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Protein

Disintegrin and metalloproteinase domain-containing protein 17

Gene

ADAM17

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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

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.By similarity

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi90Zinc; catalyticBy similarity1
Active sitei91PROSITE-ProRule annotation1
Metal bindingi94Zinc; catalyticBy similarity1
Metal bindingi100Zinc; catalyticBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: BHF-UCL
  • Notch binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processNotch signaling pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.86 6170

Protein family/group databases

MEROPSiM12.217

Names & Taxonomyi

Protein namesi
Recommended name:
Disintegrin and metalloproteinase domain-containing protein 17 (EC:3.4.24.86By similarity)
Short name:
ADAM 17
Alternative name(s):
TNF-alpha convertase
TNF-alpha-converting enzyme
CD_antigen: CD156b
Gene namesi
Name:ADAM17
Synonyms:TACE
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
Proteomesi
  • UP000008227 Componenti: Unplaced

Subcellular locationi

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3332

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000078207‹1 – ›112Disintegrin and metalloproteinase domain-containing protein 17Add BLAST›112

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Phosphorylated.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO77636
PeptideAtlasiO77636
PRIDEiO77636

Interactioni

Subunit structurei

Interacts with MAD2L1, MAPK14 and MUC1.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000009208

Chemistry databases

BindingDBiO77636

Structurei

3D structure databases

ProteinModelPortaliO77636
SMRiO77636
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini‹1 – ›112Peptidase M12BPROSITE-ProRule annotationAdd BLAST›112

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

Phylogenomic databases

eggNOGiKOG3658 Eukaryota
ENOG410XQWB LUCA
InParanoidiO77636

Family and domain databases

Gene3Di3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Fragment.

O77636-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLREQFSFDI AEEASKVCLA HLFTYQDFDM GTLGLAYVGS PRANSHGGVC
60 70 80 90 100
PKAYYSPIGK KNIYLNSGLT STKNYGKTIL TKEADLVTTH ELGHNFGAEH
110
DPDGLAECAP NE
Length:112
Mass (Da):12,201
Last modified:November 1, 1998 - v1
Checksum:iB840FBE7C2EE69FC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Non-terminal residuei1121

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF069648 mRNA Translation: AAC23532.1
UniGeneiSsc.19668

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF069648 mRNA Translation: AAC23532.1
UniGeneiSsc.19668

3D structure databases

ProteinModelPortaliO77636
SMRiO77636
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000009208

Chemistry databases

BindingDBiO77636
ChEMBLiCHEMBL3332

Protein family/group databases

MEROPSiM12.217

Proteomic databases

PaxDbiO77636
PeptideAtlasiO77636
PRIDEiO77636

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiKOG3658 Eukaryota
ENOG410XQWB LUCA
InParanoidiO77636

Enzyme and pathway databases

BRENDAi3.4.24.86 6170

Family and domain databases

Gene3Di3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR024079 MetalloPept_cat_dom_sf
IPR001590 Peptidase_M12B
PROSITEiView protein in PROSITE
PS50215 ADAM_MEPRO, 1 hit
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA17_PIG
AccessioniPrimary (citable) accession number: O77636
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: November 1, 1998
Last modified: September 12, 2018
This is version 105 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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