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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:ADAM17

Protein Summary

check button Gene summary
Gene name: ADAM17
ASpdb.0 ID: 6868
Gene
Gene symbol

ADAM17

Gene ID

6868

Gene nameADAM metallopeptidase domain 17
SynonymsADAM18|CD156B|CSVP|NISBD|NISBD1|TACE
Cytomap

2p25.1

Type of geneprotein-coding
Descriptiondisintegrin and metalloproteinase domain-containing protein 17ADAM metallopeptidase domain 18TNF-alpha convertaseTNF-alpha convertase enzymeTNF-alpha converting enzymea disintegrin and metalloproteinase 17cartilage snake venom-like proteasesnake ve
Modification date20240407
UniProtAcc

P78536


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneADAM17

GO:0001666

response to hypoxia

18276953

GeneADAM17

GO:0004222

metalloendopeptidase activity

9774383|9920899|14625290|15691827|17010968|24226769|24337742|36476876

GeneADAM17

GO:0005112

Notch binding

24226769

GeneADAM17

GO:0005737

cytoplasm

25468996

GeneADAM17

GO:0005829

cytosol

-

GeneADAM17

GO:0005886

plasma membrane

17786981|24337742

GeneADAM17

GO:0005911

cell-cell junction

14970227

GeneADAM17

GO:0005925

focal adhesion

14970227

GeneADAM17

GO:0006508

proteolysis

24227843

GeneADAM17

GO:0006509

membrane protein ectodomain proteolysis

9034190|9574564|14625290|15691827|17010968|17786981|18676862|24337742|36476876

GeneADAM17

GO:0007155

cell adhesion

14970227

GeneADAM17

GO:0007220

Notch receptor processing

24226769

GeneADAM17

GO:0008237

metallopeptidase activity

12777399

GeneADAM17

GO:0009986

cell surface

9034190|18383040|18625725

GeneADAM17

GO:0015629

actin cytoskeleton

17010968

GeneADAM17

GO:0016324

apical plasma membrane

16034137

GeneADAM17

GO:0016485

protein processing

9774383

GeneADAM17

GO:0030335

positive regulation of cell migration

26617808

GeneADAM17

GO:0032496

response to lipopolysaccharide

18383040

GeneADAM17

GO:0032587

ruffle membrane

14970227

GeneADAM17

GO:0033627

cell adhesion mediated by integrin

14970227

GeneADAM17

GO:0042987

amyloid precursor protein catabolic process

9774383

GeneADAM17

GO:0043120

tumor necrosis factor binding

25049354

GeneADAM17

GO:0043536

positive regulation of blood vessel endothelial cell migration

24813629

GeneADAM17

GO:0045121

membrane raft

17010968|17786981

GeneADAM17

GO:0045741

positive regulation of epidermal growth factor-activated receptor activity

12743035|18483258

GeneADAM17

GO:0071403

cellular response to high density lipoprotein particle stimulus

17786981

GeneADAM17

GO:1902945

metalloendopeptidase activity involved in amyloid precursor protein catabolic process

9774383

GeneADAM17

GO:1905564

positive regulation of vascular endothelial cell proliferation

24813629



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
P78536-1P78536-1_2oi0_A.pdb2OI0X-ray2.0A216477

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
P78536ADAM17P78536-1P78536-2824694695824Deletionnonenone694694

check buttonMultiple sequence alignment of our canonical and alternatively spliced ADAM17

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of ADAM17
UniProt-idENSGENSTENSP
P78536-1ENSG00000151694.15ENST00000310823.8ENSP00000309968.3

UniProt-idNM IDNP ID
P78536-1NM_003183.5NP_003174.3

check buttonAmino acid sequences of our canonical and alternatively spliced ADAM17
accession_idProtein sequence
P78536-1MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERF
SQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQS
PKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNA
GFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANS
HGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMF
SNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINA
TCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPC
TVGFCDMNGKCEKRVQDVIERFWDFIDQLSINTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMD
SASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKDPFPNSSTAAKSFEDLTDHPVTRSEKAASFK
P78536-2MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDLQTSTHVETLLTFSALKRHFKLYLTSSTERF
SQNFKVVVVDGKNESEYTVKWQDFFTGHVVGEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQS
PKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMGRGEESTTTNYLIELIDRVDDIYRNTSWDNA
GFKGYGIQIEQIRILKSPQEVKPGEKHYNMAKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANS
HGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGLAECAPNEDQGGKYVMYPIAVSGDHENNKMF
SNCSKQSIYKTIESKAQECFQERSNKVCGNSRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINA
TCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSCKVCCRDLSGRCVPYVDAEQKNLFLRKGKPC

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
ADAM17 (go to UniProt):P78536

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
P78536Topological domain693824Note=Cytoplasmic;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=695;End=824
P78536Region732824Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=695;End=824
P78536Motif731738Note=SH3-binding;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=695;End=824
P78536Motif741748Note=SH3-binding;Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=695;End=824
P78536Compositional bias734748Note=Pro residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=695;End=824
P78536Compositional bias757780Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=695;End=824
P78536Compositional bias795824Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=695;End=824


Gene Isoform Structures and Expression Levels for ADAM17

check buttonGene structures of our canonical and alternative spliced genes of ADAM17
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of ADAM17

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of P78536-1
3D view using mol* of P78536-2


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of P78536-1
all structure
pLDDT distribution across the protein length of P78536-2
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of P78536-1
all structure
Ramachandran plot of P78536-2
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
P78536-11.045801.083303.2120.5290.7820.9481.3870.6941.9981.414187,189,194,195,196,296,304,312,315,316,319,320,32
2,323,352,369,371,378,380
P78536-20.981621.019473.6830.6430.6340.7970.5480.9230.5941.068189,190,192,193,195,196,197,198,199,200,201,202,29
6,304,312,315,316,319,320,322,323,352,359,360,361,
368,369,370,371,372,373,377,378,380

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of P78536-1_P78536-1_2oi0_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P78536-1_2oi0_A_P78536-2.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P78536-1_P78536-2.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/P78536-1_vs_P78536-2.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/P78536-1_vs_P78536-2.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to ADAM17


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
P78536ADAM17DB07233N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophanexperimental
P78536ADAM17DB071214-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDEexperimental
P78536ADAM17DB070793-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiolexperimental
P78536ADAM17DB06943(3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiolexperimental
P78536ADAM17DB07145(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDEexperimental
P78536ADAM17DB07147methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylateexperimental
P78536ADAM17DB07964(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDEexperimental
P78536ADAM17DB07189(1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acidexperimental

Related Diseases to ADAM17


check button Previous studies relating to the alternative splicing of ADAM17 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in ADAM17


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance