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O14672

- ADA10_HUMAN

UniProt

O14672 - ADA10_HUMAN

Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

ADAM10

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 148 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    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. Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP). 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. Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. 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. May regulate the EFNA5-EPHA3 signaling.8 Publications

    Catalytic activityi

    Endopeptidase of broad specificity.

    Cofactori

    Binds 1 zinc ion.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi173 – 1731Zinc; in inhibited formBy similarity
    Metal bindingi383 – 3831Zinc; catalytic
    Active sitei384 – 3841
    Metal bindingi387 – 3871Zinc; catalytic
    Metal bindingi393 – 3931Zinc; catalytic

    GO - Molecular functioni

    1. endopeptidase activity Source: UniProtKB
    2. integrin binding Source: UniProtKB
    3. metalloendopeptidase activity Source: UniProtKB
    4. metallopeptidase activity Source: UniProtKB
    5. protein binding Source: BHF-UCL
    6. protein homodimerization activity Source: UniProtKB
    7. protein kinase binding Source: UniProtKB
    8. receptor binding Source: UniProtKB
    9. zinc ion binding Source: InterPro

    GO - Biological processi

    1. cell-cell signaling Source: UniProtKB
    2. cell death Source: UniProtKB-KW
    3. collagen catabolic process Source: Reactome
    4. constitutive protein ectodomain proteolysis Source: UniProtKB
    5. epidermal growth factor receptor signaling pathway Source: Reactome
    6. extracellular matrix disassembly Source: Reactome
    7. extracellular matrix organization Source: Reactome
    8. integrin-mediated signaling pathway Source: UniProtKB
    9. in utero embryonic development Source: UniProtKB
    10. membrane protein ectodomain proteolysis Source: UniProtKB
    11. monocyte activation Source: BHF-UCL
    12. negative regulation of cell adhesion Source: UniProtKB
    13. Notch receptor processing Source: Reactome
    14. Notch signaling pathway Source: UniProtKB
    15. PMA-inducible membrane protein ectodomain proteolysis Source: BHF-UCL
    16. positive regulation of cell growth Source: BHF-UCL
    17. positive regulation of cell migration Source: BHF-UCL
    18. positive regulation of cell proliferation Source: BHF-UCL
    19. positive regulation of T cell chemotaxis Source: BHF-UCL
    20. protein phosphorylation Source: UniProtKB
    21. response to tumor necrosis factor Source: BHF-UCL

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Biological processi

    Notch signaling pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:ENSG00000137845-MONOMER.
    BRENDAi3.4.24.81. 2681.
    ReactomeiREACT_118572. Degradation of the extracellular matrix.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_150401. Collagen degradation.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_9417. Signaling by EGFR.
    SignaLinkiO14672.

    Protein family/group databases

    MEROPSiM12.210.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Disintegrin and metalloproteinase domain-containing protein 10 (EC:3.4.24.81)
    Short name:
    ADAM 10
    Alternative name(s):
    CDw156
    Kuzbanian protein homolog
    Mammalian disintegrin-metalloprotease
    CD_antigen: CD156c
    Gene namesi
    Name:ADAM10
    Synonyms:KUZ, MADM
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 15

    Organism-specific databases

    HGNCiHGNC:188. ADAM10.

    Subcellular locationi

    Cell membrane; Single-pass type I membrane protein. Endomembrane system; Single-pass type I membrane protein
    Note: Is localized in the plasma membrane but is predominantly expressed in the Golgi apparatus and in released membrane vesicles derived likely from the Golgi.

