UniProtKB - P78536 (ADA17_HUMAN)
Protein
Disintegrin and metalloproteinase domain-containing protein 17
Gene
ADAM17
Organism
Homo sapiens (Human)
Status
Functioni
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). 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 (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). 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 (PubMed:26876177, PubMed:28060820).By similarity7 Publications
Catalytic activityi
- 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 (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.3 Publications EC:3.4.24.86
Cofactori
Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 184 | Zinc; in inhibited formBy similarity | 1 | |
Metal bindingi | 405 | Zinc; catalytic1 Publication | 1 | |
Active sitei | 406 | PROSITE-ProRule annotation1 Publication | 1 | |
Metal bindingi | 409 | Zinc; catalytic1 Publication | 1 | |
Metal bindingi | 415 | Zinc; catalytic1 Publication | 1 |
GO - Molecular functioni
- endopeptidase activity Source: UniProtKB
- integrin binding Source: BHF-UCL
- interleukin-6 receptor binding Source: BHF-UCL
- metal ion binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: UniProtKB
- metallopeptidase activity Source: BHF-UCL
- Notch binding Source: UniProtKB
- PDZ domain binding Source: BHF-UCL
- peptidase activity Source: ARUK-UCL
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- B cell differentiation Source: BHF-UCL
- cell adhesion Source: BHF-UCL
- cell adhesion mediated by integrin Source: BHF-UCL
- cell motility Source: BHF-UCL
- cellular response to high density lipoprotein particle stimulus Source: BHF-UCL
- defense response to Gram-positive bacterium Source: BHF-UCL
- epidermal growth factor receptor signaling pathway Source: BHF-UCL
- germinal center formation Source: BHF-UCL
- membrane protein ectodomain proteolysis Source: BHF-UCL
- membrane protein intracellular domain proteolysis Source: Reactome
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
- neutrophil mediated immunity Source: BHF-UCL
- Notch receptor processing Source: UniProtKB
- Notch signaling pathway Source: GO_Central
- positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
- positive regulation of cell growth Source: BHF-UCL
- positive regulation of cell migration Source: ARUK-UCL
- positive regulation of cell population proliferation Source: BHF-UCL
- positive regulation of cellular component movement Source: BHF-UCL
- positive regulation of chemokine production Source: BHF-UCL
- positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
- positive regulation of epidermal growth factor-activated receptor activity Source: BHF-UCL
- positive regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
- positive regulation of leukocyte chemotaxis Source: BHF-UCL
- positive regulation of protein phosphorylation Source: BHF-UCL
- positive regulation of T cell chemotaxis Source: BHF-UCL
- positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCL
- positive regulation of tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
- positive regulation of vascular endothelial cell proliferation Source: BHF-UCL
- proteolysis Source: UniProtKB
- receptor transactivation Source: BHF-UCL
- regulation of mast cell apoptotic process Source: BHF-UCL
- response to drug Source: BHF-UCL
- response to hypoxia Source: BHF-UCL
- response to lipopolysaccharide Source: BHF-UCL
- spleen development Source: BHF-UCL
- T cell differentiation in thymus Source: BHF-UCL
- tumor necrosis factor-mediated signaling pathway Source: Reactome
- wound healing, spreading of epidermal cells Source: BHF-UCL
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Biological process | Notch signaling pathway |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.24.86, 2681 |
PathwayCommonsi | P78536 |
Reactomei | R-HSA-1251985, Nuclear signaling by ERBB4 R-HSA-1442490, Collagen degradation R-HSA-177929, Signaling by EGFR R-HSA-193692, Regulated proteolysis of p75NTR R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2660826, Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691232, Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-5362798, Release of Hh-Np from the secreting cell R-HSA-75893, TNF signaling R-HSA-9662834, CD163 mediating an anti-inflammatory response R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | P78536 |
SIGNORi | P78536 |
Protein family/group databases
MEROPSi | M12.217 |
TCDBi | 8.A.77.1.2, the sheddase (sheddase) family |
Names & Taxonomyi
Protein namesi | Recommended name: Disintegrin and metalloproteinase domain-containing protein 17 (EC:3.4.24.863 Publications)Short name: ADAM 17 Alternative name(s): Snake venom-like protease TNF-alpha convertase TNF-alpha-converting enzyme CD_antigen: CD156b |
Gene namesi | Name:ADAM17 Synonyms:CSVP, TACE |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:195, ADAM17 |
MIMi | 603639, gene |
neXtProti | NX_P78536 |
VEuPathDBi | HostDB:ENSG00000151694.12 |
Subcellular locationi
Other locations
Cytoskeleton
- actin cytoskeleton Source: BHF-UCL
Cytosol
- cytosol Source: HPA
Plasma Membrane
- apical plasma membrane Source: BHF-UCL
- integral component of plasma membrane Source: BHF-UCL
- plasma membrane Source: GO_Central
Other locations
- cell surface Source: BHF-UCL
- cytoplasm Source: BHF-UCL
- membrane Source: UniProtKB
- membrane raft Source: BHF-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 215 – 671 | ExtracellularSequence analysisAdd BLAST | 457 | |
Transmembranei | 672 – 692 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 693 – 824 | CytoplasmicSequence analysisAdd BLAST | 132 |
Keywords - Cellular componenti
MembranePathology & Biotechi
Involvement in diseasei
Inflammatory skin and bowel disease, neonatal, 1 (NISBD1)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA disorder characterized by inflammatory features with neonatal onset, involving the skin, hair, and gut. The skin lesions involve perioral and perianal erythema, psoriasiform erythroderma, with flares of erythema, scaling, and widespread pustules. Gastrointestinal symptoms include malabsorptive diarrhea that is exacerbated by intercurrent gastrointestinal infections. The hair is short or broken, and the eyelashes and eyebrows are wiry and disorganized.
