Human Gene ADAM10 (ENST00000260408.8) from GENCODE V44
Description: Homo sapiens ADAM metallopeptidase domain 10 (ADAM10), transcript variant 2, mRNA. (from RefSeq NM_001320570) RefSeq Summary (NM_001110): Members of the ADAM family are cell surface proteins with a unique structure possessing both potential adhesion and protease domains. This gene encodes and ADAM family member that cleaves many proteins including TNF-alpha and E-cadherin. Alternate splicing results in multiple transcript variants encoding different proteins that may undergo similar processing. [provided by RefSeq, Feb 2016]. Gencode Transcript: ENST00000260408.8 Gencode Gene: ENSG00000137845.15 Transcript (Including UTRs) Position: hg38 chr15:58,588,809-58,749,707 Size: 160,899 Total Exon Count: 16 Strand: - Coding Region Position: hg38 chr15:58,597,547-58,749,534 Size: 151,988 Coding Exon Count: 16
ID:ADA10_HUMAN DESCRIPTION: RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10; Short=ADAM 10; EC=3.4.24.81; AltName: Full=CDw156; AltName: Full=Kuzbanian protein homolog; AltName: Full=Mammalian disintegrin-metalloprotease; AltName: CD_antigen=CD156c; Flags: Precursor; FUNCTION: 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. CATALYTIC ACTIVITY: Endopeptidase of broad specificity. COFACTOR: Binds 1 zinc ion (By similarity). SUBUNIT: 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. SUBCELLULAR LOCATION: 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. TISSUE SPECIFICITY: Expressed in spleen, lymph node, thymus, peripheral blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver. INDUCTION: In osteoarthritis affected-cartilage. DOMAIN: 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. PTM: The precursor is cleaved by a furin endopeptidase (By similarity). SIMILARITY: Contains 1 disintegrin domain. SIMILARITY: Contains 1 peptidase M12B domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14672
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa05010 - Alzheimer's disease hsa05120 - Epithelial cell signaling in Helicobacter pylori infection
BioCarta from NCI Cancer Genome Anatomy Project h_appPathway - Generation of amyloid b-peptide by PS1
Reactome (by CSHL, EBI, and GO)
Protein O14672 (Reactome details) participates in the following event(s):
R-HSA-6799350 Exocytosis of specific granule membrane proteins R-HSA-6798747 Exocytosis of tertiary granule membrane proteins R-HSA-157629 NOTCH2-ligand complex is cleaved to produce NEXT2 R-HSA-157649 Notch 4-ligand complex is cleaved to produce NEXT4 R-HSA-9013284 NOTCH3-ligand complex is cleaved to produce NEXT3 R-HSA-2168960 Collagen type XVII ectodomain shedding R-HSA-4224014 E-cadherin degradation by ADAM10, ADAM15 R-HSA-8952289 FAM20C phosphorylates FAM20C substrates R-HSA-157632 Complex of NOTCH1 with its ligand is cleaved to produce NEXT1 R-HSA-2220944 ADAM10/17 cleaves ligand-bound NOTCH1 PEST domain mutants to produce NEXT1 PEST domain mutants R-HSA-2220976 NOTCH1 HD+PEST domain mutants are cleaved by ADAM10/17 irrespective of ligand binding R-HSA-2666278 NOTCH1 t(7;9)(NOTCH1:M1580_K2555) is cleaved to produce NEXT1 R-HSA-2730752 NOTCH1 HD domain mutants are cleaved to produce NEXT1 irrespective of ligand binding R-HSA-177946 Pro-EGF is cleaved to form mature EGF R-HSA-3928665 EPH-ephrin mediated repulsion of cells R-HSA-6798695 Neutrophil degranulation R-HSA-2682334 EPH-Ephrin signaling R-HSA-156988 Receptor-ligand binding initiates the second proteolytic cleavage of Notch receptor R-HSA-2979096 NOTCH2 Activation and Transmission of Signal to the Nucleus R-HSA-1980150 Signaling by NOTCH4 R-HSA-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus R-HSA-1442490 Collagen degradation R-HSA-1474228 Degradation of the extracellular matrix R-HSA-168249 Innate Immune System R-HSA-422475 Axon guidance R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275 Post-translational protein phosphorylation R-HSA-1980145 Signaling by NOTCH2 R-HSA-157118 Signaling by NOTCH R-HSA-9012852 Signaling by NOTCH3 R-HSA-2122948 Activated NOTCH1 Transmits Signal to the Nucleus R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-2660826 Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691232 Constitutive Signaling by NOTCH1 HD Domain Mutants R-HSA-1474244 Extracellular matrix organization R-HSA-168256 Immune System R-HSA-1266738 Developmental Biology R-HSA-177929 Signaling by EGFR R-HSA-392499 Metabolism of proteins R-HSA-597592 Post-translational protein modification R-HSA-162582 Signal Transduction R-HSA-1980143 Signaling by NOTCH1 R-HSA-2644602 Signaling by NOTCH1 PEST Domain Mutants in Cancer R-HSA-2894858 Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer R-HSA-2660825 Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant R-HSA-2691230 Signaling by NOTCH1 HD Domain Mutants in Cancer R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-2644603 Signaling by NOTCH1 in Cancer R-HSA-5663202 Diseases of signal transduction R-HSA-1643685 Disease
US Server