    GO - Cellular componenti

    1. cell surface Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. extracellular vesicular exosome Source: UniProt
    4. Golgi apparatus Source: UniProtKB
    5. Golgi-associated vesicle Source: UniProtKB
    6. integral component of membrane Source: UniProtKB
    7. membrane Source: UniProtKB
    8. nucleus Source: UniProtKB
    9. perinuclear endoplasmic reticulum Source: UniProt
    10. plasma membrane Source: Reactome
    11. postsynaptic density Source: Ensembl
    12. tetraspanin-enriched microdomain Source: UniProt

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Reticulate acropigmentation of Kitamura (RAK) [MIM:615537]: A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti139 – 1391P → S in RAK. 1 Publication
    VAR_070907
    Natural varianti524 – 5241C → Y in RAK. 1 Publication
    VAR_070910
    Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset form of Alzheimer disease, a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.1 Publication
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti170 – 1701Q → H in AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced beta-amyloid plaque load and reactive gliosis. 1 Publication
    VAR_070908
    Natural varianti181 – 1811R → G in AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced beta-amyloid plaque load and reactive gliosis. 1 Publication
    VAR_070909

    Keywords - Diseasei

    Alzheimer disease, Amyloidosis, Disease mutation, Neurodegeneration

    Organism-specific databases

    MIMi615537. phenotype.
    615590. phenotype.
    Orphaneti178307. Reticulate acropigmentation of Kitamura.
    PharmGKBiPA24505.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Propeptidei20 – 213194By similarityPRO_0000029066Add
    BLAST
    Chaini214 – 748535Disintegrin and metalloproteinase domain-containing protein 10PRO_0000029067Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi222 ↔ 313By similarity
    Glycosylationi267 – 2671N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi278 – 2781N-linked (GlcNAc...)3 Publications
    Disulfide bondi344 ↔ 451By similarity
    Disulfide bondi399 ↔ 435By similarity
    Glycosylationi439 – 4391N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi484 ↔ 515By similarity
    Disulfide bondi503 ↔ 511By similarity
    Disulfide bondi524 ↔ 543By similarity
    Disulfide bondi530 ↔ 562By similarity
    Glycosylationi551 – 5511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi555 ↔ 567By similarity
    Disulfide bondi572 ↔ 598By similarity
    Disulfide bondi580 ↔ 607By similarity
    Disulfide bondi582 ↔ 597By similarity
    Disulfide bondi594 ↔ 639By similarity
    Disulfide bondi632 ↔ 645By similarity

    Post-translational modificationi

    The precursor is cleaved by a furin endopeptidase.By similarity

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

    Proteomic databases

    MaxQBiO14672.
    PaxDbiO14672.
    PRIDEiO14672.

    PTM databases

    PhosphoSiteiO14672.

    Miscellaneous databases

    PMAP-CutDBO14672.

    Expressioni

    Tissue specificityi

    Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver.2 Publications

    Inductioni

    In osteoarthritis affected-cartilage.

    Gene expression databases

    ArrayExpressiO14672.
    BgeeiO14672.
    CleanExiHS_ADAM10.
    GenevestigatoriO14672.

    Organism-specific databases

    HPAiCAB001709.

    Interactioni

    Subunit structurei

    Interacts with EPHA2 By similarity. 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.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi106616. 11 interactions.
    DIPiDIP-39889N.
    IntActiO14672. 5 interactions.
    MINTiMINT-5000775.
    STRINGi9606.ENSP00000260408.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1M1Imodel-A207-453[»]
    ProteinModelPortaliO14672.
    SMRiO14672. Positions 218-646.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 672653ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini694 – 74855CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei673 – 69321HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini220 – 456237Peptidase M12BPROSITE-ProRule annotationAdd
    BLAST
    Domaini457 – 55195DisintegrinPROSITE-ProRule annotationAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi171 – 1788Cysteine switchBy similarity
    Motifi708 – 7158SH3-bindingSequence Analysis
    Motifi722 – 7287SH3-bindingSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi555 – 673119Cys-richAdd
    BLAST

    Domaini

    The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
    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.By similarity

    Sequence similaritiesi

    Contains 1 disintegrin domain.PROSITE-ProRule annotation
    Contains 1 peptidase M12B domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH3-binding, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG271989.
    HOGENOMiHOG000008148.
    HOVERGENiHBG050455.
    InParanoidiO14672.
    KOiK06704.
    OMAiHEDDIKY.
    OrthoDBiEOG7SBNNQ.
    PhylomeDBiO14672.
    TreeFamiTF352021.

