InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ADAM17

Summary

InnateDB Protein

IDBP-27792.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ADAM17

Protein Name

ADAM metallopeptidase domain 17

Synonyms

ADAM18; CD156B; CSVP; NISBD; TACE;

Species

Homo sapiens

Ensembl Protein

ENSP00000309968

InnateDB Gene

IDBG-27788 (ADAM17)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:12441351, ECO:0000269PubMed:20592283, ECO:0000269PubMed:24226769, ECO:0000269PubMed:24227843}.

Subcellular Localization

Membrane; Single-pass type I membrane protein.

Disease Associations

Neonatal inflammatory skin and bowel disease (NISBD) [MIM:614328]: A 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. {ECO:0000269PubMed:22010916}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 26 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	27 [view]
Protein-Protein	26 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004222	metalloendopeptidase activity
GO:0005112	Notch binding
GO:0005138	interleukin-6 receptor binding
GO:0005178	integrin binding
GO:0005515	protein binding
GO:0008237	metallopeptidase activity
GO:0008270	zinc ion binding
GO:0017124	SH3 domain binding
GO:0030165	PDZ domain binding

Biological Process

GO:0001666	response to hypoxia
GO:0001934	positive regulation of protein phosphorylation
GO:0002446	neutrophil mediated immunity
GO:0002467	germinal center formation
GO:0002690	positive regulation of leukocyte chemotaxis
GO:0006508	proteolysis
GO:0006509	membrane protein ectodomain proteolysis
GO:0006915	apoptotic process
GO:0007155	cell adhesion
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007219	Notch signaling pathway
GO:0007220	Notch receptor processing
GO:0008284	positive regulation of cell proliferation
GO:0010820	positive regulation of T cell chemotaxis
GO:0022617	extracellular matrix disassembly
GO:0030183	B cell differentiation
GO:0030198	extracellular matrix organization
GO:0030307	positive regulation of cell growth
GO:0030335	positive regulation of cell migration
GO:0030511	positive regulation of transforming growth factor beta receptor signaling pathway
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0030574	collagen catabolic process
GO:0031293	membrane protein intracellular domain proteolysis
GO:0031659	positive regulation of cyclin-dependent protein kinase activity involved in G1/S
GO:0032496	response to lipopolysaccharide
GO:0032717	negative regulation of interleukin-8 production
GO:0032722	positive regulation of chemokine production
GO:0033025	regulation of mast cell apoptotic process
GO:0033077	T cell differentiation in thymus
GO:0033627	cell adhesion mediated by integrin
GO:0035313	wound healing, spreading of epidermal cells
GO:0035625	epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway
GO:0042493	response to drug
GO:0045741	positive regulation of epidermal growth factor-activated receptor activity
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048536	spleen development
GO:0048870	cell motility
GO:0051088	PMA-inducible membrane protein ectodomain proteolysis
GO:0051272	positive regulation of cellular component movement
GO:0055099	response to high density lipoprotein particle stimulus
GO:0060397	JAK-STAT cascade involved in growth hormone signaling pathway
GO:0097190	apoptotic signaling pathway

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0005911	cell-cell junction
GO:0005925	focal adhesion
GO:0009986	cell surface
GO:0015629	actin cytoskeleton
GO:0016020	membrane
GO:0016324	apical plasma membrane
GO:0032587	ruffle membrane
GO:0045121	membrane raft