Related information in OMIMOrganism-specific databases
DisGeNETi | 6868 |
MalaCardsi | ADAM17 |
MIMi | 614328, phenotype |
OpenTargetsi | ENSG00000151694 |
Orphaneti | 294023, Neonatal inflammatory skin and bowel disease |
PharmGKBi | PA24512 |
Miscellaneous databases
Pharosi | P78536, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3706 |
DrugBanki | DB07189, (1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acid DB07145, (2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE DB06943, (3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiol DB07964, (3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE DB07079, 3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol DB07121, 4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE DB07147, methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylate DB07233, N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan |
DrugCentrali | P78536 |
GuidetoPHARMACOLOGYi | 1662 |
Genetic variation databases
BioMutai | ADAM17 |
DMDMi | 14423632 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | By similarityAdd BLAST | 17 | |
PropeptideiPRO_0000029088 | 18 – 214 | 1 PublicationAdd BLAST | 197 | |
ChainiPRO_0000029089 | 215 – 824 | Disintegrin and metalloproteinase domain-containing protein 17Add BLAST | 610 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 103 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 157 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 174 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 225 ↔ 333 | 1 Publication | ||
Glycosylationi | 264 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 365 ↔ 469 | 1 Publication | ||
Disulfide bondi | 423 ↔ 453 | 1 Publication | ||
Glycosylationi | 452 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 498 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 534 ↔ 555 | By similarity | ||
Glycosylationi | 539 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 551 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 573 ↔ 582 | By similarity | ||
Disulfide bondi | 578 ↔ 591 | By similarity | ||
Disulfide bondi | 593 ↔ 600 | By similarity | ||
Glycosylationi | 594 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 735 | Phosphothreonine; by MAPK142 Publications | 1 | |
Modified residuei | 761 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 767 | PhosphoserineBy similarity | 1 | |
Modified residuei | 791 | PhosphoserineCombined sources | 1 | |
Modified residuei | 819 | Phosphoserine1 Publication | 1 |
Post-translational modificationi
The precursor is cleaved by a furin endopeptidase.By similarity
Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at THR-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.3 Publications
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, ZymogenProteomic databases
CPTACi | CPTAC-1561 |
EPDi | P78536 |
jPOSTi | P78536 |
MassIVEi | P78536 |
MaxQBi | P78536 |
PaxDbi | P78536 |
PeptideAtlasi | P78536 |
PRIDEi | P78536 |
ProteomicsDBi | 57637 [P78536-1] 57638 [P78536-2] |
PTM databases
GlyConnecti | 1180, 18 N-Linked glycans (5 sites) |
GlyGeni | P78536, 10 sites, 2 N-linked glycans (1 site) |
iPTMneti | P78536 |
PhosphoSitePlusi | P78536 |
SwissPalmi | P78536 |
Expressioni
Tissue specificityi
Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney.
Inductioni
In arthritis-affected cartilage.
