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Protein

Disintegrin and metalloproteinase domain-containing protein 17

Gene

ADAM17

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-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 (By similarity). 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).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.

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

  • membrane protein ectodomain proteolysis Source: BHF-UCL
  • Notch receptor processing Source: UniProtKB
  • Notch signaling pathway Source: UniProtKB-KW
  • positive regulation of ERK1 and ERK2 cascade Source: AgBase
  • proteolysis Source: UniProtKB
  • tumor necrosis factor-mediated signaling pathway Source: AgBase

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:3.4.24.86)
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

GO - Cellular componenti

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.
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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: March 15, 2017
This is version 103 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