Q10741 · ADA10_BOVIN

  • Protein
    Disintegrin and metalloproteinase domain-containing protein 10
  • Gene
    ADAM10
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis. Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity (By similarity).
Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' 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 heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP) (PubMed:10097139).
Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (By similarity).
Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity).
Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (By similarity).
Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity).
Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (By similarity).
Enhances the cleavage of CHL1 by BACE1 (By similarity).
Cleaves NRCAM (By similarity).
Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (By similarity).
Involved in the development and maturation of glomerular and coronary vasculature (By similarity).
During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity).
May regulate the EFNA5-EPHA3 signaling (By similarity).
Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells (By similarity).

Catalytic activity

Cofactor

Zn2+ (UniProtKB | Rhea| CHEBI:29105 )

Note: Binds 1 zinc ion per subunit.

Activity regulation

Catalytically inactive when the propeptide is intact and associated with the mature enzyme (PubMed:11481247).
The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity).

Features

Showing features for binding site, site, active site.

TypeIDPosition(s)Description
Binding site173Zn2+ (UniProtKB | ChEBI); catalytic; in inhibited form
Site213-214Cleavage; by furin and PCSK7
Binding site383Zn2+ (UniProtKB | ChEBI); catalytic
Active site384
Binding site387Zn2+ (UniProtKB | ChEBI); catalytic
Binding site393Zn2+ (UniProtKB | ChEBI); catalytic

GO annotations

AspectTerm
Cellular Componentadherens junction
Cellular Componentaxon
Cellular Componentcell surface
Cellular Componentclathrin-coated vesicle
Cellular Componentcytoplasm
Cellular Componentdendrite
Cellular ComponentGolgi apparatus
Cellular ComponentGolgi membrane
Cellular ComponentGolgi-associated vesicle
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentsynaptic membrane
Molecular Functionendopeptidase activity
Molecular Functionmetal ion binding
Molecular Functionmetalloendopeptidase activity
Molecular Functionmetalloendopeptidase activity involved in amyloid precursor protein catabolic process
Molecular Functionmetallopeptidase activity
Molecular Functionprotein homodimerization activity
Molecular Functionprotein kinase binding
Molecular FunctionSH3 domain binding
Biological Processamyloid precursor protein catabolic process
Biological Processin utero embryonic development
Biological Processmembrane protein ectodomain proteolysis
Biological Processnegative regulation of cell adhesion
Biological ProcessNotch signaling pathway
Biological Processprotein phosphorylation
Biological Processprotein processing

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Disintegrin and metalloproteinase domain-containing protein 10
  • EC number
  • Short names
    ADAM 10
  • Alternative names
    • Kuzbanian protein homolog
    • Mammalian disintegrin-metalloprotease
    • Myelin-associated metalloproteinase
  • CD Antigen Name
    • CD156c

Gene names

    • Name
      ADAM10
    • Synonyms
      MADM

Organism names

  • Taxonomic identifier
  • Strain
    • Hereford
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos

Accessions

  • Primary accession
    Q10741
  • Secondary accessions
    • A8E663

Proteomes

Organism-specific databases

Subcellular Location

Golgi apparatus membrane
; Single-pass type I membrane protein
Cell membrane
; Single-pass type I membrane protein
Cell projection, axon
Cytoplasm
Note: Is localized in the plasma membrane but is also expressed in the Golgi apparatus and in clathrin-coated vesicles derived likely from the Golgi (By similarity).
During long term depression, it is recruited to the cell membrane by DLG1 (By similarity).
The immature form is mainly located near cytoplasmic fibrillar structures, while the mature form is predominantly located at zonula adherens and the cell membrane (By similarity).
The localization and clustering of mature ADAM10 to zonula adherens is regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain20-672Extracellular
Transmembrane673-696Helical
Topological domain697-748Cytoplasmic

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis210-213Abolishes furin cleavage site, leading to defects in pro.
Mutagenesis384Decreased stimulated and constitutive secretion of APP.
Mutagenesis573Abrogates EFNA5 cleavage; when associated with Ala-578 and 579.
Mutagenesis578Abrogates EFNA5 cleavage; when associated with Ala-573 and 579.
Mutagenesis579Abrogates EFNA5 cleavage; when associated with Ala-573 and 578.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 63 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for signal, propeptide, chain, glycosylation, disulfide bond, modified residue.