Gene expression databases
Bgeei | ENSG00000151694, Expressed in oocyte and 255 other tissues |
ExpressionAtlasi | P78536, baseline and differential |
Genevisiblei | P78536, HS |
Organism-specific databases
HPAi | ENSG00000151694, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsP78536
With | #Exp. | IntAct |
---|---|---|
DLG1 [Q12959] | 7 | EBI-78188,EBI-357481 |
ITGB1 [P05556] | 2 | EBI-78188,EBI-703066 |
MAD2L1 [Q13257] | 3 | EBI-78188,EBI-78203 |
Rhbdf2 [Q80WQ6] from Mus musculus. | 2 | EBI-78188,EBI-647271 |
GO - Molecular functioni
- integrin binding Source: BHF-UCL
- interleukin-6 receptor binding Source: BHF-UCL
- Notch binding Source: UniProtKB
- PDZ domain binding Source: BHF-UCL
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 112731, 36 interactors |
DIPi | DIP-31044N |
IntActi | P78536, 30 interactors |
MINTi | P78536 |
STRINGi | 9606.ENSP00000309968 |
Chemistry databases
BindingDBi | P78536 |
Miscellaneous databases
RNActi | P78536, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | P78536 |
SMRi | P78536 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P78536 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 223 – 474 | Peptidase M12BPROSITE-ProRule annotationAdd BLAST | 252 | |
Domaini | 475 – 563 | DisintegrinPROSITE-ProRule annotationAdd BLAST | 89 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 603 – 671 | Crambin-likeAdd BLAST | 69 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 182 – 189 | Cysteine switchBy similarity | 8 | |
Motifi | 731 – 738 | SH3-bindingSequence analysis | 8 | |
Motifi | 741 – 748 | SH3-bindingSequence analysis | 8 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 96 – 99 | Poly-Val | 4 | |
Compositional biasi | 564 – 602 | Cys-richAdd BLAST | 39 |
Domaini
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).By similarity
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.
Keywords - Domaini
SH3-binding, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3658, Eukaryota |
GeneTreei | ENSGT00940000155443 |
HOGENOMi | CLU_004602_2_0_1 |
InParanoidi | P78536 |
OMAi | FYHGRVF |
PhylomeDBi | P78536 |
TreeFami | TF314733 |
Family and domain databases
CDDi | cd14246, ADAM17_MPD, 1 hit cd04270, ZnMc_TACE_like, 1 hit |
Gene3Di | 3.40.390.10, 1 hit 4.10.70.10, 1 hit |
InterProi | View protein in InterPro IPR034025, ADAM10_ADAM17 IPR032029, ADAM17_MPD IPR001762, Disintegrin_dom IPR036436, Disintegrin_dom_sf IPR024079, MetalloPept_cat_dom_sf IPR001590, Peptidase_M12B IPR002870, Peptidase_M12B_N |
Pfami | View protein in Pfam PF16698, ADAM17_MPD, 1 hit PF00200, Disintegrin, 1 hit PF01562, Pep_M12B_propep, 1 hit |
SMARTi | View protein in SMART SM00050, DISIN, 1 hit |
SUPFAMi | SSF57552, SSF57552, 1 hit |
PROSITEi | View protein in PROSITE PS50215, ADAM_MEPRO, 1 hit PS50214, DISINTEGRIN_2, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All
Isoform A (identifier: P78536-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI
60 70 80 90 100
QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD
110 120 130 140 150
GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE
160 170 180 190 200
PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV
210 220 230 240 250
DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY
260 270 280 290 300
LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM
310 320 330 340 350
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL
360 370 380 390 400
AYVGSPRANS HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD
410 420 430 440 450
LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF
460 470 480 490 500
SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT
510 520 530 540 550
CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG
560 570 580 590 600
NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC
610 620 630 640 650
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE
660 670 680 690 700
RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK
710 720 730 740 750
