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Protein

Disintegrin and metalloproteinase domain-containing protein 10

Gene

ADAM10

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Zn2+By similarityNote: 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

  • endopeptidase activity Source: UniProtKB
  • integrin binding Source: UniProtKB
  • metalloendopeptidase activity Source: UniProtKB
  • metallopeptidase activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • receptor binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • axon guidance Source: Reactome
  • cell-cell signaling Source: UniProtKB
  • collagen catabolic process Source: Reactome
  • constitutive protein ectodomain proteolysis Source: UniProtKB
  • ephrin receptor signaling pathway Source: Reactome
  • epidermal growth factor receptor signaling pathway Source: Reactome
  • extracellular matrix disassembly Source: Reactome
  • extracellular matrix organization Source: Reactome
  • integrin-mediated signaling pathway Source: UniProtKB
  • in utero embryonic development Source: UniProtKB
  • membrane protein ectodomain proteolysis Source: UniProtKB
  • monocyte activation Source: BHF-UCL
  • negative regulation of cell adhesion Source: UniProtKB
  • Notch receptor processing Source: Reactome
  • Notch signaling pathway Source: UniProtKB
  • PMA-inducible membrane protein ectodomain proteolysis Source: BHF-UCL
  • positive regulation of cell growth Source: BHF-UCL
  • positive regulation of cell migration Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of T cell chemotaxis Source: BHF-UCL
  • protein phosphorylation Source: UniProtKB
  • response to tumor necrosis factor Source: BHF-UCL
Complete GO annotation...

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_264198. EPH-ephrin mediated repulsion of cells.
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 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:188. ADAM10.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 672653ExtracellularSequence AnalysisAdd
BLAST
Transmembranei673 – 69321HelicalSequence AnalysisAdd
BLAST
Topological domaini694 – 74855CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • Golgi-associated vesicle Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: UniProtKB
  • nucleus Source: UniProtKB
  • perinuclear endoplasmic reticulum Source: UniProtKB
  • plasma membrane Source: Reactome
  • postsynaptic density Source: Ensembl
  • tetraspanin-enriched microdomain Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Reticulate acropigmentation of Kitamura (RAK)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:615537
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)1 Publication

Disease susceptibility is associated with variations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:615590
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. 2 Publications
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. 2 Publications
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
Modified residuei719 – 7191Phosphothreonine1 Publication

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

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

BgeeiO14672.
CleanExiHS_ADAM10.
ExpressionAtlasiO14672. baseline and differential.
GenevisibleiO14672. HS.

Organism-specific databases

HPAiCAB001709.
HPA050670.

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. Interacts with NGF in a divalent cation-dependent manner.By similarity2 Publications

Protein-protein interaction databases

BioGridi106616. 17 interactions.
DIPiDIP-39889N.
IntActiO14672. 5 interactions.
MINTiMINT-5000775.
STRINGi9606.ENSP00000260408.

Structurei

3D structure databases

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

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.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiO14672.
KOiK06704.
OMAiEGFIQTH.
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. AlignAdd to basket

