O77636 · ADA17_PIG
- ProteinDisintegrin and metalloproteinase domain-containing protein 17
- GeneADAM17
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids833 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins including adhesion proteins, growth factor precursors and cytokines important for inflammation and immunity (By similarity).
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2 (By similarity).
Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity).
Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity).
Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R. Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells (By similarity).
Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (By similarity).
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2 (By similarity).
Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity).
Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity).
Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R. Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells (By similarity).
Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (By similarity).
(Microbial infection) Acts as a receptor for classical swine fever virus.
Catalytic activity
- Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNFalpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | plasma membrane | |
Molecular Function | endopeptidase activity | |
Molecular Function | metal ion binding | |
Molecular Function | metalloendopeptidase activity | |
Molecular Function | Notch binding | |
Biological Process | membrane protein ectodomain proteolysis | |
Biological Process | Notch receptor processing | |
Biological Process | Notch signaling pathway | |
Biological Process | positive regulation of ERK1 and ERK2 cascade | |
Biological Process | proteolysis | |
Biological Process | tumor necrosis factor-mediated signaling pathway |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameDisintegrin and metalloproteinase domain-containing protein 17
- EC number
- Short namesADAM 17
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionO77636
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass type I membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 672-692 | Helical | ||||
Sequence: IVGSVLVFSLMLWIPVSILVH |
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for signal, chain, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-17 | |||||
Sequence: MRQCALFLTSLVPIVLA | ||||||
Chain | PRO_0000078207 | 18-833 | Disintegrin and metalloproteinase domain-containing protein 17 | |||
Sequence: PRPPDEPGFGSPQRLEKLDSLLSDYDILSLSSIRQHSVRKRDLQASTHLETLLTFSALNRHFKLYLTSSTERFSQNFKVVVVDGEDESEYPVKWQDFFSGHVVGEPDSRVLAHIGDDDITVRINTDGAEYNIEPLWRLINDTKDKRVLVYKSEDIKNVSRLQSPKVCGYIKADNEELLPKGLVDREPPDELVHRVKRRADPNPLRNTCKLLVVADHRFYKYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGERHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPIGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLRPGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGRCKDGKCVPFCEREQRLESCACNETDHSCKVCCRAPSGRCLPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWEFIDKLSINTFGKFLADNIVGSVLVFSLMLWIPVSILVHCVDKKLDKQYESLSLLHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPLQPLQPGPVLPSAPSVPVAPKLDHQRMDTIQEDPSTDSHVDEDGFEKDPFPNSSAAAKSFEDLTDHPVTRSEKASSFKLQRQSRVDSKETEC | ||||||
Disulfide bond | 365↔469 | |||||
Sequence: CPKAYYSPIGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQEC | ||||||
Disulfide bond | 423↔453 | |||||
Sequence: CAPNEDQGGKYVMYPIAVSGDHENNKMFSNC | ||||||
Disulfide bond | 534↔555 | |||||
Sequence: CQEAINATCKGVSYCTGNSSEC |
Post-translational modification
The precursor is cleaved by a furin endopeptidase.
Phosphorylated.
Keywords
- PTM
Proteomic databases
Interaction
Subunit
(Microbial infection) Interacts (via metalloproteinase domain) with classical swine fever virus envelope glycoprotein E2; this interaction allows binding and probably entry of the virus into the cell.
Interacts with MAD2L1, MAPK14 and MUC1. Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2. Interacts with FRMD8 via its interaction with iRhom1/RHBDF1 and iRhom2/RHBDF2.
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 223-474 | Peptidase M12B | ||||
Sequence: NTCKLLVVADHRFYKYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGERHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPIGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERS | ||||||
Region | 301-345 | Interaction with classical swine fever virus envelope glycoprotein E2 | ||||
Sequence: AKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDM | ||||||
Domain | 475-563 | Disintegrin | ||||
Sequence: NKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLRPGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAED | ||||||
Compositional bias | 735-756 | Pro residues | ||||
Sequence: TPGRLQPLQPLQPGPVLPSAPS | ||||||
Region | 735-760 | Disordered | ||||
Sequence: TPGRLQPLQPLQPGPVLPSAPSVPVA | ||||||
Compositional bias | 772-789 | Basic and acidic residues | ||||
Sequence: QEDPSTDSHVDEDGFEKD | ||||||
Region | 772-833 | Disordered | ||||
Sequence: QEDPSTDSHVDEDGFEKDPFPNSSAAAKSFEDLTDHPVTRSEKASSFKLQRQSRVDSKETEC | ||||||
Compositional bias | 804-833 | Basic and acidic residues | ||||
Sequence: LTDHPVTRSEKASSFKLQRQSRVDSKETEC |
Domain
Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length833
- Mass (Da)93,544
- Last updated2023-11-08 v2
- Checksum37D7603F9BF7F25E
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A4X1UB62 | A0A4X1UB62_PIG | ADAM17 | 702 | ||
A0A5G2Q9K7 | A0A5G2Q9K7_PIG | ADAM17 | 751 | ||
A0A5G2QLA4 | A0A5G2QLA4_PIG | ADAM17 | 785 | ||
K7GN11 | K7GN11_PIG | ADAM17 | 752 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 318 | in Ref. 1; AAC23532 | ||||
Sequence: L → R | ||||||
Compositional bias | 735-756 | Pro residues | ||||
Sequence: TPGRLQPLQPLQPGPVLPSAPS | ||||||
Compositional bias | 772-789 | Basic and acidic residues | ||||
Sequence: QEDPSTDSHVDEDGFEKD | ||||||
Compositional bias | 804-833 | Basic and acidic residues | ||||
Sequence: LTDHPVTRSEKASSFKLQRQSRVDSKETEC |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF069648 EMBL· GenBank· DDBJ | AAC23532.1 EMBL· GenBank· DDBJ | mRNA | ||
AB271919 EMBL· GenBank· DDBJ | BAF62294.1 EMBL· GenBank· DDBJ | mRNA |