TypeIDPosition(s)Description
Signal1-19
PropeptidePRO_000002906420-213
ChainPRO_0000029065214-748Disintegrin and metalloproteinase domain-containing protein 10
Glycosylation267N-linked (GlcNAc...) asparagine
Glycosylation278N-linked (GlcNAc...) asparagine
Disulfide bond344↔451
Disulfide bond399↔435
Glycosylation439N-linked (GlcNAc...) asparagine
Disulfide bond460↔495
Disulfide bond471↔484
Disulfide bond473↔479
Disulfide bond483↔515
Disulfide bond503↔511
Disulfide bond510↔536
Disulfide bond524↔543
Disulfide bond530↔562
Glycosylation551N-linked (GlcNAc...) asparagine
Disulfide bond555↔567
Disulfide bond572↔598
Disulfide bond580↔607
Disulfide bond582↔597
Disulfide bond594↔639
Disulfide bond632↔645
Modified residue719Phosphothreonine

Post-translational modification

The precursor is cleaved by furin and PCSK7.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed at low level in kidney, spleen, lung, adrenal, heart and peripheral nerve.

Induction

By interleukin-1 alpha in nasal cartilage.

Gene expression databases

Interaction

Subunit

Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells (PubMed:16239146).
Interacts with the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (By similarity).
Forms a ternary complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens junctions (By similarity).
Interacts with EPHA2 (By similarity).
Interacts with NGF in a divalent cation-dependent manner. Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression. Interacts with TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity, endocytosis and turnover (PubMed:23035126).
Interacts (via extracellular domain) with TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula adherens through a PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (By similarity).
Interacts with DLG1; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (By similarity).
Interacts (via extracellular domain) with BACE1 (via extracellular domain) (By similarity).
Interacts with FAM171A1 (By similarity).

Protein-protein interaction databases

Family & Domains

Features

Showing features for motif, domain, region, compositional bias.

TypeIDPosition(s)Description
Motif171-178Cysteine switch
Domain220-456Peptidase M12B
Domain457-551Disintegrin
Region704-748Disordered
Compositional bias706-722Pro residues
Motif708-715SH3-binding
Motif722-728SH3-binding
Region734-748Interaction with AP2A1, AP2A2 and AP2M1

Domain

The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins PubMed:16239146. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 (By similarity).
Stalk region is sufficient for interaction with TSPAN15 (By similarity).
The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    748
  • Mass (Da)
    84,188
  • Last updated
    1996-11-01 v1
  • Checksum
    202E29830611F9E1
MVLLRVLILLLSWVAGLGGQYGNPLNKYIRHYEGLSYDVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSEEFRVETSNAVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTHGGTFYVEPAERYIKDRTLPFHSVIYHEDDIKYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQTPQEKHAINGPELLRKKRTTVAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHCAFKSKTEKCRDDSDCAKEGICNGITALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKHGLEECTCASSDGKDDKELCHVCCMKKMEPSTCASTGSVQWNKYFLGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAYWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A452DJA5A0A452DJA5_BOVINADAM10691
A0AAA9S4M7A0AAA9S4M7_BOVINADAM1072
A0AAA9TVF8A0AAA9TVF8_BOVINADAM10687

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias706-722Pro residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
Z21961
EMBL· GenBank· DDBJ
CAA79973.1
EMBL· GenBank· DDBJ
mRNA
BC153863
EMBL· GenBank· DDBJ
AAI53864.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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