Protein detail
ADA17
Disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17) (EC 3.4.24.86) (Snake venom-like protease) (TNF-alpha convertase) (TNF-alpha-converting enzyme) (CD antigen CD156b)
Entry name ADA17 | UniProt ID | EVMP confidence score 0.25 |
Supporting publications (n) 1 | Transmembrane count 1 | Protein classification CD markersDisease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters |
EVMP confidence score
Annotation confidence score; open for threshold definitions.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40Basic Information13
Protein Names
Disintegrin and metalloproteinase domain-containing protein 17 (ADAM 17) (EC 3.4.24.86) (Snake venom-like protease) (TNF-alpha convertase) (TNF-alpha-converting enzyme) (CD antigen CD156b)
Protein Class (8)
CD markersDisease related genesEnzymesHuman disease related genesPotential drug targetsPredicted intracellular proteinsPredicted membrane proteinsTransporters
Protein Function (8)
- Human disease related genes:Immune system diseases:Other immune system diseases
- Predicted intracellular proteins
- CD markers
- Potential drug targets
- Enzymes
- ENZYME proteins:Hydrolases
- Transporters:Accessory Factors Involved in Transport
- Disease related genes
Transmembrane
672..692; Helical
Transmembrane Count
1
Ensembl
Entrez Gene Symbol
Gene Synonym (3)
CD156BcSVPTACE
Gene Description
ADAM metallopeptidase domain 17
Chromosome
2
Position
9488486-9556732
Supporting publications (n)
1
EVMP confidence score
0.25
Fluorescence & Localization2
Cell SpecificBrain excitatory neuronsSingle-Nuclei Brain SpecificLAMP5-LHX6 and Chandelier
Function & Pathway8
Protein Function (8)
- Human disease related genes:Immune system diseases:Other immune system diseases
- Predicted intracellular proteins
- CD markers
- Potential drug targets
- Enzymes
- ENZYME proteins:Hydrolases
- Transporters:Accessory Factors Involved in Transport
- Disease related genes
Cellular Component (13)
- GO:0000139 Golgi membrane
- GO:0005737 cytoplasm
- GO:0005788 endoplasmic reticulum lumen
- GO:0005829 cytosol
- GO:0005886 plasma membrane
- GO:0005911 cell-cell junction
- GO:0005925 focal adhesion
- GO:0009986 cell surface
- GO:0015629 actin cytoskeleton
- GO:0016020 membrane
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Molecular Function (14)
- GO:0004175 endopeptidase activity
- GO:0004222 metalloendopeptidase activity
- GO:0005112 Notch binding
- GO:0005138 interleukin-6 receptor binding
- GO:0005178 integrin binding
- GO:0005515 protein binding
- GO:0008233 peptidase activity
- GO:0008237 metallopeptidase activity
- GO:0017124 SH3 domain binding
- GO:0019955 cytokine binding
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Biological Process (3)
KEGG (6)
Reactome (27)
- R-hsa-2122948 activated notch1 transmits signal to the nucleus
- R-hsa-9662851 anti inflammatory response favouring leishmania parasite infection
- R-hsa-9662834 cd163 mediating an anti inflammatory response
- R-hsa-1442490 collagen degradation
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-73887 death receptor signaling
- R-hsa-1474228 degradation of the extracellular matrix
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-1474244 extracellular matrix organization
- R-hsa-982772 growth hormone receptor signaling
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Canonical Pathways (3)
- M135 Pid il5 pathway
- M17200 Sa b cell receptor complexes
- M33 Pid glypican 1pathway
Mediation Categories (6)
Adhesion and uptake mediationClinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence69
Enzyme-Mediated Modification (17)
17 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| ADAM17 | PLK2 | Q9NYY3 | S | 791 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:24338472 |
| ADAM17 | PMAIP1 | Q13794 | S | 819 | phosphorylation | Sparser_ProtMapperProtMapper | ProtMapper:25171914 |
| ADAM17 | CDK2 | P24941 | T | 735 | phosphorylation | KEA | KEA:17570479 |
| ADAM17 | GSK3B | P49841 | T | 735 | phosphorylation | KEA | KEA:17570479 |
| ADAM17 | LCK | P06239 | S | 819 | phosphorylation | KEA | KEA:15743820KEA:12621058 |
| ADAM17 | MAPK9 | P45984 | T | 735 | phosphorylation | KEA | KEA:17570479 |
| ADAM17 | RPS6KA3 | P51812 | S | 819 | phosphorylation | KEA | KEA:17570479 |
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Ligand-Receptor Signaling (37)
37 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| cell_surface | cell_surface | Surfaceome | No | No | Yes | Yes | No |
| cell_surface | cell_surface | connectomeDB2020 | No | No | Yes | Yes | No |
| cell_surface | cell_surface | OmniPath | No | No | Yes | Yes | No |
| transmembrane | transmembrane_predicted | Phobius | No | No | Yes | Yes | No |
| transmembrane_phobius | transmembrane_predicted | Almen2009 | No | No | Yes | Yes | No |
| transmembrane_sosui | transmembrane_predicted | Almen2009 | No | No | Yes | Yes | No |
| transmembrane_tmhmm | transmembrane_predicted | Almen2009 | No | No | Yes | Yes | No |
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Regulatory Interaction Network (14)
14 records.
