway;
KW Phosphoprotein; Protease; Reference proteome; SH3-binding; Signal;
KW Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000250|UniProtKB:Q9Z1K9"
FT PROPEP 18..214
FT /evidence="ECO:0000269|PubMed:9034191"
FT /id="PRO_0000029088"
FT CHAIN 215..824
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 17"
FT /id="PRO_0000029089"
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..824
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 732..824
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 MOTIF 741..748
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 734..748
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 757..780
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 795..824
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 ECO:0000269|PubMed:9520379"
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:0000269|PubMed:9520379"
FT BINDING 409
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:9520379"
FT BINDING 415
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:9520379"
FT MOD_RES 735
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000269|PubMed:12058067,
FT ECO:0000269|PubMed:20188673"
FT MOD_RES 761
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 767
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z1K9"
FT MOD_RES 791
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 819
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12621058"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 174
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 594
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 225..333
FT /evidence="ECO:0000269|PubMed:9520379"
FT DISULFID 365..469
FT /evidence="ECO:0000269|PubMed:9520379"
FT DISULFID 423..453
FT /evidence="ECO:0000269|PubMed:9520379"
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 695..824
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:9034190"
FT /id="VSP_005478"
FT VARIANT 162
FT /note="K -> E (in dbSNP:rs34431503)"
FT /id="VAR_051586"
FT VARIANT 202
FT /note="R -> G (in dbSNP:rs2230818)"
FT /id="VAR_051587"
FT CONFLICT 109
FT /note="V -> A (in Ref. 3; AAC39721)"
FT /evidence="ECO:0000305"
FT CONFLICT 563
FT /note="D -> N (in Ref. 3; AAC39721)"
FT /evidence="ECO:0000305"
FT CONFLICT 801
FT /note="T -> A (in Ref. 3; AAC39721)"
FT /evidence="ECO:0000305"
FT CONFLICT 818
FT /note="D -> N (in Ref. 3; AAC39721)"
FT /evidence="ECO:0000305"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:3L0V"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 233..238
FT /evidence="ECO:0007829|PDB:2DDF"
FT TURN 239..242
FT /evidence="ECO:0007829|PDB:3EDZ"
FT HELIX 244..263
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 276..284
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 314..324
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 332..339
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 344..346
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 349..354
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:3O64"
FT STRAND 363..365
FT /evidence="ECO:0007829|PDB:3O64"
FT STRAND 368..371
FT /evidence="ECO:0007829|PDB:2DDF"
FT TURN 372..375
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 376..379
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 382..389
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 396..410
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:3CKI"
FT TURN 421..423
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:2DDF"
FT STRAND 436..438
FT /evidence="ECO:0007829|PDB:3CKI"
FT STRAND 442..444
FT /evidence="ECO:0007829|PDB:3LGP"
FT TURN 445..448
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 452..469
FT /evidence="ECO:0007829|PDB:2DDF"
FT HELIX 583..586
FT /evidence="ECO:0007829|PDB:2M2F"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:2M2F"
FT HELIX 597..600
FT /evidence="ECO:0007829|PDB:2M2F"
FT STRAND 603..605
FT /evidence="ECO:0007829|PDB:2M2F"
FT STRAND 611..613
FT /evidence="ECO:0007829|PDB:2M2F"
FT STRAND 631..636
FT /evidence="ECO:0007829|PDB:2M2F"
FT TURN 637..639
FT /evidence="ECO:0007829|PDB:2M2F"
SQ SEQUENCE 824 AA; 93021 MW; 5B1032F6B88A837F CRC64;
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI QQHSVRKRDL
QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD GKNESEYTVK WQDFFTGHVV
GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS
PKVCGYLKVD NEELLPKGLV DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG
RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS
HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL
AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN
SRVDEGEECD PGIMYLNNDT CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA
TCKGVSYCTG NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS
INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHP SNVEMLSSMD
SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA APKLDHQRMD TIQEDPSTDS HMDEDGFEKD
PFPNSSTAAK SFEDLTDHPV TRSEKAASFK LQRQNRVDSK ETEC