    Family and domain databases

    Gene3Di3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProiIPR027053. ADAM_10.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view]
    PANTHERiPTHR11905:SF113. PTHR11905:SF113. 1 hit.
    PfamiPF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    [Graphical view]
    SMARTiSM00050. DISIN. 1 hit.
    [Graphical view]
    SUPFAMiSSF57552. SSF57552. 1 hit.
    PROSITEiPS50215. ADAM_MEPRO. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O14672-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MVLLRVLILL LSWAAGMGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK    50
    RAVSHEDQFL RLDFHAHGRH FNLRMKRDTS LFSDEFKVET SNKVLDYDTS 100
    HIYTGHIYGE EGSFSHGSVI DGRFEGFIQT RGGTFYVEPA ERYIKDRTLP 150
    FHSVIYHEDD INYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEVTQIPQEE 200
    HAANGPELLR KKRTTSAEKN TCQLYIQTDH LFFKYYGTRE AVIAQISSHV 250
    KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF 300
    LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY 350
    SDGKKKSLNT GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT 400
    PGESKNLGQK ENGNYIMYAR ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN 450
    CFVESGQPIC GNGMVEQGEE CDCGYSDQCK DECCFDANQP EGRKCKLKPG 500
    KQCSPSQGPC CTAQCAFKSK SEKCRDDSDC AREGICNGFT ALCPASDPKP 550
    NFTDCNRHTQ VCINGQCAGS ICEKYGLEEC TCASSDGKDD KELCHVCCMK 600
    KMDPSTCAST GSVQWSRHFS GRTITLQPGS PCNDFRGYCD VFMRCRLVDA 650
    DGPLARLKKA IFSPELYENI AEWIVAHWWA VLLMGIALIM LMAGFIKICS 700
    VHTPSSNPKL PPPKPLPGTL KRRRPPQPIQ QPQRQRPRES YQMGHMRR 748
    Length:748
    Mass (Da):84,142
    Last modified:January 1, 1998 - v1
    Checksum:i0881E65B17022A71
    GO
    Isoform 2 (identifier: O14672-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         19-319: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:447
    Mass (Da):49,047
    Checksum:iAAD95BF5D660C7D8
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti162 – 1621N → SERLKLRLRKLMSLELWTSC CLPCALLLHSWKKAVNSHCL YFKDFWGFSEIY in CAA88463. (PubMed:8694785)Curated
    Sequence conflicti212 – 2121K → R in CAA88463. (PubMed:8694785)Curated
    Sequence conflicti296 – 2961G → S in CAA88463. (PubMed:8694785)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti139 – 1391P → S in RAK. 1 Publication
    VAR_070907
    Natural varianti170 – 1701Q → H in AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced beta-amyloid plaque load and reactive gliosis. 1 Publication
    VAR_070908
    Natural varianti176 – 1761H → Y in a cutaneous metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_066309
    Natural varianti181 – 1811R → G in AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced beta-amyloid plaque load and reactive gliosis. 1 Publication
    VAR_070909
    Natural varianti524 – 5241C → Y in RAK. 1 Publication
    VAR_070910

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei19 – 319301Missing in isoform 2. 1 PublicationVSP_056401Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF009615 mRNA. Translation: AAC51766.1.
    AK300472 mRNA. Translation: BAG62190.1.
    AC018904 Genomic DNA. No translation available.
    AC091046 Genomic DNA. No translation available.
    Z48579 mRNA. Translation: CAA88463.1.
    CCDSiCCDS10167.1.
    RefSeqiNP_001101.1. NM_001110.3.
    UniGeneiHs.172028.
    Hs.578508.
    Hs.745136.