| Source Protein Symbol | Source UniProt ID | Target Protein Symbol | Target UniProt ID | Is Directed | Is Stimulation | Is Inhibition | Database | References |
|---|---|---|---|---|---|---|---|---|
| ADA17 | P78536 | A4 | P05067 | Yes | Yes | No | SPIKESPIKE_LCSIGNOR | SPIKE_LC:12535668SPIKE:12535668SIGNOR:9774383 |
| SRC | P12931 | ADA17 | P78536 | Yes | Yes | No | SIGNOR | SIGNOR:25371038 |
| ADA17 | P78536 | HBEGF | Q99075 | Yes | Yes | No | SIGNORACSN | ACSN:16054021SIGNOR:26284334ACSN:18372913 |
| ADA17 | P78536 | EREG | O14944 | Yes | Yes | No | SIGNOR | SIGNOR:26284334 |
| MK03 | P27361 | ADA17 | P78536 | Yes | Yes | No | WangPhosphoNetworksSparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetSIGNORphosphoELMProtMapperRLIMS-P_ProtMapperPhosphoSite_KEAKEAphosphoELM_KEAInnateDBSIGNOR_ProtMapperREACH_ProtMapperPhosphoSite_ProtMapper | ProtMapper:12058067phosphoELM:12058067ProtMapper:21570469KEA:12058067InnateDB:12058067ProtMapper:18187448SIGNOR:12058067 |
| MTR1L | Q13585 | ADA17 | P78536 | Yes | Yes | No | SIGNOR | SIGNOR:32405532 |
| ADA17 | P78536 | AREG | P15514 | Yes | Yes | No | WangSIGNOR | SIGNOR:26284334 |
| ADA17 | P78536 | NOTC1 | P46531 | Yes | Yes | No | iTALKKEGG-MEDICUSSIGNORHPRD_LRdbtalklrHPRDCui2007WangRamilowski2015HPRD_talklrCellinkerSTRING_talklrEMBRACECellCallCellTalkDBFantom5_LRdbconnectomeDB2020ACSNLRdbHPRD-phos | ACSN:19601831HPRD:10882063LRdb:10882063Cellinker:10882063ACSN:19726682CellTalkDB:10882063HPRD:9620803HPRD-phos:9620803Cellinker:9620803connectomeDB2020:9620803ACSN:19704010LRdb:96connectomeDB2020:10882063SIGNOR:10882063HPRD-phos:10882063 |
| ADA17 | P78536 | MUC1 | P15941 | Yes | No | Yes | CellTalkDBSIGNOR | SIGNOR:12441351CellTalkDB:12441351 |
| ADA17 | P78536 | GP1BA | P07359 | Yes | No | Yes | SIGNOR | SIGNOR:25297919 |
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Isolation & Detection Technology (1)
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| PRotein Organic Solvent Precipitation；Differential Ultracentrifugation | Mass spectrometry | 1 | 32384937 |
Sequence, Structure & Domains14
Sequences
Length
824
Mass
93,021
Sequence
MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQSPKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANSHGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINATCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMDSASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=A; IsoId=P78536-1; Sequence=Displayed; Name=B; IsoId=P78536-2; Sequence=VSP_005478
Alternative Sequence
695..824; Missing (in isoform B)
3D Structural Models
Turn
239..242; 372..375; 421..423; 445..448; 496..498; 516..518; 539..542; 616..619
Helix
33..38; 47..49; 87..89; 111..113; 152..155; 169..171; 191..193; 220..222; 233..238; 244..263; 314..324; 326..329; 344..346; 396..410; 427..429; 452..469; 581..584; 596..598; 648..657; 661..670; 672..702
Beta Strand
39..43; 50..53; 65..73; 78..85; 96..99; 104..107; 114..119; 122..130; 137..141; 146..151; 163..168; 182..185; 224..231; 269..271; 276..284; 300..302; 309..311; 332..339; 349..354; 355..357; 363..365; 368..371; 376..379; 382..389; 418..420; 436..438; 442..444; 480..482; 485..488; 500..502; 506..508; 520..523; 532..535; 568..570; 572..574; 577..579; 585..587; 589..591; 603..605; 607..609; 611..613; 631..634; 637..639; 642..645; 821..824
3D Structure
Electron microscopy (4); NMR spectroscopy (1); X-ray crystallography (23)
Domain & Motif Annotations
Compositional Bias
741..752; Low complexity; 768..781; Basic and acidic residues; 791..807; Basic and acidic residues; 815..824; Basic and acidic residues
Motif
182..189; Cysteine switch; 731..738; SH3-binding; 741..748; SH3-binding
Domain (CC)
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).; DOMAIN: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
Domain (FT)
223..474; Peptidase M12B; 475..563; Disintegrin
Region
603..671; Crambin-like; 732..824; Disordered
Clinical Relevance7
Related Diseases (4)
Biomarker
Phase 1/2; Preclinical; Terminated; Phase 2
Interaction Protein (3)
ENSG00000075711ENSG00000100234ENSG00000164109
Interaction Count
3
Interaction Dataset (2)
intact_biogridbiogrid_bioplex
Supporting Publications1
| PMID | Title | Abstract |
|---|---|---|
| 38207106 | Proteomic, Metabolomic, and Fatty Acid Profiling of Small Extracellular Vesicles from Glioblastoma Stem-Like Cells and Their Role in Tumor Heterogeneity. | No abstract available |