Q10741 · ADA10_BOVIN
- ProteinDisintegrin and metalloproteinase domain-containing protein 10
- GeneADAM10
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids748 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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).
Cofactor
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 173 | Zn2+ (UniProtKB | ChEBI); catalytic; in inhibited form | ||||
Sequence: C | ||||||
Site | 213-214 | Cleavage; by furin and PCSK7 | ||||
Sequence: RT | ||||||
Binding site | 383 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Active site | 384 | |||||
Sequence: E | ||||||
Binding site | 387 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 393 | Zn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: H |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameDisintegrin and metalloproteinase domain-containing protein 10
- EC number
- Short namesADAM 10
- Alternative names
- CD Antigen Name
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Ruminantia > Pecora > Bovidae > Bovinae > Bos
Accessions
- Primary accessionQ10741
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Golgi apparatus membrane ; Single-pass type I membrane protein
Cell membrane ; Single-pass type I membrane protein
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 20-672 | Extracellular | ||||
Sequence: QYGNPLNKYIRHYEGLSYDVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSEEFRVETSNAVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTHGGTFYVEPAERYIKDRTLPFHSVIYHEDDIKYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQTPQEKHAINGPELLRKKRTTVAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHCAFKSKTEKCRDDSDCAKEGICNGITALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKHGLEECTCASSDGKDDKELCHVCCMKKMEPSTCASTGSVQWNKYFLGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAE | ||||||
Transmembrane | 673-696 | Helical | ||||
Sequence: WIVAYWWAVLLMGIALIMLMAGFI | ||||||
Topological domain | 697-748 | Cytoplasmic | ||||
Sequence: KICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 210-213 | Abolishes furin cleavage site, leading to defects in pro. | ||||
Sequence: RKKR → NAQA | ||||||
Mutagenesis | 384 | Decreased stimulated and constitutive secretion of APP. | ||||
Sequence: E → A | ||||||
Mutagenesis | 573 | Abrogates EFNA5 cleavage; when associated with Ala-578 and 579. | ||||
Sequence: E → A | ||||||
Mutagenesis | 578 | Abrogates EFNA5 cleavage; when associated with Ala-573 and 579. | ||||
Sequence: E → A | ||||||
Mutagenesis | 579 | Abrogates EFNA5 cleavage; when associated with Ala-573 and 578. | ||||
Sequence: E → A |
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.
PTM/Processing
Features
Showing features for signal, propeptide, chain, glycosylation, disulfide bond, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MVLLRVLILLLSWVAGLGG | ||||||
Propeptide | PRO_0000029064 | 20-213 | ||||
Sequence: QYGNPLNKYIRHYEGLSYDVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSEEFRVETSNAVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTHGGTFYVEPAERYIKDRTLPFHSVIYHEDDIKYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQTPQEKHAINGPELLRKKR | ||||||
Chain | PRO_0000029065 | 214-748 | Disintegrin and metalloproteinase domain-containing protein 10 | |||
Sequence: TTVAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHCAFKSKTEKCRDDSDCAKEGICNGITALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKHGLEECTCASSDGKDDKELCHVCCMKKMEPSTCASTGSVQWNKYFLGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAYWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR | ||||||
Glycosylation | 267 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 278 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 344↔451 | |||||
Sequence: CEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNC | ||||||
Disulfide bond | 399↔435 | |||||
Sequence: CTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLC | ||||||
Glycosylation | 439 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 460↔495 | |||||
Sequence: CGNGMVEQGEECDCGYSDQCKDECCYDANQPEGKKC | ||||||
Disulfide bond | 471↔484 | |||||
Sequence: CDCGYSDQCKDECC | ||||||
Disulfide bond | 473↔479 | |||||
Sequence: CGYSDQC | ||||||
Disulfide bond | 483↔515 | |||||
Sequence: CCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHC | ||||||
Disulfide bond | 503↔511 | |||||
Sequence: CSPSQGPCC | ||||||
Disulfide bond | 510↔536 | |||||
Sequence: CCTAHCAFKSKTEKCRDDSDCAKEGIC | ||||||
Disulfide bond | 524↔543 | |||||
Sequence: CRDDSDCAKEGICNGITALC | ||||||
Disulfide bond | 530↔562 | |||||
Sequence: CAKEGICNGITALCPASDPKPNFTDCNRHTQVC | ||||||
Glycosylation | 551 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 555↔567 | |||||
Sequence: CNRHTQVCINGQC | ||||||
Disulfide bond | 572↔598 | |||||
Sequence: CEKHGLEECTCASSDGKDDKELCHVCC | ||||||
Disulfide bond | 580↔607 | |||||
Sequence: CTCASSDGKDDKELCHVCCMKKMEPSTC | ||||||
Disulfide bond | 582↔597 | |||||
Sequence: CASSDGKDDKELCHVC | ||||||
Disulfide bond | 594↔639 | |||||
Sequence: CHVCCMKKMEPSTCASTGSVQWNKYFLGRTITLQPGSPCNDFRGYC | ||||||
Disulfide bond | 632↔645 | |||||
Sequence: CNDFRGYCDVFMRC | ||||||
Modified residue | 719 | Phosphothreonine | ||||
Sequence: T |
Post-translational modification
The precursor is cleaved by furin and PCSK7.
Keywords
- PTM
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).
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
Structure
Family & Domains
Features
Showing features for motif, domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 171-178 | Cysteine switch | ||||
Sequence: GGCADHSV | ||||||
Domain | 220-456 | Peptidase M12B | ||||
Sequence: NTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESG | ||||||
Domain | 457-551 | Disintegrin | ||||
Sequence: QPICGNGMVEQGEECDCGYSDQCKDECCYDANQPEGKKCKLKPGKQCSPSQGPCCTAHCAFKSKTEKCRDDSDCAKEGICNGITALCPASDPKPN | ||||||
Region | 704-748 | Disordered | ||||
Sequence: PSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR | ||||||
Compositional bias | 706-722 | Pro residues | ||||
Sequence: SNPKLPPPKPLPGTLKR | ||||||
Motif | 708-715 | SH3-binding | ||||
Sequence: PKLPPPKP | ||||||
Motif | 722-728 | SH3-binding | ||||
Sequence: RRRPPQP | ||||||
Region | 734-748 | Interaction with AP2A1, AP2A2 and AP2M1 | ||||
Sequence: RQRPRESYQMGHMRR |
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).
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
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length748
- Mass (Da)84,188
- Last updated1996-11-01 v1
- Checksum202E29830611F9E1
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A452DJA5 | A0A452DJA5_BOVIN | ADAM10 | 691 | ||
A0AAA9S4M7 | A0AAA9S4M7_BOVIN | ADAM10 | 72 | ||
A0AAA9TVF8 | A0AAA9TVF8_BOVIN | ADAM10 | 687 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 706-722 | Pro residues | ||||
Sequence: SNPKLPPPKPLPGTLKR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Z21961 EMBL· GenBank· DDBJ | CAA79973.1 EMBL· GenBank· DDBJ | mRNA | ||
BC153863 EMBL· GenBank· DDBJ | AAI53864.1 EMBL· GenBank· DDBJ | mRNA |