    Genome annotation databases

    EnsembliENST00000260408; ENSP00000260408; ENSG00000137845.
    ENST00000396140; ENSP00000379444; ENSG00000137845.
    GeneIDi102.
    KEGGihsa:102.
    UCSCiuc002afd.1. human.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF009615 mRNA. Translation: AAC51766.1 .
    AK300472 mRNA. Translation: BAG62190.1 .
    AC018904 Genomic DNA. No translation available.
    AC091046 Genomic DNA. No translation available.
    Z48579 mRNA. Translation: CAA88463.1 .
    CCDSi CCDS10167.1.
    RefSeqi NP_001101.1. NM_001110.3.
    UniGenei Hs.172028.
    Hs.578508.
    Hs.745136.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1M1I model - A 207-453 [» ]
    ProteinModelPortali O14672.
    SMRi O14672. Positions 218-646.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106616. 11 interactions.
    DIPi DIP-39889N.
    IntActi O14672. 5 interactions.
    MINTi MINT-5000775.
    STRINGi 9606.ENSP00000260408.

    Chemistry

    BindingDBi O14672.
    ChEMBLi CHEMBL5028.

    Protein family/group databases

    MEROPSi M12.210.

    PTM databases

    PhosphoSitei O14672.

    Proteomic databases

    MaxQBi O14672.
    PaxDbi O14672.
    PRIDEi O14672.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000260408 ; ENSP00000260408 ; ENSG00000137845 .
    ENST00000396140 ; ENSP00000379444 ; ENSG00000137845 .
    GeneIDi 102.
    KEGGi hsa:102.
    UCSCi uc002afd.1. human.

    Organism-specific databases

    CTDi 102.
    GeneCardsi GC15M058887.
    HGNCi HGNC:188. ADAM10.
    HPAi CAB001709.
    MIMi 602192. gene.
    615537. phenotype.
    615590. phenotype.
    neXtProti NX_O14672.
    Orphaneti 178307. Reticulate acropigmentation of Kitamura.
    PharmGKBi PA24505.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG271989.
    HOGENOMi HOG000008148.
    HOVERGENi HBG050455.
    InParanoidi O14672.
    KOi K06704.
    OMAi HEDDIKY.
    OrthoDBi EOG7SBNNQ.
    PhylomeDBi O14672.
    TreeFami TF352021.

    Enzyme and pathway databases

    BioCyci MetaCyc:ENSG00000137845-MONOMER.
    BRENDAi 3.4.24.81. 2681.
    Reactomei REACT_118572. Degradation of the extracellular matrix.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_150401. Collagen degradation.
    REACT_160089. Constitutive Signaling by NOTCH1 HD Domain Mutants.
    REACT_160106. Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    REACT_9417. Signaling by EGFR.
    SignaLinki O14672.

    Miscellaneous databases

    ChiTaRSi ADAM10. human.
    GeneWikii ADAM10.
    GenomeRNAii 102.
    NextBioi 385.
    PMAP-CutDB O14672.
    PROi O14672.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14672.
    Bgeei O14672.
    CleanExi HS_ADAM10.
    Genevestigatori O14672.

