ADA17_PIG
ID ADA17_PIG Reviewed; 112 AA.
AC O77636;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 119.
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: Fragment;
GN Name=ADAM17; Synonyms=TACE;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10429942; DOI=10.1016/s0945-053x(99)00024-4;
RA Flannery C.R., Little C.B., Caterson B., Hughes C.E.;
RT "Effects of culture conditions and exposure to catabolic stimulators (IL-1
RT and retinoic acid) on the expression of matrix metalloproteinases (MMPs)
RT and disintegrin metalloproteinases (ADAMs) by articular cartilage
RT chondrocytes.";
RL Matrix Biol. 18:225-237(1999).
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. 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. Acts as an activator of Notch
CC pathway by mediating cleavage of Notch, generating the membrane-
CC associated intermediate fragment called Notch extracellular truncation
CC (NEXT). Plays a role in the proteolytic processing of ACE2. Plays a
CC role in hemostasis through shedding of GP1BA, the platelet glycoprotein
CC Ib alpha chain. Mediates the proteolytic cleavage of LAG3, leading to
CC release the secreted form of LAG3 (By similarity). Mediates the
CC proteolytic cleavage of IL6R, leading to the release of secreted form
CC of IL6R (By similarity). Mediates the proteolytic cleavage and shedding
CC of FCGR3A upon NK cell stimulation, a mechanism that allows for
CC increased NK cell motility and detachment from opsonized target cells.
CC {ECO:0000250|UniProtKB:P78536, ECO:0000250|UniProtKB:Q9Z0F8}.
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 -!- 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 -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type I
CC membrane protein {ECO:0000255}.
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 -!- PTM: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
CC -!- PTM: Phosphorylated. {ECO:0000250|UniProtKB:P78536}.
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DR EMBL; AF069648; AAC23532.1; -; mRNA.
DR AlphaFoldDB; O77636; -.
DR SMR; O77636; -.
DR STRING; 9823.ENSSSCP00000009208; -.
DR BindingDB; O77636; -.
DR ChEMBL; CHEMBL3332; -.
DR MEROPS; M12.217; -.
DR PaxDb; O77636; -.
DR PeptideAtlas; O77636; -.
DR eggNOG; KOG3658; Eukaryota.
DR InParanoid; O77636; -.
DR BRENDA; 3.4.24.86; 6170.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:BHF-UCL.
DR GO; GO:0005112; F:Notch binding; ISS:UniProtKB.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IMP:BHF-UCL.
DR GO; GO:0007220; P:Notch receptor processing; ISS:UniProtKB.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:AgBase.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IMP:AgBase.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001590; Peptidase_M12B.
DR PROSITE; PS50215; ADAM_MEPRO; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Notch signaling pathway; Phosphoprotein; Protease; Reference proteome;
KW Zinc.
FT CHAIN <1..>112
FT /note="Disintegrin and metalloproteinase domain-containing
FT protein 17"
FT /id="PRO_0000078207"
FT DOMAIN <1..>112
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT ACT_SITE 91
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 90
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT BINDING 94
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P78536"
FT NON_TER 1
FT NON_TER 112
SQ SEQUENCE 112 AA; 12201 MW; B840FBE7C2EE69FC CRC64;
MLREQFSFDI AEEASKVCLA HLFTYQDFDM GTLGLAYVGS PRANSHGGVC PKAYYSPIGK
KNIYLNSGLT STKNYGKTIL TKEADLVTTH ELGHNFGAEH DPDGLAECAP NE