QYESLSLFHP SNVEMLSSMD SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA
760 770 780 790 800
APKLDHQRMD TIQEDPSTDS HMDEDGFEKD PFPNSSTAAK SFEDLTDHPV
810 820
TRSEKAASFK LQRQNRVDSK ETEC
Computationally mapped potential isoform sequencesi
There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA6H8L4 | A6H8L4_HUMAN | ADAM17 protein | ADAM17 | 258 | Annotation score: | ||
A0A3B3IST4 | A0A3B3IST4_HUMAN | Disintegrin and metalloproteinase d... | ADAM17 | 56 | Annotation score: | ||
A0A3B3ITB5 | A0A3B3ITB5_HUMAN | Disintegrin and metalloproteinase d... | ADAM17 | 59 | Annotation score: | ||
A0A3B3ITW9 | A0A3B3ITW9_HUMAN | Disintegrin and metalloproteinase d... | ADAM17 | 38 | Annotation score: | ||
A0A3B3ISQ1 | A0A3B3ISQ1_HUMAN | Disintegrin and metalloproteinase d... | ADAM17 | 181 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 109 | V → A in AAC39721 (PubMed:9574564).Curated | 1 | |
Sequence conflicti | 563 | D → N in AAC39721 (PubMed:9574564).Curated | 1 | |
Sequence conflicti | 801 | T → A in AAC39721 (PubMed:9574564).Curated | 1 | |
Sequence conflicti | 818 | D → N in AAC39721 (PubMed:9574564).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051586 | 162 | K → E. Corresponds to variant dbSNP:rs34431503EnsemblClinVar. | 1 | |
Natural variantiVAR_051587 | 202 | R → G. Corresponds to variant dbSNP:rs2230818EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_005478 | 695 – 824 | Missing in isoform B. 1 PublicationAdd BLAST | 130 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U86755 mRNA Translation: AAB51586.1 U69611 mRNA Translation: AAB51514.1 U69612 mRNA Translation: AAB53014.1 U92649 mRNA Translation: AAC39721.1 |
CCDSi | CCDS1665.1 [P78536-1] |
RefSeqi | NP_003174.3, NM_003183.5 [P78536-1] |
Genome annotation databases
Ensembli | ENST00000310823; ENSP00000309968; ENSG00000151694 [P78536-1] |
GeneIDi | 6868 |
KEGGi | hsa:6868 |
UCSCi | uc002qzu.5, human [P78536-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Wikipedia Tumor necrosis factor alpha-converting enzyme entry |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U86755 mRNA Translation: AAB51586.1 U69611 mRNA Translation: AAB51514.1 U69612 mRNA Translation: AAB53014.1 U92649 mRNA Translation: AAC39721.1 |
CCDSi | CCDS1665.1 [P78536-1] |
RefSeqi | NP_003174.3, NM_003183.5 [P78536-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1BKC | X-ray | 2.00 | A/C/E/I | 219-474 | [»] | |
1ZXC | X-ray | 2.28 | A/B | 215-477 | [»] | |
2A8H | X-ray | 2.30 | A/B | 215-477 | [»] | |
2DDF | X-ray | 1.70 | A/B | 218-474 | [»] | |
2FV5 | X-ray | 2.10 | A/B | 216-475 | [»] | |
2FV9 | X-ray | 2.02 | A/B | 218-475 | [»] | |
2I47 | X-ray | 1.90 | A/B/C/D | 212-492 | [»] | |
2M2F | NMR | - | A | 581-642 | [»] | |
2OI0 | X-ray | 2.00 | A | 216-477 | [»] | |
3B92 | X-ray | 2.00 | A | 216-474 | [»] | |
3CKI | X-ray | 2.30 | A | 219-474 | [»] | |
3E8R | X-ray | 1.90 | A/B | 215-477 | [»] | |
3EDZ | X-ray | 1.90 | A/B | 215-477 | [»] | |
3EWJ | X-ray | 1.80 | A/B | 215-477 | [»] | |
3G42 | X-ray | 2.10 | A/B/C/D | 212-492 | [»] | |
3KMC | X-ray | 1.80 | A/B | 215-476 | [»] | |
3KME | X-ray | 1.85 | A/B | 215-476 | [»] | |
3L0T | X-ray | 1.92 | A/B | 215-476 | [»] | |
3L0V | X-ray | 1.75 | A/B | 215-476 | [»] | |
3LE9 | X-ray | 1.85 | A/B | 215-476 | [»] | |
3LEA | X-ray | 2.00 | A/B | 215-476 | [»] | |
3LGP | X-ray | 1.90 | A/B | 215-476 | [»] | |
3O64 | X-ray | 1.88 | A/B | 215-476 | [»] | |
BMRBi | P78536 | |||||
SMRi | P78536 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112731, 36 interactors |
DIPi | DIP-31044N |
IntActi | P78536, 30 interactors |
MINTi | P78536 |
STRINGi | 9606.ENSP00000309968 |
Chemistry databases
BindingDBi | P78536 |
ChEMBLi | CHEMBL3706 |
DrugBanki | DB07189, (1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acid DB07145, (2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDE DB06943, (3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiol DB07964, (3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE DB07079, 3-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiol DB07121, 4-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDE DB07147, methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylate DB07233, N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophan |
