LipidDB ID

LipidDB-9606-00554

Entry Name

UniProt Accession

P78536; O60226;

Theoretical PI

5.5

Molecular Weight

93020.96

Genbank Protein ID

AAB51586.1; AAB51514.1; AAB53014.1; AAC39721.1;

Genbank Nucleotide ID

U86755; U69611; U69612; U92649;

Protein Name

Disintegrin and metalloproteinase domain-containing protein 17

Protein Synonyms/Alias

ADAM 17; 3.4.24.86; Snake venom-like protease; TNF-alpha convertase; TNF-alpha-converting enzyme; CD156b;

Gene Name

ADAM17

Gene Synonyms/Alias

CSVP; TACE;

Created Date

20-JUN-2001

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Predicted from GPS-Lipid

Functional Description

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.

Sequence Annotation

Topological domain: 215 671 Extracellular.
Transmembrane: 672 692 Helical.
Topological domain: 693 824 Cytoplasmic.
Domain: 223 474 Peptidase M12B.
Domain: 475 563 Disintegrin.
Region: 603 671 Crambin-like.
Motif: 182 189 Cysteine switch.
Motif: 731 738 SH3-binding.
Motif: 741 748 SH3-binding.
Active site: 406 406
Metal binding site: 184 184 Zinc; in inhibited form.
Metal binding site: 405 405 Zinc; catalytic.
Metal binding site: 409 409 Zinc; catalytic.
Metal binding site: 415 415 Zinc; catalytic.
Modified residue: 735 735 Phosphothreonine; by MAPK14.
Modified residue: 791 791 Phosphoserine.
Modified residue: 819 819 Phosphoserine.

Protein Length

824 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL
GO:0016324; C:apical plasma membrane; IDA:BHF-UCL
GO:0009986; C:cell surface; IDA:BHF-UCL
GO:0005737; C:cytoplasm; IDA:HPA
GO:0005887; C:integral component of plasma membrane; IDA:BHF-UCL
GO:0016020; C:membrane; IDA:UniProtKB
GO:0045121; C:membrane raft; IDA:BHF-UCL
GO:0005886; C:plasma membrane; TAS:Reactome
GO:0005178; F:integrin binding; IPI:BHF-UCL
GO:0005138; F:interleukin-6 receptor binding; IPI:BHF-UCL
GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB
GO:0008237; F:metallopeptidase activity; IDA:BHF-UCL
GO:0005112; F:Notch binding; IDA:UniProtKB
GO:0030165; F:PDZ domain binding; IPI:BHF-UCL
GO:0008270; F:zinc ion binding; IEA:InterPro
GO:0006915; P:apoptotic process; TAS:Reactome
GO:0097190; P:apoptotic signaling pathway; TAS:Reactome
GO:0030183; P:B cell differentiation; ISS:BHF-UCL
GO:0007155; P:cell adhesion; IDA:BHF-UCL
GO:0033627; P:cell adhesion mediated by integrin; IDA:BHF-UCL
GO:0048870; P:cell motility; ISS:BHF-UCL
GO:0030574; P:collagen catabolic process; TAS:Reactome
GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:BHF-UCL
GO:0035625; P:epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway; IMP:BHF-UCL
GO:0022617; P:extracellular matrix disassembly; TAS:Reactome
GO:0030198; P:extracellular matrix organization; TAS:Reactome
GO:0002467; P:germinal center formation; ISS:BHF-UCL
GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome
GO:0006509; P:membrane protein ectodomain proteolysis; IDA:BHF-UCL
GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome
GO:0032717; P:negative regulation of interleukin-8 production; IMP:BHF-UCL
GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:UniProt
GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome
GO:0002446; P:neutrophil mediated immunity; IC:BHF-UCL
GO:0007220; P:Notch receptor processing; IDA:UniProtKB
GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW
GO:0051088; P:PMA-inducible membrane protein ectodomain proteolysis; IDA:BHF-UCL
GO:0030307; P:positive regulation of cell growth; IMP:BHF-UCL
GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL
GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL
GO:0051272; P:positive regulation of cellular component movement; ISS:BHF-UCL
GO:0032722; P:positive regulation of chemokine production; IMP:BHF-UCL
GO:0031659; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle; IDA:BHF-UCL
GO:0045741; P:positive regulation of epidermal growth factor-activated receptor activity; IDA:BHF-UCL
GO:0002690; P:positive regulation of leukocyte chemotaxis; IC:BHF-UCL
GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL
GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL
GO:0030511; P:positive regulation of transforming growth factor beta receptor signaling pathway; ISS:BHF-UCL
GO:0006508; P:proteolysis; IDA:UniProtKB
GO:0033025; P:regulation of mast cell apoptotic process; ISS:BHF-UCL
GO:0042493; P:response to drug; ISS:BHF-UCL
GO:0055099; P:response to high density lipoprotein particle; IDA:BHF-UCL
GO:0001666; P:response to hypoxia; IDA:BHF-UCL
GO:0032496; P:response to lipopolysaccharide; IDA:BHF-UCL
GO:0048536; P:spleen development; ISS:BHF-UCL
GO:0033077; P:T cell differentiation in thymus; ISS:BHF-UCL
GO:0035313; P:wound healing, spreading of epidermal cells; IEP:BHF-UCL

Interpro

InterPro; IPR001762; Blood-coag_inhib_Disintegrin
InterPro; IPR024079; MetalloPept_cat_dom
InterPro; IPR001590; Peptidase_M12B
InterPro; IPR002870; Peptidase_M12B_N

Pfam

Pfam; PF00200; Disintegrin;
Pfam; PF01562; Pep_M12B_propep;

SMART

SMART; SM00050; DISIN;

PROSITE

PROSITE; PS50215; ADAM_MEPRO;
PROSITE; PS50214; DISINTEGRIN_2;
PROSITE; PS00142; ZINC_PROTEASE;

PRINTS