    Family and domain databases

    Gene3Di 3.40.390.10. 1 hit.
    4.10.70.10. 1 hit.
    InterProi IPR027053. ADAM_10.
    IPR001762. Blood-coag_inhib_Disintegrin.
    IPR024079. MetalloPept_cat_dom.
    IPR001590. Peptidase_M12B.
    IPR002870. Peptidase_M12B_N.
    [Graphical view ]
    PANTHERi PTHR11905:SF113. PTHR11905:SF113. 1 hit.
    Pfami PF00200. Disintegrin. 1 hit.
    PF01562. Pep_M12B_propep. 1 hit.
    [Graphical view ]
    SMARTi SM00050. DISIN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF57552. SSF57552. 1 hit.
    PROSITEi PS50215. ADAM_MEPRO. 1 hit.
    PS50214. DISINTEGRIN_2. 1 hit.
    PS00142. ZINC_PROTEASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases."
      Rosendahl M.S., Ko S.C., Long D.L., Brewer M.T., Rosenzweig B., Hedl E., Anderson L., Pyle S.M., Moreland J., Meyers M.A., Kohno T., Lyons D., Lichenstein H.S.
      J. Biol. Chem. 272:24588-24593(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 216-237.
    2. "Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types."
      Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.
      Biochem. J. 317:45-50(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 109-748 (ISOFORM 1).
    3. "Analysis of the DNA sequence and duplication history of human chromosome 15."
      Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
      , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
      Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Placenta.
    5. "Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes."
      McKie N., Edwards T., Dallas D.J., Houghton A., Stringer B., Graham R., Russell G., Croucher P.I.
      Biochem. Biophys. Res. Commun. 230:335-339(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    6. "ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles."
      Gutwein P., Mechtersheimer S., Riedle S., Stoeck A., Gast D., Joumaa S., Zentgraf H., Fogel M., Altevogt P.
      FASEB J. 17:292-294(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    7. "The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein."
      Vincent B., Paitel E., Saftig P., Frobert Y., Hartmann D., De Strooper B., Grassi J., Lopez-Perez E., Checler F.
      J. Biol. Chem. 276:37743-37746(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "ADAM-10 protein is present in human articular cartilage primarily in the membrane-bound form and is upregulated in osteoarthritis and in response to IL-1alpha in bovine nasal cartilage."
      Chubinskaya S., Mikhail R., Deutsch A., Tindal M.H.
      J. Histochem. Cytochem. 49:1165-1176(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    9. "Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells."
      Lemjabbar H., Basbaum C.
      Nat. Med. 8:41-46(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    10. "Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans."
      Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.
      Cell 123:291-304(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION IN A COMPLEX WITH EFNA5 AND EPHA3, FUNCTION IN EFNA5-EPHA3 SIGNALING.
    11. "Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach."
      Lewandrowski U., Moebius J., Walter U., Sickmann A.
      Mol. Cell. Proteomics 5:226-233(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278.
      Tissue: Platelet.
    12. Cited for: FUNCTION IN CLEAVAGE OF FASLG.
    13. "Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis."
      Martin L., Fluhrer R., Haass C.
      J. Biol. Chem. 284:5662-5670(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CLEAVAGE OF ITM2B.
    14. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278.
      Tissue: Liver.
    15. "Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
      Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
      Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278.
      Tissue: Leukemic T-cell.
    16. Cited for: FUNCTION IN CLEAVAGE OF JAM3.
    17. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. "Ectodomain shedding and autocleavage of the cardiac membrane protease corin."
      Jiang J., Wu S., Wang W., Chen S., Peng J., Zhang X., Wu Q.
      J. Biol. Chem. 286:10066-10072(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN CLEAVAGE OF CORIN.
    19. "Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity."
      Kim M., Suh J., Romano D., Truong M.H., Mullin K., Hooli B., Norton D., Tesco G., Elliott K., Wagner S.L., Moir R.D., Becker K.D., Tanzi R.E.
      Hum. Mol. Genet. 18:3987-3996(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AD18 HIS-170 AND GLY-181, CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181.
    20. "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma."
      Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., Rudloff U., Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.
      Hum. Mutat. 32:E2148-E2175(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TYR-176.
    21. "Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease."
      Kono M., Sugiura K., Suganuma M., Hayashi M., Takama H., Suzuki T., Matsunaga K., Tomita Y., Akiyama M.
      Hum. Mol. Genet. 22:3524-3533(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS RAK SER-139 AND TYR-524.
    22. "ADAM10 missense mutations potentiate beta-amyloid accumulation by impairing prodomain chaperone function."
      Suh J., Choi S.H., Romano D.M., Gannon M.A., Lesinski A.N., Kim D.Y., Tanzi R.E.
      Neuron 80:385-401(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181.

    Entry informationi

    Entry nameiADA10_HUMAN
    AccessioniPrimary (citable) accession number: O14672
    Secondary accession number(s): B4DU28, Q10742, Q92650
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 28, 2003
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 148 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Peptidase families
      Classification of peptidase families and list of entries
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3