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

        10         20         30         40         50
MVLLRVLILL LSWAAGMGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK
60 70 80 90 100
RAVSHEDQFL RLDFHAHGRH FNLRMKRDTS LFSDEFKVET SNKVLDYDTS
110 120 130 140 150
HIYTGHIYGE EGSFSHGSVI DGRFEGFIQT RGGTFYVEPA ERYIKDRTLP
160 170 180 190 200
FHSVIYHEDD INYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEVTQIPQEE
210 220 230 240 250
HAANGPELLR KKRTTSAEKN TCQLYIQTDH LFFKYYGTRE AVIAQISSHV
260 270 280 290 300
KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF
310 320 330 340 350
LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY
360 370 380 390 400
SDGKKKSLNT GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT
410 420 430 440 450
PGESKNLGQK ENGNYIMYAR ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN
460 470 480 490 500
CFVESGQPIC GNGMVEQGEE CDCGYSDQCK DECCFDANQP EGRKCKLKPG
510 520 530 540 550
KQCSPSQGPC CTAQCAFKSK SEKCRDDSDC AREGICNGFT ALCPASDPKP
560 570 580 590 600
NFTDCNRHTQ VCINGQCAGS ICEKYGLEEC TCASSDGKDD KELCHVCCMK
610 620 630 640 650
KMDPSTCAST GSVQWSRHFS GRTITLQPGS PCNDFRGYCD VFMRCRLVDA
660 670 680 690 700
DGPLARLKKA IFSPELYENI AEWIVAHWWA VLLMGIALIM LMAGFIKICS
710 720 730 740
VHTPSSNPKL PPPKPLPGTL KRRRPPQPIQ QPQRQRPRES YQMGHMRR
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. 2 Publications
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. 2 Publications
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:
EMBLi
GenBanki
DDBJi
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. [O14672-1]
RefSeqiNP_001101.1. NM_001110.3. [O14672-1]
UniGeneiHs.172028.
Hs.578508.
Hs.745136.

Genome annotation databases

EnsembliENST00000260408; ENSP00000260408; ENSG00000137845.
GeneIDi102.
KEGGihsa:102.
UCSCiuc002afd.1. human. [O14672-1]

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:
EMBLi
GenBanki
DDBJi
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. [O14672-1]
RefSeqiNP_001101.1. NM_001110.3. [O14672-1]
UniGeneiHs.172028.
Hs.578508.
Hs.745136.

3D structure databases

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

Protein-protein interaction databases

BioGridi106616. 17 interactions.
DIPiDIP-39889N.
IntActiO14672. 5 interactions.
MINTiMINT-5000775.
STRINGi9606.ENSP00000260408.

Chemistry

BindingDBiO14672.
ChEMBLiCHEMBL5028.

Protein family/group databases

MEROPSiM12.210.

PTM databases

PhosphoSiteiO14672.

Proteomic databases

MaxQBiO14672.
PaxDbiO14672.
PRIDEiO14672.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260408; ENSP00000260408; ENSG00000137845.
GeneIDi102.
KEGGihsa:102.
UCSCiuc002afd.1. human. [O14672-1]

Organism-specific databases

CTDi102.
GeneCardsiGC15M058887.
HGNCiHGNC:188. ADAM10.
HPAiCAB001709.
HPA050670.
MIMi602192. gene.
615537. phenotype.
615590. phenotype.
neXtProtiNX_O14672.
Orphaneti178307. Reticulate acropigmentation of Kitamura.
PharmGKBiPA24505.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG271989.
GeneTreeiENSGT00670000097974.
HOGENOMiHOG000008148.
HOVERGENiHBG050455.
InParanoidiO14672.
KOiK06704.
OMAiEGFIQTH.
OrthoDBiEOG7SBNNQ.
PhylomeDBiO14672.
TreeFamiTF352021.

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_264198. EPH-ephrin mediated repulsion of cells.
REACT_9417. Signaling by EGFR.
SignaLinkiO14672.

Miscellaneous databases

ChiTaRSiADAM10. human.
GeneWikiiADAM10.
GenomeRNAii102.
NextBioi35475079.
PMAP-CutDBO14672.
PROiO14672.
SOURCEiSearch...

Gene expression databases

BgeeiO14672.
CleanExiHS_ADAM10.
ExpressionAtlasiO14672. baseline and differential.
GenevisibleiO14672. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "Nerve growth factor inhibits metalloproteinase-disintegrins and blocks ectodomain shedding of platelet glycoprotein VI."
    Wijeyewickrema L.C., Gardiner E.E., Gladigau E.L., Berndt M.C., Andrews R.K.
    J. Biol. Chem. 285:11793-11799(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NGF.
  17. Cited for: FUNCTION IN CLEAVAGE OF JAM3.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  19. "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.
  20. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  21. "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.
  22. "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.
  23. "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.
  24. "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: July 22, 2015
This is version 158 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.