ADAM17

Protein identityUniProt · HPA

UniProt accession

P78536

Gene

ADAM17

Ensembl

ENSG00000151694

Chromosome

2

Canonical length

824 aa

Protein class

CD markers, Disease related genes, Enzymes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biologic processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. The encoded preproprotein is proteolytically processed to generate the mature protease. The encoded protease functions in the ectodomain shedding of tumor necrosis factor-alpha, in which soluble tumor necrosis factor-alpha is released from the membrane-bound precursor. This protease also functions in the processing of numerous other substrates, including cell adhesion proteins, cytokine and growth factor receptors and epidermal growth factor (EGF) receptor ligands, and plays a prominent role in the activation of the Notch signaling pathway. Elevated expression of this gene has been observed in specific cell types derived from psoriasis, rheumatoid arthritis, multiple sclerosis and Crohn's disease patients, suggesting that the encoded protein may play a role in autoimmune disease. Additionally, this protease may play a role in viral infection through its cleavage of ACE2, the cellular receptor for SARS-CoV and SARS-CoV-2. [provided by RefSeq, Aug 2020]

Canonical amino-acid sequenceUniProt

824 residues, UniProt reviewed canonical sequence.

>P78536|ADAM17
     1  MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI QQHSVRKRDL
    61  QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD GKNESEYTVK WQDFFTGHVV
   121  GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS
   181  PKVCGYLKVD NEELLPKGLV DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG
   241  RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM
   301  AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS
   361  HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL
   421  AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN
   481  SRVDEGEECD PGIMYLNNDT CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA
   541  TCKGVSYCTG NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC
   601  KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS
   661  INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHP SNVEMLSSMD
   721  SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA APKLDHQRMD TIQEDPSTDS HMDEDGFEKD
   781  PFPNSSTAAK SFEDLTDHPV TRSEKAASFK LQRQNRVDSK ETEC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAM17 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.36

Highest tissue expression

18 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADAM17.

Disease | AllUniProt

Conditions ADAM17 is implicated in, by any mechanism.

• Inflammatory skin and bowel disease, neonatal, 1 (NISBD1) MIM:614328

Disease | GeneticClinVar

26 pathogenic / likely-pathogenic of 643 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Inflammatory skin and bowel disease, neonatal, 1
• Inborn genetic diseases
• Neonatal inflammatory skin and bowel disease

Disease | ImmuneIEDB

Conditions an epitope on ADAM17 was assayed in.

• ovarian cancer T cell
• prostate cancer T cell
• breast cancer T cell
• melanoma T cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.28

gnomAD pLI

1

gnomAD missense Z

2.45

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid precursor protein catabolic process
• B cell differentiation
• cell adhesion
• cell adhesion mediated by integrin
• cell motility
• cellular response to high density lipoprotein particle stimulus
• commissural neuron axon guidance
• cytokine precursor processing
• defense response to Gram-positive bacterium
• epidermal growth factor receptor signaling pathway
• ERBB2-EGFR signaling pathway
• germinal center formation
• membrane protein ectodomain proteolysis
• negative regulation of cold-induced thermogenesis
• negative regulation of neuron projection development
• negative regulation of transforming growth factor beta receptor signaling pathway
• neutrophil mediated immunity
• Notch receptor processing
• Notch signaling pathway
• phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of blood vessel endothelial cell migration
• positive regulation of cell growth
• positive regulation of cell migration
• positive regulation of cell population proliferation
• positive regulation of chemokine production
• positive regulation of epidermal growth factor receptor signaling pathway
• positive regulation of G1/S transition of mitotic cell cycle
• positive regulation of leukocyte chemotaxis
• positive regulation of T cell chemotaxis
• positive regulation of tumor necrosis factor production
• positive regulation of tumor necrosis factor-mediated signaling pathway
• positive regulation of vascular endothelial cell proliferation
• production of molecular mediator involved in inflammatory response
• protein processing
• proteolysis
• regulation of axon regeneration
• regulation of neuron migration
• response to hypoxia
• response to lipopolysaccharide
• response to xenobiotic stimulus
• signal release
• spleen development
• T cell differentiation in thymus
• wound healing, spreading of epidermal cells
• regulation of mast cell apoptotic process

Molecular functions

• cytokine binding
• endopeptidase activity
• integrin binding
• interleukin-6 receptor binding
• metal ion binding
• metallodipeptidase activity
• metalloendopeptidase activity
• metalloendopeptidase activity involved in amyloid precursor protein catabolic process
• metallopeptidase activity
• Notch binding
• PDZ domain binding
• peptidase activity
• SH3 domain binding
• tumor necrosis factor binding

Cellular components

• actin cytoskeleton
• apical plasma membrane
• cell surface
• cytoplasm
• cytosol
• endoplasmic reticulum lumen
• Golgi membrane
• membrane
• membrane raft
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M12B, ADAM/reprolysin
• Disintegrin domain
• Metallopeptidase, catalytic domain superfamily
• ADAM10/ADAM17 catalytic domain
• Disintegrin domain superfamily
• Disintegrin and Metalloproteinase Domain-Containing
• Disintegrin
• Metallo-peptidase family M12B Reprolysin-like
• ADAM17, membrane-proximal domain
• Membrane-proximal domain, switch, for ADAM17

KeywordsUniProt

• Cell membrane
• Cleavage on pair of basic residues
• Disulfide bond
• Glycoprotein
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Notch signaling pathway
• Phosphoprotein
• Protease
• SH3-binding
• Signal
• Transmembrane
• Transmembrane helix
• Zinc
• Zymogen

InteractionsUniProt · HPA

Protein binding partners of ADAM17 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FRMD8
• MAD2L1
• MAPK14
• MUC1
• TSPAN8
• DLG1
• TIMP3