DrugCentrali | P78536 |
GuidetoPHARMACOLOGYi | 1662 |
Protein family/group databases
MEROPSi | M12.217 |
TCDBi | 8.A.77.1.2, the sheddase (sheddase) family |
PTM databases
GlyConnecti | 1180, 18 N-Linked glycans (5 sites) |
GlyGeni | P78536, 10 sites, 2 N-linked glycans (1 site) |
iPTMneti | P78536 |
PhosphoSitePlusi | P78536 |
SwissPalmi | P78536 |
Genetic variation databases
BioMutai | ADAM17 |
DMDMi | 14423632 |
Proteomic databases
CPTACi | CPTAC-1561 |
EPDi | P78536 |
jPOSTi | P78536 |
MassIVEi | P78536 |
MaxQBi | P78536 |
PaxDbi | P78536 |
PeptideAtlasi | P78536 |
PRIDEi | P78536 |
ProteomicsDBi | 57637 [P78536-1] 57638 [P78536-2] |
Protocols and materials databases
ABCDi | P78536, 34 sequenced antibodies |
Antibodypediai | 2540, 917 antibodies |
DNASUi | 6868 |
Genome annotation databases
Ensembli | ENST00000310823; ENSP00000309968; ENSG00000151694 [P78536-1] |
GeneIDi | 6868 |
KEGGi | hsa:6868 |
UCSCi | uc002qzu.5, human [P78536-1] |
Organism-specific databases
CTDi | 6868 |
DisGeNETi | 6868 |
GeneCardsi | ADAM17 |
HGNCi | HGNC:195, ADAM17 |
HPAi | ENSG00000151694, Low tissue specificity |
MalaCardsi | ADAM17 |
MIMi | 603639, gene 614328, phenotype |
neXtProti | NX_P78536 |
OpenTargetsi | ENSG00000151694 |
Orphaneti | 294023, Neonatal inflammatory skin and bowel disease |
PharmGKBi | PA24512 |
VEuPathDBi | HostDB:ENSG00000151694.12 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3658, Eukaryota |
GeneTreei | ENSGT00940000155443 |
HOGENOMi | CLU_004602_2_0_1 |
InParanoidi | P78536 |
OMAi | FYHGRVF |
PhylomeDBi | P78536 |
TreeFami | TF314733 |
Enzyme and pathway databases
BRENDAi | 3.4.24.86, 2681 |
PathwayCommonsi | P78536 |
Reactomei | R-HSA-1251985, Nuclear signaling by ERBB4 R-HSA-1442490, Collagen degradation R-HSA-177929, Signaling by EGFR R-HSA-193692, Regulated proteolysis of p75NTR R-HSA-2122948, Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2660826, Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691232, Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-5362798, Release of Hh-Np from the secreting cell R-HSA-75893, TNF signaling R-HSA-9662834, CD163 mediating an anti-inflammatory response R-HSA-982772, Growth hormone receptor signaling |
SignaLinki | P78536 |
SIGNORi | P78536 |
Miscellaneous databases
BioGRID-ORCSi | 6868, 7 hits in 882 CRISPR screens |
ChiTaRSi | ADAM17, human |
EvolutionaryTracei | P78536 |
GeneWikii | ADAM17 |
GenomeRNAii | 6868 |
Pharosi | P78536, Tchem |
PROi | PR:P78536 |
RNActi | P78536, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000151694, Expressed in oocyte and 255 other tissues |
ExpressionAtlasi | P78536, baseline and differential |
Genevisiblei | P78536, HS |
Family and domain databases
CDDi | cd14246, ADAM17_MPD, 1 hit cd04270, ZnMc_TACE_like, 1 hit |
Gene3Di | 3.40.390.10, 1 hit 4.10.70.10, 1 hit |
InterProi | View protein in InterPro IPR034025, ADAM10_ADAM17 IPR032029, ADAM17_MPD IPR001762, Disintegrin_dom IPR036436, Disintegrin_dom_sf IPR024079, MetalloPept_cat_dom_sf IPR001590, Peptidase_M12B IPR002870, Peptidase_M12B_N |
Pfami | View protein in Pfam PF16698, ADAM17_MPD, 1 hit PF00200, Disintegrin, 1 hit PF01562, Pep_M12B_propep, 1 hit |
SMARTi | View protein in SMART SM00050, DISIN, 1 hit |
SUPFAMi | SSF57552, SSF57552, 1 hit |
PROSITEi | View protein in PROSITE PS50215, ADAM_MEPRO, 1 hit PS50214, DISINTEGRIN_2, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ADA17_HUMAN | |
Accessioni | P78536Primary (citable) accession number: P78536 Secondary accession number(s): O60226 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2001 |
Last sequence update: | May 1, 1997 | |
Last modified: | February 10, 2021 | |
This is version 229 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references